QRS 2nd BDS Jyotsna Rao

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in
Contents
Foreword vii Topic 3 Tissue Repair: Regeneration,

Preface ix Healing and Fibrosis 136
Acknowledgements xi
Topic 4 Haemodynamic Disorders,
Thrombosis and Shock 141
Section I Topic 5 Diseases of the Immune System 161
Dental Materials Topic 6 Neoplasia 170
Topic 1 Introduction 3 Topic 7 Genetic and Paediatric Diseases 186
Topic 2 Structure of Matter and Principles Topic 8 Environmental and Nutritional
of Adhesion 4 Disorders 187
Topic 3 Physical Properties of Dental Materials 5 Topic 9 Infections and Infestations 192
Topic 4 Mechanical Properties of Topic 10 Heart and Blood Vessels 194
Dental Materials 9 Topic 11 Haematopoietic and Lymphoid
Topic 5 Dental Polymers 11 Systems 196
Topic 6 Solid Solutions Phases in Cast Alloys 13 Topic 12 Lung 214
Topic 7 Biocompatibility of Dental Materials 13 Topic 13 Diseases of Oral Cavity and Salivary
Topic 8 Impression Materials 14 Glands 215
Topic 9 Gypsum Products 24 Topic 14 Liver, Gallbladder and Biliary Tract 221
Topic 10 Dental Waxes 29 Topic 15 Male and Female Genital System 222
Topic 11 Casting Investments and Procedures 33 Topic 16 Endocrine System 222
Topic 12 Finishing and Polishing Materials 44 Topic 17 Musculoskeletal System 224
Topic 13 Bonding 47 Topic 18 Skin 227
Topic 14 Restorative Resins 50 Topic 19 Nervous System 229
Topic 15 Dental Cements 55 Topic 20 Miscellaneous 230
Topic 16 Dental Amalgam 70 Key Points to Remember 231
Topic 17 Direct Filling Gold 78
Topic 18 Dental Ceramics 85
Topic 19 Denture Base Resins 89
Section III
Topic 20 Dental Implants 96
Microbiology
Key Points to Remember 97 Part I: GENERAL MICROBIOLOGY
Topic 1 Historical Introduction 241
Section II Topic 2 Morphology and Physiology
General Pathology of Bacteria 242
Topic 1 Cell Injury, Cell Death and Topic 3 Sterilization and Disinfection 248
Adaptations 109 Topic 4 Culture Media 256
Topic 2 Acute and Chronic Inflammation 120 Topic 5 Culture Methods 260
xiii
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xiv Contents
Topic 6 Identification of Bacteria Topic 30 Herpes Viruses 324

and Bacterial Taxonomy 264 Topic 31 Adenoviruses and Picornaviruses 326
Topic 7 Bacterial Genetics 264 Topic 32 Orthomyxo and Paramyxo Viruses 327
Topic 8 Infection 267 Topic 33 Arbo and Rhabdoviruses 328
Topic 9 Immunity 269 Topic 34 Hepatitis Viruses 330
Topic 10 Antigens and Antibodies: Topic 35 Oncogenic Viruses 332
Immunoglobulins, Antigen–Antibody Topic 36 Human Immunodeficiency Virus
Reactions 273 (HIV)/AIDS 333
Topic 11 Complement Systems 277
Topic 12 Structure and Function of Immune Part IV: SYSTEMIC MYCOLOGY
System, Immune Response and Topic 37 Fungal Diseases 336
Immunodeficiency Diseases 277
Topic 13 Hypersensitivity 280 Part V: MEDICAL PARASITOLOGY
Topic 14 Autoimmunity, Immunology Topic 38 Protozoans 339
of Transplantation and Malignancy 285 Topic 39 Helminthes 347
Topic 15 Miscellaneous 286
Part VI: DENTAL MICROBIOLOGY
Part II: SYSTEMIC BACTERIOLOGY
Topic 40 Dental Microbiology 350
Topic 16 Staphylococcus, Streptococcus,
Key Points to Remember 353
Pneumococcus and Neisseria 288
Topic 17 Corynebacterium 297
Topic 18 Mycobacterium (Tuberculosis, Section IV
Atypical Mycobacteria and Pharmacology
Mycobacterium Leprae) 301
Topic 19 Clostridium 304 Part I: ENERAL PHARMACOLOGICAL
G
Topic 20 Nonsporing Anaerobes 308 PRINCIPLES
Topic 21 Enterobacteriaceae (Coliforms: Topic 1 Definitions, Routes of Drug
Proteus, Shigella and Salmonella) 309 Administration 361
Topic 22 Vibrio 312 Topic 2 Pharmacokinetics 367
Topic 23 Pseudomonas, Yersinia, Pasteurella, Topic 3 Pharmacodynamics 372
Francisella, Haemophilus, Bordetella Topic 4 Adverse Drug Effects 378
and Brucella 314
Topic 24 Spirochetes: Treponema Pallidum, Part II: RUGS ACTING ON
D
Borrelia Vincentii 315 AUTONOMIC NERVOUS SYSTEM
Topic 25 Actinomycetes, Rickettsiaceae Topic 5 Cholinergic System and Drugs 383
and Chlamydiae 319 Topic 6 Anticholinergic Drugs and Drugs
Topic 26 Miscellaneous 319 Acting on Autonomic Ganglia 388
Topic 7 Adrenergic System and Drugs 394
Part III: MEDICAL VIROLOGY Topic 8 Antiadrenergic Drugs 400
Topic 27 General Properties of Viruses 321
Topic 28 Bacteriophage: Structure Part III: UTOCOIDS AND RELATED
A
DRUGS
and Significance 324
Topic 29 Poxviruses 324 Topic 9 Histamines and Antihistamines 404
Contents xv
Topic 10 5-Hydroxytryptamine, Its Antagonists Topic 29 CNS Stimulants and Cognition

and Drug Therapy of Migraine, Enhancers 476
Prostaglandins, Leukotrienes
(Eicosanoids) and Platelet-Activating Part VIII: CARDIOVASCULAR DRUGS
Factor 407 Topic 30 Drugs Affecting Renin-Angiotensin
Topic 11 Nonsteroidal Anti-inflammatory System and Plasmakinins 477
Drugs and Antipyretic Analgesics 409 Topic 31 Cardiac Glycosides and Drugs
Topic 12 Additional Drugs for Rheumatoid for CHF 477
Arthritis and Drugs for Gout 416 Topic 32 Antiarrhythmic Drugs 479
Topic 33 Antianginal and other Anti-ischaemic
Part IV: RESPIRATORY SYSTEM Drugs 480
Topic 13 Drugs for Cough and Bronchial Topic 34 Antihypertensive Drugs 484
Asthma 417
Part IX: DIURETICS AND ANTIDIURETICS
Part V: ORMONES AND RELATED
H Topic 35 Diuretics and Antidiuretics 489
DRUGS
Part X: RUGS AFFECTING BLOOD
D
Topic 14 Anterior Pituitary Hormones, Thyroid
AND BLOOD FORMATION
Hormone and Thyroid Inhibitors 420
Topic 15 Insulin, Oral Hypoglycaemics and Topic 36 Haematinics and Erythropoietin 494
Glucagon 423 Topic 37 Drugs Affecting Coagulation,
Topic 16 Corticosteroids 431 Bleeding and Thrombosis 499
Topic 17 Gonadal Hormones (Sex Hormones) Topic 38 Hypolipoproteinaemic Drugs
and their Antagonists 437 and Plasma Expanders 507
Topic 18 Oxytocin and Drugs Acting on
Part XI: GASTROINTESTINAL DRUGS
Uterus 438
Topic 19 Drugs Affecting Calcium Balance 438 Topic 39 Drugs for Peptic Ulcer 509
Topic 40 Emetics, Antiemetics and Other
Part VI: RUGS ACTING ON
D Gastrointestinal Drugs 514
PERIPHERAL NERVOUS SYSTEM Topic 41 Drugs for Constipation and
Topic 20 Skeletal Muscle Relaxants 442 Diarrhoea 517
Topic 21 Local Anaesthetics 446
Part XII: ANTIMICROBIAL DRUGS
Part VII: D
RUGS ACTING ON CENTRAL Topic 42 General Considerations 519
NERVOUS SYSTEM Topic 43 Sulphonamides, Co-trimoxazole
Topic 22 General Anaesthetics 451 and Quinolones 522
Topic 23 Ethyl and Methyl Alcohol 458 Topic 44 Beta-Lactam Antibiotics 526
Topic 24 Sedatives/Hypnotics 458 Topic 45 Tetracyclines and Chloramphenicol 537
Topic 25 Antiepileptic Drugs 464 Topic 46 Aminoglycoside Antibiotics 541
Topic 26 Antiparkinsonian Drugs 467 Topic 47 Macrolide and other Antibacterial
Topic 27 Drugs Used in Mental Illness: Drugs in Treatment of Urinary Tract
Antipsychotic and Antianxiety Infections 544
Drugs 469 Topic 48 Antitubercular Drugs 546
Topic 28 Opioid Analgesics and Antagonists 471 Topic 49 Antileprotic Drugs 551
xvi Contents
Topic 50 Antifungal Drugs 553 Topic 61 Dental Pharmacology 572

Topic 51 Antiviral Drugs 555
Key Points to Remember 577
Topic 52 Antimalarial Drugs 557
Topic 53 Antiamoebic and other
Antiprotozoal Drugs 558 Section V
Topic 54 Anthelmintics 560 Self-Assessment Questions
Multiple Choice Questions 585
Part XIII: C
HEMOTHERAPY OF Viva Questions 621
NEOPLASTIC DISEASES
Topic 55 General Considerations 561
Section VI
Part XIV: MISCELLANEOUS Previous Years’ Question Bank
Section I Dental Materials 633
Topic 56 Immunosuppressants, Gene Therapy
Section II General Pathology 641
and Drugs Acting on Skin and
Section III Microbiology 649
Mucous Membranes 564
Section IV Pharmacology 657
Topic 57 Antiseptics, Disinfectants
and Ectoparasiticides 565 Index 677
Topic 58 Chelating Agents 567
Topic 59 Vitamins 569 Online university exam patterned
Topic 60 Vaccines and Sera 571 MCQs and solved papers
Section I
Dental Materials
Topic 1 Introduction 3
Topic 2 Structure of Matter and Principles of Adhesion 4
Topic 3 Physical Properties of Dental Materials 5
Topic 4 Mechanical Properties of Dental Materials 9
Topic 5 Dental Polymers 11
Topic 6 Solid Solutions Phases in Cast Alloys 13
Topic 7 Biocompatibility of Dental Materials 13
Topic 8 Impression Materials 14
Topic 9 Gypsum Products 24
Topic 10 Dental Waxes 29
Topic 11 Casting Investments and Procedures 33
Topic 12 Finishing and Polishing Materials 44
Topic 13 Bonding 47
Topic 14 Restorative Resins 50
Topic 15 Dental Cements 55
Topic 16 Dental Amalgam 70
Topic 17 Direct Filling Gold 78
Topic 18 Dental Ceramics 85
Topic 19 Denture Base Resins 89
Topic 20 Dental Implants 96
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Section I
Dental Materials
Topic 1
Introduction
l Father of dentistry: Pierre Fauchard ADA
l Father of modern dentistry: GV Black Specification
List of American National Standards Institute/American No. Title
Dental Association Specifications for dental materials, in- 21. Zinc–silicon–phosphate cement
struments and equipments: 22. Intraoral dental radiographic film
23. Dental excavating burs
ADA
Specification 24. Dental base plate wax
No. Title 25. Dental gypsum products
1. Alloy for dental amalgam 26. Dental X-ray equipment
2. Gypsum-bonded casting investment for dental 27. Direct filling resins
gold alloy
28. Endodontic files and reamers
3. Dental impression compound
29. Hand instruments
4. Dental inlay casting wax
30. Zinc oxide- eugenol restorative materials
5. Dental casting gold alloy
31. Exposure time designation for timers of X-ray
6. Dental mercury machines
7. Dental wrought gold wire alloy 32. Orthodontic wires
8. Dental zinc phosphate cement 33. Dental terminology
9. Dental silicate cement 34. Dental aspirating syringes
10. Denture rubber (obsolete) 35. High-speed air-driven handpicks
11. Dental agar impression material 36. Diamond rotary instruments
12. Denture base polymers 37. Dental abrasive powders
13. Denture cold-curing repair resin 38. Porcelain–alloy systems
14. Dental base metal casting alloy 39. Pit and fissure sealant
15. Synthetic resin teeth 40. Dental implants
16. Dental impression paste zinc oxide eugenol type a. Unalloyed titanium for dental implants
17. Denture base temporary relining resin b. Cast cobalt–chromium–molybdenum
alloys for dental implants
18. Dental alginate impression material
41. Recommended standard practices for
19. Elastomeric dental impression materials
biological evaluation of dental materials
20. Dental duplicating material
42. Phosphate-bonded investment
3
4 Quick Review Series: BDS 2nd Year
ADA ADA
Specification Specification
No. Title No. Title
43. Mechanical amalgamators 68. Aspirating syringes not operating on the
harpoon mechanism
44. Dental electrosurgical equipment
69. Dental ceramics
45. Porcelain teeth
70. Dental X-ray protective aprons and accessory
46. Dental chairs
devices
47. Dental units
71. Root canal-filling condensers and spreaders
48. Ultraviolet activators and disclosing lights
72. Endodontic spreaders
49. Analgesic equipment
73. Dental absorbent points
50. Casting machines (deleted)
74. Dental stools
51. Gas furnaces (deleted)
75. Resilient denture liners
52. Uranium content in dental porcelain and
76. Nonsterile latex gloves for dentistry
porcelain teeth
77. Stiffness of tufted area of toothbrushes
53. Crown and bridge resins
78. Dental obtruding point
54. Dental needles
79. Dental vacuum pumps
55. Dispensers of mercury and alloy for dental
amalgam 80. Colour stability test procedure
56. Dental floss (deleted) 81. Magnets and keepers used for intraoral and
extraoral retainers for prosthetic restorations
57. Endodontic filling materials
82. Combined reversible/irreversible hydrocolloid
58. Root canal files, type H (Hedstrom)
impression materials
59. Portable steam autoclave sterilizer
83. Indicator pastes
60. Jet injectors (deleted)
84. Panoramic X-ray equipment
61. Zinc polycarboxylate cement
85. Prophy angles
62. Dental abrasive pastes
86. Intraligamentary and perio syringes
63. Rasps and barbed broaches
87. Impression trays
64. Dental explorers
88. Impression alloys
65. Low-speed handpicks
89. Dental operating lights
66. Glass ionomer cements
90. Rubber dams
67. Ligament injection syringes
Topic 2
Structure of Matter and Principles of Adhesion

SHORT NOTES
Q. 1. Contact angle l Contact angle determines the extent to which an adhe-
Ans. sive wets the surface of an adherend.
l It is used as a measure of wettability.
l The angle formed at the interface of the adhesive and l No wetting occurs at a contact angle of 180°, and com-
adherend is known as contact angle. plete wetting occurs at an angle of 0°.
Section | I Dental Materials 5
Q. 2. Wetting agent l A space lattice can be defined as any arrangement of

Ans. atoms in space such that every atom is situated similarly
to every other atom.
A wetting agent is a surface-active substance that reduces l Space lattice is also known as crystal structure and
the surface tension of a liquid to promote wetting or adhe- may be the result of primary, secondary or metallic
sion. bonds.
l Although there are 14 possible lattice types or forms,
Q. 3. Space lattice most of the metals used in dentistry belong to cubic
Ans. system.
Topic 3
Physical Properties of Dental Materials

LONG ESSAYS
Q. 1. What are tarnish and corrosion? What are the Examples:
causes of corrosion? How do you avoid the same? l In the oral cavity, various sulphides like hydrogen sul-
phide or ammonium sulphide corrode silver, copper,

Ans.
mercury and similar metals present in dental amalgam
and dental alloys.
l Water, oxygen and chloride ions also contribute to cor-
TARNISH rosion attack, various acid solutions such as phosphoric
l Tarnish is a surface discolouration on a metal or acid, acetic acid and lactic acid are also present. At
even a light loss or alteration of the surface finish or times and at proper concentration and pH, these can
lustre. promote corrosion.
l Tarnish generally occurs in the oral cavity due to the l Among the specific ions responsible for corrosion,
following: oxygen and chloride have been said to be responsible

l Deposits on the tooth or restoration surface for amalgam corrosion both at tooth interface and
l Formation of hard deposits, e.g. calculus and soft within the body of amalgam. Sulphide has been impli-
deposits, e.g. plaque cated for corroding silver-containing casting alloys.
l Stains—pigment-producing bacteria, foods contain-
Protection against corrosion can be obtained by the follow-
ing sulphur or chlorides, drinks like coffee and tea,
ing methods:
drugs containing iron and use of tobacco cause tar-
1. Passivation
nish and discolouration of restorations and tooth
2. Increasing noble metal content
structure
3. Polishing restorations
l Surface films—formation of thin surface films of
4. Avoid dissimilar metal restorations
oxides, sulphides or chlorides causes discolouration
of restorations
Passivation
CORROSION
l Certain metals readily form strong adherent oxide film
l Corrosion is an actual deterioration of a metal by the on their surface, which protects them from corrosion.
reaction with the environment. Such a metal is said to be passive.
l Tarnish is often the forerunner of corrosion.
l In due course, there is disintegration of the metal, Since this oxide film is passive to oxidative chemical
which leads to rapid mechanical failure of the attack, their formation is called passivation, e.g. chromium,
structure. titanium and aluminium.
If more than 12% Cr is added to iron or cobalt, we get

l
Polishing Restorations
stainless steel or cobalt-chromium alloys, which are
lightly corrosion resistant and suitable for dental use. Well-polished metallic restoration to a high lustre removes
crevices and surface roughness, minimizing crevice or cell
corrosion.
Increasing Noble Metal Content
Alloys with a noble metal content below 65% may tar-
l
Avoid Dissimilar Metal Restorations
nish. So it has been suggested that at least 50% atoms in
a dental alloy should be gold, platinum and palladium to l In case of two dissimilar metals in contact, paints or
ensure against corrosion. another nonconductive film can be used to advantage if
l Noble metals resist corrosion because their electromo- it is applied to the more noble metal.
tive force (EMF) is positive with regard to any of l Iron, steel and certain other metals that are subjected to cor-
the common reduction reactions found in the oral rosion may also be electroplated with nickel followed by
environment. chromium for corrosion protection and aesthetic reasons.
SHORT ESSAYS
Q. 1. Types of corrosion
Ans. Corrosion is an actual deterioration of a metal by the TYPES OF ELECTROLYTIC CORROSION
reaction with the environment.
Galvanic Corrosion
Various types of corrosion are as follows:
Galvanic corrosion occurs when dissimilar metals lie in
direct physical contact with each other and saliva with its
CLASSIFICATION OF CORROSION salts provides a weak electrolyte.
a. Dry corrosion or chemical corrosion Examples:
b. Aqueous or electrolytic corrosion l If a gold restoration comes in contact with an amalgam
i. Galvanic corrosion restoration, the amalgam forms the anode and starts
ii. Heterogeneous composition corrosion corroding. The electric couple created when the two
iii. Stress corrosion restorations touch causes sharp pain called galvanic
iv. Concentration cell corrosion or crevice corrosion shock.
l It can be minimized by painting a varnish on the
surface of the amalgam restoration. However, the

Dry Corrosion or Chemical Corrosion
best precaution is to avoid dissimilar metals in
Dry corrosion or chemical corrosion is a nonaqueous corro- contact.
sion in which the metal reacts to form oxides and sulphides
in the absence of electrolytes.
Heterogeneous Compositions Corrosion
Examples:
This kind of corrosion occurs within the structure of the
l Formation of Ag2S in dental alloys containing silver
restoration itself. Heterogeneous (mixed) compositions can
l Oxidation of alloy particles in dental amalgam
cause galvanic corrosion.
l Tarnishing of brass due to formation of sulphides
l Discolouration of surfaces of castings caused by oxidation Examples:

l When an eutectic alloy is immersed in an electrolyte,
the metallic grains with the lower electrode potential are

Electrochemical Corrosion
attacked and corrosion results
l It is also known as electrolytic or electrochemical or wet l Cored structures in a single phase alloy grains
corrosion or aqueous corrosion. l Grain boundaries in metals or homogenized alloys. The
l It occurs in oral environment by electrochemical grain boundaries may act as anodes and the interior of
reactions. the grain as the cathode
l It requires the presence of water or other fluid electro- l Solder joints may also corrode due to the inhomoge-
lytes. There is formation of free electrons and the electro- neous composition
lyte provides the pathway for the transport of electrons. l Impurities in any alloy enhance corrosion
TABLE 3.1 Differences between Tarnish and Corrosion

Stress Corrosion
Tarnish Corrosion
A metal that has been stressed by cold working becomes
1. It is a process by which 1. It is not a surface discolou-
more reactive at the site of maximum stress. If stressed and a metal surface is ration but actual deteriora-
unstressed metals are in contact in an electrolyte, the stressed dulled or discoloured tion of a metal by the reac-
metal will become the anode of a galvanic cell and will cor- when a reaction with a tion with the environment
rode, e.g. if an orthodontic wire has been cold worked, stress sulphide, oxide, chlo- 2. The various causes of cor-
corrosion may occur and cause the wire to break. ride or other chemical rosion are as follows:
causes a thin film to a. In the oral cavity, various
form sulphides like hydrogen
2. Tarnish generally occurs sulphide or ammonium
Concentration Cell Corrosion or Crevice in the oral cavity due to sulphide, corrode silver,
Corrosion the following: copper, mercury and
a. Deposits on the similar metals present in
l Electrolyte concentration cell: In a metallic restoration tooth or restoration dental amalgam and
that is partly corroded by food debris, the composition surface dental alloys
of the electrolyte under the debris will differ from that b. Stains: produced b. Water, oxygen and
by pigment-pro- chloride ions, various
of saliva, and this can contribute to the corrosion of the ducing bacteria, acids and solutions
restoration. foods containing such as phosphoric,
l Oxygen concentration cell: Differences in oxygen ten- sulphur or chlo- acetic and lactic acids
sion between parts of the same restoration cause corro- rides, drinks like present in oral cavity at
sion of the restoration. Greater corrosion in the part of coffee and tea, times and at proper
drugs containing concentration and pH
the restoration having lower concentration of oxygen. iron and use of to- can promote corrosion
bacco c. Among the specific
Q. 2. Classification and causes of corrosion c. Surface films: for- ions responsible for
mation of thin sur- corrosion, oxygen and
Ans. face films of ox- chloride have been
ides, sulphides or said to be responsible
l Corrosion is not a surface discolouration but actual chlorides cause for amalgam corrosion
deterioration of a metal by the reaction with the envi- discolouration of both at tooth interface
ronment. Tarnish is often the forerunner of corrosion. restorations and within the body of
In due course, there is disintegration of the metal, 3. Tarnish can be pre- amalgam
which leads to rapid mechanical failure of the structure. vented by the following: 3. Protection against corro-
a. Good oral prophy- sion can be obtained by
l For classification of corrosion, refer to the answer of
laxis following methods:
Short Essays, Q. 1. b. Reducing the intake a. Passivation
l The various causes of corrosion are as follows: of coffee and tea b. Increasing noble metal
l In the oral cavity various sulphides like hydrogen and use of content
sulphide or ammonium sulphide, corrode silver, cop- tobacco c. Polishing restorations
d. Avoid dissimilar metal
per, mercury and similar metals present in dental restorations
amalgam and dental alloys.
l Water, oxygen and chloride ions also contribute to
Q. 4. Electrolytic corrosion
corrosion attack.
l Various acids and solutions such as phosphoric, acetic Ans.
and lactic acids present in oral cavity at times and at
proper concentration and pH can promote corrosion.
l Among the specific ions responsible for corrosion,
ELECTROLYTIC OR ELECTROCHEMICAL
oxygen and chloride have been said to be responsible OR WET CORROSION
for amalgam corrosion both at tooth interface and 1. This requires the presence of water or other fluid elec-
within the body of amalgam. trolytes. There is formation of free electrons and the
l Sulphide has been implicated for corroding silver
electrolyte provides the pathway for the transport of
containing casting alloys. electrons.
Types of aqueous or electrolytic corrosion are as follows:
Q. 3. Write briefly on tarnish and corrosion, and dif-
a. Galvanic corrosion
ferentiate between them.
b. Heterogeneous composition corrosion
Ans. Refer to the answer of Long Essays, Q. 1 for the c. Stress corrosion
introductory briefs of tarnish and corrosion (Table 3.1). d. Concentration cell corrosion or crevice corrosion
2. An electrolytic cell is as follows: M1 1 e2 n M0
M0 n M1 1 e2 2H1 1 2e2 n H2
2H2O 1 O2 1 4e2 n 4(OH)2
he anode is the surface where positive ions are formed.
T
hese reactions occurring at the cathode are referred to
T
This metal surface corrodes since there is loss of electrons.
as reduction reactions.
This reaction is sometimes referred to as oxidation reaction.
4. Since the anode loses electrons and the cathode con-
3. At the cathode, a reaction must occur that will consume sumes, the surface of anode corrodes due to loss of
the free electrons produced at the anode. electrons.
SHORT NOTES
Q. 1. Hue, value and chroma Q. 5. Coefficient of thermal expansion
Ans. Ans. The change in length per unit of original length of a
material when its temperature is raised by 1°K is known as
Hue: Dominant colour of an object, e.g. red, green or blue coefficient of thermal expansion.
Value: Relative lightness or darkness of a colour
Chroma: Degree of saturation of a particular hue Q. 6. Thermal conductivity (coefficient of thermal
conductivity)
Q. 2. Tarnish and corrosion
Ans. The property that describes the thermal energy trans-
Ans. Refer to the answer of Long Essays, Q. 1.
port in Watts per second through a specimen 1 cm thick
with a cross-sectional area of 1 cm2, when the temperature
Q. 3. Electrochemical corrosion differential between the surfaces of the specimen perpen-
dicular to the heat flow is 1°K, is known as coefficient of
Ans.
thermal conductivity.
l Electrolytic or electrochemical corrosion is also known
as wet corrosion. Q. 7. Dry corrosion or chemical corrosion
l It requires the presence of water or other fluid electrolytes.
l There is formation of free electrons, and the electrolyte Ans. Corrosion in which the metal reacts to form oxides
provides the pathway for the transport of electrons. and sulphides in the absence of electrolytes, e.g. oxidation
of Ag2S in dental alloys containing silver, oxidation of alloy
An electrolytic cell is as follows: particles in dental amalgam.
M0 n M1 1 e2
The anode is the surface where positive ions are formed. Q. 8. Galvanic corrosion
This metal surface corrodes since there is loss of electrons. Ans. The oral cavity, because of saliva, with its salts, provides
This reaction is sometimes referred to as oxidation reaction. a weak electrolyte. Galvanic corrosion is an important type of
At the cathode a reaction must occur that will consume electrolytic corrosion, which occurs when combination of dis-
the free electrons produced at the anode. The reaction oc- similar metals lies in direct physical contact with each other.
curring at the cathode is referred to as reduction reaction. If a gold restoration comes in contact with an amalgam
Hence the anode loses electrons and the cathode con- restoration, the amalgam can form the anode of an electri-
sumes them. The surface of anode corrodes due to loss of cal cell and starts corroding. The electric couple created
electrons. causes sharp pain called galvanic shock. The pain usually
occurs immediately after insertion and can be minimized by
Q. 4. Stress corrosion
painting a varnish on the surface of the amalgam restora-
Ans. tion. However, the best procedure is to avoid dissimilar
metals to be in contact.
l A metal that has been stressed by cold working becomes
more reactive at the site of maximum stress. Q. 9. Creep
l If stressed and unstressed metals are in contact in an
electrolyte, the stressed metal will become the anode of Ans.

a galvanic cell and will corrode. l Time-dependent plastic strain of a material under a
For example, if an orthodontic wire has been cold worked, static load or constant stress is known as creep.
stress corrosion may occur and cause the wire to break. l It is a dimensionless quantity.
Topic 4
Mechanical Properties of Dental Materials

SHORT ESSAYS
Q. 1. Define stress and strain, and mention different l The tests most frequently used in determining the hard-
types of tests for testing hardness. ness of dental materials are as follows:
1. Brinell hardness test
Ans.
2. Rockwell hardness test
3. Vickers hardness test
4. Knoop hardness test
STRESS 5. Barcol hardness test
Stress is defined as force per unit area within a structure 6. Shore hardness test
subjected to an external force or pressure.
Hardness tests
Force
(F )
Strees 5
Area
(A) Micro hardness tests Macro hardness tests
– Knoop hardness test – Brinell hardness test
– Vickers hardness test – Rockwell hardness test
STRAIN
Strain is defined as change in length per unit length and
BRINELL HARDNESS TEST
is the relative deformation of an object subjected to a
stress. l The Brinell hardness test has been used extensively for
determining the hardness of metals and metallic materi-
als used in dentistry.
Deformation or change in length e l In the Brinell test, a hardened steel ball is pressed under
Strain
orig inal length a specified load into the polished surface of a material.
The load is divided by the area of the projected surface
It is a dimensionless quantity and may be elastic or of the indentation, and the quotient is referred to as the
plastic or a combination of the two. Brinell hardness number (BHN).
HARDNESS ROCKWELL HARDNESS TEST

Hardness is a property that is used to predict the wear resis- l It is somewhat similar to Brinell hardness test in which
tance of a material and its ability to abrade opposing dental a steel ball or a conical diamond point is used. Here the
structures. depth of penetration is measured directly by a dial
The tests most frequently used in determining the hard- gauge on the instrument.
ness of dental materials are as follows: l Rockwell hardness number (RHN) is designated ac-
1. Brinell hardness test cording to particular indenter and load employed.

2. Rockwell hardness test l Neither Brinell hardness test nor the Rockwell hardness
3. Vickers hardness test test is suitable for brittle materials.

4. Knoop hardness test
5. Barcol hardness test
VICKERS HARDNESS TEST
6. Shore hardness test
l It employs same principle as that used in Brinell
Q. 2. Hardness tests test; instead of steel ball, a square based pyramid is
Ans. used.
l Here the load is divided by the projected area of inden-
l Hardness is defined as the resistance of a material to tation.

plastic deformation typically measured under an inden- l It is suitable for determining the hardness of brittle ma-
tation load. terials, e.g. tooth structure, casting gold alloys, etc.
The projected area is divided into the load to give the

KNOOP HARDNESS TEST l
Knoop hardness number (KHN).

l It employs a diamond-tipped tool rhombic in l The hardness values for exceedingly hard and soft
outline. materials can be obtained by this test.
SHORT NOTES
Q. 1. Ductility and malleability l There are many surface hardness tests. Tests most
frequently used in determining the hardness of dental
Ans.
materials are as follows:
1. Brinell hardness test
2. Rockwell hardness test
DUCTILITY
3. Vickers hardness test
l Ductility represents the ability of a material to sustain a 4. Knoop hardness test
large permanent deformation under a tensile load before 5. Barcol hardness test
it fractures, e.g. gold, silver, copper, etc. 6. Shore hardness test
l Gold is the most ductile and malleable pure metal, silver
being the second. Platinum ranks third in ductility. Q. 4. Resilience

l Ductilities can be compared by
Ans.
l their percentage of elongation or strain,
l percentage decrease of areas of cross sections, or l The relative amount of elastic energy per unit volume re-
l the number of cold bends at fracture. leased on unloading of a test specimen is known as resilience.
l The modulus of resilience is the maximum amount
MALLEABILITY of energy a material can absorb without undergoing

permanent deformation.
l The ability of a material to sustain considerable permanent l It can be expressed by the following formula:
deformation without rupture under compression, as in ham-
mering or rolling into a sheet, is known as malleability. R 5 P2/2E
l Malleability of metals can be determined by measuring
here P is the proportional limit and E is the modulus
w
the percentage increase in the area at fracture. of elasticity.
For example, gold is the most ductile and malleable pure l The units of resilience are expressed in terms of energy
metal, silver the second, and copper ranks third in malleability. per unit volume, i.e. J/m3.
Q. 2. Brinell hardness number Q. 5. Compressive and tensile stress
Ans. Ans.
l The Brinell hardness test is one of the oldest tests

employed for determining the hardness of metals. COMPRESSIVE STRESS
l In the Brinell test, a hardened steel ball is pressed under
l When a body is placed under a load that tends to com-
a specified load into the polished surface of a material. press or shorten it, the internal resistance to such a load
The load is divided by the area of the projected surface is called compressive stress.
of the indentation, and the quotient is referred to as the l To calculate compressive stress, the applied force is di-
Brinell hardness number (BHN). vided by the cross-sectional area perpendicular to the
l For a given load, the smaller the indentation, the larger
force direction.
is the number, and the harder is the material.
l The Brinell hardness test has been used extensively for
determining the hardness of metals and metallic materi-

TENSILE STRESS
als used in dentistry. Tensile stress is caused by a load that tends to stretch or
elongate a body. It is always accompanied by tensile strain.
Q. 3. Hardness Tests
Q. 6. Modulus of elasticity
Ans.
Ans.
l Hardness is a property that is used to predict the wear
resistance of a material and its ability to abrade oppos- l Modulus of elasticity is also known as elastic modulus
ing dental structures. or Young’s modulus.
l It describes the relative stiffness or rigidity of a material. 4. Flexural strength

l Ratio of elastic stress to elastic strain or tensile stress/ 5. Impact strength
tensile strain or compressive stress/compressive strain
gives a proportionality constant known as elastic modu- Ultimate Tensile Strength
lus or modulus of elasticity.
l Modulus of elasticity is given in units of force per unit
The maximum stress that a material can undergo in tension
area, i.e. giganewtons per square metre (GN/m2) or without fracture is known as the tensile strength or the ulti-
gigapascals (GPa). mate tensile strength (UTS).
Q. 7. Proportional limit Shear Strength

Ans. Shear strength is the maximum shear stress at the point of
l The proportional limit is the maximum stress at which fracture of a test specimen.
stress is proportional to strain and above which plastic
deformation occurs. Compressive Strength
l The proportional limit is the greatest elastic stress pos-
sible in accordance with Hooke’s law. Compressive stress within a compression test specimen at
the point of fracture is known as compressive strength.
Q. 8. Elastic limit
Ans. The elastic limit of a material is defined as the great- Flexural Strength
est stress to which a material can be subjected such that Flexural strength is also known as bending strength or
it returns to its original dimensions when the force is modulus of rupture. It is defined as force per unit area at the
released. point of fracture of a test specimen subjected to flexural
loading.
Q. 9. Name types of strength. Discuss importance of
strength in the study of dental materials. Impact Strength
Ans. Impact strength is defined as the energy required to fracture
l Strength is the stress necessary to cause either fracture a material under an impact force.
or a specified amount of plastic deformation.
Q. 10. Poisson’s ratio
l Strength is a measure of the interatomic forces collec-
tively over the entire wire, cylinder, implant, crown pin Ans. When a tensile force is applied along one axis to pro-
or whatever structure is stressed. duce elongation, compressive strain is produced at right
l Various types of strength are as follows: angles proportionately.
1. The ultimate tensile strength
Lateral strain
2. Shear strength Axial strain
3. Compressive strength Poisson, s ratio
Topic 5
Dental Polymers
LONG ESSAY
Q. 1. Describe polymerization mechanisms of composite POLYMERIZATION MECHANISMS
resins. Add a note on stages in addition polymerization.
As the resins are dimethacrylate monomers, they polymerize
Ans. by the addition mechanism that is initiated by free radicals.
The free radical can be generated by chemical activation or In some units, the light source is remote and is transmit-
external energy (heat, light). ted to the site of restoration through a light guide.
Based on the mode of activation of polymerization, two
types of composites are available:
CHEMICAL STAGES OF POLYMERIZATION
1. Chemically activated resins
2. Light-activated resins They can be described as occurring in four stages.
Chemically Activated Resins 1. Induction or Initiation Period

Chemically activated materials are supplied as two pastes, It is the time during which the molecules of the initiator
one of which contains the benzoyl peroxide initiator and become energized or activated and start transferring en-
the other a tertiary amine activator (i.e. N-N dimethyl- ergy to the monomer. The dental resin polymerization
p-toluidine). When the two pastes are spatulated, the amine processes are usually activated by one of the three induc-
reacts with the benzoyl peroxide to form free radicals, and tion systems:
polymerization is initiated. a. Heat activation: Most denture base resins are polymer-
ized by this method. For example, the free radicals lib-
erated by heating benzoyl peroxide will initiate the po-
Light-Activated Resins lymerization of methyl methacrylate monomer.
These are of two types: UV light-activated systems and b. Chemical activation: This system consists of at least two
visible light-activated resins. reactants and undergoes chemical reaction by liberating
free radicals when they are mixed, e.g. the use of benzoyl
peroxide and an aromatic amine (dimethyl-p-toluidine) in
UV Light-Activated Systems the self-cured dental resins.
The first light-activated system used was ultraviolet (UV) light. c. Light activation: In this system, photons of light en-
ergy activate the initiator to generate free radicals
Their limitations were as follows:
that, in turn, can initiate the polymerization process,
1. Limited depth of penetration of the light into the resin;
e.g. camphorquinone and an amine will react to form
thus it was difficult to polymerize thick sections.
free radicals, when they are irradiated with visible
2. Lack of penetration through tooth structure.
light.
Visible Light-Activated Resins 2. Propagation

They were developed later and have totally displaced the
Once the growth has started, only 5000–8000 calories per
UV light system. They are also more widely used than the
mole are required. The process continues at considerable
chemically activated resins.
velocity. The chain reactions should continue with the evo-
Light-curable composite resin restoratives are supplied
lution of heat until all the monomer has changed to poly-
as single paste that contains the following:
mer. Actually, the polymerization is never complete.
a. Photoinitiator: camphorquinone (0.25 wt%)
b. Amine accelerator: diethyl-amino-ethyl-methacrylate
(0.15 wt%) 3. Termination
When unexposed to light, they do not interact. However, The chain reactions can be terminated either by direct cou-
when exposed to light of the correct wavelength, the photo- pling or by exchange of a hydrogen atom from one growing
initiator is activated and interacts with the amine to form chain to another.
free radicals.
Camphorquinone has an absorption range between 400
Chain Transfer
and 800 mm. This is in the blue region of the visible light
spectrum. In some cases, inhibitors are added to enhance its The chain termination can also result from chain transfer.
stability to room light or dental operatory light. The process differs from the termination where ions
in the active state are transferred from an inactivated
radical to an inactive molecule. New nucleus of growth is
Light Devices
created.
The light source is usually a tungsten halogen bulb. The white In the same manner, an already terminated chain
light generated passes through a filter that removes the infrared might be reactivated by chain transfer and continue to
and visible spectrum for wavelengths greater than 500 mm. grow.
Topic 6
Solid Solutions Phases in Cast Alloys

SHORT NOTES
Q. 1. Solid solutions l When sugar is dissolved in water, the water is referred
to as the solvent and the sugar as the solute.
Ans. Solid solution (metallic) is a solid crystalline l When two metals are mutually soluble in the solid state,
phase containing two or more elements, at least one of the solvent is that metal whose crystal structure persists.
which is a metal, that are initially combined at the l In palladium-silver alloys, the two metals are com-
atomic level. pletely soluble in all proportions and the same type of
crystal structure occurs throughout the alloy system. In
such a case, the solvent is defined as the metal whose
Q. 2. Solute and solvent
atoms occupy the majority of the total number of posi-
Ans. tions in the crystal structure.
Topic 7
Biocompatibility of Dental Materials

SHORT ESSAYS
Q. 1. Define biocompatibility and explain pulpal response
to glass ionomer cement. PULP-CAPPING AGENTS
Ans. l Pulp-capping agents are the agents for pulp protection,
e.g. cavity varnishes, liners and bases.
l They are used as adjuncts to the use of restorative mate-
BIOCOMPATIBILITY rials to protect the pulp against various types of injuries

like thermal, chemical, etc.
It is the ability of a material to elicit an appropriate bio-
l In addition to serving as insulation against temperature
logical response in a given application in the study.
change, as a barrier against irritants released from re-
storative materials and as sealing agents against inter-
PULPAL RESPONSE TO GLASS IONOMER facial leakage with associated bacterial invasion, some
CEMENT of these agents may also provide caries prevention
benefits.
l Glass ionomer cement exhibits mild pulp response. l Typical cavity varnishes are principally natural gums,
l The glass ionomer cement is kind to the pulp, eliciting e.g. copal or resins, or synthetic resins, dissolved in
a response comparable to that of polycarboxylate an organic solvent, such as acetone, chloroform or
cement. ether.
l The glass ionomer cement is a biocompatible material,
Varnish must be applied in thin consistency. They re-
thus no pulp-protective agent is required except in the duce the pulpal irritation.
case of an actual exposure. l Cavity liner: Thin layer of cement, such as a cal-
cium hydroxide suspension in an aqueous or resin

Q. 2. Define biocompatibility of dental materials. Add a
carrier (after evaporation), used for protection of the
note on pulp-capping agents.
pulp, certain glass ionomer cements that are used as
Ans. Biocompatibility of dental materials is defined as an intermediate layer between tooth structure and
an ability of a material to elicit an appropriate biological composite restorative material are also considered
response in a given application in the body. liners.
Bases: In contrast to liners, bases are applied in much

Level I Tests
l
thicker layers (. 0.75 mm) under restorations to pro-

tect the pulp against thermal injury, galvanic shock Screening tests in which the material is evaluated for acute
and chemical irritation, depending on the particular systemic toxicity and for its cytotoxic, irritational, aller-
restorative material used. genic and carcinogenic potentials.
Examples include zinc phosphate cement, zinc oxide
eugenol, zinc polycarboxylate and glass ionomer cements. Level II Tests
Q. 3. Evaluation of toxicity of dental materials These are usage tests in which the material is evaluated in
experimental animals under conditions that simulate the
Ans. clinical use of the material.
If the screening and the usage tests show that the mate-
TOXIC EVALUATION OF DENTAL rial is safe, then level III tests are performed.
MATERIALS
Various tests are now available for evaluation of toxicity
Level III Tests
of dental materials. These tests can be classified into the The material is tested in humans for reactions and perfor-
following three categories: mance in the clinical situation.
Topic 8
Impression Materials
LONG ESSAYS
Q. 1. Classify impression materials and write in detail ALGINATE
about alginate material. The word alginate comes from algin, a peculiar mucous
Or, extract yielded by certain brown seaweed (algae).
Types:
Clarify impression materials, and write in detail about
l Type I: fast setting
the composition, chemical reaction and properties of
l Type II: normal setting
irreversible hydrocolloid impression material.
Ans. Available as follows:
l A powder that is packed in
See Table 8.1 for classification of impression materials. l bulk containers (tins, bins or sachets)
l preweighed packets for single impression

TABLE 8.1 Classification of Impression Materials
2. A plastic scoop for dispensing the bulk powder, and a
By Setting plastic cylinder for measuring the water.
Mechanism By Elasticity Modified alginates are also available
Chemical reaction Inelastic or Elastic materials
(irreversible) rigid l in the form of a sol, containing water. A reactor of plas-
materials ter of Paris is supplied separately.
l as a two-paste system; one contains the alginate sol,
l Plaster l Alginate hydrocolloid
of Paris l Nonaqueous elastomers while the second contains the calcium reactor.
l Zinc l Polysulphide
oxide l Polyether These materials are said to contain silicone and have supe-
eugenol l Condensation silicone rior resistance to tearing when compared to unmodified algi-
l Addition silicone nates. They may be supplied in both tray and syringe viscosity.
Thermally-induced Compound Agar hydrocolloid
physical reaction wax Application
(reversible)
It is used
1. for impression making sodium alginate sol, excess water, filler particles and
a. when there are undercuts. reaction by-products. It is a crosslinked structure. Cal-
b. in mouths with excessive salivation. cium is responsible for crosslinking.
c. for partial dentures with clasps.
2. for making preliminary impressions for complete dentures.
Properties of Alginate Hydrocolloid
3. for impressions to make study models and working casts.
4. for duplicating models. Taste and Odour
Alginate has a pleasant taste and smell. A variety of co-
Composition lours, odours and tastes have been added to make it as
pleasant as possible to the patient. Flavours include straw-
See Table 8.2 for composition of alginate.
berry, orange, mint, vanilla, etc.
TABLE 8.2 Composition of Alginate
Ingredients by Flexibility
Sl. no. Percentage Weight Functions It is about 14% at a stress of 1000 g/cm2. Lower W/P ratio
1. Sodium or Dissolves in water and (thick mixes) results in lower flexibility.
potassium or reacts with calcium ions
triethanolamine
alginate—15% Elasticity and Elastic Recovery
2. Calcium sulphate Reacts with potassium Alginate hydrocolloids are highly elastic but less when
(reactor)—16% alginate and forms
compared to agar, and about 97.3% elastic recovery occurs.
insoluble calcium alginate
Thus permanent deformation is more for alginate (about
3. Zinc oxide—4% Acts as a filler 1.2%). Permanent deformation is less if the set impression
4. Potassium titanium Gypsum hardener is removed from the mouth quickly.
fluoride—3%
5. Diatomaceous Acts as a filler
Reproduction of Tissue Detail
earth—60%
6. Sodium phosphate Reacts preferentially with Detail reproduction is also lower when compared to agar
(retarder)—2% calcium sulphate hydrocolloid.
7. Colouring and Traces, e.g. wintergreen,
flavouring agent peppermint, orange, etc. Strength
Compressive strength ranges between 5000 and 8000 g/cm2
Setting Reaction or 0.343–0.70 MPa.
l When alginate powder is mixed with water, a sol is Tear strength ranges between 350 and 700 g/cm2.
formed, which later sets to a gel by a chemical reaction. Factors affecting gel strength are as follows:
l The final gel, i.e. insoluble calcium alginate is produced l Water/powder (W/P ratio) too much or too much water
when soluble sodium alginate reacts with calcium sulphate reduces gel strength.
(reactor). This reaction proceeds too fast. There is not l Mixing time: Over and under mixing both reduce strength.
enough working time. So the reaction is delayed by addi- l Time of removal of impression: Strength increases if the
tion of a retarder (sodium phosphate) by the manufacturer. time of removal is delayed for few minutes after setting.
l Calcium sulphate prefers to react with the retarder first.
Only after the supply of the retarder is over does calcium

Dimensional Stability
sulphate react with sodium alginate. This delays the reac-
tion and ensures adequate working time for the dentist. Set alginates have poor dimensional stability due to evapo-
l In other words, two main reactions occur during setting ration, syneresis and imbibition. Therefore, the cast should
as follows: be poured immediately. If storage is unavoidable, keeping
l First, sodium phosphate reacts with the calcium sul- in a humid atmosphere of 100% relative humidity (humi-
phate to provide adequate working time. dor) results in the least dimensional change.
l After the sodium phosphate is used up, the remaining
calcium sulphate reacts with sodium alginate to form

Adhesion
insoluble calcium alginate which forms a gel with water.
l Gel Structure: The final gel consists of a brush heap of Alginate does not adhere well to the tray. Good adhesion is
calcium alginate fibril network enclosing unreacted important for the accuracy of the impression. Retention to
the tray is achieved by mechanical locking features in the l Undermixing results in

tray or by applying an adhesive. l inadequate wetting, lack of homogeneity and re-
duced strength.
l the mix being grainy and poor recording of detail.
Biological Properties l Working time
1
Silica particles present in the dust, which rises from the can l Fast set alginate: 1 ⁄4 min
after fluffing alginate powder, are a possible health hazard. l Normal set alginate: 2 min
Avoid breathing the dust. Presently, some manufacturers l Gelation time (setting time)
supply dust-free alginate. Dustless alginates contain glycol. Type I (fast set): 1–2.0 min
It acts by coating the powder. Types II (normal): 2–4.5 min
l Control of gelation time
l Gelation time is best controlled by adding retarders

Shelf Life and Storage by the manufacturers.
Alginate material deteriorates rapidly at elevated tempera- l The dentist can best control the setting time by alter-
tures and humid environment. ing the temperature of the water for mixing alginate
l The material should be stored in a cool, dry environ- material.
ment (not above 37°C). l Colder the water, longer is the gelation time.
l The lid of bulk package can/must be replaced after every l Warmer the water, shorter is the gelation time.
use, so as to minimize moisture contamination.

l Stock only for 1 year. Tray Selection
As alginate has poor adhesion, tray selection is very impor-
Manipulation tant. Alginate can be retained by the following:
l Mechanical locking features in the tray
l Fluff or aerate the powder by inverting the can several
l A rim lock
times to ensure uniform distribution of the filler before
l Perforations (holes or slits) in the tray
mixing. The top of the can should be taken off carefully to
l Applying a suitable adhesive (available as liquid or
prevent the very fine silica particles from being inhaled.
l A clean flexible plastic bowl and clean wide bladed,
sprays)
l A combination of the above
reasonably stiff metal spatula.
l The proper Water/Powder ratio as specified by the The tray should cover the entire impression area and
manufacturer should be used. Usually one measures provide a space of at least 3 mm on all sides.
water with two-level scoops of powder.
l The measured quantity of the powder is sprinkled in the
measured amount of water in the rubber mixing bowl, Loading the Tray
and the lid of the metal can is replaced immediately. l The mixed alginate is pressed and swiped into a perfo-
l The mixing is started with a stirring motion to wet the rated rim lock tray so that the material is forced out
powder with water. Once the powder has been moist- through the holes in the tray, thereby locking itself
ened, rapid spatulation by swiping against the side of mechanically into the tray.
the bowl is done. l A small amount of material is taken on the index finger
l A vigorous figure ‘8’ motion can also be used, which and applied on the occlusal surfaces of the teeth and
helps to remove most of the air bubbles. on the rugae area. This helps to reduce air voids and
l Mechanical devices are available for spatulating algi- improve accuracy.
nate. Their main advantages are as follows:
l Speed
Seating the Tray
l Convenience
l Elimination of the human variable Since the material sets from tissues towards periphery, any
l A proper mix is smooth and creamy with minimum movement during gelation may result in distortion. So once
voids and does not drip off the spatula when it is raised the tray is seated, it must be held in place firmly without
from the bowl. any movement.
l Mixing time
l For fast-set alginate: 45 s

Time of Removal
l For normal set alginate: 60 s
l Overmixing results in The alginate impression should be left in the mouth for at
l reduction in final strength, as the gel fibrils are least 2–3 min after initial gelation. The strength and elasticity
destroyed. of the alginate gel continues to increase for several minutes
l reduction in working time. after initial gelation.
Removal of the Impression Ans. Hydrocolloids are classified based on the mode of
gelation as follows:
The impression must be removed suddenly, with a jerk.
Reversible hydrocolloids: They are called reversible be-
Storage of Alginate Impression cause their physical state can be reversed and are reusable.
Irreversible hydrocolloids: Once these set, these are
Alginate impressions must be poured as soon as possible. usually permanent and, so, are known as irreversible.
l If it becomes necessary to store the impression, the
following methods may be used: REVERSIBLE HYDROCOLLOIDS (AGAR)
l Wrap the impression lightly in a wet paper towel and
cover with a rubber bowl. l Agar hydrocolloid was the first successful elastic im-
l Keep the impression in a plastic bag.
pression material to be used in dentistry.
l It is an organic hydrophilic colloid (polysaccharide)
extracted from certain types of seaweed. It is a sulphuric

Construction of Cast ester of a linear polymer of galactose.
l See Table 8.3 for composition of agar hydrocolloid.
l The stone cast should not be separated for at least 30 min.
For alginate, best results are obtained if the cast is re-
moved at 1 h. TABLE 8.3 Composition of Agar Hydrocolloid
l The cast should not be left in the impression for too long
Ingredients Percentage of Weight (wt%)
a period either because
Agar 13–17
l it can result in a rough and chalky surface.
l alginate dries and stiffens. Removal can break the Borates 0.2–0.5
teeth and other thin portions of the cast. Potassium sulphate 1–2
Wax (hard) 0.5–1
Impression Disinfection Thixotropic materials 0.3–0.5
The irreversible hydrocolloids may be disinfected by 10 min. Alkylbenzoates 0.1

immersion in, or spraying of, some antimicrobial agent (e.g. Colouring and flavouring Traces
sodium hypochlorite, glutaraldehyde) without significant agents
dimensional changes.
Water Balance (around 84)
Advantages of Alginate
Functions of Each Ingredient
Alginate is a popular material because
l it is easy to mix and manipulate. l Agar: Basic constituent, 13–17% for tray material and
l minimum requirement of equipment and cost-effective. 6–8% for syringe material.
l flexibility of the set impression and accuracy if properly l Borates: It improves the strength of the gel.
handled. It gives a good surface detail even in presence l Potassium sulphate: It counters retarding effect of
of saliva. borates, thereby ensures proper setting of the cast

l comfortable to the patient. or dye.
l Wax (hard) or zinc oxide or diatomaceous earth or sil-
ica, clay, rubber, etc.

Disadavantages of Alginate They act as fillers, which affect the strength, viscosity
l Poor dimensional stability and poor tear strength. and rigidity of the gel.
l It cannot be electroplated so metal dyes not possible. l Thixotropic materials, e.g. glycerine and thymol.
l Distortion may occur without it being obvious if the They act as plasticizer and thymol acts as bactericide also.
material is not held steady while it is setting and it can- l Alkylbenzoates: These act as preservative.
not be corrected. l Colouring and flavouring agents: These are used for
l Because of the above drawbacks, it is not recommended patient comfort.

when a high level of accuracy is required, e.g. cast RPD, l Water: It acts as the dispersion medium.
crown and bridge, etc.
Q. 2. Classify hydrocolloid impression materials. De-

Manipulation
scribe the composition and manipulation of revers- Agar hydrocolloid requires special equipments as follows:
ible hydrocolloids. Mention briefly about wet field 1. Hydrocolloid conditioner
technique. 2. Water-cooled rim lock trays
The hydrocolloid conditioner consists of the following: removed rapidly from the mouth with a single stroke or
snap.
l The impression is rinsed thoroughly with water, and the
Boiling section 10 min in boiling water (100°C)
or The sol should be homogeneous excess water is removed by shaking the impression.
Liquefaction section and free of lumps.
Every time the material is reliquefied,
3 min should be added as it is more Storage of Agar Impression
difficult to break down the agar brush
heap structure after a previous use. l Storage of agar impression is to be avoided at all costs,
and no satisfactory medium for storage is available.
Storage section 65–68°C temperature is ideal. It can
l The cast should be poured immediately.
be stored in the sol condition till
needed. l Storage in air results in dehydration, and storage in water
results in swelling of the impression. Storage in 100%

Tempering section 46°C for about 2 min with the mate-
rial loaded in the tray. This is done relative humidity results in shrinkage as a result of con-
to reduce the temperature so that tinued formation of the agar network agglomeration.
this can be tolerated by the sensitive l If storage is unavoidable, it should be limited to 1 h in
oral tissues. It also makes the mate- 100% relative humidity.
rial viscous.
Wet Field Technique

Impression Trays
l This is a relatively new technique, which has become
l Rim lock trays with water circulating devices: The rim popular.
lock is a beading on the inside edge of the tray that l The areas to be recorded are actually flooded with warm
helps to retain the material (as agar does not adhere to water. Then the syringe material is introduced quickly,
the tray). liberally and in bulk to cover the occlusal and/or incisal
l It also has an inlet and outlet for connecting the water areas only.
tubes. l While the syringe material is still liquid, the tray material
l The tray should allow a space of 3 mm occlusally and is seated. The hydraulic pressure of the viscous tray materi-
laterally and extend distally to cover all teeth. als forces the fluid syringe hydrocolloid down into the ar-
eas to be recorded. This motion displaces the syringes
Making the Impression materials as well as blood and debris throughout the sulcus.
l The tray containing the tempered material is removed Q. 3. Zinc oxide eugenol impression paste
from the bath. The outer surface of the agar sol is
Ans. Zinc oxide eugenol (ZOE) impression paste
scrapped off, then the water hoses are connected and the
tray is positioned in the mouth by the dentist. It is widely used in dentistry as
l Water is circulated at 18–21°C through the tray until
gelation occurs. Rapid cooling (e.g. ice cold water) is l cementing and insulating medium;
not recommended as it can induce distortion. l temporary filling and root canal filling material;
l surgical pack in periodontal surgical procedures;
l To guide the tray into position, three stops of compound
l temporary relining material for dentures and
are prepared on noninvolved teeth. A postdam is con-
l impression material for edentulous patients.
structed with compound to prevent distal flow of the
impression material.
l In a deep palate case, compound is placed on the palatal
CLASSIFICATION
aspect of the tray in order to provide a uniform thick-
ness of the hydrocolloid. According to ADA Specification No. 16, zinc oxide euge-
l The mandibular tray is prepared by placing compound nol impression paste is of following types:
on the distal aspect to limit the impression material. l Type I or hard
Black tray compound is used as it is not affected in the l Type II or soft
tempering bath.
AVAILABLE AS
Removal of Impression ZOE is available in paste form in two tubes as follows:
l When the agar has gelled, the peripheral seal around l Base paste (white in colour)
the impression is broken, and the impression is l Accelerator in reactor or catalyst paste (red in colour)
COMPOSITION OF ZINC OXIDE EUGENOL SETTING TIME

IMPRESSION PASTE Once the material is in place, it should set fast.
The impressions should be seated in the mouth before
Base Paste Accelerator Paste the initial set.
Zinc oxide—87% Oil of cloves or eugenol—12%
Fixed vegetable—13% Gum or polymerized rosin—50% Type of ZOE Initial Setting Final Setting
Filler (silica type)—20%
Paste Time Time
Lanolin—3%
Resinous balsam—10% Type I 3–6 min 10 min
Accelerator solution (CaCl2) and
colouring agents—5% Type II 3–6 min 15 min
Zinc oxide should be finely divided and should contain

PROPERTIES
l
slight amount of water.

l Fixed vegetable or mineral oil acts as plasticizer and
Consistency and Flow
also aids in masking the action of eugenol as an irritant.
l Oil of cloves contains 70–85% eugenol. It is sometimes A paste of thick consistency can compress the tissues. A
used in preference to eugenol because it reduces burn- thin free-flowing material copies the tissues without distort-
ing sensation. ing them.
l Gum or polymerized rosin speeds the reaction.
According to ADA Specification No. 16, the spread is:
l Canada balsam and Peru balsam improve flow and mix-
l Type I pastes: 30–50 mm.
ing properties.
l Type II pastes: 20–45 mm.
l Calcium chloride acts as an accelerator of setting reaction.
Clinically, these materials have a very good flow.
Other accelerators are as follows:
l Zinc acetate Detail Reproduction
l Primary alcohols
It registers surface details quite accurately due to the good flow.
l Glacial acetic acid
Rigidity and Strength

SETTING REACTION
The impression should resist fracture and be unyielding
The setting reaction is a typical acid–base reaction to form
when removed from the mouth. The compressive strength
a chelate. This reaction is also known as chelation and the
of hardened ZOE is 7 MP at 2 hours after mixing.
product is called zinc eugenolate.
1 . ZnO 1 H2O n Zn(OH)2
2. Zn(OH)2 1 2HE n ZnE2 1 2H2O
Base acid (eugenol) The salt (zinc eugenolate) The dimensional stability is quite satisfactory. A negligible
shrinkage less than 0.1% may occur during hardening.
MICROSTRUCTURE
Biological Considerations
l The chelate (zinc eugenolate) forms a matrix surround-
ing a core of zinc oxide particles. The chelate is thought Some patients experience a burning sensation in the mouth
to form as an amorphous gel that tends to crystallize due to eugenol. It can also cause tissue irritation. This may
giving strength to the set mass. be overcome by using a noneugenol paste.
l Formation of crystalline zinc eugenolate is greatly en-
hanced by zinc acetate dehydrate (accelerator), which is

MANIPULATION
more soluble than Zn(OH)2 and can supply zinc ions
more rapidly. The mixing is done on an oil-impervious paper or glass
slab. Two ropes of paste of the same length and width, one
from each tube, are squeezed onto the mixing slab. A flex-
WORKING TIME ible stainless steel spatula is used. The two ropes are com-
There should be sufficient time for mixing, loading onto the bined with the first sweep of the spatula and mixed until a
tray and seating the impression into the mouth. uniform colour is observed.
ADVANTAGES l Minor defects can be corrected locally without discard-

ing a good impression.
l It has sufficient body so as to make up for any minor un-
der extensions in the tray itself during impression making.
l It has enough working time to complete border moulding.
DISADVANTAGES
l It can be checked in the mouth repeatedly without l It requires a special tray for impression making.
deforming. l It is sticky in nature and adheres to tissues.
l It registers accurate surface details and it is dimension- l Eugenol can cause burning sensation and tissue irri
ally stable. tation.
l It does not require any separating media since it does l It cannot be used for making impression of teeth and
not stick to the cast material. undercut areas as it is inelastic in nature.
SHORT ESSAYS
Q. 1. Properties and applications of alginate impression Adhesion
material
Alginate does not adhere well to the tray. Good adhesion is
Ans. important for the accuracy of the impression. Retention to
the tray is achieved by mechanical locking features in the
tray or by applying an adhesive.
PROPERTIES OF ALGINATE HYDROCOLLOID
Taste and Odour Biological Properties

Alginate has a pleasant taste and smell. A variety of co- The dust which rises on fluffing alginate powder contains
lours, odours and tastes have been added to make it as silica particles which are a possible health hazard. Avoid
pleasant to the patient. breathing the dust. Presently, some manufacturers supply
dust-free alginate. Dustless alginates contain glycol.
Flexibility
Shelf Life and Storage
It is about 14% at a stress of 1000 g/cm2. Lower W/P ratio
(thick mixes) results in lower flexibility. Alginate material deteriorates rapidly at elevated tempera-
tures and humid environment.
Elasticity and Elastic Recovery l The material should be stored in a cool, dry environ-
ment (not above 37°C).
Alginate hydrocolloids are highly elastic but less when l The lid of bulk package can or must be replaced after
compared to agar and about 97.3% elastic recovery occurs. every use so as to minimize moisture contamination.
l Stock only for 1 year.
Reproduction of Tissue Detail

Detail reproduction is also lower when compared to agar
APPLICATIONS OF ALGINATE
hydrocolloid. HYDROCOLLOID
l It is used for impression making
l when there are undercuts.
Strength
l in mouths with excessive salivation.
l Compressive strength ranges between 5000 and l for partial dentures with clasps.
8000 g/cm2 or 0.343 and 0.70 MPa. l for making preliminary impressions for complete dentures.
2
l Tear strength ranges between 350 and 700 g/cm . l for impressions to make study models and working
casts.
l for duplicating models.
Set alginates have poor dimensional stability due to evapo- Q. 2. What are the uses of zinc oxide eugenol impression
ration, syneresis and imbibition. Therefore, the cast should paste? Add a note on composition and setting reaction
be poured immediately. of zinc oxide eugenol impression paste.
Ans. Zinc oxide eugenol impression paste is widely used SETTING REACTION
in dentistry as:
The setting reaction is a typical acid–base reaction to form
l cementing and insulating medium. a chelate. The reaction is also known as chelation and the
l temporary filling and root canal filling material. product is called zinc eugenolate.
l surgical pack in periodontal surgical procedures. ZnO 1 H2O n Zn(OH)2
l temporary relining material for dentures. Zn(OH)2 1 2HE n ZnE2 1 2H2O
l impression material for edentulous patients. Base acid (eugenol) The salt (zinc eugenolate)
l the impression paste is used for making final impression
l The chelate (zinc eugenolate) formed is a matrix sur-
and as a corrective lining in the primary impression.
rounding free zinc oxide particle. The reaction can take
place either in solution or at the surface of the zinc
COMPOSITION oxide particles.
l The chelate is thought to form an amorphous gel that tends
It is available commercially in paste form in two tubes as
to crystallize imparting increased strength to the set mass.
follows:
l Formation of the crystalline zinc eugenolate is greatly
1. Base paste (white in colour)
enhanced when the setting reaction is accelerated by
2. Accelerator paste or reactor paste or catalyst paste (red
zinc acetate dehydrate, which is more soluble than
in colour)
Zn(OH)2 and can supply zinc ions more rapidly.
l The incorporation of rosin reduces crystallization of the
Base Paste Accelerator Paste chelate gel. An acid, such as acetic, is a more active ac-
Zinc oxide—87% Oil of cloves or eugenol—12% celerator for the setting reaction than is water, since it
Fixed vegetable or mineral Gum or polymerised rosin
increases the speed for formation of the zinc hydroxide.
oil—13% —50% l High atmospheric temperature and humidity are also
very effective accelerators of the setting reaction. The

Filler—20%
water formed in the setting reaction aids in binding
Lanolin—20% the individual chelate units together in a chain or in an
Resinous balsam—10% octahedral structure, or the water may be merely ab-
Accelerator solution (CaCl2) and
sorbed by the excess zinc oxide. The free eugenol
colouring agents—5% content of the set cement is probably very low.
Q. 3. Properties and advantages and disadvantages of

FUNCTIONS OF EACH CONSTITUENT zinc oxide eugenol impression paste/material
l Zinc oxide should be finely divided and should contain Ans. Refer to the answer of Long Essays Q. 3.
slight amount of water.
l Fixed vegetable or mineral oil acts as a plasticizer.
Q. 4. Impression compound
l Oil of cloves contains 70–85% eugenol. It is sometimes
used in preference to eugenol because it reduces burn- Ans. When a compound is used for edentulous impression,
ing sensation in the soft tissues. it is also called modelling plastic. It is classified as a rigid,
l Gum or polymerized rosin facilitates the speed of the reversible impression material that sets by physical change.
reaction and a smoother, more homogenous product
results.
l Canada balsam and Peru balsam are often used, to in-
CLASSIFICATION
crease flow and improve mixing properties.
l Calcium chloride acts as an accelerator of setting reaction. According to ADA Specification No. 3, dental impression
compounds are classified into two types as follows:
Other chemicals that can be used as an accelerator are as
follows: 1 . Type I: Impression compound
l Zinc acetate 2. Type II: Tray compound
l Primary alcohols
l Glacial acetic acid

APPLICATIONS
l A filler such as wax or an inert powder such as kaolin,
talc or diatomaceous earth may be added to one or both 1 . For making a primary impression
of the original pastes. 2. For individual tooth impression
3 . Peripheral tracing or border moulding l Pressure is used as it is not free flowing, and so irons out
4. To check undercuts in inlay preparation. details.
l Distortion due to its poor dimensional stability.
COMPOSITION
MANIPULATION
l In general, compounds are composed of a mixture of
waxes, thermoplastic resins, filler and a colouring agent. l Small amounts of compounds are softened over a flame.
l Shellac, stearic acid and gutta percha are added to im- When a direct flame is used, the compound should not
prove plasticity and workability. be allowed to boil or ignite; otherwise, the plasticizers
l The waxes or resins in the impression compound are the are volatilized.
principal ingredients that comprise the matrix. l When a large amount of compound is to be softened, it
l The filler increases the viscosity at temperatures above is difficult to heat the compound uniformly.
that of the mouth and increase the rigidity of the com- l The compound is softened in a thermostatically con-
pound at room temperature. trolled water bath. After the compound is removed from
the water bath, it is usually worked or kneaded with the
fingers in orders to obtain uniform plasticity throughout
THERMAL PROPERTIES the mass.
The thermal conductivity of impression compound is very
The safest method for removing the cast from the im-
low, i.e. they are poor conductors of heat.
pression is to immerse it in warm water until the compound
softens sufficiently to permit easy separation from the cast.
FLOW
Q. 5. Advantages of elastomeric impression material
Flow of the impression material could be advantageous as
well as harmful. Flow is desirable once the material has Ans. Advantages of elastomeric impression material are
been softened. During this period when it is pressed against listed in Table 8.4.
the tissues, it should flow into all the details of the tissue
contour. Greater the flow, more accurate the impression.
Once the compound hardens, it should have minimum flow; TABLE 8.4 Advantages of Elastomeric Impression Material
otherwise it will get distorted. Name of the Elastomeric
According to ADA Specification No. 3 Sl. no. Material Advantages
l Type I: Flow not more than 6% at 37°C (mouth tem- 1. Polysulphide Long working time
perature) High tear resistance
Margins easily seen
Flow not less than 80% and not more than 85% Modest cost
at 45°C
2. Condensation silicone Putty for custom tray
l Type II: Flow not more than 2% at 37°C
(putty wash) Clean and pleasant
Flow not less than 70% and not more than 85% Good working time
at 45°C. Easily seen margins
3. Vinyl polysiloxane One material
DISTORTION Putty for custom tray
Automix dispense
l The release of strains is unavoidable, the safest proce- Clean and pleasant
dure to prevent distortion is to pour the cast immedi- Easily seen margins
Ideally elastic
ately or at least within the first hour. Another cause of
Pour repeatedly
warpage is removal of the impression before it is thor- Stable delay pour
oughly cooled in the mouth.
4. Polyether Fast setting
Clean
DISADVANTAGES Automix dispense
Least hydrophobic
l Because of its high viscosity, it is difficult to record Easily seen margins
details. Good stability
Delay pour
l The soft tissues will be compressed while making im-
Shelf life—2 years
pression, due to pressure.
SHORT NOTES
Q. 1. Imbibition and syneresis FUNCTION OF EACH INGREDIENT
Ans. l Agar: 13–17% for tray material and 6–8% for syringe
material. It is the basic constituent.
l Process of water sorption by hydrocolloids is known as l Borates: 0.2–0.5%. It improves the strength of the gel.
imbibition. l Potassium sulphate: 1–2%. It ensures proper setting of
l Syneresis is a process where the gel may lose water by
the gypsum model and dye materials against the agar and
exudation of fluid. to provide good surfaces on gypsum models or dyes.
l Syneresis and imbibition can result in dimensional
l Wax, (hard) 0.5–1%. It acts as a filler.
changes and therefore inaccurate casts. l Thixotropic materials: 0.3–0.5%, e.g. glycerine, thy-
l To avoid this hydrocolloids should be poured immediately.
mol. It acts as a plasticizer.
l Alkylbenzoates: 0.1%. It acts as a preservative.
Q. 2. Types of rubber base impression materials
l Colouring and flavouring agents: traces.
Ans. The current ADA Specification No. 19 recognizes l Water: balance (average 84%). It acts as the dispersion
three types of rubber-like impression materials. medium.
The type classification based upon selected elastic proper-
Q. 4. Classification of impression materials
ties and dimensional change of the set materials is as follows:
Ans.
Maximum
Maximum Maximum Dimensional
Impression Permanent Flow in Change See Tables 8.6 and 8.7 for classification of impression materials.
Material Deformation Compression in 24 h
Table 8.6 Classification of Impression Materials
Type I 2.5 0.5 –0.5
Type II 2.5 0.5 –1.0 Reactions Material Use
Chemical Plaster of Paris Edentulous ridge
Type III 5.5 2.0 –0.5
reaction Zinc oxide eugenol Interocclusal
(irreversible) Hydrocolloids records
l Alginate Teeth and soft
Each type is further divided into four viscosity classes as
hydrocolloid tissues
determined by the consistency test as follows: l Agar
1. Class I: Heavy bodied hydrocolloid
2. Class II: Regular/medium bodied l Elastomers
3. Class III: Light bodied l Polysulphides Teeth and soft
l Polyether tissues
4. Class IV: Putty (a very heavy viscosity)
l Silicones
Q. 3. Composition of agar agar Thermally- Compound wax Preliminary
induced physical impression
Ans. The composition of reversible hydrocolloid (agar reaction
agar) impression material is listed in Table 8.5. (reversible)
TABLE 8.5 Composition of Reversible Hydrocolloid (Agar

TABLE 8.7 Classification of Impression Materials by
Agar) Impression Material
Elasticity and Use
Percentage by
Inelastic or Rigid Elastic
Ingredient Weight (wt%)
Material Use Material Use
Agar 13–17
1. Plaster Edentulous 1. Hydrocolloids Teeth
Borates 0.2–0.5
of ridge a. Alginate hydro- and
Potassium sulphate 1–2 Paris Interocclu- colloid soft
2. Zinc sal records b. Agar hydrocolloid tissues
Wax (hard) 0.5–1 oxide Preliminary 2. Nonaqueous elasto-
Thixotropic materials 0.3–0.5 euge- impression mers
nol a. Polysulphides Teeth
Alkylbenzoates 0.1 3. Com- b. Polyether and
Colouring and flavouring agents Traces pound c. Condensation sili- soft
wax cone tissues
Water Balance d. Addition silicone
Q. 5. Advantages of elastomeric impression materials 3 . Root canal filling material

4. Surgical pack in periodontal surgical procedures
Ans.
5. As a corrective impression and bite registration paste
See Table 8.8 for advantages of elastomeric materials. 6. Temporary relining material for dentures
7. Impression material for edentulous patients
TABLE 8.8 Elastomeric Impression Materials Advantages 8. The impression paste is used for making final impression
and as a corrective lining in the primary impression.
Name of the
Elastomeric
Q. 7. Noneugenol paste
Sl. no. Material Advantages
1. Polysulphide Long working time Ans.
High tear resistance
Easily seen margins l To overcome one of the chief disadvantages of the ZOE
Cost-effective pastes, i.e. stinging or burning sensation caused by the
2. Condensation Sufficient working time
eugenol that leaches out and contacts soft tissues the
silicone As putty for custom tray noneugenol paste is a best substitute.
(putty wash) Clean and pleasant to use l Zinc oxide can react with various carboxylic acids and
Clearly seen margins form ZOE like materials. Orthoethoxybenzoic acid, com-
3. Vinyl One material, automix dispense monly abbreviated as EBA, is a valuable substitute for
polysiloxane Putty for custom tray eugenol in this regard. The reaction is well understood,
Clean and pleasant with easily and it is not greatly affected by temperature or humidity.
seen margins Bactericidal agents and other medicaments can be incor-
Ideally elastic and can be
poured repeatedly
porated without interfering with the reaction.
Stable delay pour
Q. 8. Laminate technique
4. Polyether Short setting time
Least hydrophobic Ans.
Automix dispense
Clean and easily seen margins l Laminate technique (alginate–agar method) is the com-
Good stability, delay pour bined agar–alginate technique.
Shelf life—2 years l The hydrocolloid in the tray is replaced with a mix of
chilled alginate that bonds with the agar expressed from

a syringe.
Q. 6. Uses of zinc oxide eugenol (ZOE)
l The alginate gels by a chemical reaction, whereas the
Ans. The mixture of zinc oxide and eugenol has a wide agar gels by means of contact with the cool alginate
application in dentistry. It can be used as follows: rather than with the water circulating through the tray.
1. Cementing and insulating medium l This laminate technique is the most cost-effective way
2. Temporary filling sedative of producing an impression with adequate detail.
Topic 9
Gypsum Products
LONG ESSAYS
Q. 1. Discuss plaster of Paris.
l Because of its rigidity and nonelastic nature, it often had
Ans. to be fractured for its removal from undercut areas in the
mouth. The fractured pieces were then reassembled
outside and a cast was poured.
TYPE I OR IMPRESSION PLASTER l It is not so widely used now as an impression
l Plaster of Paris is also known as impression plaster and material, but it is more useful as a bite registration
was one of the earliest impression materials in dentistry. material.
USES This reaction takes place whenever any gypsum mate-

rial is used. It is an exothermic reaction as heat is evolved
l For making impressions in complete denture and maxil- during its setting.
lofacial prosthetics
l Bite registration material
THEORIES OF SETTING
IDEAL PROPERTIES Two theories are put forth to explain the setting mechanism
of gypsum. They are as follows:
l The setting time should be under accurate control. l Crystalline theory
The dentist must have sufficient time to mix, load the l Gel theory
impression tray, carry loaded tray to the patient’s mouth
and place it in position. The crystalline theory is the more acceptable.
l The plaster should harden promptly once in position, so
that there is minimum discomfort to the patient. Crystalline Theory

l The desirable setting time is 3–5 min.
l The setting expansion should be low for better accuracy.

This theory was proposed by a French chemist Henry Louis
l Both setting time and expansion are controlled by
Chatelier in 1885, and later it was supported by a German
modifiers (accelerators and retarders) added by the chemist Van’t Hoff.
manufacturers. l When hemihydrate is mixed in water, a suspension is
l The plaster should have enough strength to fracture formed, which is fluid and workable. Some dihydrates
cleanly without crumbling to facilitate its removal from are formed due to the reaction.
undercut areas. l The hemihydrate dissolves until it forms a saturated
solution.
l The solubility of dihydrate is much less than the hemi-
COMPOSITION
hydrate. The saturated hemihydrate is supersaturated
l Impression materials are composed of with respect to the dihydrate.
1. dental plaster l As all supersaturated solutions are present in an unsta-
2. K2SO4 ble condition, the dihydrate crystals precipitate out of
3. borax the solution to bring the solution to saturation, which is
4. colouring and flavouring agents. more stable.
l Impression plaster flavoured to make it more acceptable l As the dihydrate precipitates out of the solution, more
by the patient. calcium sulphate hemihydrate is dissolved because the
l It is coloured to help the dentist and technician distin- solution is no longer saturated with hemihydrate.
guish between the cast material and the impression. l This process continues till hemihydrate is converted
l Impression plaster sometimes contains potato starch to into dihydrate. Either new crystals of dihydrate are
make it soluble. formed or further growth of those already present takes
After the cast has hardened, the impression and cast are place. Thus the reaction is continuous and repeated until
put in hot water. The starch swells and the impression dis- hemihydrate is converted to dihydrate.
l Initially there is little reaction and thus little or no rise
integrates, making it easy to separate the cast from the im-
pression. This type is often called soluble plaster. in temperature. That time is referred to as induction
period.
l Later there is thickening of the mass, which allows the
Q. 2. What is gypsum? Write in detail the chemistry of
setting, manipulation and its uses. mix to be poured. As the amount of gypsum formed in-
creases, the mass thickens and then hardens into needle-
Ans. Gypsum is a mineral mined in various parts of the like clusters called spherulites. Finally, the intermeshing
world. Chemically, the gypsum used for dental purpose is of crystals of gypsum leads to a strong, solid structure.
nearly pure calcium sulphate dihydrate (CaSO4·2H2O).
MANIPULATION
SETTING REACTION
l The plaster or stone is mixed in a flexible rubber or
When plaster is mixed with water, it takes up 1½ molecule
plastic bowl with a stiff-bladed spatula.
of water, i.e. it regains its water of crystallization and be-
l The mixing equipment must be meticulously clean. If
comes calcium sulphate dihydrate.
particles of set plaster from a previous mix stick to the
CaSO4 2H2O 1 3H2O n 2(CaSO4·2H2O) 1 Heat bowl or spatula, they will act as additional nuclei of
(3900 cal) crystallization and cause acceleration of setting time.
l No air must be trapped in the mixed mass, as the pres- l Type III: Dental stone
ence of air bubbles is not only unsightly, but may cause l Type IV: Dye stone
loss of surface detail and weaken the cast. l Type V: High strength and high expansion dye stones
l Take a measured quantity of water in the rubber bowl
and sift a weighed quantity of powder into it, and tap the
bowl on the table to jar it. DRY CALCINATIONS
l Spatulate with a rapid stirring motion with frequent
l Gypsum is ground and heated in an open kettle or kiln
jarring, squeezing, turning of the bowl to avoid
at a temperature of 110–130°C. The process is called
air bubble. Spatulation should be completed in
dry calcination.
45–60 s.
l Beta-calcium sulphate hemihydrate is formed, which has
l Vibrate the mix and pour it into the impression. The cast
spongy, irregular large orthorhombic crystal particles.
can be poured by inversion or boxing method.
CaSO 4 .2H 2 O 110 130°C

 → CaSO 4 . 2 H 2 O
1
Mechanical Mixing
(Dry (Calcium (Calcium
Although the equipment is expensive mechanical mixing calcination) sulpp hate sulphate
under vacuum gives stronger and denser casts. hemihydrate) dihydrate)
USES l Type I (impression plaster) and type II (model plaster)

are formed by this method.
General Use
For preparing statues and in construction work
WET CALCINATIONS
When gypsum is ground and heated under steam
Medical Use in Orthopaedics l
pressure at a temperature of 110–130°C in a closed

For splinting and making plaster casts kettle or kiln or an autoclave the process is called wet
calcination.
l Alpha-calcium sulphate hemihydrate is formed, which
In Dentistry consists of smaller, regularly-shaped crystalline parti-
l Impression plaster was used extensively for impressions cles in the form of rods or prisms.
of the mouth and face. l Type III (dental stone or hydrocal or class I stone) is
l Various types of plasters are used to make moulds, casts formed by this method.
and dyes over which dental prostheses and restorations l Microscopically crystals of type III (dental stone) are in
are made. the form of rods and prisms.

l To mount the casts on articulators.
l For bite registration (e.g. to record centric jaw

DEHYDRATION BY BOILING
relation).
l Dental investments: When plaster is mixed with silica,
WITH CHEMICALS
it is known as dental investment, mainly used to form l The gypsum is calcined by boiling it in 30% calcium
moulds into which molten metal is cast. chloride solution. The chlorides are then washed away
or autoclaved in presence of sodium succinate 0.5%.
Q. 3. What are different methods of manufacturing gyp- l Improved stone is manufactured by this method. These
sum products? Write the setting reaction of gypsum. particles are denser among all three types.
Mention the uses of gypsum products. l After controlled grinding, these powders have an even
higher apparent density, and microscopically the parti-

Ans. Different methods of manufacturing gypsum are as
cles that are cuboidal in shape yield an even stronger set
follows:
material.
l Dry calcination
l Wet calcination
l Dehydration by boiling with chemicals SETTING REACTION

l Synthetic
l When plaster is mixed with water, it takes up 1½ mol-
Different methods of manufacturing gypsum have pro- ecules of water, i.e. it regains its water of crystalliza-
duced different types of gypsum products as follows: tion and becomes calcium sulphate dihydrate.
l Type I: Impression plaster CaSO4·2H2O 1 2H2O n 2(CaSO4·2H2O) 1 Heat
l Type II: Model plaster (3900 cal)
l The reaction is exothermic. This reaction takes place the mass thickens and then hardens in to needlelike
whenever any gypsum material is used. clusters called spherulites.
l The reaction is continuous and repeated until hemihy- l Finally the intermeshing of crystals of gypsum leads to
drate is converted to dihydrate. a strong, solid structure.
l Initially there is little reaction, and thus little or no rise
in temperature. This period of time is referred to as

induction period. USES
l Later there is thickening of the mix, which allows it to
be poured. As the amount of gypsum formed increases, Refer to the answer of Long Essays Q. 2.
SHORT ESSAYS
Q. 1. Dye stone 2. Metals Electroformed/electroplated sprayed metals’
amalgams
Ans.
3. Polymers Metal-filled resins or inorganic-filled resins,
l Dye stone is also known as type IV or improved dental epoxy resins
stone or high-strength stone. 4. Cements Silicophosphate or polyacrylic acid-bonded
l Dye stone is the strongest and hardest variety of gypsum cements
product. 5. Ceramic For direct baking of porcelain crown or
or preparation of wax patterns, die materials for
refractory casting
USES
l It is used when high strength and surface hardness is
required, e.g. dyes used for inlay, crown and bridge
IDEAL PROPERTIES OF DYE MATERIALS
patterns.
l A thick mix is prepared as per manufacturer’s instruc- l It should be dimensionally accurate.
tion and vibrated into a rubber-base impression. l It should have high abrasion resistance, should possess
l The base for such a model is poured in dental stone or good strength and have a smooth surface.
rubber-base impression. l Toughness—to allow brushing of foil and resist breakage
l Dye stone should be left for 24 h to gain maximum l Ability to reproduce all fine details in the impression
hardness, and the cast should be separated 1 h after l Compatibility with all impression materials
pouring. l Colour contrast with wax, porcelain and alloys
l The abrasion resistance of dye stone is not high as other l Easy and quick manipulation and rapid fabrication (set-
dye materials. ting time)

l Noninjurious to health or biologically acceptable
l Should be economical or cost-effective.

Q. 2. Define a dye and a cast. Mention different types of
dye materials.
Q. 3. Compare plaster of Paris and dental stone.
Ans.
Ans.
l Dye is a reproduction of a prepared tooth made from a
These two materials are chemically identical, but they
gypsum product, epoxy resin, a metal or a refractory
differ in the following properties:
material.
l Cast is a reproduction of the shape and features of a
surface made from an impression of the surface. Plaster of Paris Dental Stone
Different types of dye materials are as follows:
Manufacture Dry calcination Wet calcination
Particle Larger, irregular and Smaller, regular and
1. Gypsum Dental stone, high-strength type IV porous dense, nonporous
Dental stone, high-strength, high-expansion
type V W/P ratio 0.5 0.3
Dental stone 1 lignosulphonates (this wetting Porosity More porous Less porous
agent reduces the water requirement of a
stone and thus enables the production of a Mechanical Less strength and Greater strength and
harder, stronger and more dense set gypsum) hardness hardness
Application Used when Used where strength Q. 5. High-strength, high-expansion dental stone (type V)
mechanical and hardness is
Ans.
properties are not of required, e.g. dyes
primary importance for crowns, denture
l High-strength, high-expansion dental stone is type V
like diagnostic construction,
casts, mounting of bridges and inlay stone.
models, orthodontic work, as binder in l It is the most recent gypsum product, having an even
study models casting investments higher compressive strength than type IV stone.
l Improved strength is attained by making it possible to
lower the W/P ratio even further.

Q. 4. Setting reaction of plaster of Paris l Setting expansion has been increased from a maximum
Ans. of 0.10 to 0.30%. This is for compensating for the

shrinkage of base metal alloy, during solidification.
Refer to the answer of Long Essays, Q. 3. l It is used mainly to prepare dyes.
SHORT NOTES
Q. 1. Control of setting time of gypsum products A. PENETRATION TESTS
Ans. The factors affecting setting time of gypsum products These tests can be determined by different types of pene-
are as follows: trometres like
1. Manufacturing process a. Vicat needle
2. Time and rate of mixing and spatulation b. Gillmore needles
3. Water/powder ratio
4. Temperature
a. Vicat Needle
5. Modifiers
l The needle is 1 mm in diameter and is 5 cm long, and
Q. 2. Gillmore test for final setting of gypsum the rod holding the needle is 300 g in weight.
l The time that elapses from the start of mixing till the
Ans. The time elapsing from the start of mixing until that needle does not penetrate the bottom of the plaster is the
time when the point of the heavier, i.e. 1 lb, Gillmore nee- setting time.
dle no longer penetrates the surface of the set plaster or it l With the Vicat needle, only one setting time is defined.
leaves only a barely perceptible mark on the surface is l The setting time obtained with the Vicat needle is the same
called the final setting time. as initial setting time obtained by the Gillmore needle.
Q. 3. Impression plaster b. Gillmore Needle

Ans. l The time elapsing from the start of mixing till the time
when the point of the 1/4 lb is the setting time. Gillmore
needle no longer penetrates the surface of plaster than
IMPRESSION PLASTER OR TYPE 1 PLASTER what is known as the initial setting time.
l The time elapsing from the start of mixing till that time
l This impression material is composed of plaster of
when the point of the large 1 lb Gillmore needle no
Paris, to which modifiers have been added to regulate
longer penetrates the surface of the set plaster is known
the setting time and the setting expansion.
as the final setting time.
l As impression plaster has been replaced by less rigid
materials, such as the hydrocolloids and elastomers, it is

rarely used anymore for dental impressions. B. LOSS OF GLOSS METHOD
l Plaster is primarily restricted to use as a final impres-
According to this method, the setting time is defined as the
sion or wash impression in the construction of full time from the start of mixing till the gloss disappears from
dentures. the surface of plaster mix.
Q. 4. Measurement of setting time in dental plaster
C. EXOTHERMIC REACTION
Ans. The setting time is usually measured by penetration
tests, but occasionally, various other testing methods are The temperature rise of the mass may also be used for mea-
also employed as discussed below. surement of setting time, as the setting reaction is exothermic.
Q. 5. Mounting plaster COMPOSITION

Ans. Contains beta-hemihydrate and modifiers.
The requirements of an ideal cast material like mounting
plaster are as follows: USES
1. It should set rapidly while giving adequate time for
manipulation. Model plaster or laboratory type II plaster is now in use
2. It should set to a very hard and strong mass. especially for
3. After mixing, consistency should be such that it can 1 . making study casts and models.
flow into all parts of the impression and reproduce all 2. to make moulds for curing dentures.
the minute details. 3. for mounting casts on articulator.
4. It should neither contract nor expand while setting.
5. After setting, it should not warp or change shape. Type II model plaster is relatively weak as evidenced by
6. It should not lose its strength when subjected to mould- a compressive strength as low as 9 MPa and a tensile
ing and curing procedures. strength of 0.6 MPa.
Topic 10
Dental Waxes
LONG ESSAY
Q. 1. Classify waxes in dentistry. Write the composition COMPOSITION OF CASTING WAX
of casting waxes. Explain the procedures for obtaining
1 . Paraffin wax
the wax pattern for an inlay restoration.
2. Gum dammar
Ans. 3. Carnauba or candelilla
4. Colouring agents
CLASSIFICATION OF DENTAL WAXES
1. Paraffin Wax (40–60%)
According to Origin Main ingredient.
l
Dental Waxes It is used to establish the melting point, with which dif-
l
ferent melting points can be produced.

l Paraffin wax flakes when trimmed and does not give a
smooth surface, so other waxes are added to modify.

1. Mineral wax 2. Plant wax 3. Insect wax 4. Animal wax l Ceresin (10%) partially replaces paraffin. Increases
(paraffin, ceresin) (carnauba, candelilla) (beeswax) (spermaceti) toughness and makes it easy to carve.
2. Gum Dammar (1%) or Dammar Resin

According to Use l It is a natural derivative from pine tree.
l It improves the smoothness in moulding and makes it
Dental Waxes
more resistant to tracking and flaking.
l It also increases toughness of the wax and enhances the
lustre of the surface.

1. Pattern waxes 2. Processing waxes 3. Impression waxes
a. Inlay casting wax a. Boxing wax a. Corrective wax
b. RPD casting wax b. Utility wax b. Bite registration
3. Carnauba Wax (25%)
c. Baseplate wax c. Sticky wax wax l This wax is quite hard and has high melting point.
l It is combined with paraffin to decrease the flow at l Withdraw the wax pattern carefully in the long axis of
mouth temperature. It has an agreeable odour and gives the preparation. The pattern should be touched as little
glossiness to the wax surface. as possible with the hands to avoid temperature changes.
4. Candelilla Wax Indirect Technique

l It can be added to replace carnauba wax. l Inlay pattern is prepared over a lubricated dye. If molten
l It possesses the same qualities as carnauba wax, but its wax is used, very little residual stresses occur.
melting is lower. Also, it is not as hard as carnauba wax.
l Carnauba wax is often replaced partly by certain syn-
Dipping Method
thetic waxes (Montan). Because of their high melting
point, more paraffin can be incorporated and the general In case of full crowns, the dye can be dipped repeatedly into
working qualities are improved. hot liquid wax. The wax is allowed to cool, carved and is
removed from the dye.
MANIPULATION OF INLAY WAX Softening in Warm Water

This technique is not recommended as
Direct Technique l soluble constituents may leach out and the properties
l Hold the stick of wax over the visible flame, and rotate of wax will change.
it rapidly until it becomes plastic taking care not to l water gets into the wax causing splattering on the
volatilize the wax. flame, interference with the softening of the wax sur-
l The softened wax is shaped approximately to the form face and distortion of the pattern on thermal changes.
of the prepared cavity.
l The wax should be allowed to cool gradually to mouth
Adding in Layers
temperature. Cooling rapidly by application of cold
water results in differential contraction and develop- The wax is melted and added in layers using a spatula or a
ment of internal stresses. brush.
l Localized reheating of wax with warm carving instru-
ments has a similar effect, and more distortion may oc-

Polishing
cur. A cold carving instrument should be used for direct
wax pattern. Polishing is done by rubbing with a silk cloth.
SHORT ESSAYS
Q. 1. Manipulation of inlay wax as possible with the hands to avoid temperature
Ans. Different techniques in manipulation of inlay wax are changes.
as follows:
Indirect Technique
l Inlay pattern is prepared over a lubricated die. If molten
Direct Technique wax is used, very little residual stresses occur.
l Hold the stick of wax over the visible flame, and rotate
it rapidly until it becomes plastic taking care not to Dipping Method
volatilize the wax. The softened wax is shaped approxi- In case of full crowns, the die can be dipped repeatedly into
mately to the form of the prepared cavity and is held hot liquid wax. The wax is allowed to cool, carved and re-
under finger pressure while it solidifies. moved from the dye.
l The wax should be allowed to cool gradually to mouth
temperature. Cooling rapidly by application of cold

Softening in Warm Water
water results in differential contraction and develop-
ment of internal stresses. This technique is not recommended as
l Localized reheating of wax with warm carving instruments l soluble constituents may leach out and the properties of
has a similar effect, and more distortion may occur. A cold wax will change.
carving instrument should be used for direct wax pattern. l water gets into the wax causing splattering on the flame,
l Withdraw the wax pattern carefully in the long axis of interference with the softening of the wax surface and
the preparation. The pattern should be touched as little distortion of the pattern on thermal changes.
Adding in Layers CERESIN (10%)

The wax is melted and added in layers using a spatula or a brush. l Partially replaces paraffin.
l It increases toughness and is easy to carve.
Polishing
GUM DAMMAR (1%) OR DAMMAR RESIN
Polishing is done by rubbing with a silk cloth.
l It is a natural derivative from pine tree, improves the
Q. 2. Baseplate materials smoothness in moulding and makes it more resistant to
cracking and flaking.
Ans. Baseplate materials are classified according to ADA
l It also increases toughness of the wax and enhances the
Specification No. 24 as follows:
lustre of the surface.
1. Type I: Soft for building veneers
2. Type II: Medium tried in mouths in normal climatic
conditions CARNAUBA WAX (25%)
3. Type III: Hard for trial in mouths
l This wax is quite hard, and it has high melting point.
Mode of supply: Available in the form of sheets of pink l It is combined with paraffin to decrease the flow at
or red colour. mouth temperature.
l It has an agreeable odour and gives glossiness to the
wax surface.
COMPOSITION OF BASEPLATE MATERIALS
l Candelilla wax can be added to replace carnauba wax. It
contributes the same qualities as carnauba wax, but its

Ceresin 80% melting is lower. Also, it is not as hard as carnauba wax.
Beeswax 12%
Carnauba 2.5% SYNTHETIC WAXES
Natural or synthetic 3% In modern inlay waxes, carnauba wax is often replaced
Microcrystalline 2.5% partly by certain synthetic waxes like Montan. Because of
their high melting point, more paraffin can be incorporated
and the general working qualities are improved.
APPLICATIONS
Q. 4. Properties of inlay casting wax
l To make occlusion rims, which is used on the baseplate
tray to establish the vertical dimension, the plane of oc- Ans.
clusion and the initial arch form in the technique for
l Type I inlay wax exhibits a marked plasticity or flow at
complete denture construction. This wax may also be
a temperature slightly above mouth temperature.
used to form all or a portion of the tray itself.
l The wax begins to harden at approx 50°C and is solid
l To produce the desired contour of the denture after teeth
below approx 40°C.
are set in position.
l The maximum flow for type I waxes at 37°C is 1%. The
l To make patterns for orthodontic appliances and pros-
low flow at this temperature allows carving and removal
theses other than complete dentures, which are to be
of the pattern from the cavity at mouth temperature
constructed of plastics.
without distortion.
l To check various articulating relations in the mouth and
l Both type I and type II waxes must have a minimal flow
to transfer them to mechanical articulators.
of 70% at 45°C and a maximum of 90%. It is at this
Q. 3. Inlay wax temperature the wax is inserted into the prepared cavity.
If the wax does not have sufficient plasticity, it does not
Ans. Composition of inlay wax is as follows: flow into all the details of the prepared cavity.
1. Paraffin wax: 40–60%
2. Ceresin: 10% Q. 5. Thermal properties
3. Gum dammar: 1%
Ans.
4. Carnauba or candelilla: 25%
5. Colouring agents
THERMAL PROPERTIES OF WAXES
PARAFFIN WAX (40–60%) Thermal Conductivity
l It is the main ingredient used to establish the melting point. The thermal conductivity of waxes is low, and time is re-
l Paraffin wax flakes when trimmed and does not give a quired to heat the wax uniformly and to cool them to body
smooth surface, so other waxes are added to modify. or room temperature.
Coefficient of Thermal Expansion l If wax is not at uniform temperature when inserted in

the cavity. Some parts of the wax pattern may ther-
Inlay wax has a high coefficient of thermal expansion. The mally contract more than others when stresses are in-
wax may have a linear expansion of 0.7% with increase in troduced.
temperature of 20°C. Its thermal changes are higher than l If wax is not held under uniform pressure during cooling.
any other dental materials. l If the wax is melted and added in an area of deficiency,
This property is less significant in indirect technique as it the added wax will introduce stresses during cooling.
is not subjected to a change from mouth to room temperature. l During carving some molecules of wax will be dis-
turbed and stresses will result.

Q. 6. Causes and prevention of wax distortion Prevention of wax distortion can be achieved by the
Ans. Wax distortion is the most serious problem in inlay following:
wax. It is due to release of stresses in the pattern. l Minimal carving and change in temperature.
l Minimal storage of pattern: Invest immediately.
l Use warm instruments for carving.
l Store it in a refrigerator, if necessary.

CAUSES OF DISTORTION
l Some relaxation and distortion of pattern occurs regard-
Factors causing distortion under control of the operator less of the method used. It cannot be totally eliminated.
cannot be totally eliminated. Distortion of the wax can It can only be reduced to a point which is not of clinical
occur in the following cases: importance.
SHORT NOTES
Q. 1. Properties of inlay wax 4. Carnauba or candelilla (25%): This wax is quite hard
and it has high melting point and flow at mouth tem-
Ans.
perature. It gives glossiness to the wax surface.
l Type I inlay wax exhibits a marked plasticity or flow at 5. Colouring agents.
a temperature slightly above mouth temperature. The
wax begins to harden at approx. 50°C, and it is solid Q. 3. Baseplate waxes
below approx. 40°C. Ans. They are classified under pattern waxes because they
l The maximum flow for type I waxes at 37°C is 1%. The are used in the construction of dentures and other appli-
low flow at this temperature allows carving and removal ances made of acrylic and like materials.
of the pattern from the cavity at mouth temperature
without distortion. USES
l Both type I and type II waxes must have a minimal flow
of 70% at 45°C and a maximum of 90%. It is at this These waxes are used
temperature the wax is inserted into the prepared cavity. l to make occlusion rims.
l to form the desired contour of the denture after teeth are set.
l to make patterns for orthodontic appliances and other

THERMAL PROPERTIES
prostheses which are to be constructed of plastics.
Thermal Conductivity
The thermal conductivity of waxes is low and time is re- CLASSIFICATION (ADA SPECIFICATION
quired to heat the wax uniformly and to cool them to body No. 24)
or room temperature. 1 . Type I (Soft)—for building veneers
2. Type II (Medium)—to use in mouths in normal climates
Coefficient of Thermal Expansion 3. Type III (Hard)—for use in tropical climates
Inlay wax has a high coefficient of thermal expansion. The
wax may have a linear expansion of 0.7% with increase in SUPPLIED AS
temperature of 20°C. Its thermal changes are higher than
Pink or red colour sheets
any other dental materials.
Q. 2. Composition of inlay wax COMPOSITION

Ans. Composition of inlay wax is listed as under: 1. Paraffin or ceresin 80.0%
1. Paraffin wax (40–60%): It is the main ingredient. 2. Beeswax 12.0%
2. Ceresin (10%): It increases toughness and is easy to carve. 3. Carnauba 2.5%
3. Gum dammar (1%): It improves the smoothness and 4. Natural or synthetic resins 3.0%
makes it more resistant to cracking and flaking and en-
5. Microcrystalline 2.5%
hances the lustre of the surface.
Topic 11
Casting Investments and Procedures

LONG ESSAYS
Q. 1. Write in detail about casting defects. Various types of surface roughness can be avoided as follows:
1. Air bubbles can be avoided by the following:
Or,
a. Proper mixing of investment
Classify defective castings. What precautions should be b. Vibration of mix or by vacuum investing
observed to prevent defects in casting? c. Application of wetting agent
2. Fins can be avoided by the following (Table 11.1):
Ans. The casting may have some defects if procedure is not a. Heating the ring gradually to 700°C in at least 1 h.
followed properly and results in poor aesthetic and mechanical b. Rough casting can be avoided by using correct W/P
properties. Casting defects are classified by Coombe as follows: ratio and select investment of correct particle size.
1. Distortion c. Complete the casting as soon as the ring is heated
2. Surface roughness and ready.
3. Porosity d. Using 15 lb/inch2 of air pressure or three to four
4. Incomplete casting turns of centrifugal casting machine.
5. Contamination of casting due to oxidation
TABLE 11.1 Rough Surface and Fins on Casting

DISTORTION
Caused by Can Be Avoided by
1. Distortion of the casting is usually due to distortion of
wax pattern. Rough surface 1. Investment 1. Avoid overheating
breakdown of mould and
2. Some distortion of wax occurs when the investment 2. Air bubbles on alloy
hardens or due to hygroscopic and setting expansion, wax (nodules 2. Correct use of
and some more distortion of wax occurs during manipu- on casting) wetting agent
lation, because of the release of internal stresses. 3. Weak surface 3. Vacuum investing
of investment 4. Avoid too high
W/P ratio
Distortion can be minimized by 5. Avoid dilution of
1. manipulation of wax at high temperature, investment from
2. investing pattern within 1 h after finishing and application of too
3. storing in a refrigerator if necessary. much wetting
agent
Fins on casting 1. Cracking of 1. Rapid heating of

SURFACE ROUGHNESS investment investment
Surface roughness usually occurs due to the following
(Table 11.1):
1. Air bubbles on wax pattern, cause nodules on the casting.
2. Too rapid heating results in cracking of the investment
POROSITY
resulting in fins. Porosity may be internal or external. External porosity can
3. Higher W/P ratio and larger particle size of investment cause discolouration of the casting. Internal porosity weak-
gives a rough casting. ens the restoration.
4. Prolonged heating of investment causes disintegration
of mould cavity. According to Phillips, porosities are classified as follows:
5. Overheating of gold alloy also has the same effect. It 1. Those caused by solidification shrinkage (irregular in
disintegrates the investment. shape)
6. Too high or too low casting pressure. a. Localized shrinkage porosity
7. Composition of the investment b. Suck back porosity
a. Proportion of the quartz and binder influences the c. Microporosity
surface texture of casting. 2. Those caused by gas (usually spherical in shape)
b. Coarse silica will give coarse casting. a. Pinhole porosity
8. Foreign body inclusion shows sharp, well-defined b. Gas inclusions
deficiencies. c. Subsurface porosity
3. Those caused by air trapped in the mould—back pres- TABLE 11.2 Summary of Porosity
sure porosity.
Type of
Porosity Caused by Prevented by
Localized Shrinkage or Shrink-Spot Porosity Irregular Shrinkage on Use correct sprue
cooling of alloy thickness
1. It occurs when the cooling sequence is incorrect and the
sprue freezes before the rest of the casting. The subse- Attach sprue at thick part
of wax pattern
quent shrinkage produces voids or pits known as shrink-
spot porosity. Use reservoir
2. These are large irregular voids usually found near the Irregular Inclusion of foreign Heat mould upside down
sprue-casting junction. voids particles so that particles fall out
Spherical Occluded gases in Avoid overheating and
Suck Back Porosity voids molten alloy prolonged heating of
alloy
1. It is a variation of the shrink-spot porosity. This is an Rounded Back pressure effect; Use adequate casting
external void usually seen in the inside of a crown op- margins air unable to escape force
posite the sprue. from mould
2. A hot spot is created by the hot metal impinging on the Use porous investment
mould wall near the sprue.
Avoid wax residue in
The hot spot causes this region to freeze last. Since the mould
sprue has already solidified, no more molten material is Place pattern 6–8 mm
available and the resulting shrinkage causes a peculiar type away from end of ring
of shrinkage called suck back porosity. It is avoided by re- Use vents
ducing the temperature difference between the mould and
Regular Turbulent flow of Correct placement of
the molten alloy.
large molten alloy into the sprue
voids mould
Microporosity
These are fine irregular voids within the casting. It is seen
when the casting freezes too rapidly. INCOMPLETE CASTING (Table 11.3)
An incomplete casting may result when
Pinhole Porosity 1. insufficient alloy used.
Many metals dissolve gases when molten. Upon solidifica- 2. alloy not able to enter thin parts of mould.
tion the dissolved gases are expelled causing tiny voids, e.g. 3. when mould is not heated to casting temperature.
platinum and palladium absorb hydrogen. Copper and sil- 4. premature solidification of alloy.
ver dissolve oxygen. 5. sprues are blocked with foreign bodies.
6. back pressure due to gases in mould cavity.
7. low casting pressure.
Gas Inclusion Porosities 8. alloy not sufficiently molten or fluid.
Gas inclusion porosities are also spherical voids but are Casting defects dimensional errors in casting according to
larger than the pinhole type. They are more likely due to Coombe are listed in Table 11.3.
gases carried in or trapped by the molten metal. A poorly
adjusted blow torch can also occlude gases.
Back Pressure Porosity TABLE 11.3 Dimension Errors in Casting Defects

1 . This is caused by inadequate venting of the mould.
Problem Cause Precaution
2. If the bulk of the investment is too great, the escape of air
Casting too large Excessive expansion Use correct
becomes difficult causing increased pressure in the mould.
temperature
3. The gold will then solidify before the mould is com- Use correct
pletely filled resulting in a porous casting with rounded investment
short margins.
Casting too small Too little mould Heat the mould
4. Avoided by using adequate casting force. expansion sufficiently
5. Use of investment of adequate porosity—place pattern
Distorted casting Distorted wax pattern Correct handling
not more than 6–8 mm away from the end of the ring.
of wax
Porosity can be summarized as listed in Table 11.2.
CONTAMINATION WAX PATTERN

The casting gets contaminated by the following: A pattern of the final restoration is made with type II inlay
1. Due to oxidation when molten alloy is over heated wax or other casting waxes with all precautions to avoid
2. Use of oxidizing zone of the flame distortion. Before making the pattern, a dye lubricant is ap-
3. Failure to use flux plied to help separate the wax pattern from the dye.
4. Due to formation of sulphur compounds
Contamination can be avoided by the following:
SPRUE FORMER
1. Not overheating alloy
2. Using reducing zone of the flame A sprue former is made of wax, plastic or metal. Thickness
3. Using flux is in proportion to the wax pattern. A reservoir is attached
to the sprue or the attachment of the sprue to the wax pat-
Black casting can result due to the following reasons:
tern is flared.
1. Overheating the investment above 700°C causes it to
Functions of sprue former or sprue are as follows:
decompose liberating sulphur or sulphur compounds.
1. To form a mount for the wax pattern
They readily combine with the metals in gold alloy
2. To create a channel for elimination of wax during burnout
forming a sulphide film. This gives a dark casting which
3. Forms a channel for entry of molten alloy during casting
cannot be cleaned by pickling.
4. Provides a reservoir of molten metal which compen-
2. A black casting can also be formed as a result of incom-
sates for alloy shrinkage during solidification
plete elimination of the wax pattern, as a result of heat-
ing the mould at too low temperature. A carbonized wax
remains which sticks to the surface of the casting. It can CASTING RING LINING
be removed by heating over a flame.
A ring liner is placed inside of the casting ring. It should be
Q. 2. Explain various steps in casting procedures for a short at one end. Earlier asbestos liners were used. Its use
gold inlay. What are the possible errors that can happen has been discontinued due to health hazard from breathing
in these steps that can lead to defective castings? Add a its dust.
note on casting machines. Types of nonasbestos ring liners used are as follows:
1. Fibrous ceramic aluminous silicate
Ans. Various steps in making a cast restoration are as follows: 2. Cellulose (paper)
1. Tooth/teeth preparation 3. Ceramic–cellulose combination
2. Impression Functions of the ring liner are as follows:
3. Dye preparation 1. Allows for mould expansion (acts as a cushion).
4. Wax pattern fabrication 2. When the ring is transferred from the furnace to the
5. Attachment of sprue former casting machine it reduces heat loss as it is a thermal
6. Ring liner placement insulator.
7. Assembly of casting ring 3. Permits easy removal of the investment after casting.
8. Investing
9. Burn out or wax elimination
10. Casting INVESTING
11. Recovery Apply wetting agent (to reduce air bubbles) on the wax pat-
12. Pickling tern. Seat the casting ring into the crucible former taking
13. Polishing care that it is located near the centre of the ring.
Mix the investment and vibrate. Some investment is ap-
TOOTH/TEETH PREPARATION plied on the wax pattern with a brush to reduce trapping air
bubbles. The ring is reseated on the crucible former and
The teeth are prepared by the dentist to receive a cast resto-
placed on the vibrator and gradually filled with the remain-
ration.
ing investment mix. Allow it to set for 1 h.
IMPRESSION
WAX ELIMINATION (BURNOUT)
An accurate impression of the tooth/teeth is made, usually
with elastomeric impression materials. AND THERMAL EXPANSION
The purpose of burnout is (i) to eliminate the wax (pattern)
from the mould and (ii) to expand the mould (thermal ex-
DYE PREPARATION
pansion).
A dye is prepared from dye stone or the impression is elec- Separate the crucible former from the ring. If a metal-
troformed. A dye spacer is coated or painted over the dye lic sprue former is used, it should be removed before
which provides space for the luting cement. burnout.
Burnout is started when the mould is wet. Store in a casting. When the alloy is molten it has a mirror-like appear-
humidor. If burnout is to be delayed the heating should be ance like a ball of mercury. Release the arm and allow it ro-
gradual. Rapid heating produces steam which causes the tate till it comes to rest. This creates centrifugal force which
walls of the mould cavity to flake. In extreme cases an ex- forces the liquid metal into the mould cavity. The ring is al-
plosion may occur. Rapid heating also causes cracks in the lowed to cool for 10 min till the glow of the metal disappears.
investment due to uneven expansion.
The ring is placed in a burnout furnace and heated
QUENCHING (FOR GOLD ALLOYS)
gradually to 400°C in 20 min. Maintain it for 30 min. In the
next 30 min, raise the temperature to 700°C and again The ring is then immersed into water. This leaves the casting
maintain it for 30 min. The casting should be completed as metal in an annealed (softened) condition and also helps to
soon as the ring is ready. If casting is delayed the ring cools fragment the investment. Base metal alloys are not quenched.
and the investment contracts. The crown becomes smaller.
RECOVERY OF CASTING
CASTING The investment is removed and the casting is recovered. A
It is a process by which molten alloy is forced into the pneumatic (air driven) chisel may be used to remove the
heated investment mould. investment.
Fusion of Noble Metal Alloy SANDBLASTING

Alloys can be melted by the following ways: The casting is held in a sandblasting machine to clean the
1. Blow torch remaining investment from its surface.
2. Electrical resistance or induction
PICKLING
Blow Torch The surface oxides from the casting are removed (when
The fuel used is a combination of necessary) by pickling in 50% hydrochloric acid. HCl is
heated, but not boiled with the casting in it (done for gold
1 . natural or artificial gas and air, or alloys). Pickling is not a routine procedure and is per-
2. oxygen and acetylene gas (high fusion alloys). formed only when indicated.
The flame has four zones as follows:
1. Combustion zone: This surrounds the inner zone. It is
green in colour. It is a zone of partial combustion and POLISHING
has an oxidizing nature. Minimum polishing is required if all the procedures from
2. Reducing zone: It is a blue zone just beyond the green the wax pattern to casting are followed meticulously (for
zone. It is the hottest part of the flame. This zone is used details see Short Essays, Chapter 12).
for fusion of casting alloy.
3. Oxidizing zone: Outermost zone in which final combus-
CASTING MACHINES
tion between the gas and surrounding air occurs. This
zone is not used for fusion. They are of two general types as follows:
1. Centrifugal force type
The air and gas mixture is adjusted to get a reducing
2. Air pressure type
flame, which is used to melt the alloy, because it does not
contaminate the alloy and is the hottest part of the flame. Centrifugal machines may be spring driven or motor
The hot casting ring is shifted from the burnout furnace driven. The main advantage of the centrifugal machines is
to the casting machine. The ring is placed in the casting the simplicity of design and operation, with the opportunity
cradle so that the sprue hole adjoins the crucible. Slide the to cast both large and small castings on the same machine.
crucible against the ring to avoid spilling of molten metal. In air pressure type of machine, either compressed air or
The alloy may be melted by a torch or by induction heating. gases like CO2 or nitrogen can be used to force the molten
In an induction casting machine the molten metal is metal into the mould. This type of machine is satisfactory
driven into the mould by centrifugal force. One arm of the for making small castings.
machine has a counter weight which balances the weight of Attached vacuum system casting machines (both cen-
the arm carrying the crucible and mould as it rotates. The trifugal and gas pressure type) with attached vacuum system
red-hot crucible and the casting ring are visible in the ma- are available. The vacuum creates a negative pressure within
chine. The induction coil (copper coloured) is half visible the mould, which helps to draw the alloy into the mould.
and is used to melt the metal. Sprinkle flux powder over the For casting defects refer to the above answer of Long
molten metal to reduce the oxides and increase fluidity for Essays, Q. 1.
Q. 3. Classify investment materials. Describe the com- binder used for dental casting gold alloys is dental stone,
position of gypsum-bonded investment materials. i.e. alpha-calcium sulphate hemihydrate.
The investments used for casting cobalt–chromium al-
Ans.
loys utilize sodium silicate, ethyl silicate, ammonium sul-
phate and sodium phosphate.
TYPES OF INVESTMENT MATERIALS

Other Chemicals
There are three types of investment materials as follows:
1. Gypsum-bonded investments: They are used for casting Usually a mixture of refractory materials and a binder alone
gold alloys. They can withstand temperature up to 700°C. is not enough to produce all the desirable properties of an
2. Phosphate-bonded investments: They are used for metal investment. Other chemicals such as sodium chloride, boric
ceramic and cobalt–chromium alloys. They can with- acid, potassium sulphate, graphite, copper powder or mag-
stand higher temperatures. nesium oxide often are added in small quantities to modify
3. Ethyl silica-bonded investments: They are an alternative the physical properties.
to the phosphate-bonded investments for high tempera-
ture casting. They are principally used in the casting of
base metal alloy partial dentures. FUNCTION OF EACH CONSTITUENT
All the above investment materials contain silica as the Gypsum: Alpha-hemihydrate
refractory material. The type of binder used is different.
1. It acts as a binder for silica in casting gold alloys with a
melting range below 1000°C.
GYPSUM-BONDED INVESTMENTS 2. It imparts strength to the mould.
3. Contributes to mould expansion by setting expansion.
Classification
When gypsum is heated to high temperature, it shrinks
According ADA Specification No. 2 for casting invest- and fractures. At 700°C, it shows slight expansion and then
ments for dental gold alloys, gypsum-bonded investments great amount of contraction. The shrinkage is due to decom-
are of three types as follows: position and release of sulphur dioxide. It contaminates the
Type I: Those used for the casting of inlays and crowns, casting with the sulphides of silver and copper. So the gyp-
and major compensation of casting shrinkage is accom- sum-bonded investments should not be heated above 700°C.
plished principally by thermal expansion of the investment.
Type II: These are used for casting of inlays or crowns
and major mode of compensation is by hygroscopic expan- Silica: Quartz or Cristobalite
sion of the investment. 1 . Acts as a refractory during heating
Type III: These are utilized for construction of partial 2. Regulates thermal expansion
dentures with gold alloys. 3. Provides mould expansion
The dental stone shrinks when heated. With addition of
Composition proper from of silica in the investment, such a contraction
is eliminated and changed to an expansion during heating.
Silica 60–65% Silica exists in at least four allotropic forms as follows:
Alpha-hemihydrate or dental stone 30–35% 1. Quartz
Chemical modifiers 5%
2. Tridymite
3. Cristobalite
4. Fused quartz
Refractory Material Quartz or cristobalite or a combination of the two is
1. They are forms of silica (silicon dioxide) such as quartz, used. Depending on the type of silica used, the dental in-
tridymite, cristobalite or a mixture of these. vestments are classified as quartz investments or cirsto-
2. They serve two functions as follows: balite investments.
a. Provide refractory material during heating
b. Regulate the thermal expansion
Modifiers
Modifiers used are as follows:
Binder 1. Reducing agents
Since the refractory materials alone do not form a coherent 2. Modifying chemicals
solid mass, some kind of binder is needed. The common 3. Colouring matter
Reducing Agents 10. The material should be economical.

They reduce any oxides formed on the metal by providing
a nonoxidizing atmosphere in the mould when the mould PHOSPHATE-BONDED INVESTMENTS
alloy enters, e.g. carbon or copper powder.
Uses
Modifying Chemicals For casting high fusing alloys, e.g. high fusing noble metal
alloys, metal ceramic alloys, and base metal alloys like
They regulate setting expansion and setting time and also
nickel–chromium and cobalt–chromium.
prevent shrinkage of gypsum when heated above 300°C,
e.g. boric acid and sodium chloride.
Supplied As
Q. 4. Classify dental investments and mention the re-
quirements of ideal investment material. Write in detail Powder in packets with special liquid.
about the phosphate-bonded investments.
Ans. Composition
The investment materials are classified as follows: Powder contains the following:
1. Gypsum-bonded investments: They are used for casting 1. Ammonium diacid phosphate (NH4H2PO4)
gold alloys. They can withstand temperature up to 700°C. a. It gives strength at room temperature.
2. Phosphate-bonded investments: They are used for metal b. It is soluble in water and provides phosphate ions.
ceramic and cobalt–chromium alloys. They can with- c. It reacts with silica at high temperature to increase
stand higher temperatures. strength at casting temperatures.
3. Ethyl silica-bonded investments: They are an alternative 2. Silica: Refractory material
to the phosphate-bonded investments for high tempera- 3. Magnesium oxide: It reacts with phosphate ions.
ture casting. They are principally used in the casting of 4. Liquid: The phosphate-bonded investments are mixed
base metal alloy partial dentures. with a special liquid supplied by the manufacturer. This
liquid is a form of silica sol in water, which gives higher
All the above investment materials contain silica as the thermal expansion.
refractory material. The type of binder used is different.
Requirements of an ideal investment material are as follows:
Setting Reaction
1. The investment mould must expand to compensate for
the alloy shrinkage which occurs during the cooling of At room temperature ammonium diacid phosphate reacts
the molten alloy. with magnesium oxide to give the investment green
2. The powder should have a fine particle size to give a strength, or room temperature strength.
smooth surface to the casting.
NH4H2PO4 1 MgO n NH4MgPO4 1 H2O
3. The manipulation should be easy. It should have a suit-
able setting time. The ammonium diacid phosphate is used in a greater
4. The material should have a smooth consistency when amount than is necessary for this reaction, so that the
mixed. additional amount can react with silica at an elevated
5. The set material should be porous enough to permit air temperature. At higher temperature there is probably a
in the mould cavity to escape easily during casting. superficial reaction between P2O5 and SiO2 to form silico-
6. At higher temperatures, the investment must not decom- phosphate, which increases the strength of investment at
pose to give off gases that may corrode the surface of higher temperature.
the alloy.
7. It must have adequate strength at room temperature to
Manipulation
permit handling, and enough strength at higher tempera-
tures to withstand the impact force of the molten metal. The powder is mixed with a measured amount of liquid us-
8. Casting temperatures should not be critical. ing a bowl and spatula. Hand mixing or mechanical mixing
9. The casting should break away readily from the surface under vacuum can be done. The mixed material is vibrated
of the metal and should not react chemically with it. into the casting ring or agar mould.
SHORT ESSAYS
Q. 1. Classify investment materials and discuss expan- b. W/P ratio: The higher the W/P ratio of the original
sions in investment material. investment water mixture, the less is the HSE.
Ans. The investment materials can be classified as follows: c. Temperature: Higher the temperature of immersion
1. Gypsum-bonded investments: They are used for casting water, less is the surface tension and hence, greater
gold alloys. They can withstand temperature up to 700°C. is the expansion.
2. Phosphate-bonded investments: They are used for metal d. Effect of time of immersion: Immersion before the
ceramic and cobalt–chromium alloys, and they can initial set results in greater expansion.
withstand higher temperatures. e. Effect of shelf life of the investment: The older the
3. Ethyl silica-bonded investments: They are principally investment, the less is the hygroscopic expansion.
used in the casting of base metal alloy partial dentures. f. Effect of the amount of added water: More the
They are an alternative to the phosphate-bonded invest- amount of water added during the setting period,
ments, for high temperature casting. more is the expansion.
a. All three types of investment materials contain silica
as the refractory material, only the type of binder Thermal Expansion (TE)
used is different.
1. In case of gypsum investments, thermal expansion (TE)
b. Expansions in investment: Three types expansions
is achieved by placing the mould in a furnace at a tem-
observed in investments are as follows:
perature not greater than 700°C. If it exceeds this tem-
i. Normal setting expansion
perature, gases are released, contaminating the gold al-
ii. Hygroscopic setting expansion
loys and the investment breaks down.
iii. Thermal expansion
2. The amount of thermal expansion required depends on
method used for casting shrinkage compensation.
Normal Setting Expansion If hygroscopic expansion technique is used, then TE of
l A mixture of silica and dental stone results in a setting 0.5–0.6% is sufficient. But, if the compensation is by
expansion which is greater than when the gypsum prod- TE together with normal setting expansion, then the TE
uct is used alone. should be 1–2%.
l The silica particles probably interfere with the inter-
3. Factors affecting thermal expansion:
meshing of the crystals as they form. Thus, the thrust of a. TE is related to the amount and type of silica used.
the crystals is outwards during growth. b. Effect of the W/P ratio: More the water, less the TE.
l ADA Specification No. 2 for type I investment permits
c. Effect of chemical modifiers: Small amounts of so-
a maximum setting expansion in air of 0.5%. dium chloride, potassium chloride and lithium chlo-
l Modern investments show setting expansion of 0.4%. It
ride increase TE and eliminate the contraction caused
is regulated by retarders and accelerators. by gypsum.
Q. 2. Dye stone
Hygroscopic Setting Expansion (HSE)
Ans. Various recommended dye materials are as follows:
l When gypsum products are allowed to set in contact 1. Stone dyes type IV and type V
with water, the amount of expansion exhibited is much 2. Electroformed dyes
greater than the normal setting expansion. 3. Epoxy resins
l The increased amount of expansion is because water 4. Refractory or ceramic materials
helps the outward growth of crystals.
l This expansion is known as hygroscopic setting expan-
sion. The investment should be immersed in water before

Improved Dental Stone or Dye Stone
initial set is complete. l The most accurate and commonly used die materials are
l ADA Specification No. 2 for type II investments requires still alpha-hemihydrate type IV and type V gypsum
a minimal 1.2% and maximum 2.2% expansion. products.
l Factors affecting hygroscopic setting expansion are as l Type IV gypsum products have cuboidal-shaped parti-
follows: cles and the reduced surface area produce the required
a. Composition properties of strength, hardness and minimal setting
i. Higher the silica content, greater is the expansion.
expansion. l The most recent gypsum product having an even higher
ii. The finer the particle size of the silica, the compressive strength than the type IV is dental stone.
greater is the HSE. High strength, high expansion—type V.
l The setting expansion has been increased from 0.01 to wax pattern reduces HSE. This effect is much more
0.30%. This higher setting expansion is required in pronounced on the HSE than on the normal setting
the stone used for the dye to aid in compensation for expansion.
the base metal alloy solidification shrinkage. 8 . Effect of the amount of added water: More the amount
of water added during the setting period, more is the
Advantages expansion.
Advantages of dye stone are as follows: Q. 4. Ideal requisites of a dye material and mention
1. Easy manipulation and excellent working time different types of dye materials.
2. Gets quickly and have smooth, hard surface
Ans. Ideal requisites of dye materials are as follows:
3. Good strength and compatible with impression materials
1. It should be dimensionally accurate.
4. Minimal shrinkage
2. It should have high abrasion resistance, should possess
5. Can be easily trimmed
good strength and have a smooth surface.
6. Have good colour contrast
3. Its toughness should allow burnishing of foil and resist
7. Is economical
breakage.
4. Ability to reproduce all fine details in the impression.
Disadvantages 5. Compatibility with all impression materials.
6. Colour contrast with wax, porcelain, and alloys.
1 . Brittle. 7. Easy and quick manipulation and rapid fabrication.
2. Edges and occlusal surface may be rubbed off by re- 8. Noninjurious to health by touch or inhalation.
peated contact. 9. Economical.
Q. 3. Hygroscopic expansion Various types of dye materials are listed in Table 11.4.
Ans.
TABLE 11.4 Types of Dye Materials
l When gypsum products are allowed to set in contact 1. Gypsum Dental stone, high strength—type IV
with water, the amount of expansion exhibited is much Dental stone, high strength, high
greater than the normal setting expansion. The increased expansion—type V
amount of expansion is because water helps the outward Dental stone 1 lignosulphonates
growth of crystals. This expansion is known as hygro- 2. Metals Electroformed/electroplated
scopic setting expansion. Sprayed metals
l The investment should be immersed in water before Amalgam
initial set is complete. ADA Specification No. 2 for 3. Polymers Metal-filled resins or inorganic-filled
type-II investments requires a minimal 1.2% and maxi- resins, e.g. epoxy
mum 2.2% expansion. 4. Cements Silicophosphate or polyacrylic acid-
l Factors affecting hygroscopic setting expansion are as bonded cements
follows: 5. Ceramic or For direct baking of porcelain crown or
1. Composition refractory dye preparation of wax patterns of casting
a. The finer the particle size of the silica, the greater is materials
the HSE.
b. Higher the silica content, greater is the expansion.
c. Alpha-hemihydrate produces a greater expansion Q. 5. Types and advantages of casting machines
than beta-hemihydrate. Ans.
2. W/P ratio: The higher the W/P ratio of the original in-
vestment water mixture, the less is the HSE. 1. All casting machines can be divided into two general
3. Temperature: Higher the temperature of immersion wa- types, which force the metal into the mould. They are
ter, less is the surface tension and hence, greater is the a. centrifugal force type and
expansion. b. air pressure type.
4. Effect of time of immersion: Immersion before the ini- 2. Numerous modifications and variations of these princi-
tial set results in greater expansion. ples are employed in different instruments.
5. Spatulation: Shorter the mixing time, the less is Casting machines both centrifugal and gas pressure type
the HSE. with an attached vacuum system are also available.
6. Effect of shelf life of the investment: The older the in- 3. A variety of centrifugal machines are available.
vestment, the less is the hygroscopic expansion. a. It is spring driven or motor driven.
7. Confinement of the investment: Confinement of the b. Alloy is fused by electric resistance or induction
investment by the walls of the container or the furnace or on a refractory tray by a blowtorch.
4. The main advantages of the centrifugal machines is the b. Gas inclusions—spherical

simplicity of design and operation, with the opportunity to c. Subsurface porosity—in shape
cast both large and small castings on the same machine. 3. Those caused by air trapped in the mould—back pres-
5. In air pressure type of machine, either compressed air or sure porosity.
gases like carbon dioxide or nitrogen can be used to
force the molten metal into the mould. This type of ma-
Localized Shrinkage or Shrink-Spot Porosity
chine is satisfactory for making small castings.
l It occurs when the cooling sequence is incorrect and the
Q. 6. Back pressure porosity sprue freezes before the rest of the casting. The subse-
Ans. quent shrinkage produces voids or pits known as shrink-
spot porosity.
1. When mounting the sprue pattern on the crucible former, l These are large irregular voids usually found near the
it should be adjusted so that there is not more than 1⁄4 inch sprue-casting junction.
thickness of the investment between the bottom of the
casting ring and the nearest part of the wax pattern.
Suck Back Porosity
2. When the molten metal enters the mould, the air inside
is pushed out through the investment at the bottom. l It is a variation of the shrink-spot porosity. This is an
3. If the bulk of the investment is too great the escape of external void usually seen in the inside of a crown op-
air may be allowed. The gold will then solidify before posite the sprue.
the mould is completely filled resulting in a porous cast- l A hot spot is created by the hot metal impinging on the
ing with rounded short margins. mould wall near the sprue.
The hot spot causes this region to freeze last. Since the
Q. 7. Electroformed dyes sprue has already solidified, no more molten material is
Ans. available and the resulting shrinkage causes a peculiar type
of shrinkage called suck back porosity.
Advantages of electroformed/electroplated casts and dyes: It is avoided by reducing the temperature difference
1. Dimensional accuracy between the mould and the molten alloy.
2. Hard, abrasion resistance
3. Imparts a smooth surface to the wax pattern in contact
Microporosity
4. Not very expensive
5. Better marginal definition These are fine irregular voids within the casting. It is seen
6. Does not absorb oil or water when the casting freezes too rapidly.
7. Prevents cuspal wear due to repeated contact with oppos-
ing cast
Pinhole Porosity
Disadvantages of electroformed/electroplated casts and
Many metals dissolve gases when molten. Upon solidifica-
dyes:
tion the dissolved gases are expelled causing tiny voids, e.g.
1. Difficult to trim
platinum and palladium absorb hydrogen. Copper and sil-
2. Silver bath—health hazard
ver dissolve oxygen.
3. Not compatible with all impression materials
4. Colour contract not as good as dye stone
5. Adaptation of wax not as good as to the alpha-hemihydrate. Gas Inclusion Porosities
Pattern tends to lift from margins.
Gas inclusion porosities are also spherical voids but are
Q. 8. Porosities in dental castings larger than the pinhole type. They are more likely due to
gases carried in or trapped by the molten metal. A poorly
Ans. Porosity may be internal or external. External poros- adjusted blowtorch can also occlude gases.
ity can cause discolouration of the casting. Internal porosity
weakens the restoration.
Back Pressure Porosity
According to Phillips, porosities are classified as follows: l This is caused by inadequate venting of the mould.
1. Those caused by solidification shrinkage l If the bulk of the investment is too great, the escape of air
a. Localized shrinkage porosity becomes difficult causing increased pressure in the mould.
b. Suck back porosity—irregular l The gold will then solidify before the mould is com-
c. Microporosity—in shape pletely filled resulting in a porous casting with rounded

2. Those caused by gas short margins.
a. Pinhole porosity—usually l Avoided by—using adequate casting force.
l Use of investment of adequate porosity—place pattern 5. The set material should be porous to allow air in the
not more than 6–8 mm away from the end of the ring. mould cavity to escape easily during casting.
6. At higher temperatures, the investment must not de-
Q. 9. Mention ideal requirements of investment materials. compose to give off gases that may corrode the surface
Ans. The ideal requirements of investment materials are as of the alloy.
follows: 7. It must have adequate strength at room temperature
1. The investment mould must expand to compensate for and at higher temperatures to permit handling and
the alloy shrinkage. withstanding the impact force of the molten metal re-
2. The powder should have a fine particle size to give a spectively.
smooth surface to the casting. 8. Casting temperatures should not be critical and the
3. Should be easy to manipulate and should have a suit- investment should break away readily from the surface
able setting time. of the metal.
4. When mixed the material should have a smooth con- 9. It should not react chemically with it.
sistency. 10. The material should be economical.
SHORT NOTES
Q. 1. Suck back porosity to the sprue or the attachment of the sprue to the wax pat-
Ans. Suck back porosity is a variation of the shrink-spot tern is flared.
porosity. Functions of sprue former are as follows:
1. To form a mount for the wax pattern
l This is an external void usually seen in the inside of a 2. To create a channel for the elimination of wax during
crown opposite the sprue. burnout
l A hot spot is created by the hot metal impinging on the 3. Forms a channel for entry of molten alloy during
mould wall near the sprue. The hot spot causes this region casting
to freeze last. Since the sprue has already solidified, no 4. Provides a reservoir of molten metal which compen-
more molten material is available and the resulting sates for alloy shrinkage during solidification
shrinkage is of a peculiar type called suck back porosity.
l It can be avoided by reducing the temperature difference Q. 4. Epoxy resin dyes
between the mould and the molten alloy. Ans. Epoxy resin dyes are most effective with rubber im-
pression materials and are available as two components—
Q. 2. Localized shrinkage porosity
resin paste and hardener.
Ans.
Localized shrinkage or shrink-spot porosity is caused

l
Advantages
by solidification shrinkage.
l These are large irregular voids usually found near the 1. Tougher and more effective with rubber impression
sprue casting junction. materials
l It occurs when the cooling sequence is incorrect and
the sprue freezes before the rest of the casting. During

Disadvantages
a correct cooling sequence, the sprue should freeze last.
1 . Slight shrinkage (0.1%)
Q. 3. Sprue and sprue former 2. Viscous, does not flow readily
Ans. 3. Setting may take up to 24 h
Q. 5. Pickling
Sprue Ans.
The mould channel through which molten metal or ceramic
flows into the mould cavity is known as sprue. l The surface oxides from the casting are removed when
necessary by pickling in 50% HCl.
l HCl is heated, but not boiled with the casting in it, usu-
Sprue Former ally done for gold alloys.
A sprue former is made of wax, plastic or metal. Thickness l Pickling is not a routine procedure and is performed
is in proportion to the wax pattern. A reservoir is attached only when indicated.

Q. 6. Hygroscopic expansion is completely filled resulting in a porous casting with

rounded short margins.
Ans.
3. The back pressure porosity can be avoided by the following:
The amount of setting expansion that occurs when a a. Using adequate casting force
gypsum-bonded casting investment is immersed in water b. Using investment of adequate porosity
usually heated to approximately 38°C is known as hygro- c. Place pattern not more than 6–8 mm away from the
scopic expansion. end of the ring
d. Providing vents in large castings
Q. 7. Divestment
Q. 10. Incomplete casting
Ans.
Ans.
l The combination of dye material and investing medium
An incomplete casting may result when
is known as divestment.
l A gypsum-bonded material called divestment is mixed 1 . insufficient alloy is used.
with a colloidal silica liquid. The dye with the wax pat- 2. alloy not able to enter thin parts of mould.
tern is invested in divestment. 3. when mould is not heated to casting temperature.
l The setting expansion of divestment is 0.9% and ther- 4. premature solidification of alloy.
mal expansion 0.6% when heated to 677°C. 5. sprues are blocked with foreign bodies.
l As it is a gypsum-bonded material it is not recom- 6. back pressure due to gases in mould cavity.
mended for high fusing alloys like those used in metal 7. low casting pressure.
ceramic restorations. 8. alloy not sufficiently molten or fluid.
l It is a highly accurate technique for conventional gold
alloys especially for extracoronal preparations. Q. 11. Porosity

l Divestment phosphate (DVP) is a phosphate-bonded
Ans.
investment that is used in the same manner as divest-
ment and is suitable for use with high fusing alloys. l Porosity may be internal or external.
l Internal porosity weakens the restoration while external
Q. 8. Phosphate-bonded investments porosity can cause discolouration of the casting.
Ans. According to Phillips, porosities are classified as follows:
1. Those caused by solidification shrinkage
1. The phosphate-bonded investments consists of three a. Localized shrinkage porosity
different types of components as follows: b. Suck back porosity
a. Ammonium diacid phosphate (NH4H2PO4) c. Microporosity
i. It gives strength at room temperature. 2. Those caused by gas
ii. It is soluble in water and provides phosphate ions. a. Pinhole porosity
iii. It reacts with silica at high temperature to in- b. Gas inclusions
crease strength of casting temperature. c. Subsurface porosity
b. Silica: Refractory material 3. Those caused by air trapped in the mould—back pres-
c. Magnesium oxide: Reacts with phosphate ions sure porosity.
NH4H2PO4 1 MgO n NH4MgPO4 1 H2O To avoid porosity:
2. The phosphate-bonded investments are mixed with a 1. Use correct sprue thickness and correct placement of sprue
special liquid supplied by the manufacturer. This liquid 2. Use reservoir
is a form of silica sol in water which gives higher ther- 3. Use adequate casting force
mal expansion. 4. Use porous investment and proper vents
5. Place pattern 6–8 mm away from end of ring
Q. 9. Back pressure porosity
Q. 12. Reservoir
Ans. The back pressure porosity is caused by the following:
1. Inadequate venting or air escape of the mould. Ans.
2. When the molten metal enters the mould, the air inside l The reservoir is a piece of wax attached to the sprue
is pushed out through the porous investment at the bot- former approximately 1 mm from the pattern.
tom. If the bulk of the investment is too great, the escape l A reservoir can be used as an added precaution. The purpose
of air becomes difficult causing increased pressure in of the reservoir is to prevent localized shrinkage porosity.
the mould. The gold will then solidify before the mould
Topic 12
Finishing and Polishing Materials

LONG ESSAYS
Q. 1. Abrasive and polishing agents
3. Garnet
Ans.
l It is composed of different minerals that possess similar
physical properties and crystalline form. The mineral
comprises of silicates of aluminium, cobalt, magne-
CLASSIFICATION OF ABRASIVES
sium, iron and manganese.
. Finishing abrasives
A l Garnet is coated on paper or cloth with glue. It is used
B. Polishing abrasives on discs that are operated on hand pieces.
C. Cleansing abrasives
4. Pumice
Finishing Abrasives
l It is a highly siliceous material of volcanic origin and is
Finishing abrasives are hard, coarse abrasives that are used used either as an abrasive or polishing agent depending
initially to develop contour and remove gross irregularities, on particle size.
e.g. coarse stones. l Its use ranges from smoothening dentures to polishing
teeth in the mouth.

Polishing Abrasives
Polishing abrasives have finer particle size and are less hard
5. Kieselguhr
than abrasives used for finishing. They are used for smooth- l Consists of siliceous remains of minute aquatic plants
ening surface that have been roughened by finished abra- known as diatoms.
sives, e.g. polishing cakes, pumice, etc. l The coarser form (diatomaceous earth) is used as a filler
in many dental materials. It is excellent as a mild abra-

sive and polishing agent.
Cleansing Abrasives
Cleansing abrasives are soft materials with small particle
sizes and are intended to remove soft deposits that adhere
6. Tripoli
to enamel or a restorative material. l This mild abrasive and polishing agent is often con-
fused with kieselguhr. True tripoli originates from
certain porous rocks, first found in North Africa, near
TYPES OF ABRASIVES
Tripoli.
Various types of abrasives are as follows:
7. Rouge
1. Emery
l Rouge is a fine red powder composed of iron oxide.
l Emery consists of a natural oxide of aluminium called l It is used in cake form. It may be impregnated on paper
corundum. or cloth known as crocus cloth. It is an excellent polish-
l The greater the content of alumina, the finer the grade ing agent for gold and noble metal alloys.
of emery. Pure alumina is also used as a polishing agent.
8. Tin Oxide
2. Aluminium Oxide
l Putty powder used as polishing agent for teeth and me-
l Pure alumina is manufactured from bauxite. tallic restorations in the mouth.
l It can be produced in fine grain sizes and has partially l It is mixed with water, alcohol or glycerin and used as
replaced emery for abrasive purpose. paste.
9. Chromic Oxide l The Vickers hardness number of the tempered steel bur
is 800, whereas that of enamel is 261–300.
l A relatively hard abrasive capable of polishing a variety
of metals. Used as a polishing agent for stainless steel.
2. Tungsten Carbide Burs
10. Diamond l Tungsten carbide is a product of powder metallurgy.
l Tungsten carbide powder: 90 parts
l It is the hardest and most effective abrasive for tooth l Cobalt powder: 10 parts
enamel.
l The chips are impregnated in a binder or plated onto a
They are mixed and placed under pressure and vacuum
metal shank to form the diamond stones and discs. and heated to approximately 1350°C (2460°F), a partial al-
loying or sintering of the metals takes place. A eutectic
Vickers hardness number: 1650–1700 VHN.
11. Zirconium Silicate
l The blank of tungsten carbide bur is cut with diamond
l Occurs in nature as zircon. tools. The cutting head is fastened to a steel shank by
l This mineral is ground to various particle sizes and used soldering or electric butt welding.
as a polishing agent. l In some cases, the entire tool including the shank and
l It is used in dental prophylactic pastes and in abrasive shaft are made of tungsten carbide alloy.
impregnated polishing strips and discs.
12. Zinc Oxide FACTORS AFFECTING THE CUTTING

EFFICIENCY OF BURS
l Zinc oxide in alcohol can be used for polishing amal-
gam restorations. l The force exerted by the blade: If it is insufficient to induce
stress to exceed the elastic limit of the material, it causes
Q. 2. Classify dental burs and mention factors affecting
only deformation of the surface, without chip formation.
the cutting efficiency of burs.
l This explains that, for any rotational speed, there is
Ans. minimal load that needs to be exerted to produce cutting.

l The magnitude of load exerted on a bur: The greater the
l Dental burs are miniature milling cutters as used in in- load exerted, the more the blade bites into the work and
dustry. more material is removed. However, there is a limit to the
l Dental burs are available in various sizes and shapes
magnitude of load exerted on a bur at a particular speed.
depending on the purposes in preparation for finishing l When the load is held constant, the rate of cutting can
cavities and restoration. be increased by increasing the rotational speed. This
is because more blades contact the work per unit of
CLASSIFICATION OF DENTAL BURS AS PER time and blades follow each other very rapidly so that
COMPOSITION AND MANUFACTURE the energy required for the second blade to cause elas-
tic deformation of the surface is less. This is because
Classified as per their composition, burs are of the follow- the second blade contacts with the surface which is
ing two types: permanently deformed previously by the first blade
1. One type is made from hypereutectoid steel with hard- rapidly. Thus the efficiency of cutting is increased.
ening agent added in minor amounts. Burs of this type l The amount of material removed per tooth, at the higher
are called as carbon steel burs or steel burs. speed is greater than at the lower speed under the same
2. The second type is tungsten carbide burs or carbide burs. conditions of loading.
1. Steel Burs Q. 3. Differences between abrasive and polishing agents
l They are cut from blank stock by rotating cutter that Ans.
cuts parallel to the axis of the bur, e.g. straight fissure
bur. The bur is then hardened and tempered.
DIFFERENCES BETWEEN ABRASION
During cutting enamel: The edges of steel burs are
l
AND POLISHING AGENTS
turned, chipped and worn during its contact with tooth
enamel. The different between an abrasive agent and a polishing agent
l During cutting dentine the steel bur cuts effectively. is difficult to define. The terms are generally interchangeable.
1. Particle Size 3. Speed

A given agent having a large particle size acts as an abra- The optimum speed for polishing is higher than that for
sive, producing scratches. The same abrasive with a smaller abrading. Linear speed as high as 10,000 ft/min may be
particle size is a polishing agent. used. It varies with the polishing agent. Average speed is
approximately 7500 ft/min.
2. Material Removed
Very little of the surface is removed during polishing—not
more than 0.005 mm (0.002 inch).
SHORT ANSWERS
Q. 1. Negative rake angle in dental bur Q. 5. Bur design
Ans. Ans. Dental bur is a small milling cutter. Design of burs
includes the following:
Rake Angle
i. Blade or Cutting Edge
The face of the bur tooth is at an angle to the radial line
from the centre to the cutting edge. The angle is known as Blade or cutting edge is in contact with the horizontal line
rake angle. or work.
Negative Rake Angle ii. Tooth Face

If the face is beyond or leading the radial line in reference Sides of tooth ahead of the cutting edge in the direction of
to the direction of rotation, the angle formed between the rotation is the tooth face.
face and the radial line is called negative rake angle.
Q. 2. Rouge iii. Back or Flank of the Tooth

Ans. The opposite of the face or following surface is the back or
flank of the tooth.
l Rouge is fine red powder composed of iron oxide.
It is used in cake form. It may be impregnated on paper
l
iv. Rake Angle
or cloth known as crocus cloth.
l It is an excellent polishing agent for gold and noble The face of the bur tooth is at an angle to the radial line
metal alloys but is likely to be dirty to handle. from the centre to the cutting edge. The angle is known as
rake angle.
Q. 3. Clearance angle and its importance
Ans. v. Negative Rake Angle
l The angle between the back of the tooth and the work is If the face is beyond or leading the radial line in reference
known as clearance angle. to the direction of rotation, the angle formed between the
l The plane surface immediately following the cutting face and the radial line is called negative rake angle.
edge is called land. The angle it makes with the work is
known as primary clearance. The angle between the
vi. Zero or Radial Rake Angle
back and the work is called secondary clearance.
Where the radial line and the face contour correspond, the
Q. 4. Diamond abrasives rake angle is zero. In such an instance, the bur tooth is said
Ans. to have a zero radial rake angle.
The hardest and most effective abrasive for tooth enamel

l
vii. Positive Rake Angle
is composed of diamond chips.
l The chips are impregnated in a binder or plated on to a When the radial line leads the face so that the rake angle is
metal shank to form the diamond stones and discs, on the inside of the radial line, the rake angle is said to be
which are very popular in the dental profession. positive.
viii. Clearance Angle Paper/Plastic Coated

The angle between the back of the tooth and the work is The abrasive particles may be glued on to a paper or plastic
known as clearance angle. disc that can be attached to a hand piece, e.g. sand paper.
ix. Tooth Angle Stainless Steel Coated Strips

It is the measurement between the face and the back or The abrasive may be attached to stainless steel or plastic
between the face and the land. strips, e.g. diamond.
x. Flute or Chip Space Electroplating Bonding

It is the space between the successive teeth. Number of In case of diamond-rotary instruments, the diamond chips
teeth in a bur is 6 or 8. The dental burs provide a negative are attached to steel wheels, discs and cylinders by electro-
rake angle. The clearance angle of most burs is straight and plating with nickel-based matrix.
clearly defined.
Q. 6. Dental bur Bonded Stones

Ans. Refer to the answer of Long Essays, Q. 2. In grinding wheels and dental stones, the abrasive particles
are mixed with a bonding agent that holds the
particles together. Before hardening, the matrix material
Q. 7. Bonded abrasives with the abrasive is moulded to form tools of desired
Ans. shapes.
Topic 13
Bonding
SHORT ESSAYS
Q. 1. Acid etching 2. Etching
Ans. The acid etch technique is one of the most effective a. The tooth surface is etched by applying etchant
ways of improving the bond and marginal seal between gel on the enamel, originally the length of
resin and enamel. application was set at 60 s but now it has
been shown that 15 s provide as strong
a bond.
Mode of Action b. The etching time also depends on the history of
l It creates microporosities by discrete etching of the the tooth, e.g. a tooth with high fluoride content
enamel, i.e. by selective dissolution of enamel rod cen- requires longer etching time.
tres, or peripheries, or both. 3. Washing: The acid should be rinsed off thoroughly
l Etching increases the surface area. with a stream of water for 15 s.
l Etched enamel has a high risk surface energy, allowing 4. Drying
the resin to wet the tooth surface better and penetrate a. The enamel surface is dried thoroughly with a
into the microporosities. When polymerized, it forms mild stream of air.
resin tags which forms a mechanical bond to the enamel. b. After drying the enamel should have a white,
l Acid used: 37% phosphoric acid is used for etching. frosted appearance. This surface must be kept
l Procedure: The steps in etching technique are as clean and dry until the resin is placed.
follows: 5. Application of bonding agent: The bonding agent is
1. Cleaning: The tooth is cleaned and polished with applied immediately before the etched surface gets
pumice before etching. contaminated.
Q. 2. Pit and fissure sealants l The glass ionomer can also be etched with the help of
phosphoric acid to improve retention. In addition it also
provides an anticariogenic effect due to its fluoride re-
Ans.
lease. When used in this context it is often referred to as
l Pits and fissures on the occlusal surface of permanent sandwich technique.
posterior teeth are susceptible to decay as they provide
shelter for organisms and obstruct oral procedures. Q. 4. Bonding agents
Various materials have been advocated to seal these ar- Ans.
eas, especially in the child patient they are known as pit
and fissure sealants. l Bonding agents are those materials that help to improve
l The most popular sealant techniques make use of resin the bond between the tooth and the restoration. They are
systems. The objective is for the resin to penetrate into the materials of low viscosity, when applied on the tooth
the pits and fissures and to polymerize, thereby sealing surface form a thin film after setting.
these areas against oral flora and debris. l Bonding agents may be classified according to the fol-
l Many resin systems have been employed. They include lowing:

a. cyanoacrylates, 1. The mechanism of bonding:
b. polyurethanes and a. Mechanical bonding, e.g. composite resins, bis-
c. bis-GMA. GMA, TEGDMA, cyanoacrylates
l The most commonly and successfully used one is the bis- b. Chemical bonding, e.g. polycarboxylate cements
GMA resin. It may be cured chemically (amine–peroxide (ZnPolyC), GIC
system) or by light activation. 2. The application:
l Two types of resins are available. They include a. Enamel bonding agents
a. filled and b. Dentine bonding agents
b. unfilled.
l The unfilled resins are colourless or tinted transparent
Enamel Bonding Agents
materials, while the filled resins are opaque and avail-
able as tooth-coloured or white materials. l They were the earliest agents.
l The sealant must be of relatively low viscosity so that l The enamel bonding agents helped to improve the bond by
they will flow readily into the depths of the pits and fis- flowing into all the microporosities of the etched enamel.
sures and wet the tooth. The physical properties of the l They are unfilled resins similar to that of the resin ma-
sealants are closer to those of unfilled direct resins than trix of composite resin, diluted by other monomers to
to those of composite resins. lower the viscosity.
l Careful case selection and meticulous application of the l These materials have been largely replaced by agents
material is essential for clinical success. that bond to dentine also.

l Surfaces that are free of caries should be selected and
For example: Thin composite resins, TEGDMA, cyano-
the placed sealant should be examined every 6 months
acrylates, and glass ionomers.
to confirm its integrity.
Q. 3. Sandwich technique Dentine Bonding Agents

Ans. Dentine bonding agent is a thin layer of resin between con-
ditioned dentine and the resin matrix of a composite. For
l The process of restoring a prepared tooth by initially
example: Several dimethacrylate systems, NPG-GMA, bis-
placing a layer of type II glass ionomer cement for fluo-
GMA, polyurethanes, 4-META, ferric oxalate systems, etc.
ride release followed by an overlying layer of resin-
based composite for strength durability is known as Dentine bonding agents are classified as follows:
sandwich technique. 1. First generation (developed before 1980s): They used
l Composite does not bond adequately to dentine, there-
glycerophosphoric acid dimethacrylate to provide a bi-
fore during polymerization, a gap may result if the cav- functional molecule. The hydrophilic phosphate part
ity margin is situated in dentine. reacted with calcium ions of the hydroxyapatite. The
l The bond to dentine can be improved by placing a
hydrophobic methacrylate groups bonded to the acrylic
glass ionomer liner between the composite restoration restoration resin. The main advantage was their low
and dentine. The glass ionomer bonds to the dentine bond strength.
through chemical adhesion whereas to the resin it 2. Second generation (early 1980s): Developed as adhe-
bonds mechanically through porosities and crazing sive agents for composite resins which had replaced
present on the surface of the glass ionomer liner. acrylic restorations.
Disadvantage: Adhesion was short term, the bond even- 5. Fifth generation: The most recent product is the single
tually hydrolyzed, e.g. Prisma, Universal Bond, Clearfil, bond adhesive. Unlike the previous generations, this
Scotch Bond. system is more simple to use as it needs only a single
3 . Third generation (late 1980s): These coupling agents step application, e.g. 3M Single Bond, One Step
had bond strengths comparable to that of resin to etched (BISCO), Prime and Bond (Dentsply).
enamel. However, their use is more complex and re-
quires two to three application steps. A primer is applied Advantages:
first followed by application of a polymerizable mono- a. Single step application
mer, e.g. Tenure, Scotchbond 2, Prisma, Universal b. Less technique sensitive as it can bond to moist dentine
Bond, Mirage Bond. c. Less volatile liquid
4. Fourth generation: All bond-2 system consists of two d. Pleasant odour
primers (NPG-GMA and biphenyl dimethacrylate e. Higher bond strength
(BPDM)) and an unfilled resin adhesive (40% bis- 6 . Sixth and seventh generations: These are single compo-
GMA, 30% UDMA, 30% HEMA). This system bonds nent system liquids, which require single application
composite not only to dentine but to most dental related without washing. For example: Organic phosphates,
surfaces like enamel, casting alloys, amalgam, porcelain polyurethanes, HEMA 1 bis-GMA 1 maleic acid, poly-
and composite. alkenoites (trade name: VLC)
SHORT ANSWERS
Q. 1. Sandwich technique 5. Polyacrylic acids: They bond to the hydroxyapatite in
Ans. The process of restoring a prepared tooth by initially dentine.
placing a layer of type II glass ionomer cement for fluoride
Q. 4. Pit and fissure sealants
release followed by an overlayer of resin-based composite
for strength durability is known as sandwich technique. Ans.
l Pit and fissure sealants are various materials that have

Q. 2. Dentine bonding agents been advocated for preventing caries in the susceptible pit
Ans. Dentine bonding agent is a thin layer of resin between and fissure areas of posterior teeth, particularly in the
conditioned dentine and the resin matrix of a composite. child patient or for the high caries risk patients in general.
l The most popular sealant techniques make use of resin
For example: Several dimethacrylate systems, NPG- systems that can be applied to the occlusal surfaces of
GMA, bis-GMA, polyurethanes, 4-META, hydroxyethyl the teeth.
methacrylate (HEMA), ferric oxalate systems, etc. l The objective of sealant use is for the resin to penetrate
into the pits and fissures and to seal these areas against
Q. 3. Bonding agents the oral bacteria and debris.
l Several types of resins, both filled and unfilled, have been
Ans. Several systems have been employed as bonding
agents as follows: employed as pit and fissure sealants. These resin systems
include cyanoacrylates, polyurethanes and bis-GMA.
1. Ferric oxalate—NPG-GMA system
a. The acidic ferric oxalate has combined cleansing and Q. 5. Acid etch technique
mordanting functions. This is followed by applica- Ans. The acid etch technique is one of the most effective
tion of NPG-GMA. ways of improving the bond and marginal seal between
b. Ferric oxalate produced a black stain and so alu- resin and enamel.
minium oxalate was substituted.
2. Hydroxyethyl methacrylate (HEMA) plus glutaraldehyde
a. EDTA is applied first as primer.
b. The glutaraldehyde provides bonding to the colla-
Procedure
gen in dentine, whereas HEMA is a polymerizable The steps in etching technique are as follows:
monomer. 1. Cleaning and polishing the tooth with pumice before
3. Bis-GMA plus HEMA: Maleic acid in a solution of etching.
HEMA is applied first as primer. This is followed by 2. Etching the tooth surface by applying etchant gel for
application of a polymerizable monomer composed of about 15 s.
bis-GMA and HEMA. 3. Washing the acid by rinsing off thoroughly with a
4. 4-Methyloxyethyltrimellitic acid (4-META): It is dis- stream of water for 15 s.
solved in methyl methacrylate and is a potential cou- 4. Drying the enamel surface thoroughly with a mild
pling agent to collagen. stream of air.
5. Application of bonding agent immediately before the tooth surface better and penetrate into the microporosi-
etched surface gets contaminated. ties. When polymerized, it forms resin tags which forms
a mechanical bond to the enamel.
Mode of Action
l It creates microporosities, increases the surface area and
surface energy of enamel, allowing the resin to wet the
Topic 14
Restorative Resins
LONG ESSAYS
Q. 1. Classify composite resin restorative material.
1 . Organic phase or resin phase is the matrix.
What are the components and their role in it? Mention
2. Inorganic phase or filler particles are dispersed in resin
the advantages and disadvantages of light cure compos-
matrix to increase the strength.
ite resin restorative material.
3. Interfacial phase or coupling or keying agent—
Ans. Classification of composite resin restorative material act as adhesive agent that promotes adhesion
can be on following basis: between filler particles and resin matrix by chemical
bonding.
The advantages of light-cure (both UV and visible light)
CURING MECHANISM composite resin restorative material as compared to chemi-
l Chemically activated cal cure composites are as follows:
l Light-activated l Easy manipulation, no mixing is required.
l Infinite working and short-controlled setting time.
l Amount of finish and polish required is very less.

SIZE OF FILLER PARTICLE l Less waste of material.
l Conventional: 8–12 µm
The advantages of visible light-cured composites compared
l Small particle: 1–5 µm
to UV light cured composites are as follows:
l Microfilled: 0.04–0.4 µm
l They can be cured to greater depth (2–2.5 mm) in a
l Hybrid: 0.6–1.0 µm
relatively short time of 20–40 seconds.
l Health hazard is virtually eliminated.
Composition and Structure l No warm up time and no decrease in the intensity of
light source.
The essential components of a composite resin are as follows:
l To maintain adhesion to cavity walls in a deep cavity
l Resin matrix/binder—BIS-GMA or urethane dimeth-
incremental technique can be used.
acrylate
l Filler—quartz, colloidal silica of heavy metal glasses The disadvantages of light-cured composite resin restor-
l Coupling agent—organosilanes ative materials are as follows:
l The use of UV light resins has declined due to lack of
They also contain the following:
depth of curing, health hazards and slow decrease in
l Hydroquinone—inhibitor to prevent premature polym-
intensity of UV light.
erization
l The drawbacks of visible light-cured composites are
l UV absorbers—to improve colour stability
that the degree of polymerization is not uniform
l Opacifiers —titanium dioxide and aluminium oxide
throughout the entire mass of the material and they ex-
l Colour pigments—to match tooth colour.
hibit polymerization shrinkage towards external surface
close to light source.
Structure
Composite resins set by addition polymerization reaction. Q. 2. Enumerate the aesthetic filling materials used in
Dental composites are made up of three structurally differ- restorative dentistry. Write in detail about composite
ent phases as follows: resin, its composition, classification and applications.
Ans. The aesthetic filling materials used in restorative Ideal requirements of dental resins are as follows:
dentistry are as follows: i. They should be tasteless, odourless, nontoxic and non-
l Silicate cement irritant to the oral tissues.
l Glass ionomer cement ii. They should be aesthetically satisfactory, i.e. should
l Acrylic resin be transparent or translucent and easily pigmented.
l Composite resins The colour should be permanent.
l Porcelain iii. They should be dimensionally stable. It should not
expand, contract or warp during processing and subse-
CLASSIFICATION OF COMPOSITE RESIN quent use by the patient.
iv. They should have enough strength, resilience and
RESTORATIVE MATERIAL abrasion resistance.
v. They should be insoluble and impermeable to oral fluids.
Based on Curing Mechanism vi. They should have a low specific gravity (light in
l Chemically activated weight).
l Light-activated vii. They should tolerate temperatures well above the tem-
perature of any hot food or liquids taken in the mouth
Based on Size of Filler Particle without undue softening or distortion.
viii. They should be easy to fabricate and repair.
l Conventional: 8–12 µm
ix. They should have good thermal conductivity.
l Small particle: 1–5 µm
x. They should be radio opaque.
l Microfilled: 0.04–0.4 µm
xi. When used as a filling material it should
l Hybrid: 0.6–1.0 µm
l bond chemically with the tooth.
l have coefficient of thermal expansion which match

COMPOSITION AND STRUCTURE that of tooth structure.
The essential components of a composite resin are as follows:
l Resin matrix/binder—BISGMA or urethane dimethac- Composition
rylate They are supplied as powder and liquid.
l Filler—quartz, colloidal silica of heavy metal glasses
l Coupling agent—organosilanes The powder contains the following:

l Hydroquinone—inhibitor to prevent premature polym- l Polymethyl methacrylate—as beads or grindings
l Benzoyl peroxide—initiator
erization.
l Colour pigments
l UV absorbers—to improve colour stability
l Opacifiers—titanium dioxide and aluminium oxide Liquid contains

l Colour pigments—to match tooth colour. l Methyl methacrylate monomer
l Ethylene dimethacrylate (5%) crosslinking agent
APPLICATIONS OF COMPOSITE RESINS l Hydroquinone (0.06%) inhibitor
l Restoration of anterior and posterior teeth (directly or as The monomer is supplied in brown bottles, to protect
inlays) them from ultraviolet light which can initiate polymerization.
l Veneering metal crowns and bridges
l Building up cores (post core) Manipulation of Acrylic Resins

l Cementation of orthodontic brackets, Maryland bridges
and ceramic crowns, inlays, onlays and laminates i. Pressure Technique or Bulk Technique
l Pit and fissure sealant Monomer and polymer mix at dough stage is placed in the
l Aesthetic laminates cavity. Pressure is applied with a matrix strip to prevent its
l Repair of chipped porcelain restorations pulling away from the cavity margins while it contracts
during polymerization.
Q. 3. Classify resins used in dentistry, enumerate ideal
requirements of dental resins. Write in detail about the ii. Nonpressure or Bead Technique
supply, composition and manipulation of acrylic resins. Mix is filled in the cavity in small increments with a brush
Mention their advantages. and not in one bulk. This compensates for the polymeriza-
Ans. tion shrinkage.
Various resins used in dentistry are as follows: i ii. Flow Technique

a. Type I—unfilled acrylic resins A thin mix (fluid resin) is made and filled into the prepared
b. Type II—filled or composite resins cavity. A matrix is held against it without pressure. The
matrix helps to contain the resin and ensures proper contact l Dentures (bases, liners and artificial teeth)
and contour. Close adaptation is achieved due to the fluid l Cavity filling materials (composites)
nature of the resin. l Sealants
l Impression materials
iv. Cavity Lining Agents l Cements (resin based)
Adhesion can be improved by specially formulated lining
agents which may be supplied by the manufacturer. It is
Uses
applied prior to insertion of the resin. The hydrophilic lin-
ing is more attractive to the hydrophobic resin. l Dental resins are used mainly to restore and replace
tooth structure and missing teeth.
l These resins can be bonded with other resins directly to
Applications of Resins in Dentistry tooth structure or to other restorative materials.
Synthetic resins are used in a variety of dental applications. l If all teeth are missing, a denture base with attached
Typical uses include the following: denture teeth can be made to restore chewing ability.
SHORT ESSAYS
Q.1. Classification of composite resins and role of fillers In visible light-activated composites:
in composite resins. l Camphorquinone 0.2 wt% is the initiator.
l Visible light of 460–480 nm wavelength is the activator.
Ans. The light sources used are as follows:

l Light emitting diodes (LED Lamps)
Classification of composite resins: l Quartz tungsten halogen lamps (QTH)
l Plasma arc curing lamps (PAC)

1. Based on curing mechanism:
l Argon laser lamps.
l Chemically activated composite resins
l Light-activated composite resins Advantages of light cured composites are as follows:

2. Based on size of filler particles: l Easy manipulation, no mixing is required.
l Conventional composite resins: 8–12 µm l Infinite working and short controlled setting time.
l Small particle composite resins: 1–5 µm l Easy to finish and polish, less waste of material.
l Microfilled composite resins: 0.04–0.4 µm
l Hybrid composite resins: 0.6–1.0 µm

The use of UV light resins has declined due to lack of depth
In composite resins three types of fillers are commonly of curing, health hazards and slow decrease in intensity of
used as follows: UV light.
a. Ground quartz The advantages of visible light cured composites com-
b. Colloidal silica pared to UV light cured composites are as follows:
c. Glasses or ceramic containing heavy metals i. They can be cured to greater depth (2–2.5 mm).
ii. No health hazard.
Addition of filler particles into the resin matrix significantly iii. No warm up time and no decrease in the intensity of
improves its properties. light source.
l As less resin is present, the curing shrinkage is reduced.
Q.3. Fillers and their role in composite resins
l Reduces water sorption and coefficient of thermal expansion.
l Improves mechanical properties like strength, stiffness, Ans.
hardness and abrasion resistance.
l Filler particles are added to resin matrix to significantly
Q.2. Light-cured composites improve its properties as follows:
1. The polymerization shrinkage is reduced as com-
Ans. pared to unfilled resins, as less resin is present.
There are two types of light-activated composites. 2. Reduces water sorption and coefficient of thermal
expansion.
a . UV light-activated composites 3. Improves mechanical properties like compressive
b. Visible-light activated composites strength, tensile strength, modulus of elasticity, hard-
In UV light-activated composites: ness and abrasion resistance.
l Benzoin methyl ether is the initiator.
4. Less heat evolved during polymerization.
l Important factors with regard to fillers that determine
l UV light of 360 nm wavelength is the activator.
the properties and clinical application of composites are
1. amount of filler added, (500–300 m2/g) thus, even small amounts of microfill-
2. size of particles and its distribution, ers thicken the resin.
3. index of refraction,
Glasses or Ceramics Containing Heavy Metals
4. radiopacity and
5. hardness. l These fillers provide radiopacity to the resin restoration.
l They have a refractive index of 1.5, e.g. barium, zirco-

Particle size distribution: In order to increase the filler nium and strontium glasses. The most commonly used
loading of the resin it is necessary to add the fillers in a is barium glass.
range of particle sizes so that smaller particles can then fill l It is not as inert as quartz. Some barium may leach out
up the spaces between large particles. in an aqueous medium.
Refractive index: For aesthetics, the filler should have a trans-
lucency similar to tooth structure. In order to achieve good trans- Q.4. Classification and uses of composite resins
lucency, the refractive index of the filler should closely match that
of the resin. Most glass and quartz fillers have a refractive index Ans.
of 1.5, which matches that of bis-GMA and TEGDMA.
l In composite resins three types of fillers are used as Classification of Composite Resins
follows:
1. Based on curing mechanism
1. Ground quartz
l Chemically activated
2. Colloidal silica
l Light-activated
3. Glasses or ceramic containing heavy metals
2. Based on size of filler particles
l Conventional composite resins: 8–12 µm
Quartz Fillers
l Small particle composite resins: 1–5 µm
l They are obtained by grinding or milling quartz. They
l Microfilled composite resins: 0.04–0.4 µm
are mainly used in conventional composites.
l Hybrid composite resins: 0.6–1.0 µm
l They are chemically inert but are very hard. This makes
it more difficult to polish and may cause abrasion of Composite resins are used for
opposing teeth and restorations.
1. restoration of anterior and posterior teeth (directly or as
inlays),
Colloidal Silica 2. veneering metal crowns and bridges,
l They are referred to as microfillers obtained by a pyro- 3. building up cores (post core),
lytic or a precipitation process. 4. cementation of orthodontic brackets, Maryland bridges,
l They are added in small amounts (5 wt%) to modify the and ceramic crowns,
paste viscosity. 5. inlays, onlays and laminates,
l The amount of filler that can be incorporated into the 6. pit and fissure sealant,
resin matrix is affected by the surface area of the fill- 7. aesthetic laminates and
ers. Colloidal silica particles have large surface area 8. repair of chipped porcelain restorations.
SHORT ANSWERS
Q.1. Activators in composite resin Q. 2. Composition of composite resin
Ans. Ans. The essential components of a composite resin are as
Activator is a source of energy to activate an initiator and follows:
l Resin matrix/binder—BISGMA or urethane dimethacrylate
produce free radicals.
l Filler—quartz, colloidal silica of heavy metal glasses
Three possible energy sources can be used to dissociate
l Coupling agent—organosilanes
an initiator into free radicals as follows:
l Hydroquinone—inhibitor to prevent premature polym-
1 . heat that supplies thermal energy, erization
2. an electron donating chemical such as a tertiary amine, l UV absorbers—to improve colour stability
3. visible light that supplies energy for photoinitiation in l Opacifiers—titanium dioxide and aluminium oxide
the presence of a photosensitizer such as camphorqui- l Colour pigments—to match tooth colour.
none (CQ).
Q. 3. Uses of composite restorative resins
Dental composites for direct placement use chemical acti-
vation or light activation or a combination of the two. Ans.
Uses of composite restorative resins are as follows: l Average filler particle size ranges from 0.8 to 5.0 µm.
1. Restoration of anterior and posterior teeth either directly The filler volume ranges from 42 to 67% in current
or as inlays, products.
2. To veneer metal crowns and bridges, l They are supplied as single paste packages in unit dose
3. To build up cores (post core), compules and syringes.

4. Cementation of orthodontic brackets, Maryland bridges, l Setting occurs primarily by light cure polymerization.
and ceramic crowns, inlays, onlays and laminates,

5. Pit and fissure sealant, Q. 7. Hybrid composite
6. Aesthetic laminates, Ans.
7. Repair of chipped porcelain restorations.
l Hybrid composites consist of two types of filler particles
Q. 4. Marginal percolation as follows:
a. Colloidal silica (microfillers)
Ans.
b. Barium glasses (heavy metal)
1. When the gingival margins of the cavity preparation are l Particle size of fillers varies from 0.6 to 1 µm
located in dentine, cementum or both, and the resin is l The filler load varies from 70% to 80% by weight and
firmly anchored to the etched enamel at the other mar- 60% to 65% by volume.
gins, the material tends to pull away from the gingival l The microfillers contribute significantly to the proper-
margins during curing because of polymerization shrink- ties and provide increased surface area. Barium glasses
age. This leads to formation of a gap at that interface. are helpful in detection of secondary caries and various
Subsequently, leading to the risk for marginal leakage. other diagnostic tasks.
2. Ensuing problems of marginal leakage are marginal l Clinical significance
staining and secondary caries. 1. Widely used for anterior restorations due to their
3. This is one of the greatest problems of composites used surface smoothness and good strength.
for class II and class V restorations. 2. Widely used for stress bearing areas especially pos-
4. Every measure must be taken to maintain the integrity terior restorations.
of the dentine resin or cementum resin interfaces.
Q. 8. Define composite. Mention the advantages and
Q. 5. Bis-GMA disadvantages of direct posterior composites.
Ans. Ans.
1. Bis-GMA was developed by RL Bowen (Bowen’s resin) l In materials and science, a solid formed from two or
in the early 1960s. Its properties were superior to those more distinct phases that have been combined to produce
of acrylic resins. properties superior to or intermediate to those of the in-
2. Bis/glycidyl methacrylate (Bis-GMA) is a high molecu- dividual constituents is known as Composite. It is also a
lar weight monomer formed by reaction between a term used in dentistry to describe a dental composite.
molecule of ethylene glycol of bisphenol A and glycidyl l A composite may also be described as a three-dimen-
methacrylate. sional combination of at least two or more chemically

3. A few limitations of bis-GMA are as follows: different materials, insoluble in each other with a dis-
l A high viscosity and high water sorption tinct interphase separating the components.
l Difficulty in synthesizing a pure composition l The advantages of direct posterior composites are as
l Strong air inhibition to polymerization follows:

l Polymerization shrinkage and thermal dimensional l Good aesthetics
changes still existed l Adhesion to enamel if acid etched
l It does not adhere to tooth structure like other resins. l Reduced polymerization shrinkage if they are incre-
mentally built up
Q. 6. Compomers l Commandible setting properties in the light-activated
materials
Ans.
l No health hazards
l Compomers are modification of composites with poly- l The disadvantages of direct posterior composite restor-
acid groups which are used for restorations in low stress ative materials are as follows:
bearing areas. l Poor wear resistance and marginal leakage
l Composition of compomers contain monomers modi- l Polymerization shrinkage
fied by polyacid groups with fluoride releasing silicate l Difficult to finish and polish as the margins are not
glasses. easily recognized

Topic 15
Dental Cements
LONG ESSAYS
Q. 1. Classify dental cements and write in detail about Phillips classification of dental cements is given in Table 15.2.
manipulation, composition and uses of GICs. TABLE 15.2 Phillips’ Classification of Dental Cements
Or, Cement Principal Uses Secondary Uses
Classify dental cements. Write a note on chemistry of Zinc phosphate Luting agent for res- Intermediate resto-
setting, mechanism of adhesion and uses of glass iono- torations and orth- rations, thermal in-
mer cements. odontic bands sulating bases,
root canal restora-
Or,
tions
Classify dental cements. Discuss in detail the composi- Zinc phosphate Intermediate restora-
tion, properties and uses of GICs. with silver or tions
Or, copper salts
Mention the types of GICs. What is the composition of Copper phos- Temporary and inter-
phate (red or mediate restorations
GICs? Add a note on mechanism of adhesion of GICs to black)
the tooth.
Zinc oxide eu- Temporary and inter- Root canal restora-
Ans. Various classifications of dental cements are as follows: genol restora- mediate restorations, tions, periodontic
tions luting agent, thermal bandage
insulating base, pulp
Classification according to Craig is given in Table 15.1. capping agent
Polycarboxylate Luting agent, thermal Luting agent for
TABLE 15.1 Craig’s Classifications of Dental Cements insulating base orthodontic bands,
intermediate resto-
Functions Cements
rations
Final cementation of completed Zinc phosphate, zinc silico-
restorations phosphate, reinforced zinc Silicate Anterior fillings
oxide eugenol, zinc poly- Silicophosphate Luting agent for res- Intermediate resto-
carboxylate, glass ionomer torations rations, luting
Temporary cementation of com- Zinc oxide eugenol, noneu- agent for orth-
pleted restorations or cementa- genol zinc oxide odontic appliances
tion of temporary restorations Glass ionomer Coating for eroded Pit and fissure seal-
High-strength bases Zinc phosphate, reinforced areas, luting agent for ant, anterior resto-
zinc oxide eugenol, zinc poly- restorations rations, thermal in-
carboxylate, glass ionomer sulating bases
Temporary fillings Zinc oxide eugenol, rein- Resin Luting agent Temporary restora-
forced zinc oxide eugenol, tions
zinc polycarboxylate Calcium hy- Pulp capping agent,
Low-strength bases Zinc oxide eugenol, cal- droxide thermal base
cium hydroxide
Liners Calcium hydroxide in a sus-
pension Classification According to EC Coombe
Varnishes Resin in a solvent The materials may be classified as follows:
Root canal sealer Zinc oxide eugenol, zinc 1. Acid-base reaction cements
polycarboxylate 2. Polymerizing materials
Gingival tissue pack Zinc oxide eugenol a. Cyanoacrylates
Surgical dressing Zinc oxide eugenol, zinc
b. Dimethacrylate polymers
oxide preparation c. Polymer-ceramic composites
3. Other materials
Cementation of orthodontic Zinc phosphate, zinc poly-
bands carboxylate
a. Calcium hydroxide
b. Gutta-percha
Orthodontic bonding Acrylic resin, composite resin c. Varnishes
GLASS IONOMER CEMENTS (GICs) The fluoride component acts as a ceramic flux whereas
1. Glass ionomer cements are adhesive tooth-coloured lanthanum, strontium, barium or zinc oxide additions
anticariogenic restorative materials. provide radiopacity.
2. It was named glass ionomer because, the powder is
glass and the setting reaction and adhesive bonding to Liquid
tooth structure is due to ionic bond.
3. Due to its adhesive bonding to tooth structures this In most current cements, the liquid contains the following:
cement requires minimal cavity preparation. 1. Polyacrylic acid (in the form of copolymer with iticonic
acid, maleic acid, and tricarballylic acid): Copolymer-
izing with iticonic, maleic acid, etc tends to increase
Uses reactivity of the liquid, decrease viscosity and reduce
1. Anterior aesthetic restorative material for class III tendency for gelation.
cavities 2. Tartaric acid: Tartaric acid improves the handling
2. For eroded areas and class V restorations characteristics, increases working time, and shortens
3. As a luting agent setting time.
4. As liners and bases 3. Water: Water is the most important constituent of the
5. For core build up cement liquid. It is the medium of reaction and it hy-
6. To a limited extent as pit and fissure sealants drates the reaction products. The amount of water in the
liquid is critical. Too little water impairs the reaction
and subsequent hydration.
Classification of GICs
1 . Type I: For luting Setting Time
2. Type II: For restorations
3. Type III: Liners and bases 1 . Type I GICs: 4.5 min
2. Type II GICs: 7 min
Various other types of GICs available are as follows:
1. Pit and fissure sealants
2. Metal modified GICs, e.g. miracle mix (silver alloy admix), Properties of GICs
glass cermet cement (ketac silver) Properties of GICs are as follows:
3. Resin modified, GICs, e.g. compomer
4. Fuji VII: Worlds first high-fluoride nonresin containing .
1 Mechanical Properties
autocure GICs. 1. Compressive strength (150 Mpa): It is less than silicate.
5. Fuji VIII and Fuji IX: New high-viscosity GICs (atrau- 2. Tensile strength (6.6 Mpa): Higher than silicate.
matic restorative material (ART)) 3.
Hardness (49 KHN): Less harder than silicates. The
They are dispensed as follows: wear resistance is less when compared to composites.
1. Powder/liquid in bottles 4. Fracture toughness: A measure of energy required to pro-
2. Preproportioned powder/liquid in capsules duce fracture is known as fracture toughness. Compared to
3. Light cure system composites the fracture toughness of type II GICs is low.
4. Powder/distilled water
. Solubility and Disintegration
2
1. The initial solubility is high (0.4%) due to leaching of
COMPOSITION intermediate products.
2. The complete setting reaction takes place in 24 h; there-
Powder fore should be protected from saliva in the mouth during
The powder is an acid soluble calcium fluoro-alumino this period.
silicate glass. It is similar to that of silicate, but has a higher 3. Glass ionomer cements are more resistant to attack by
alumina-silica ratio. This increases its reactivity with liquid. organic acids.
Silica (SiO2) 41.9% . Adhesion

3
Alumina (Al2O3) 28.6%
1. It adheres well to enamel and dentine.
2. The glass ionomer bonds chemically to tooth structure. The
Aluminium fluoride (AlF3) 1.6% bonding is due to the reaction between the carboxyl groups
Calcium fluoride (CaF2) 15.7% of the polyacids and the calcium in the enamel and dentine.
Sodium fluoride (NaF) 9.3% 3. The bond to enamel is always higher than that to den-
tine, probably due to the greater inorganic content of
Aluminium phosphate (AlPO4) 3.8%
enamel and its greater homogeneity.
. Aesthetics
4 Low P/L ratio reduces mechanical properties and in-
1. Aesthetically they are inferior to silicates and compos- creases the chances of cement degradation.
ites. They lack translucency and have a rough surface a. Manual mixing: The powder and liquid is dispensed
texture. They may accumulate stain with time. just prior to mixing. A cool and dry glass slab is
preferred as it allows all the powder to be incorpo-
. Biocompatibility
5 rated into the mix and yet maintain its plasticity.
1. Pulpal response is mild. Type II glass ionomers are rela- Spatula used is agate or plastic.
tively biocompatible. The powder is divided into two equal increments.
2. The pulpal reaction is greater than that of zinc oxide The first increment is incorporated into the liquid
eugenol cements but less than that produced by zinc rapidly with the stiff bladed spatula to produce a
phosphate cement. homogenous milky consistency. The remainder of
3. Type I GICs are more acidic than type II, because of the the powder is then added. The mixing is done in a
slower set and lower powder/liquid ratio. folding method in order to preserve the gel structure.
4. Pulp protection in deep cavities, the smear layer should Mixing time: 45 s.
not be removed as it acts as a barrier to acid penetration. Insertion: The mix is immediately packed into the
Deep areas are protected by a dab of calcium hydroxide cavity with a plastic instrument.
cement. b. Mechanical mixing: GIC supplied in capsule form
containing preproportioned powder and liquid is
. Anticariogenic Properties
6 mixed in an amalgamator, which is operated at a
1. Type II glass ionomer releases fluoride in amounts com- very high speed. The capsule has a nozzle, and so the
parable to silicate cements initially and continue to do mix can be injected directly into the cavity.
so over an extended period of time. 2 . Advantages
2. In addition, due to its adhesive effect they have the poten- a. Better properties due to controlled P/L ratio
tial for reducing infiltration of oral fluids at the cement- b. Less mixing time required
tooth interface, thereby preventing secondary caries. c. Convenient
3. Disadvantages
Manipulation a. Cement quantity limited by the manufacturer
b. Shade selection is limited, colours cannot be blended
The steps involved in manipulation of GICs are as follows:
1. Preparation of tooth surface
2. Manipulation of material 3. Protection of Cement During Setting
3. Protection of cement during setting GIC is extremely sensitive to air and water during setting.
4. Finishing Thus, immediately after placement into the cavity, a pre-
shaped matrix is applied to
1. Preparation of Tooth Surface 1. protect the cement from the environment during initial set.
2. provide maximum contour so that minimal finishing is
1. The tooth should be clean for effective adhesion of ce- required.
ment. The smear layer present after cavity preparation 3. the matrix is removed after 5 min. Immediately after
which tends to block off the tooth surface should be removal, the cement surface is again protected with
removed to achieve adhesive bonding. a. a special varnish supplied by manufacturer or
2. This is achieved by b. an unfilled light cured resin bonding agent or
a. pumice wash and c. cocoa butter.
b. polyacrylic acid.
Apply 10% polyacrylic acid for 10–15 s then rinse with
water for 30 s. Very deep areas of the preparation should 4. Finishing
be protected by a dab of calcium hydroxide. 1. Excess material and the cement from the margins is re-
3. Eroded areas: The dentine and cementum are first moved carefully.
cleaned with pumice slurry followed by swabbing with 2. Hand instruments are preferred to rotary tools to avoid
polyacrylic acid for 5 s or more. ditching.
After conditioning and rinsing, the surface is dried but 3. Further finishing is done after 24 h if required.
not desiccated. It should be kept free of contamination
with saliva or blood, as these will interfere with bonding. Q. 2. Classify dental cements. Write composition, prop-
erties and uses of polycarboxylate cement.
2. Manipulation of Material Or,
1. Proportioning and mixing Classify dental cements. Write in detail about zinc poly-
Powder/liquid ratio: 3 : 1 by weight carboxylate cement.
Ans. For classification of dental cements refer to above 2. The marginal dissolution of cement is more when used
answer of Long Essays, Q. 1 of the same topic. as cementing medium.
Polycarboxylate cement was the first cement system 3. A reduction in the P/L ratio results in a significantly
developed with a potential for adhesion to tooth structure. higher solubility and disintegration in the oral cavity.
MODE OF SUPPLY 3. Biocompatibility

The polycarboxylate cement is available as powder and 1. The polycarboxylate cement, in terms of pulpal re-
liquid in bottles. sponse, is classified as mild.
Some manufacturers supply this cement as precapsu- 2. The pH of the liquid is 1.0–1.7 and that of freshly mixed
lated powder/liquid system. cement is 3.0–4.0. After 24 h, pH of the cement is 5.0–6.0.
3. They are less irritant to the pulp than zinc phosphate
COMPOSITION cement, because
a. the liquid is rapidly neutralized by the powder. The
Powder pH of polycarboxylate cement rises more rapidly
than that of zinc phosphate.
1 . Zinc oxide: Basic ingredient
b. penetration of polyacrylic acid into the dentinal tu-
2. Magnesium oxide: Principle modifier and also aids in
bules is less because of its higher molecular weight
sintering
and larger phosphate molecules.
3. Other oxides like bismuth and aluminium: Small amounts
c. the histological reactions are similar to zinc oxide eu-
4. Stannous fluoride: Increases strength, modifies setting
genol cements, but more reparative dentine is observed
time and imparts anticariogenic proprieties
with polycarboxylate.
Liquid
4. Adhesion
Aqueous solution of polyacrylic acid or copolymer of
acrylic acid with other unsaturated carboxylic acids, i.e. iti- 1. An outstanding characteristic of zinc polycarboxylate
conic, maleic or tricarboxylic acid. cement is that, the cement bonds chemically with the
tooth structure due to the ability of the carboxyl group
in the polymer molecules to chelate with calcium in the
SETTING TIME tooth structure.
1 . Setting time is 7–9 min. 2. The bond strength to enamel ranges from 3.4 to
2. The setting time can be increased by cooling the glass 13.1 Mpa and that of dentine is 2.07 Mpa.
slab. It also depends on the method of manufacture of 3. The adhesion of a polycarboxylate to clean dry surface
powder and liquid. of enamel is much greater than that of other cements
under ideal conditions of manipulation.
PROPERTIES
5. Optical Properties
1. Mechanical Properties 1. They are very opaque due to large quantities of unre-
1. Compressive strength: Polycarboxylate cement is infe- acted zinc oxide.
rior to zinc phosphate cement (55 Mpa or 8000 psi).
2. Tensile strength: Its tensile strength is slightly higher 6. Thermal Properties
than that of zinc phosphate cement (6.2 Mpa or 900 psi).
3. Powder/liquid (P/L) ratio: Increase in P/L ratio in- 1. Polycarboxylate cements are good thermal insulators.
creases strength.
4. Molecular weight of polyacrylic acid also affects the USES
strength.
5. A mix from a low viscosity liquid is weaker than a high 1. It is primarily used for cementation of restoration and
viscosity. thermal insulating base.
2. It is also used as an intermediate restoration.
3. Primarily for luting permanent restorations.
2. Solubility and Disintegration 4. As bases and liners.
1. It tends to absorb water and is slightly more soluble than 5. Used in orthodontics for cementation of bands.
zinc phosphate (0.06%). 6. Also used as root canal fillings in endodontics.
Q. 3. Give composition and method of manipulation of liable to be abraded by the silicate powder leading to discol-
silicate cements. ouration of the mix.
Ans. Procedure
1. Powder/liquid ratio: Approximately around 1.6 g of
COMPOSITION OF SILICATE CEMENT powder per 4 mL of liquid.
2. The powder is dispensed on a thick, cool, dry glass slab
Silicate cements are available as powder and liquid. The pow- and divided into two or three large increments. The in-
der is a finely ground ceramic that is essentially an acid solu- crements are then rapidly folded into the liquid over a
ble glass. The composition of silicate cement is as follows: small area, in order to preserve the gel structure.
3. Particles of the powder should be properly wetted. Mix
Powder (Table 15.3) for 1 min.
4. The mixed material should have consistency like putty.
TABLE 15.3 Composition of Silicate Cement as Powder The surface of the mix should have a shiny appearance.
5. If the mix is too thick it produces crumbly mass.
Components Approximate wt% Functions 6. Too much of liquid increases the setting time, reduces
Silica (SiO2) 40 Provides strength and pH and strength, increases solubility and makes it more
translucency prone to staining.
Alumina 30 Provides Al, Ca, K 7. The mixed material should be inserted into the cavity in
(Al2O3) ions by reacting with one portion. If small increments are used complete
phosphoric acid bonding between the portions will not occur and the set
Sodium fluoride 23 Acts as a flux, melting material will be weaker.
(NaF), cryolite point, or fritting 8. A cellulose acetate strip is held against the setting mate-
(Na3AlF6), temperature
rial in the cavity. The strip is removed after the material
calcium fluoride
(CaF2) sets. Gross excess cement is then removed from the
margins at that time. The restoration is then painted with
Calcium 7 Acts as modifiers
a water-insoluble varnish to protect it from contact with
phosphate (opacifiers)
Ca(H2PO4)2, oral fluids.
H2O or lime 9. Finishing and polishing: The final finishing should
(CaO) be delayed for several days. Early finish could disturb
or fracture the margin before maximum properties are
attained.
Liquid (Table 15.4) Silicate cements are subject to dehydration throughout
TABLE 15.4 Composition of Silicate Cement as Liquid their lifetime. Therefore during subsequent operative proce-
dures, they should be protected from exposure to air by a
Components Approximate wt% Functions coat of vanish or silicone grease.
Phosphoric acid 52 Reactor
Q. 4. Write in detail about zinc oxide eugenol cement.
Aluminium phosphate 2 Buffers
Zinc phosphate or 6 Controls setting Ans.
magnesium phosphate time
1. Zinc oxide eugenol (ZOE) cements have been used ex-
Water 40 Controls pH tensively in dentistry since 1890s.
2. They are cements of low strength. Also they are the least
irritating of all dental cements and are known to have an
MANIPULATION
obtundant effect on exposed dentine.
1 . Dry field is required during manipulation. 3. To improve the strength many modified zinc oxide euge-
2. Exposure of the cement to oral fluids prior to formation nol cements have been introduced, e.g. EBA—alumina
of final reaction products results in increased solubility modified and polymer-reinforced zinc oxide eugenol
and a poor surface. cements.
The liquid is dispensed just prior to the mixing, in order 4. Recently noneugenol zinc oxide cements have become
to preserve the acid-water balance. available. They are suitable for patients sensitive to eu-
Mixing is done with an agate, plastic, or cobalt-chromium genol. Experimental vanillate and syringe cements
spatula. The steel spatulas are contraindicated, as they are without eugenol are presently under investigation.
CLASSIFICATION he chelate formed is an amorphous gel that tends to

T
crystallize imparting strength to the set mass.
According to ADA Specification no. 30, there are four
4 . Structure of set cement: The set cement consists of
types of ZOE cements as follows:
particles of zinc oxide embedded in a matrix of zinc
1. Type I ZOE: For temporary cementation
eugenolate.
2. Type II ZOE: Permanent cementation
5. Setting time is around 4–10 min.
3. Type III ZOE: Temporary filling and thermal insulation
4. Type IV ZOE: Cavity liners The setting time is affected by the following:
a. Particle size: Smaller zinc oxide particles set faster.
ZOE cement is available as
b. Powder to liquid ratio: Higher the ratio, faster the set.
1. powder and liquid or
c. Addition of accelerators, e.g. alcohol, glacial acetic acid
2. two-paste system.
and water makes the cement set faster.
d. Cooling the glass slab: Slows the reaction.
COMPOSITION e. The set can be retarded by addition of glycol and glyc-
erine which act as retarders.
Powder (Table 15.5)
TABLE 15.5 Composition of Zinc Oxide Eugenol Cement
PROPERTIES OF ZOE CEMENT
as Powder Properties of ZOE cement are as follows:
Components Approximate wt% Functions
Zinc oxide 69 Principal ingredient 1. Mechanical Properties
White rosin 29.3 To reduce brittleness 1. Compressive strength: They are relatively weak cements.
of set cement The compressive strength therefore ranges from as low as
Zinc stearate 1 Accelerator, plasticizer 3 to 4 MPa up to 50 to 55 MPa. The strength can also be
increased by reinforcing with alumina-EBA or polymers.
Zinc acetate 0.7 Accelerator, improves
strength
2. Tensile strength: Ranges from 0.32 to 5.3 MPa.
3. Modulus of elasticity (0.22–5.4 GPa) this is an important
Magnesium Is added in some property for those cements intended for use as bases.
oxide powders, acts with
eugenol in a similar
manner as zinc oxide. 2. Thermal Properties
1. Thermal conductivity: 3.98 [Cal. s21 cm22 (°C/cm)21]
Liquid (Table 15.6) 3 1024. Their thermal insulating properties are excel-
lent and are approximately the same as for human den-
TABLE 15.6 Composition of Zinc Oxide Eugenol Cement
tine. The thermal conductivity of zinc oxide eugenol is
as Liquid
in the range of insulators like cork and asbestos.
Components Approximate wt% Functions 2. Coefficient of thermal expansion: 35 3 1026/°C.
Eugenol 85 Reacts with zinc oxide
Olive oil 15 Plasticizer 3. Solubility and Disintegration

1. The solubility of the set cement is highest among the
cements (0.4 wt%).
SETTING REACTION 2. They disintegrate in oral fluids. This breakdown is due
1. The setting reaction and microstructure of ZOE cement to hydrolysis of the zinc eugenolate matrix to form zinc
are same as that of the zinc oxide eugenol impression hydroxide and eugenol.
pastes. 3. Solubility is reduced by increasing the P/L ratio.
2. In the first step hydrolysis of zinc oxide to its hydroxide
takes place. Water is essential for the reaction (dehy-
4. Film Thickness
drated zinc oxide will not react with dehydrated eugenol).
1. The film thickness of zinc oxide eugenol cements is
ZnO 1 H2O n Zn(OH)2
25 µm which is higher than other cements.
3. The reaction proceeds as a typical acid-base reaction.
Zn(OH)2 1 2HE n ZnE2 1 2H2O 5. Adhesion
Base acid salt 1. Their adhesion to enamel or dentine is poor, because of
(Zinc hydroxide) (Eugenol) (Zinc eugenolate) this reason they are not often used for final cementation
of crowns and bridges. The other reasons are low b. Kalzinol

strength and high solubility.
These were introduced to improve the mechanical prop-
erties of zinc oxide eugenol cement.
6. Biological Properties
1. pH and effect on pulp: (pH is 6.6–8.0). They are the USES
least irritating of all cements. They exhibit mild pulpal
1 . As luting cement
response.
2. As base
2. Bacteriostatic and obtundant properties: They inhibit
3. As temporary filling material
the growth of bacteria and have an anodyne or soothing
4. As cavity liner
effect or obtundant effect on the pulp in deep cavities,
reducing pain. Q. 5. Manipulation of zinc phosphate cement
Ans. The steps involved in the manipulation of zinc phos-
7. Optical Properties phate cement are as follows:
1. The set cement is opaque. 1. A cool glass slab is used in order to delay the setting and
allow more powder to be incorporated before the matrix
formation occurs.
MANIPULATION 2. The liquid should be dispensed just before mixing.
1. Powder-Liquid System 3. The powder is added in small increments.
4. A large area is covered during mixing in order to dissi-
Powder/liquid ratio: 4:1–6:1 wt% pate the exothermic heat.
After shaking the bottles gently, measured quantity of 5. Maximum amount of powder should be incorporated in the
powder and liquid are dispensed onto a cool glass slab. The liquid to ensure minimum solubility and maximum strength.
bulk of the powder is incorporated into the liquid and satu- 6. An appropriate consistency is attained by addition of
rated thoroughly in a circular motion with a stiff bladed more powder to the liquid and not by allowing a thin
stainless steel spatula. Smaller increments are then added mix to thicken.
until the mix is complete.
Procedure
2. Two Paste System
1. The recommended powder to liquid ratio is 1.4 g/0.5 mL.
Equal lengths of each paste are dispersed and mixed until a 2. On a cool dry glass slab the required amount of powder
uniform colour is observed. is taken first. The liquid should be dispensed just before
mixing.
Setting Time: 4–10 min
3. The powder is divided into small increments.
ZOE cements set quickly in the mouth due to moisture and heat. 4. A stainless steel cement spatula is used for mixing.
5. Mixing is initiated by addition of a small amount of
Modified Zinc Oxide Eugenol Cements
powder at a time into the liquid. Each increment is
The modified ZOE cements are as follows: mixed for 15–20 s before the next increment is added.
a. EBA-alumina modified cements Mixing time is 1 min and 15 s.
b. Polymer reinforced ZOE cements 6. Spatulation is carried out with a brisk, circular motion
Commercial names: of the spatula, covering a large area for mixing in order
a. IRM to dissipate the heat-exothermic reaction.
SHORT ANSWERS
Q. 1. Luting cement Temporary Cementation
Ans. Cementation is the process by which crowns, restora- l Temporary cementation of crowns and bridges are often
tions and other devices are fixed or attached to tooth struc- required to stay in place only until the permanent struc-
ture using an intermediate material called cement. The ture is ready. Therefore it must be weak enough to be
same cement can be used for more than one purpose. easily removed when the permanent structure is ready
The synonyms of luting are bonding, cementing. for cementation.
l This cement should have some soothing effect on the
Types of luting or cementation are as follows:
1. Temporary cementation pulp of the freshly prepared vital tooth, which would
2. Permanent cementation have been traumatized during the preparation.
l Permanent structures (e.g. crowns or bridges) are also pulp. The paste form is applied in the cavity and then light
sometimes cemented temporarily to allow the patient to cured.
take it for a home trial. Once the patient feels the per-
manent structure is satisfactory, it is removed and ce-
mented permanently. CEMENT BASE
For example: Zinc oxide eugenol based cement called
A base is a layer of cement placed beneath a permanent
Temp Bond.
restoration to encourage recovery of the injured pulp and to
protect it against numerous types of insults to which it may
Permanent Cementation
be subjected.
1. A permanent cementing material on the other hand
should be strong and insoluble in oral fluids.
2. It would also be advantageous if it had some chemical
Types of Bases
bonding to the tooth structure. In addition, it should be Bases are of two categories as follows:
fluid enough to flow well to ensure the complete seating 1. High-strength bases
of the crown or bridge. 2. Low-strength bases
For example: Zinc phosphate cement, glass ionomer
cement, resin cement, polycarboxylate cements etc.
High-Strength Bases
Q. 2. Liners and bases These are used to provide thermal protection for the pulp,
Or, as well as mechanical support for the restoration. For ex-
ample: Zinc phosphate, zinc polycarboxylate, glass iono-
Classify bases and write briefly about bases. mer and reinforced ZOE cements.
Ans.
Low-Strength Bases
Low-strength bases have minimum strength and low ri-
CAVITY LINERS gidity. Their main functions are to act as a barrier to ir-
A cavity liner is used like a cavity varnish to provide barrier ritating chemicals and to provide therapeutic benefit to
against the passage of irritants from cements or other restor- the pulp. For example: Calcium hydroxide and zinc oxide
ative materials and to reduce the sensitivity of freshly cut eugenol.
dentine. For example: Suspensions of calcium hydroxide in
a volatile solvent, type III glass ionomer, type IV ZOE PROPERTIES OF BASES
Composition and Properties i. Thermal Properties
l Suspension of calcium hydroxide in an organic liquid The base must provide thermal protection to the pulp. This
such as methyl ethyl ketone or ethyl alcohol. Acrylic property is important especially when the tooth is restored
polymer beads of barium sulphate and calcium mono- with metallic restorations.
fluoro-phosphate.
l Upon the evaporation of the volatile solvent, the liner
ii. Protection Against Chemical Insults
forms a thin film on the prepared tooth surface.
l The calcium hydroxide liners are soluble and should not The cement base also serves as a barrier against penetration
be applied at the margins of restorations. of irritating constituents, e.g. acids, monomer, etc. from
l Fluoride compounds have been added to some cavity liners restorative materials.
in an attempt to reduce the possibility of secondary carries For example: Calcium hydroxide and zinc oxide euge-
around permanent restorations or to reduce sensitivity. nol are most effective for this especially in deep cavities.
l Cavity liners either possess mechanical strength or pro- Polycarboxylate and glass ionomer bases are also used as
vides any significant thermal insulation. chemical barriers in more moderate cavities.
Manipulation iii. Therapeutic Effect

Cavity liners are fluid in consistency and can be easily Some bases are used for their therapeutic benefit to the
flowed or painted over dentinal surfaces. The solvents pulp.
evaporate to leave a thin film residue that protects the For example: Calcium hydroxide, zinc oxide eugenol.
iv. Strength Q. 4. Composition and chemistry of setting reaction

of GICs
The cement base must have sufficient strength to
Or,
1 . withstand the forces of condensation, and
2. withstand fracture or distortion under masticatory stresses, Uses of glass ionomer cements
transmitted to it through the permanent restoration.
Ans. Glass ionomer cements (GICs) are adhesive tooth-
Q. 3. Composition, uses or application of cavity varnish coloured anticariogenic restorative materials.
Ans.
l Cavity varnish is a solution of one or more resins which COMPOSITION

when applied on to the cavity walls, evaporates leaving
a thin resin film that serves as a barrier between the Powder
restoration and the dentinal tubules.
The powder is an acid-soluble calcium fluoro-alumino-
l The film thickness ranges between 2 and 400 µm.
silicate glass. It is similar to that of silicate, but has a
l Supplied as liquid in dark-coloured bottles.
higher alumina-silica ratio. This increases its reactivity
with liquid.
COMPOSITION
l Natural gum such as copal, rosin or synthetic resin dis- Silica (SiO2) 41.9%
solved in an organic solvent like alcohol, acetone or Alumina (Al2O3) 28.6%
ether.
Aluminium fluoride (AlF3) 1.6%
l Medicinal agents such as chlorobutanol, thymol and
eugenol may be added. Calcium fluoride (CaF2) 15.7%

l Some varnishes also contain fluorides. Sodium fluoride (NaF) 9.3%

APPLICATION OF CAVITY VARNISH
l It reduces the postoperative sensitivity by reducing the The fluoride component acts as a ceramic flux whereas
microleakage around the margins of newly placed amal- lanthanum, strontium, barium or zinc oxide additions pro-
gam restorations. vide radiopacity.
l It reduces passage of irritants into the dentinal tubules
from the overlying restoration or base, e.g. silicate. Liquid

l They also prevent penetration of corrosion products in
to the dentinal tubules in amalgam restorations, thus, In most current cements, the liquid contains the following:
minimizing tooth discolouration. 1. Polyacrylic acid (in the form of copolymer with itaconic
l They may be used as a surface coating over certain
acid, maleic acid and tricarballylic acid)
restorations to protect them from dehydration or con- 2. Tartaric acid
tact with oral fluids, e.g. silicate and glass ionomer 3. Water
restorations.
l They may be applied as a temporary protection on the SETTING REACTION OF GICs
surface of metallic restoration in cases of galvanic
shock. When the polyacrylic acid is mixed with powder, during
l Varnish applied over the metallic restorations serves as
early stages of mixing Ca11 ions are released more rapidly
a temporary electrical insulator in cases where electro- which are primarily responsible for reacting with polyacids
surgery is to be done adjacent to metallic restorations. to form calcium polysalt gel. The polysalt binds unreacted
l Fluorides are released by varnishes containing fluoride.
glass particles in a cement.
l The use of varnishes is contraindicated with
a. composite resins, USES

b. glass ionomer and
c. some cements like zinc oxide eugenol and calcium Uses of GICs are as follows:
hydroxide, when therapeutic action is expected from 1. Anterior aesthetic restorative material for class III cavities
them. 2. For eroded areas and class V restorations
3 . As a luting agent 2 . It is also used as an intermediate restoration.

4. As liners and bases 3. Primarily for luting permanent restorations.
5. For core build up 4. Used as bases and liners.
6. To a limited extent as pit and fissure sealants 5. Used in orthodontics for cementation of bands.
6. Also used as root canal fillings in endodontics.
Q. 5. Polycarboxylate cement
Q. 6. Calcium hydroxide cement
Ans.
Or,
l Polycarboxylate cement was the first cement system de-
veloped with a potential for adhesion to tooth structure. Uses of calcium hydroxide cement
l The polycarboxylate cement is available as powder and
liquid in bottles. Some manufacturers supply this cement Ans.

as precapsulated powder/liquid system. l Calcium hydroxide is relatively weak cement com-
monly employed as direct or indirect pulp capping
COMPOSITION agents.
l Recently, a light-cured calcium hydroxide base material
Powder and a calcium hydroxide root canal sealing paste have

been introduced.
1 . Zinc oxide: Basic ingredient l Uses of calcium hydroxide cement:
2. Magnesium oxide: Principal modifier and also aids in 1. For direct and indirect pulp capping.
sintering 2. As low-strength bases beneath silicate and composite
3. Other oxides like bismuth and aluminium: Small restorations for pulp protection.
amounts stannous fluoride: Increases strength, modifies 3. Apexification procedure in young permanent teeth
setting time and imparts anticariogenic properties where root formation is incomplete.
Liquid AVAILABLE AS
Aqueous solution of polyacrylic acid or copolymer of 1. Two paste system containing base and catalyst pastes in
acrylic acid with other unsaturated carboxylic acids, i.e. collapsible tubes
itaconic, maleic or tricarboxylic acid. 2. Light-cured system
3. Single paste in syringe form
PROPERTIES 4. Powder form (mixed with distilled water)
1. Compressive strength: Polycarboxylate cement is infe-

rior to zinc phosphate cement (55 Mpa or 8000 psi). COMPOSITION
2. Tensile strength: Its tensile strength is slightly higher
than that of zinc phosphate cement (6.2 Mpa or 900 psi). Base Paste (Table 15.7)
3. It tends to absorb water and is slightly more soluble than
zinc phosphate.
4. The polycarboxylate cement exhibits mild pulpal re-
sponse. The pH of freshly mixed cement is 3–4. After
TABLE 15.7 Composition of Calcium Hydroxide Cement as
24 h, pH of the cement is 5–6.
Base Paste
5. An outstanding characteristic of zinc polycarboxylate
cement is that, the cement bonds chemically with the Approximate
tooth structure due to the ability of the carboxyl group Components wt% Functions
in the polymer molecules to chelate with calcium in the Glycol salicylate 40 Reacts with Ca(OH)2
tooth structure. and ZnO
6. Polycarboxylate cements are good thermal insulators. Calcium sulphate 30 Provides strength and
colour to the paste
Uses Titanium dioxide 14 Inert fillers, pigments
1. It is primarily used for cementation of restoration and Calcium tungstate 16 Acts as opacifiers,
thermal insulating base. or barium sulphate provides radiopacity
Catalyst Paste (Table 15.8) 2. For core build-up of grossly destructed teeth
TABLE 15.8 Composition of Calcium Hydroxide Cement as Properties

Catalyst Paste
1. Mechanical properties
Components Approximate wt% Functions a. As compared to that of conventional cement the
Calcium 50 Principal reactive strength of either type of metal modified cement
hydroxide ingredient (150 MPa) is not greatly improved.
Zinc oxide 10 Reactive ingredient b. The fracture toughness of GIC, whether modified or
not is extremely low.
Zinc stearate 0.5 Accelerator
c. It is far more resistant to wear than type II GIC.
Ethylene toluene, 39.5 Oily compound, 2. Anticariogenic property
sulphonamide acts as carrier
a. Both metal modified ionomers have anticariogenic
capability due to leaching of fluoride.
3. Aesthetics
PROPERTIES a. As they are grey in colour because of metallic phases
1. Calcium hydroxide cements have poor mechanical within them, they are unsuitable for use in anterior
properties. It has a low compressive and tensile teeth.
strengths.
2. The low elastic modulus limits their use to areas not GLASS IONOMER-RESIN COMBINATION
critical to the support of the restoration. MATERIALS
3. Some solubility of the calcium hydroxide cement is
necessary to achieve its therapeutic properties. These are relatively new materials having various names
4. Formation of secondary dentine: The high alkalinity and like compomer, resin ionomers, RMGI, light-cured GIC,
its consequent antibacterial and proteinlysing effect dual cure GIC and tricure GIC.
helps in the formation of reparative dentine.
Recently, a root canal sealer containing calcium hydrox- CLASSIFICATION
ide has been developed.
These materials have been classified by McClean et al
Q. 7. Recent advances in glass ionomers depending on the predominant component in them as
follows:
Or,
1. Resin-modified glass ionomer cement (RMGI), e.g. Fuji
Resin-modified glass ionomers II LC, Vitremer, Photac Fill
2. Poly acid-modified composites (PMC), e.g. Dyract,
Ans. Variglass VLC
l In order to improve the strength, fracture toughness and Recent advances in GICs are as follows:
abrasion resistance GICs have been modified by addition 1. Fuzi VII: The world’s first high-fluoride nonresin con-
of metal powder or resin fibres. taining autocure glassionomer cement
l Two varieties of modification are as follows: 2. Fuzi VIII and Fuzi IX: High-viscosity GICs mainly de-
1. Metal-modified veloped for use in atraumatic restorative therapy (ART)
2. Resin-modified
Uses
METAL-MODIFIED GICs 1 . Restoration of class I, III or V cavities
There are two types of metal-modified cements as follows: 2. As bases and liners
1. Silver alloy admixed (miracle mix): Spherical amalgam 3. As adhesives for orthodontic brackets
alloy powder is mixed with type II GIC powder. 4. Cementation of crowns and bridges
2. Glass cermet cement (ketac silver): Silver particles 5. Repair of damaged amalgam cores or cusps
are bonded to glass particles. This is done by sintering 6. Retrograde root filling
of a mixture of the two powders at a high temperature.
Supplied As
Uses They are supplied as follows:
1. Restoration of small class I cavities as an alternative 1. Chemically cured
to amalgam or composite resins. They are particularly 2. Light cured
useful in young patients who are prone to caries. 3. Dual cured (combined chemical and light cured)
All of them are usually supplied as powder and liquid. Powder (Table 15.9)
The light cured type is supplied in dark shaded bottles for
light protection. TABLE 15.9 Composition of Zinc Phosphate Cement as
Powder

Properties of Resin-Modified GICs Zinc oxide 90.2 Principal
constituent
1. Strength: When compared to conventional GICs the
compressive strength is slightly lower (105 MPa), Magnesium oxide 8.2 Aids in sintering
whereas the diametric tensile strength is greater Other oxides (like 0.2 Improves
(20 MPa) because of the plastic nature of the resin bismuth trioxide, smoothness
component. calcium oxide, of mix
2. Hardness: The hardness (40 KHN) is comparable to barium oxide, etc)
that of conventional GICs. Silica 1.4 Filler, aids in
3. Adhesion: The bonding mechanism to tooth structure is sintering
similar to that of conventional GICs.
4. Microleakage: These materials have a greater amount Liquid (Table 15.10)
of microleakage when compared to GICs. This may
be partly due to the polymerization shrinkage and TABLE 15.10 Composition of Zinc Phosphate Cement as
partly due to the reduced wetting of the tooth by the Powder
cement.
Approximate
5. Anticariogenicity: They have a significant anticario-
Components wt% Functions
genic effect because of the fluoride release.
6. Aesthetics: They are less translucent because of the Phosphoric acid 38.25 Reacts with
zinc oxide
significant differences in the refractive index between
the resin matrix and powder particles. Water 36 Controls rate
of reaction
Q. 8. Composition of zinc phosphate cement Aluminium phosphate or 16.2 Buffers, to re-
sometimes zinc phosphate duce rate of
Ans. Zinc phosphate cement is available as powder and reaction
liquid system. Composition of zinc phosphate cement is
Aluminium 2.5
listed in Tables 15.9 and 15.10.
Zinc 7.1
SHORT NOTES
Q. 1. Cermet and composite restorative material are also considered
Ans. liners.
l They provide barrier against passage of irritants from
l A glass ionomer cement that has been reinforced with restorative materials to dentine and pulp.
filler particles prepared by fusing silver particles to l They reduce the penetration of oral fluids at restoration
glass is known as cermet. tooth interface and prevent marginal leakage.
l Cermet ionomer system was developed by Dr Maclean l They provide some therapeutic benefits to pulp and
in 1985. reduce the sensitivity of freshly cut dentine.
l Cermet cement contains glass metal powder sintered to
high density which reacts with active solution of poly- Q. 3. Cavity varnish
acrylic acid to form cement. Ans.
Q. 2. Cavity liners l Cavity varnish is a material used to provide the barrier
Ans. against the passage of irritants from the restorative ma-
terials and to reduce the penetration of oral fluids at the
l Thin layer of cement, such as a calcium hydroxide sus- restoration tooth interface into the pulp.
pension in an aqueous or resin carrier, used for protec- l Cavity varnish is a solution of natural gum, synthetic
tion of the pulp; certain glass ionomer cements that resins or resins dissolved in a volatile solvent, such as
are used as intermediate layer between tooth structure acetone, ether or chloroform.
l Functions of varnish are as follows: Q. 7. Classification of GICs

1. Reduces the marginal leakage
Ans.
2. Pulp protection
3. Reduces tooth discolouration
Q. 4. Bases CLASSIFICATION OF GICs

Ans. 1 . Type I: For luting
2. Type II: For restorations
l Base is a layer of insulating, sometimes medicated 3. Type III: Liners and bases
cement, placed in the deep portion of the preparation to
protect pulpal tissue from thermal and chemical injury. Q. 8. Composition of GICs
l They should be applied in a sufficiently thick layer
Ans.
around 0.75–2 mm.
l They are classified as follows: Composition of GICs is as follows:
1. According to strength properties Powder

The powder is an acid-soluble calcium fluoro-alumino-silicate
glass. It is similar to that of silicates, but has a higher alumina-
Low-strength bases High-strength bases
silica ratio. This increases its reactivity with the liquid.
(Ca(OH)2 cement, ZOE cement) (ZnPO4 cement, GIC)
Silica (SiO)2 41.9%
2. According to chemical nature or pH Alumina (Al2O3) 28.6%
Aluminium fluoride (AlF3) 1.6%
Calcium fluoride (CaF3) 15.7%
Acidic Neutral Alkaline
Sodium fluoride (NaF) 9.3%
(GIC, ZnPO4) (ZOE) (Ca(OH)2)
Q. 5. Luting cement The fluoride component acts as a ceramic flux. Lantha-

num, strontium, barium or zinc oxide additions provide
Ans.
radiopacity.
l Luting cement is a viscous material placed between
tooth structure and a prosthesis that hardens through Liquid
chemical reactions to firmly attach the prosthesis to the
tooth structure. Earlier the liquid was a 50% concentration aqueous solution
l Luting or cementing materials are of two types as follows: of polyacrylic acid. It was very viscous and had a tendency
a. Temporary luting agent to gel.
b. Permanent luting agent In most current cements the liquid contains
l Temporary luting agents are the low strength interface 1. polyacrylic acid (in the form of copolymer with iticonic
materials between tooth structure and permanent restora- acid, maleic acid and tricarballylic acid),
tion for trial of appliance. For example: ZnOE, Ca(OH)2. 2. tartaric acid and
3. water.
Q. 6. Uses of GICs
Q. 9. Metal-modified GICs
Ans.
Ans.
Uses of GICs are as follows:
1. Anterior aesthetic restorative material for class III cavities
2. For eroded areas and class V restorations METAL-MODIFIED GICs
3. As a luting agent
4. As liners and bases There are two types of metal-modified cements as follows:
5. For core build up 1. Silver alloy admixed (miracle mix): Spherical amalgam
6. To a limited extend as pit and fissure sealants. alloy powder is mixed with type II GIC powder.
2. Glass cermet cement (ketac silver): Silver particles are

bonded to glass particles. This is done by sintering of a CAVITY VARNISH
mixture of the two powders at a high temperature.
Cavity varnish is a solution of one or more resins which
when applied onto the cavity walls, evaporates leaving a
Uses thin resin film that serves as a barrier between the restora-
tion and the dentinal tubules. For example:
1. Restoration of small class I cavities as an alternative to
1. Natural gums such as copal, resin or synthetic resin
amalgam or composite resins. They are particularly use-
dissolved in an organic solvent such as alcohol, acetone,
ful in young patients who are prone to caries.
or ether.
2. For core build up of grossly destructed teeth
2. Medicinal agents such as chlorobutanol, thymol, and
eugenol may be added. Some varnishes also contain
Properties of Metal-Modified GICs fluorides.
1. Mechanical properties: As compared to that of conven- Q. 12. Zinc phosphate
tional cement the strength of either type of metal-modi-
fied cement (150 MPa) is not greatly improved. Ans.
2. Anticariogenic property: Both metal-modified ionomers
l Zinc phosphate is the oldest of the luting cements and
have anticariogenic capability due to leaching of fluoride.
serves as a standard with which newer cements can be
3. Aesthetics: As they are grey in colour because of metal-
compared.
lic phases within them, they are unsuitable for use in
l The terms crown and bridge and zinc oxyphosphate
anterior teeth.
have also been used for this cement.
Q. 10. Sandwich technique
Ans. The process of restoring a prepared tooth by initially APPLICATIONS
placing layer of type II glass ionomer cement for fluoride 1 . Luting of restorations
release followed by an overlayer of resin-based composite 2. High-strength bases
for strength and durability is known as sandwich technique. 3. Temporary restorations
4. Luting of orthodontic bands and brackets
Q. 11. Pulp protecting cements
Ans. Pulp protecting cements are cavity liners, bases and CLASSIFICATION
varnishes. ADA Specification no. 8 designates them as follows:
1. Type I: Fine grained for luting
2. Type II: Medium grained for luting and filling
CAVITY LINERS
Q. 13. Polycarboxylate cements
Thin layer of cement, such as a calcium hydroxide suspen-
sion in an aqueous or resin carrier after evaporation, used Or,
for protection of the pulp.
Uses of polycarboxylate cements
For example: Type IV ZOE and GICs are also used as
cavity liner. Ans.
l Polycarboxylate cement was the first cement system

CEMENT BASE developed with a potential for adhesion to tooth
A base is a layer of cement placed under the permanent structure.
restoration to encourage recovery of the injured pulp and to l It is primarily used for cementation of restoration and
protect it against numerous types of insult to which it may thermal insulating base. It is also used as an intermediate
be subjected. restoration and luting agent for orthodontic purposes.
Types
APPLICATIONS
1 . Primarily for luting permanent restorations
High-strength bases Low-strength bases 2. As bases and liners
(zinc phosphate, eugenol glass iono- (calcium hydroxide and zinc 3. Used in orthodontics for cementation of bands
mer and reinforced ZOE cements) oxide) 4. Also used as root end fillings in endodontics
Q. 14. Zinc oxide eugenol cements Uses of calcium hydroxide cement

Ans. Ans.
l These cements have been used extensively in dentistry l Calcium hydroxide cements are relatively weak ce-
since 1890s. ments commonly employed as direct or indirect pulp
l Depending on their use they vary widely in their proper- capping agents.
ties. In general, they are cements of low strength. Also l Due to their alkaline nature they also serve as protective
they are the least irritating of all dental cements, and barrier against irritants from certain restorations.
are known to have an obtundant or sedative effect on l Recently, a light-cured calcium hydroxide base material
exposed dentine. and calcium hydroxide root canal sealing pastes have
l To improve the strength many modified zinc oxide eu- been introduced.
genol cements have been introduced. For example: l Uses
EBA-alumina modified and polymer-reinforced zinc a. For direct and indirect pulp capping
oxide eugenol cements b. As low-strength bases beneath silicate and compos-
l Recently, noneugenol zinc oxide cements have become ite restorations for pulp protection
available. They are suitable for patients sensitive to eugenol.
l ZOE cement is used for lining cavities, cementing res-
Q. 17. Intermediate restorative materials
torations, as bases, root canal sealants, periodontal
dressings and temporary and intermediate restorations. Ans. Tooth filling or prosthesis that is placed for a limited
period, from several days to months and is designed to seal
teeth and maintain their position until a long-term restora-
CLASSIFICATION tion is placed is called a temporary restoration.
ADA Specification no. 30 has listed four types of zinc oxide
eugenol restorative materials. Q. 18. Manipulation of zinc phosphate cement
1. Type I ZOE: Temporary cementation
2. Type II ZOE: Permanent cementation Ans.
3. Type III ZOE: Temporary filling material and thermal
insulation
4. Type IV ZOE: Cavity liners Manipulation of Zinc Phosphate Cement
l Maximum amount of powder should be incorporated in
Q. 15. Advances of EBA cements the liquid to ensure minimum solubility and maximum
Ans. strength.
l A cool glass slab is used in order to delay the setting and
1. EBA-alumina modified cements were introduced in an allow more powder to be incorporated before the matrix
effort to improve the mechanical properties of zinc oxide formation occurs.
eugenol cement. l The liquid should be dispensed just before mixing and
2. Composition the powder is added in small increments.
l A large area is covered during mixing in order to dissi-
Powder pate the exothermic heat.

l An appropriate consistency is attained by addition of
Zinc oxide 70% more powder to the liquid and not by allowing a thin
Alumina 30%
mix to thicken.
Procedure
Liquid
l The recommended powder to liquid ratio is 1.4 g/0.5 mL.
EBA 62.5% l On a cool dry glass slab the required amount of
Eugenol 37.5% powder is taken first. The liquid should be dispensed
just before mixing. The powder is divided into small
increments.
3. In general, their properties are better than that of l A stainless steel cement spatula is used for mixing.
unmodified ZOE. Compressive strength is increased Mixing is initiated by addition of a small amount of
55 Mpa (8000 psi). Solubility and disintegration in powder at a time into the liquid.
water is decreased (0.05 wt%). l Spatulation is carried out with a brisk, circular motion
of the spatula, covering a large area for mixing to dis-

Q. 16. Calcium hydroxide cement
sipate the heat—exothermic reaction. Each increment is
Or, mixed for 15–20 s before the next increment is added.
l Mixing time is 1 min and 15 s. 2. At the time of insertion it has a pH of 2.8 and even after
one month, it remains below 7.
Q. 19. Biological properties of silicate cement. 3. Silicate serves as a standard for comparing the pulpal
Ans. response to other material.
4. In deep cavities the pulp is protected with a layer of zinc
Biological properties of silicate cement are as follows: oxide eugenol or calcium hydroxide or by coating the
1. It is a severe irritant to the pulp. walls with varnish.
Topic 16
Dental Amalgam
LONG ESSAYS
Q. 1. Discuss the types, physical properties and uses of 5. Based on size of alloy
dental amalgam alloys. Add a note on high copper alloys.
Ans.
Microcut alloy Macrocut alloy
TYPES OF AMALGAM ALLOYS PROPERTIES OF AMALGAM

1. Microleakage
1. Based on copper content
1. Dental amalgam has tendency to minimize marginal
leakage.
2. It is a self-sealing material. The small amount of leakage
Low copper alloys High copper alloys
under amalgam restorations is unique. The leakage de-
Contain less than 6% copper Contain more than 6% copper creases as the restoration ages in the mouth due to the
(conventional alloys)
corrosion products that is formed in the tooth-restoration
interface. These products over a period of time seal the
Admixed or dispersion or Single composition or interface and thereby prevent leakage. Thus amalgam is
blended alloys unicomposition alloys a self-sealing restoration.
2. Based on zinc content

2. Dimensional Change
1. Amalgam may expand or contract, depending on its ma-
nipulation. Ideally, dimensional change should be small.
Zinc-containing alloys Zinc-free alloys
2. Measurement of dimensional change: ADA Specifica-
(Contain more than 0.01% zinc) (Contain less than 0.01% zinc) tion No. 1 requires that amalgam should not expand or
contract more than 20 µm/cm at 37°C, between 5 min
3. Based on shape of the alloy particle
and 24 h from the beginning of trituration.
3. Strength
Lathe-cut alloys Spherical alloys Spheroidal alloys
(irregular shape) l Hardened amalgams have good compressive strength.
4. Based on number of alloyed metals Compressive strength 1h 7 days

Low copper 145 Mpa 343 Mpa
Admixed 137 Mpa 431 Mpa
Binary alloys Ternary alloys Quaternary alloys
Single composition 262 Mpa 510 Mpa
(silver–tin) (silver–tin–copper) (silver–tin–copper–indium)
Tensile Strength 2. The total copper content ranges from 9 to 20 wt% in ad-
1. Amalgam cannot withstand high tensile or bending mixed alloy powder which usually contains 30–55 wt%
stresses. spherical high copper powder.
2. The cavity design should be such that the restoration 3. Setting Reaction
will receive compression forces and minimize tension a. Silver enters the mercury from the silver–copper eu-
or shear forces in service. tectic alloy particles, and both silver and tin enter the
3. The tensile strength is 48–70 MPa. mercury from the silver–tin alloy particles. The mer-
cury dissolved in the silver–tin particles will react like
low copper alloys and will form the g1 and g2 phases,
4. Creep leaving some silver–tin particles unreacted.
1. Creep is defined as a time-dependent plastic deformation. b. The newly formed g2 phase (Sn8Hg) will react with
2. Creep of dental amalgam is a slow progressive perma- silver–copper particles forming Cu6Sn5 (g or eta)
nent deformation of set amalgam, which occurs under phase. Some g1 phase (Ag2Hg3) will also form
constant stress (static creep) or intermittent stress around the silver–copper particles.
(dynamic creep). 4. The reaction may be shown as follows:
Creep values
Ag3Sn Ag–Cu
Low copper amalgam 0.8–8% Ag3Sn1 Ag2Cu1Hgn Ag2Hg31 Sn8Hg1 unreacted1 unreacted
High copper amalgam 0.4–0.1% (g) (eutectic) (g1) (g2) (g) (eutectic)
and later,
5. Retention of Amalgam Sn6Hg 1 Ag–Cu n Cu6Sn5 1 Ag2Hg3
1 . Amalgam does not adhere to tooth structure. (g2) (eutectic) (h) (g1)
2. Rather retention of the amalgam filling is obtained
In the above reaction, g 2 has been eliminated and is re-
through mechanical locking. This is achieved by proper
placed by g phase. To accomplish this, it is necessary to have
cavity design.
a net copper content of at least 12% in the alloy powder.
3. Additional retention if needed can be obtained by plac-
ing pins within the cavity.
Microstructure of Set Amalgam (Fig. 16.1)
6. Tarnish and Corrosion The Cu6Sn5 is present surrounding as a halo around the
Amalgam restorations often tarnish and corrode in the mouth. Ag–Cu particles.
Final set material consists of the following:
HIGH COPPER ALLOYS
Core
1 . High copper alloys contain more than 6 wt% copper. l Unreacted Ag3Sn(g phase) and
2. The weakest g2 phase is eliminated in high copper l Unreacted Ag–Cu surrounded by Cu6Sn5 (h)
amalgam.
3. They are preferred because of their improved me-
chanical properties, resistance to corrosion and better
marginal integrity.
4. Types of high copper alloys are as follows:
a. Admixed alloy powder
b. Single-composition alloy powder
Ag-Cu
ADMIXED ALLOY POWDER

1. The overall composition of admixed alloy powder is as
follows:
Silver 69%
Tin 17%
Copper 13% FIGURE 16-1 The microstructure of high copper admixed
amalgam where (g) phase is Ag3Sn, (g1) phase is Ag2Hg3 and (h)
Zinc 1% Cu6Sn5, Ag–Cu is eutectic.
Matrix
l g 1 phase is (Ag2Hg3)
SINGLE-COMPOSITION ALLOYS
In single-composition alloy, each particle of the alloy pow-
der has the same composition. Therefore, they are called
single-composition or unicompositional alloys.
Composition AgSnCu
(unreacted)
40–60%
Tin 22–30%
Cu6Sn5
Copper 13–30%
Zinc 0–4%
FIGURE 16.2 The microstructure of high copper single com-
Indium or palladium small amounts position amalgam.
Setting Reaction Applications (Uses)

When triturated, silver and tin from Ag–Sn phases dissolve 1. As a permanent filling material in class I and class II
in mercury. Very little copper dissolves in mercury. The cavities, and class V cavities where aesthetics is not
Ag2–Hg3 (g1) crystals grow forming a matrix that binds important
together the partially dissolved alloy particles. Later, Cu6– 2. In combination with retentive pins to restore a crown
Sn5 (h) crystals are formed at the surface of alloy particles. 3. For making dyes
4. In retrograde root canal fillings
The overall reaction is as below: 5. As a core material
AgSnCu 1 Hg n Cu6Sn5 1 Ag2Hg3 1 AgSnCu
Q. 2. Classify dental amalgam alloys and state various
(g 1 E) (h) (g 1) (unreacted)
merits and demerits of dental amalgam.
The difference between the elimination of the g2 phase
Ans. For classification of dental amalgam alloys refer
in an admixed and unicompositional alloy is that, in the
above to the answer of Long Essays Q. 1.
admixed type the g 2 forms around the silver–tin (lathe-cut)
particles and is eliminated around the silver–copper (spher- The merits of dental amalgam restorations are as follows:
ical) particles. In unicompositional alloy, the particles at the 1. They are reasonably easy to insert.
beginning of the reaction function like silver–tin particles 2. They are not overly technique-sensitive.
of the admixed type, and later the same particles function 3. They maintain anatomic form well.
like the silver–copper particles of the admixed type, elimi- 4. They have adequate resistance to fracture.
nating g2 phase. 5. They prevent marginal leakage after a period of time.
6. They have reasonably long service life.
Microstructure of Set Amalgam (Fig. 16.2) The demerits of dental amalgam restorations are as follows:
Final set material consists of the following: 1. The colour does not match tooth structure.
2. They are more brittle and less tough than desirable.
Core 3. They are subject to corrosion and galvanic action.
l Unreacted Ag3Sn (g phase)
4. They eventually show marginal breakdown.
l Unreacted Ag–Cu (E)
5. They do not bond to tooth structure.
Matrix Q. 3. Give the composition of dental amalgam alloys and

write in detail about the manipulation and properties of
l g1 (Ag2Hg3)
high copper amalgam.
Cu6Sn5(h) is present in the g 1 matrix rather than as a
halo surrounding Ag–Cu. Or,
Give the composition of dental amalgam alloy. Write 2. Mercury: Alloy Ratio (Proportioning)
various stages of manipulation of amalgam alloy.
The better method of reducing the mercury content is to
Ans. reduce the original mercury:alloy ratio. This method is
known as the minimal mercury or the Eames technique
(mercury: alloy 1:1).
COMPOSITION
1. Amalgam alloys contain at least 3. Trituration
a. 65 wt% silver, a. The main objective of trituration is to wet all of the
b. 29 wt% tin and surfaces of the alloy particles with mercury.
c. less than 6 wt% copper. b. Trituration is achieved either by hand or more com-
2. A composition close to that recommended by GV Black monly by mechanical amalgamators.
in 1896. During the 1970s many amalgam alloys having i. Hand mixing: A glass mortar and the pestle are used.
an increased copper between 6 and 30 wt% were devel- ii. Mechanical trituration: Mechanical amalgamators
oped. These high copper alloys produce amalgams that are used to triturate.
are superior in many respects to the traditional low copper c. With a mechanical amalgamator the mixing time is re-
amalgams. duced and the procedure is more readily standardized.
3. American Dental Association (ADA) Specification No. 1 The amalgamators have automatic timer and speed con-
requires that amalgam alloys be predominantly silver trol device.
and tin.
4. Alloys containing zinc in excess of 0.01% are desig-
nated as zinc-containing. Those alloys containing zinc 4. Mulling
equal to or less than 0.01% are designated as nonzinc or a. Mulling is actually continuation of trituration. It is done
zinc-free alloys. There is no specification for low copper to improve the homogeneity of the mass and get a con-
or high copper alloys. sistent mix.
TECHNICAL CONSIDERATIONS 5. Condensation

(MANIPULATION OF AMALGAM)
a. The amalgam is placed in the cavity after trituration,
A good modern dental amalgam can be manipulated so that and force is applied to the amalgam using suitable in-
the restoration obtained is satisfactory in every respect. The struments in order to adapt it to the cavity wall.
clinical success of most amalgam restorations is highly b. Remove excess mercury.
dependent on the correct manipulation of the alloy. c. Enhance packing of amalgam and reduce the risk of void
formation. This increases the strength and decreases the
creep of the amalgam. Condensation can be effected
STAGES OF MANIPULATION OF manually or mechanically.
AMALGAM ALLOY
1. Selection of Materials 6. Trimming and Carving
1. Alloys for amalgam should be selected from prod- a. After the amalgam is overfilled into the prepared
ucts certified to meet or exceed the properties listed cavity, the mercury rich layer can be trimmed away and
in ADA Specification No. 1 for dental amalgam filling is carved to reproduce the proper tooth anatomy.
alloys. b. The carving should not be started until the amalgam is
2. There is only one requisite for selection of dental mer- hard enough to offer resistance to the carving instrument.
cury, that is its purity. c. Amalgam should be carved using sharp instruments
3. The delivery system provided by the manufacturer is with strokes proceeding from tooth surface to amalgam
convenient, expedient and capable of reducing human surface.
errors or variables.
4. Preproportioned capsules containing alloy particles and 7. Burnishing
mercury in compartments separated by a membrane are
available, before use, the membrane is ruptured by com- 1. After the carving, the restoration should be smooth-
pression of the capsule and the capsule is then placed in ened by burnishing the surface and the margins of the
a mechanical amalgamator. restoration.
2. Burnishing of the occlusal anatomy can be done by us- Types of High Copper Alloys
ing a ball burnisher with light stroke proceeding from
1 . Admixed alloy powder
the amalgam surface to the tooth surface.
2. Single-composition alloy powder
3. More pressure should not be applied and heat genera-
tion should be avoided during burnishing.
4. If the temperature rises above 60°C, it causes release of Advantages of High Copper Alloys
mercury, which will accelerate corrosion and fracture at
1. High copper alloys contain more than 6 wt% copper.
margins. Final smoothing can be done by rubbing the
The weakest g2 phase is eliminated in high copper
surface with a moist cotton pellet or by a rubber polishing
amalgam.
cup and polishing paste.
2. They are preferred because of their (Table 16.1)
a. improved mechanical properties,
8. Polishing b. resistance to corrosion and
c. better marginal integrity.
1. The objective of finishing and polishing is the removal
of superficial scratches and irregularities. TABLE 16.1 Advantages of High Copper Amalgam
2. This minimizes corrosion and prevents adherence of
plaque. Admixed high copper Spherical high copper
amalgam amalgam
3. The polishing should be delayed for at least 24 h after
condensation, or preferably longer. 1. Longer working time 1. Faster set
4. Wet polishing is advised, so a wet abrasive in a paste 2. Less dimensional change 2. Lower residual mercury
form is used. Dry polishing powders and disks can raise 3. Displacement of matrix 3. Lower creep during
the temperature above 60°C. condensation
Q. 4. Classify dental amalgam. Discuss advantages of 4. Faster finishing

high copper amalgam. 5. Higher early strength
Ans. For classification of amalgam alloys refer to the an- 6. Low condensation
pressure
swer of Long Essays Q. 1.
SHORT ESSAYS
Q. 1. High copper amalgam l Admixed alloy powders usually contain 30–55 wt%
Ans. spherical high copper powder. The total copper content
in admixed alloys ranges from 9 to 20 wt%.
l High copper alloys contain more than 6 wt% copper. l Composition: The overall composition is approximately
l They were developed to eliminate some undesirable as follows:
properties of low copper alloys.
Silver 69%
l High copper alloys have become the materials of choice
because of their improved mechanical properties, resis- Tin 17%

tance to corrosion and better marginal integrity, as com- Copper 13%
pared with traditional low copper alloys.
Zinc 1%
l There are two types of high copper alloy powders as
follows:
1. Admixed alloy powder Setting Reaction
2. Single composition alloy powder l When mercury reacts with an admixed powder, silver
enters the mercury from the silver–copper eutectic alloy
Admixed Alloy particles, and both silver and tin enter the mercury from
l It was developed in the year 1963. It is a type of high cop- the silver–tin alloy particles.
per alloy powder made by mixing one part silver–copper l The mercury dissolved in the silver–tin particles will
eutectic alloy (high copper spherical particles) with two react like low copper alloys and will form the g1 and g2
parts silver–tin alloy (low copper lathe-cut particles). phases, leaving some silver–tin particles unreacted. In a
l Amalgam made from admixed powders is stronger than relatively short time, the newly formed g2 phase (Sn8Hg)
amalgam made from lathe-cut low copper powder be- will react with silver–copper particles forming Cu6Sn
cause of the silver copper particles which act as fillers (h or eta) phase. Some g1 phase (Ag2Hg3) will also form
in amalgam matrix, hence strengthening the amalgam. around the silver–copper particles.
l The reaction may be simplified as follows: of an inert gas through a fine crack into a large chamber. If
the droplets solidify before hitting a surface, the spherical
Ag3Sn1 Ag–Cu Ag2Hg1 Sn8Hg2 Ag3Sn Ag–Cu shape is preserved. Like the lathe-cut powders, spherical
1Hgn unreacted1 unreacted
powders are aged.
(g) (eutectic) (g1) (g2) (h) (eutectic)
In Spherical Alloys
and later,
1. particles are spherical,
Sn8Hg 1 Ag–Cu n Cu6Sn5 1 Ag2Hg3 2. manufactured by atomization of molten alloy,
(g2) (eutectic) (h) (g1) 3. more plastic, hence a contoured and wedged matrix is
In the above reaction g2 has been eliminated and is essential to establish proximal contour,
replaced by g phase. To accomplish this, it is necessary to 4. requires less mercury hence has better properties and
have a net copper concentration of at least 12% in the alloy 5. the spherical alloy particles are 5–40 µm in size.
powder. 6. Composition
Single-Composition Alloys Silver 40–60%

l Unlike admixed alloy powders, each particle of these Tin 22–30%
alloy powders have the same chemical composition. Copper 13–30%
Therefore, they are called single-composition or uni-
Zinc 0–4%
compositional alloys.
l The spherical alloy particles are 5–40 µm in size.
1. Composition 7. Spherical single-composition alloy powder when triturated

with mercury, silver and tin from Ag–Sn phases dissolve in
mercury. Very little copper dissolves in mercury.
Silver 40–60%
8. The Ag–Hg g1 crystals grow, forming a matrix that
Tin 22–30% binds together the partially dissolved alloy particles.
Copper 13–30% 9. The overall simplified reaction is
Zinc 0–4% Ag3Sn 1 Cu, Sn 1 Hg n Cu6Sn5 1 Ag2Hg3
(g ) (E) (h) (g1)
2. Single-composition alloy powder when triturated
with mercury, silver and tin from Ag–Sn phases dis- Q. 3. Trituration of dental amalgam
solve in mercury. Very little copper dissolves in
mercury. The Ag–Hg g 1 crystals grow, forming a Ans.
matrix that binds together the partially dissolved al- l Trituration is the process of grinding powder, especially
loy particles. within a liquid.
l In dentistry, the term is used to describe the process of
3. The overall simplified reaction is mixing the amalgam alloy particles with mercury in an
Ag3Sn 1 Cu, Sn 1 Hg n Cu6Sn5 1 Ag2Hg3 amalgamator. Objective is to wet all the surfaces of the
(g) (E) (h) (g1) alloy particles with mercury.
1. Trituration is the mixing procedure to remove the oxide
4. The difference between the elimination of the g2 film by friction and enhance the amalgamation reactions.
phase in an admixed and unicompositional alloy is 2. Trituration can be carried out by either of two methods:
that, in the admixed type the g2 forms around the a. Hand trituration using glass mortar and pestle
silver–tin (lathe-cut) particles and is eliminated b. Mechanical trituration by using amalgamators
around the silver–copper (spherical) particles. In
unicompositional type, the particles at the beginning
of the reaction function like silver–tin particles of the Hand Mixing
admixed type, and later the same particles function l A glass mortar and pestle are used. The mortar has its
like the silver–copper particles of the admixed type, inner surface roughened to increase the friction between
eliminating g2 phase. amalgam and glass surface. A rough surface can be
maintained by occasional grinding with carborundum
Q. 2. Spherical amalgam alloy
paste. A pestle is a glass rod with a round end.
Ans. The spherical amalgam alloy is prepared by atomiza- l The three factors to obtain a well-mixed amalgam mass are
tion process. The liquid alloy is sprayed under high pressure a. the number of rotations,
b. the speed of rotation and Q. 4. Burnishing and polishing of amalgam

c. the magnitude of pressure placed on the pestle. Ans.
Typically a 25–45 s period is sufficient.
Mechanical Trituration
BURNISHING
Mechanical amalgamators are more commonly used to
triturate amalgam alloy and mercury (Fig. 16.3). l The restoration should be smoothened after the carving
by burnishing the surface and the margins of the
restoration.
l Burnishing of the occlusal anatomy can be done by us-
ing a ball burnisher with light stroke proceeding from

the amalgam surface to the tooth surface.
l More pressure should not be applied and heat genera-
tion should be avoided during burnishing.

l If the temperature rises above 60°C, it causes release of
mercury, which will accelerate corrosion and fracture at

margins. Final smoothing can be done by rubbing the
surface with a moist cotton pellet or by a rubber-polishing
cup and polishing paste.
POLISHING
FIGURE 16.3 Mechanical amalgamators (disposable capsule l The removal of superficial scratches and irregularities is
and mortar).
the objective of finishing and polishing.
l This minimizes corrosion and prevents adherence of
plaque.
1. The disposable capsule serves as a mortar. A cylindrical l The polishing should be delayed for at least 24 h after
metal or plastic piston is placed in the capsule, which condensation, or preferably longer. Wet polishing is
serves as the pestle. The capsule is inserted between the advised, so a wet abrasive in a paste form is used. Dry
arms on top of the machines. When put on, the arms polishing powders and disks can raise the temperature
holding the capsule oscillate at high speed, thus triturat- above 60°C.
ing the amalgam.
2. Reusable capsules are available with friction fit or Q. 5. Delayed expansion in amalgam
screw-type lids. At one time not more than two pellets
Ans.
alloy should be mixed in a capsule.
a. With either type, the lid should fit the capsule tightly, 1. If a zinc-containing low copper or high copper amalgam
otherwise, the mercury will spray out from the cap- is contaminated by moisture during trituration or con-
sule, and the inhalation of fine mist of mercury drop- densation, a large expansion can take place.
lets is a health hazard. 2. It usually starts after 3–5 days and may continue for
b. The amalgamators have automatic timer and speed months, reaching values greater than 400 µm (4%). This
control device. The speed used is recommended by is known as delayed expansion or secondary expansion.
the manufacturer. High copper alloys require higher 3. H2O 1 Zn n ZnO 1 H2 (gas)
mixing speeds. This hydrogen gas does not combine with the amalgam,
c. Spherical alloys usually require less amalgamation but collects within the restoration, creating extreme in-
time than do lathe-cut alloys. A large mix requires ternal pressure and expansion of the mass. This causes
slightly longer mixing time than a smaller one. protrusion of the restoration out of the cavity, increased
d. Advantages of mechanical trituration creep, increased microleakage, pitted surfaces and cor-
i. Shorter mixing time rosion.
ii. More standardized procedure 4. Dental pain, recurrence of caries and fracture of the
iii. Requires less mercury when compared to hand restoration are seen as a result of these poorly inserted
mixing technique restorations.
SHORT NOTES
Q. 1. Trituration l However, it is still necessary to squeeze mercury out of
the mix using the increasing dryness technique. Hence,
Ans.
with this technique, 50% or less mercury will be in the
l Trituration is the process of grinding powder, especially final restoration, with obvious advantages.
within a liquid. l The usual Hg/Alloy ratios used are as follows:
l In dentistry, the term is used to describe the process of 1. Hg/Alloy ratio for high copper alloys is—1:1
mixing the amalgam alloy particles with mercury in an 2. Hg/Alloy ratio for low copper—40:60
amalgamator.
l Trituration is the mixing procedure to remove the oxide
Q. 5. Creep in amalgam
film by friction and enhance the amalgamation reactions. Ans.
l Trituration can be carried out by either of two methods
as follows: l The creep in amalgam is the time-dependent strain or

1. Hand trituration by using glass mortar and pestle deformation that is produced by a stress.
2. Mechanical trituration by using amalgamators l The creep process can cause an amalgam restoration to
extend out of the cavity preparation, thereby increasing

Q. 2. Admixed alloy its susceptibility to marginal breakdown.
Ans. Q. 6. Mercury: alloy ratio
l Admixed alloys were developed in the year 1963. It is a Ans.
type of high copper alloy powder.
l They are made by mixing 1 part silver–copper eutectic l The recommended mercury : alloy ratios for most modern
alloy (high copper spherical particles) with 2 parts lathe-cut alloys is approximately 1:1 or 50% mercury ac-
silver–tin alloy (low copper lathe-cut particles). cording to Eames minimum mercury technique.
l Amalgam made from the admixed powders is stronger l The mercury: alloy ratio by volume is 1:1.5 as the density
than amalgam made from lathe-cut low copper pow- of mercury is 1.5 times the powder. The volume dispensers
der, because of the silver copper particles, which act as are now incorporated in the amalgamator itself.
filters in amalgam matrix, hence strengthening the
amalgam. Q. 7. Amalgam alloy composition
l Admixed alloy powders usually contain 30–55 wt% Ans.
spherical high copper powder. The total copper content
in admixed alloys ranges from 9 to 20 wt%. 1. The composition of low copper amalgam alloys (lathe-
cut or spherical)
Q. 3. Amalgam bond
Silver 63–70%
Ans. Tin 26–8%
l More recently, bonding agents employing M-R-X Copper 2–5% (,6%)
type coupling agents have achieved some clinical suc- Zinc 0–2%
cess. One system uses 4-methacryloxyethyl trimellitate
anhydride. 2. The composition of high copper amalgam alloys
l The mechanism responsible for bonding amalgam to resin
a. Admix or disperse alloy
is predominantly mechanical in nature. It is produced by
condensing the plastic amalgam mass into a plastic resin Silver 50–60%
layer, there by producing macroretentive areas within the
Tin 20–25%
resin after the resin has polymerized.
l Amalgam bonding agents have a place as an adjunct to
Copper 13–30%
conventional retentive means if properly employed. Zinc 0–2%
Q. 4. Eames technique b. Single-composition alloy

Ans. Silver 40–60%
l The better method of reducing mercury content is to Tin 22–30%

reduce the original mercury : alloy ratio. This is known Copper 13–30%
as the minimal mercury or Eames technique (mercury:
Zinc 0–4%
alloy 1:1).
Q. 8. High copper amalgam alloys l The g2 phase is the weakest component. The hardness of
g2 is approximately 10% of the hardness of g1, whereas
Ans.
the g phase hardness is somewhat higher than that of g1.
l High copper amalgams have become the materials of l The g2 phase is also the least stable in a corrosive
choice compared with traditional low copper amalgams environment and may suffer corrosion attack, espe-
due to their improved mechanical properties, corrosion cially in crevices of the restorations. In general,
characteristics, better marginal integrity and improved g (Ag3Sn) and pure g1 (Ag2Hg3) phases are stable in
performance in clinical trials. an oral environment.
l Two different types of high copper alloy powders are
available. The first is an admixed alloy powder and the Q. 11. Burnishing and polishing in dental amalgam
second is a single-composition alloy powder. Both types Ans.
contain more than 6 wt% copper.
Q. 9. Delayed expansion
Burnishing
Ans.
l The restoration is smoothened after the carving by bur-
l The gradual setting expansion after few days (3–7 days), nishing the surface and the margins of the restoration.
that takes place in zinc-containing amalgam alloys, if l Burnishing of the occlusal anatomy can be done by us-
there is moisture contamination during restoration it is ing a ball burnisher with light stroke proceeding from
known as delayed expansion. the amalgam surface to the tooth surface.
l This is associated with hydrogen gas development l More pressure should not be applied and heat generation
due to electrolysis of trapped water into hydrogen and should be avoided during burnishing. If the temperature
oxygen. rises above 60°C, it causes release of mercury, which
H2O 1 Zn n H2 1 ZnO will accelerate corrosion and fracture at margins of
restoration.
l The H2 gas produced will gradually accumulate and
exert large internal pressures causing this expansion
after few days. Polishing
l Clinically the large expansion causes severe pain and
l The objective of finishing and polishing is the removal
sometimes the fracture of thin cavity walls.
of superficial scratches and irregularities which mini-
Q. 10. Gamma-2 (g2) phase in amalgam alloys mizes corrosion and prevents adherence of plaque.
l The polishing should be delayed for at least 24 h after
Ans. condensation or preferably longer.
l Wet polishing is advised, so a wet abrasive in a paste
l The stoichiometric formula of g2 phase in amalgam
form is used. Dry polishing powders and disks can raise
alloys and set dental amalgams is Sn8Hg.
the temperature above 60°C.
Topic 17
Direct Filling Gold

LONG ESSAYS
Q. 1. What is direct filling gold? Enumerate various a. Sheet
forms of direct filling gold and its fabrication. i. Cohesive
Ans. Direct filling gold is a direct filling restorative material. ii. Noncohesive
b. Ropes
c. Cylinders
d. Laminated foil
Classification e. Platinized foil
1. Foil 2 . Electrolytic precipitate (crystalline gold)
a. Mat gold 2. Mat gold is preferred because it is easy to buildup the in-
b. Mat foil (mat gold plus gold foil) ternal bulk of the restoration, as it can be more easily
c. Gold–calcium alloy compacted and adapted to the cavity. Gold foil is generally
3 . Granulated gold (encapsulated gold powder) recommended for the external surface of the restoration.
GOLD FOIL Mat Foil

1. Gold is malleable, beating of gold to a submicroscopic 1. Mat foil is a sandwich of electrolytic precipitated gold
thickness of 15 µm or 25 µm is called gold foil. powder between sheets of no. 3 gold foil.
2. It is the oldest of all products available. 2. The sandwich is sintered and cut into stirps of differing
3. It is available as sheets. widths. The dentist can then cut these to the desired
4. Gold foil is supplied as flat square sheets of varying lengths. This type is no longer marketed.
thickness.
No. 4 thickness Wt. 4 grains (0.259 g) 0.51 µm thick Alloyed Electrolytic Precipitate
No. 3 thickness Wt. 3 grains (0.194 g) 0.38 µm thick 1. An alloy of gold and calcium (0.1–0.5% by wt) is called
electroly. For greater ease of handling, the alloy is sand-
wiched between two layers of gold foil.
Cohesive and Noncohesive Gold Foil 2. Calcium produces stronger restorations. Alloying with
1. The manufacturer supplies the gold essentially free of calcium alters the crystalline structure, so that the hard-
surface contaminants, and is inherently cohesive. This ness and strength will be increased.
type of gold is known as cohesive gold foil.
2. The manufacturer can subject the foil to a volatile agent POWDER GOLD
such as ammonia, which is adsorbed on the surface of
the gold and acts as a protective film to prevent absorp- 1. A fine powder is formed by chemical precipitation
tion of nonvolatile materials and premature cohesion of or by atomizing the metal. This powder is a blend of
pellets in their container. The ammonia-treated foil is powders of varying particle sizes (maximum—74 µm,
called noncohesive foil. average—15 µm).
3. No. 3 gold foil is used in the manufacture of electrolytic 2. The pellets are mixed with soft wax (which is burnt off
and powder products. later), and then wrapped with no. 3 gold foil, rather than
4. Ropes and cylinders made from no. 4 foil that has been sintering the mass, like for mat gold.
carbonized or corrugated are nowadays available in 3. The use of pellets of powdered gold increases cohesion
preformed shapes. during compaction and reduces the time required for
5. Platinized foil is a laminated foil in which pure plati- placing the restoration. This is because each pellet con-
num foil is sandwiched between two sheets of pure gold tains 10 times, more metal by volume than are compa-
foil. The layers of platinum and gold are bonded to- rable sized pellet of gold foil.
gether by a cladding process during the rolling opera-
tion. The object of adding platinum to the gold foil is to Manipulation of Direct Filling Gold
increase the hardness of the restoration. This product is Comprises
available only in no. 4 sheet form.
i. Desorbing or degassing
ii. Compaction
ELECTROLYTIC PRECIPITATE
1. Another form of gold for direct filling is crystalline gold I. Desorbing or Degassing
powder formed by electrolytic precipitation. By sinter-
ing the powder is formed into shapes or strips. 1. This heating process that removes surface gases and
2. Electrolytic precipitate can be available as mat, mat foil ensures a clean surface is called desorbing or degassing.
and alloyed. 2. Desorbing is essential in order to remove the surface
gases like oxygen, nitrogen, ammonia, moisture or sul-
phur dioxide, which may be present due to improper
Mat Gold storage.
1. Mat gold is crystalline, electrolytically precipitated 3. Decontamination of the gold surface is essential in order
gold, formed into strips. These strips can be cut by the to attain cohesion and maximal physical properties in
dentist into the desired size. the restoration.
4. Direct filling gold may be heated by one of two meth- to get the desired compaction without using forces that
ods as follows: might damage oral structures.
a. In bulk on a tray, heated by either a gas flame or
electricity c. Pressure Application
b. Piece by piece, in a well-adjusted alcohol flame 1. Originally, pressure was applied by the use of a special
5. In practice all but the powder gold may be desorbed, mallet. In recent years, there has been a tendency to
on a tray heated electrically. The electric annealer is apply the pressure by hand.
maintained at a temperature between 340°C (650°F) 2. Compaction with mechanical devices like electromag-
and 370°C (700°F). The time required varies from 5 to netic or spring-loading condensers is quite rapid and is
20 min depending on the temperature and the quantity accomplished with greater comfort for the patient.
of gold on the tray.
6. Powder gold must be heated in a flame to ensure the Q. 2. In what forms are gold used in dentistry? Describe
complete burning away of the wax. in detail the various types of direct filling gold available.
7. The method of flame desorption consists of picking up Briefly mention degassing techniques.
each piece individually, heating it directly in the open Or,
flame, and placing it in the prepared cavity. The fuel
for the flame may be alcohol or gas, but alcohol is Discuss in detail fabrication of direct filling gold and its
preferred as there is less danger of contamination. The properties.
alcohol should be pure methanol or ethanol without
colourants or other additives. Ans. For various forms of direct filling refer to above an-
8. Underheating should be avoided because it does not swer of Long Essays Q. 1.
adequately remove the impurities and thus results in Manipulation of direct filling gold comprises
incomplete cohesion, pitting and flaking of the surface.
9. Overheating leads to oversintering and possibly, con- i. desorbing or degassing and
tamination from tray, instruments or flame. This results ii. compaction.
in incomplete cohesion, embrittlement of the portion
being heated and poor compaction characteristics.
10. Earlier gold foil was compacted entirely by impact with I. Desorbing or Degassing
a mallet. Recent techniques use a mechanical device for 1. This heating process that removes surface gases and
applying the pressures required to weld the foil. ensures a clean surface is called desorbing or degassing.
Desorbing is essential in order to remove the surface gases
II. Compaction like oxygen, nitrogen, ammonia, moisture or sulphur di-
oxide, which may be present due to improper storage.
a. Condensers 2. Decontamination of the gold surface is essential in order
1. The original foil condensers had a single pyramid- to attain cohesion and maximal physical properties in
shaped face, but recent instruments have a series of the restoration.
small pyramidal serrations on the face. These serrations 3. Direct filling golds may be heated by one of two meth-
act as swaggers, exerting lateral force on their inclines ods as follows:
in addition to providing direct compressive forces, as a. In bulk on a tray, heated by either a gas flame or
the load is applied to the condenser. They also tend to electricity
cut through the outer layers to allow air trapped below b. Piece by piece, in a well-adjusted alcohol flame
the surface to escape. 4. In practice all but the powder gold may be desorbed, on a
2. Each increment of gold must be carefully stepped by tray heated electrically. The electric annealer is main-
lacing the condenser point in successive adjacent posi- tained at a temperature between 340°C (650°F) and
tions, as the compaction force is applied. The stepping 370°C (700°F). The time required varies from 5 to 20 min
may be more readily accomplished and standardized by depending on the temperature and the quantity of gold on
mechanical condensers. the tray.
5. Problems associated with electric annealing are as
. Size of the Condenser Point
b follows:
1. The diameter of circular points should be 0.5 mm and a. Pellets may stick together, if the tray is moved.
1 mm. The size of the condenser point is an important b. Air currents may affect the uniformity of heating.
factor in determining the effectiveness of compaction. c. Difficult to anneal appropriate amounts of gold.
2. The force distribution to the gold depends on the area of d. Oversintering
the point. Small condenser points are indicated in order e. Greater exposure to contamination
f. Size selection among the pieces of desorbed gold is 2. Compaction with mechanical devices like electromag-
limited. netic or spring-loading condensers is quite rapid and is
6. Powder gold must be heated in a flame to ensure the accomplished with greater comfort for the patient.
complete burning away of the wax.
7. The method of flame desorption consists of picking up
PHYSICAL PROPERTIES OF COMPACTED
each piece individually, heating it directly in the
open flame, and placing it in the prepared cavity. The GOLD (Table 17.1)
fuel for the flame may be alcohol or gas, but alcohol . Strength
1
is preferred as there is less danger of contamination. 1. Transverse or bending strength is most representative of
The alcohol should be pure methanol or ethanol clinical applications, as it is a reflection of all three
without colourants or other additives. types of stress—compressive, tensile and shear.
8. Advantages of flame desorption are as follows: 2. Transverse strength is a measure of cohesion in direct
a. Ability to select a piece of gold of the desired size filling golds. The failure occurs from tensile stress, due
b. Desorption of only those pieces used to incomplete cohesion.
c. Less exposure to contamination between time of
degassing and use
Type of Gold Transverse Strength
d. Less danger of oversintering
9. Underheating should be avoided because it does not Mat gold 161–169 MPa (23,000–24,100 psi)
adequately remove the impurities and thus results in Powdered gold 155–190 MPa (22,200–27,100 psi)
incomplete cohesion, pitting and flaking of the surface.
Gold foil 265–296 MPa (37,900–42,300 psi)
10. Overheating leads to oversintering and possibly, con-
tamination from tray, instruments or flame. This results
in incomplete cohesion, brittlen of the portion being . Hardness: Indicates the overall quality of compacted
2
heated and poor compaction characteristics. gold. Low hardness probably indicates the presence of
11. Earlier gold foil was compacted entirely by impact with porosity.
a mallet. Recent techniques use a mechanical device for
applying the pressures required to weld the foil. 3. Density: Apparent density is measured due to the voids.
II. Compaction TABLE 17.1 Physical Properties of Compacted Gold

a. Condensers Type of Gold Hardness Density
1. The original foil condensers had a single pyramid-shaped Mat gold 52–60 KHN 14.3–14.7 g/cm
face, but recent instruments have a series of small pyrami- Powdered gold 55–64 KHN 14.4–14.9 g/cm
dal serrations on the face. These serrations act as swag-
Gold foil 69 KHN 15.8–15.9 g/cm
gers, exerting lateral force on their inclines in addition to
providing direct compressive forces, as the load is applied Mat gold and gold foil 70–75 KHN 15.0–15.1 g/cm
to the condenser. They also tend to cut through the outer Mat gold 52–60 KHN 14.3–14.7 g/cm
layers to allow air trapped below the surface to escape.
Powdered gold 55–64 KHN 14.4–14.9 g/cm
2. Each increment of gold must be carefully stepped by
lacing the condenser point in successive adjacent posi- Gold foil 69 KHN 15.8–15.9 g/cm
tions, as the compaction force is applied. The stepping Mat gold and gold foil 70–75 KHN 15.0–15.1 g/cm
may be more readily accomplished and standardized by
mechanical condensers.
. Size of the Condenser Point

b . Tarnish and Corrosion Resistance
4
1. The diameter of circular points should be 0.5 mm and If the compaction is good there is very little marginal leak-
1 mm. The size of the condenser point is an important age between the gold filling and cavity walls, hence tarnish
factor in determining the effectiveness of compaction. and corrosion resistance of gold is good.
2. The force distribution to the gold depends on the area of
the point. Small condenser points are indicated in order . Biocompatibility
5
to get the desired compaction without using forces that 1. It is biocompatible, if compacted properly it produces
might damage oral structures. only a minimal pulpal response.
2. The technique, however, does involve a certain amount
c. Pressure Application of trauma to the tooth and its supporting tissues. The
1. Originally, pressure was applied by the use of a special mechanical condenser causes lesser trauma than manual
mallet. In recent years, there has been a tendency to ap- technique. Therefore the direct filling gold is not used
ply the pressure by hand. extensively.
SHORT ESSAYS
Q. 1. Degassing and compaction procedures in direct l Overheating leads to oversintering and possibly, con-
filling gold tamination from tray, instruments or flame. This results
Ans. in incomplete cohesion, brittlen of the portion being
heated and poor compaction characteristics.
Manipulation of direct filling gold comprises l Earlier gold foil was compacted entirely by impact with
a mallet. Recent techniques use a mechanical device for

1 . Desorbing or degassing
applying the pressures required to weld the foil.
2. Compaction
DESORBING OR DEGASSING COMPACTION

1. Condensers
l A heating process that removes surface gases
and ensures a clean surface is called desorbing or l The original foil condensers had a single pyramid-
degassing. shaped face, but recent instruments have a series of small

l Decontamination of the gold surface is essential in order pyramidal serrations on the face which act as swaggers.
to attain cohesion and maximal physical properties in l Each increment of gold must be carefully stepped by
the restoration. lacing the condenser point in successive adjacent posi-

l Direct filling golds may be heated by one of two methods: tions, as the compaction force is applied.
1. In bulk on a tray, heated by either a gas flame or
2. Size of the Condenser Point
electricity
2. Piece by piece, in a well-adjusted alcohol flame l The diameter of circular points should be 0.5 mm and
l In practice all but the powder gold may be desorbed, on a 1 mm. The size of the condenser point is an important
tray heated electrically. The electric annealer is main- factor in determining the effectiveness of compaction.
tained at a temperature between 340°C (650°F) and l The small condenser points are indicated in order to get
370°C (700°F). The time required varies from 5 to 20 min the desired compaction without using forces that might
depending on the temperature and the quantity of gold on damage oral structures.
the tray.
3. Pressure Application
l Problems associated with electric annealing are as
follows: l Originally, pressure was applied by the use of a special
1. Pellets may stick together, if the tray is moved. mallet. In recent years, there has been a tendency to
2. Air currents may affect the uniformity of heating. apply the pressure by hand.
3. Difficult to anneal appropriate amounts of gold. Compaction with mechanical devices like electromag-
4. Oversintering. netic or spring-loading condensers is quite rapid and is ac-
5. Greater exposure to contamination. complished with greater comfort.
6. Size selection among the pieces of desorbed gold is
limited. Q. 2. Classify direct gold restorative material and add a
l Powder gold must be heated in a flame to ensure the
note on degassing procedure in direct gold
complete burning away of the wax. Ans.
l The method of flame desorption consists of picking up
each piece individually, heating it directly in the open

flame, and placing it in the prepared cavity. The fuel for Classification
the flame may be alcohol or gas, but alcohol is preferred
as there is less danger of contamination. The alcohol 1. Foil
should be pure methanol or ethanol without colourants a. Sheet
or other additives. i. Cohesive
l Advantages of flame desorption are as follows: ii. Noncohesive
1. Ability to select a piece of gold of the desired size b. Ropes
2. Desorption of only those pieces used c. Cylinders
3. Less exposure to contamination between time of d. Laminated foil
degassing and use e. Platinized foil
4. Less danger of oversintering 2. Electrolytic precipitate (crystalline gold)
l Underheating should be avoided because it does not a. Mat gold
adequately remove the impurities and thus results in b. Mat foil (mat gold 1 gold foil)
incomplete cohesion, pitting and flaking of the surface. c. Gold–calcium alloy
3. Granulated gold (encapsulated gold powder) Type of Gold Transverse Strength

Mat gold 161–169 MPa (23 000–24 100 psi)
For degassing procedure refer to answer of Short Essays Q. 1.
Powdered gold 155–190 Mpa (22 200–27 100 psi)
Q. 3. Properties and uses of direct gold restorative Gold foil 265–296 Mpa (37 900–42 300 psi)
materials
Ans. The physical properties of direct gold restorative 2. Hardness: Indicates the overall quality of compacted gold.
materials are as follows: Low hardness probably indicates the presence of porosity.
3. Density: Apparent density is measured due to the voids.

1. Strength (Table 17.2)
. Tarnish and corrosion resistance: If the compaction
4
TABLE 17.2 Physical Properties of Compacted Gold is good there is very little marginal leakage between the
Type of Gold Hardness Density gold filling and cavity walls, hence tarnish and corrosion
resistance of gold is good.
Mat gold 52–60 KHN 14.3–14.7 g/cm
Powdered gold 55–64 KHN 14.4–14.9 g/cm 5. Biocompatibility
Gold foil 69 KHN 15.8–15.9 g/cm l It is biocompatible, if compacted properly it produces
Mat gold and gold foil 70–75 KHN 15.0–15.1 g/cm only a minimal pulpal response.
l The technique, however, does involve a certain amount of
trauma to the tooth and its supporting tissues. The mechani-

cal condenser causes lesser trauma than manual technique.
l Transverse or bending strength is most representative of
Therefore the direct filling gold is not used extensively.
clinical applications, as it is a reflection of all three
types of stress—compressive, tensile and shear. 6. Direct filling gold is used for
l Transverse strength is a measure of cohesion in direct a. pits and small class I restorations,
filling golds. The failure occurs from tensile stress, due b. repair of casting margins and
to incomplete cohesion. c. class II and class V restorations.
SHORT NOTES
Q. 2. Annealing of direct filling gold
Q. 1. Types of direct gold
Ans.
Ans. Various types of direct filling gold that are cur-
rently available may be divided into three categories as l Controlled heating and cooling process designed to
follows: produce desired properties in a metal is known as
annealing.
1 . Foil (fibrous gold)
l The annealing process usually is intended to soften met-
2. Electrolytic precipitate (crystalline gold)
als, to increase their plastic deformation potential, to
3. Granular gold (also called powdered gold)
stabilize shape and to increase machinability.
They are further classified as follows: l The process of desorption or degassing is commonly
1. Foil called annealing or heat treatment.

a. Sheet l The objective is to remove adsorbed ammonia gas and
i. Cohesive other surface impurities.

ii. Noncohesive
b. Ropes Q. 3. Cold welding
c. Cylinders Ans.
d. Laminated foil
e. Platinized foil l The process of plastically deforming a metal usually at
2. Electrolytic precipitate (crystalline gold) room temperature accompanied by strain hardening is
a. Mat gold known as cold welding.
b. Mat foil (mat gold 1 gold foil) l Cold welding refers to the process of forming atomic
c. Gold–calcium alloy bonds between pellets, segments, or layers as a result of

3. Granulated gold (encapsulated gold powder) condensation.
Q. 4. Mat gold l Gold is malleable, beating of gold to a submicroscopic

thickness of 15 µm or 25 µm is called gold foil.
Ans. l It is the oldest of all products available.
l It is available as sheets.
l Mat gold is an electrolytically precipitated crystalline
l Gold foil is supplied as flat square sheets of varying
form that is sandwiched between sheets of gold foil and
formed into strips which can be cut by the dentist into thickness.
the desired size.
No. 4 thickness Wt. 4 grains (0.259 g) 0.51 µm thick
l This form is often preferred for its ease in building
up the internal bulk of the restoration because it can No. 3 thickness Wt. 3 grains (0.194 g) 0.38 µm thick
be more easily compacted within, and adapted to, the
retentive portions of the prepared cavity. l No. 3 gold foil is used in the manufacture of electrolytic
l Because it is loosely packed, it is friable and contains and powder products.
numerous void spaces between particles. Therefore it is l Ropes and cylinders made from no. 4 foil that has been
generally not recommended for the external surface of carbonized or corrugated are nowadays available in
the restoration. preformed shapes.
l The loosely packed crystalline form of the mat powder l Platinized foil is a laminated foil in which pure platinum foil
with its large surface area does not permit easy welding is sandwiched between two sheets of pure gold foil. The lay-
into a solid mass as does gold foil. Therefore there is a ers of platinum and gold are bonded together by a cladding
greater tendency for voids that may be seen as pits to process during the rolling operation. The object of adding
form if mat gold is used on the surface of the restoration. platinum to the gold foil is to increase the hardness of the
restoration. This product is available only in no. 4 sheet form.
Q. 5. Platinised foil
Q. 8. Cohesive and noncohesive gold
Ans.
Ans.
l This form of gold foil is a laminated structure that can
be produced in one of two ways: l The manufacturer supplies the gold essentially free of
1. Two sheets of no. 4 pure gold foil and a layer of surface contaminants, and is inherently cohesive. This
pure platinum foil sandwiched between them can be type of gold is known as cohesive gold foil.
hammered until the thickness of a no. 4 sheet is l The manufacturer can subject the foil to a volatile agent
obtained. such as ammonia, which is adsorbed on the surface of

2. Layers of platinum and gold can be bonded together the gold and acts as a protective film to prevent absorp-
by a cladding process during the rolling operation tion of nonvolatile materials and premature cohesion of
and thus the sandwich is already welded together pellets in their container. The ammonia-treated foil is
before the hammering procedure begins. This prod- called noncohesive foil.
uct is available only in no. 4 sheet form.
l The objective of adding platinum to the gold foil is to Q. 9. Electrolytic gold
increase the hardness and wear resistance of restorations. Ans.
Q. 6. Degassing l Another form of gold for direct filling is crystalline gold
Ans. powder formed by electrolytic precipitation. By sinter-
ing the powder is formed into shapes or strips.
l The process of removing gases or other impurities from l Electrolytic precipitate can be available as mat, mat foil
a solid or a liquid is known as degassing. and alloyed.

l The primary purpose of desorption degassing is to remove
surface impurities.
Mat Gold
l Decontamination of the gold surface is essential in order
to attain cohesion and maximal physical properties in l Mat gold is crystalline, electrolytically precipitated
the restoration. gold, formed into strips. These strips can be cut by the
l Direct filling gold may be heated by one of two methods dentist in to the desired size.
as follows: l Mat gold is preferred because it is easy to buildup the
1. In bulk on a tray, heated by either a gas flame or internal bulk of the restoration.
electricity
2. Piece by piece, in a well-adjusted alcohol flame
Mat Foil
Q. 7. Gold foil l Mat foil is a sandwich of electrolytic precipitated gold
Ans. powder between sheets of no. 3 gold foil.
l The sandwich is sintered and cut into strips of differing a. Karat

widths. The dentist can then cut these to the desired
lengths. This type is no longer marketed. It is the number of parts of pure gold in 24 parts of alloys.
The term karat is rarely used to describe gold content in
current alloys.
Alloyed Electrolytic Precipitate
l An alloy of gold and calcium (0.1–0.5% by wt) is called Example:
electroly. For greater ease of handling, the alloy is sand-
wiched between two layers of gold foil. 1 . 24 karat gold is pure gold.
l Calcium produces stronger restorations. Alloying with
2. 22 karat gold is 22 parts of pure gold and remaining
calcium alters the crystalline structure, so that the hard- 2 parts of other metal.
ness and strength will be increased.
b. Fineness
Q. 10. Karat and fineness of gold
Fineness of a gold alloy is the parts per thousand of pure
Ans. Traditionally the gold content of dental casting alloys gold. Pure gold is 1000 fine. Thus, if three-fourth of the
have been referred to in terms of gold alloy is pure gold, it is said to be 750 fine.
a . karat and
b. fineness.
Topic 18
Dental Ceramics
Q. 1. Firing of porcelain
Medium Bisque Stage
Ans. The process of firing carried out for fusing the porce-
l There is cohesion of powder particles.
lain is known as sintering.
l It is still porous, lacks translucency and high glaze.
l After condensation the compacted mass supported l There is definite shrinkage.
by the matrix should be placed on a fire clay tray and

inserted into the muffle of the ceramic or porcelain High Bisque Stage
furnace.
l The condensed mass is gradually heated by first placing l The shrinkage is complete with maximum volume con-
it in front of the muffle of a preheated furnace and later traction and the mass exhibits smooth surface.
inserting into the furnace. l Slight porosity may be seen. The body does not appear
l Stages of firing: During firing the porcelain goes through to be glazed.

different stages known as bisque or biscuit stages. The l During firing the porcelain shrinks 30–40% by volume.
temperature at which each stage occurs depends on the As shrinkage is anticipated the porcelain is built up of a
type of porcelain used. larger size before firing.
l During firing, there is partial fusion of the particles at
their point of contact. As the temperature is raised the

Low Bisque Stage fused glass gradually flows to fill up air spaces. As the
l In this stage as the temperature increases gradually sur- fused mass is viscous all the air cannot escape and some
face of the particles begin to soften and loose particles get trapped, giving rise to voids or porosity. Vacuum
just begin to join. offset firing is done to reduce porosity in porcelain.
l The material becomes rigid and is very porous. l At any stage the work can be removed, cooled and addi-
l Particles lack cohesion and do not have translucency tions can be made. Less the number of firings, higher is
and glaze. the strength and better the aesthetics. Too many firings
l There is very little shrinkage. give a lifeless, over translucent porcelain.
Q. 2. Properties and methods of strengthening dental Introduction of Residual Compressive

ceramics Stresses
Ans. Some of the techniques for introducing residual compres-
sive stresses are
1. ion exchange or chemical tempering,
PROPERTIES OF FUSED PORCELAIN 2. thermal tempering and
3. thermal expansion coefficient mismatch.
1. Strength: Porcelain is a material having good strength.
However, it is brittle and tends to fracture. The strength
of dental porcelain is usually measured in terms of its Ion Exchange
flexure strength or modulus of rupture. l Here the porcelain article is immersed in molten KNO3
a. Flexure strength: It is a combination of compres- solution for few minutes (20–30 min) the smaller Na1
sive, tensile, as well as shear strength. Glazed ions are exchanged by the K1 ions which are 30% big-
porcelain (141.1 MPa) is stronger than ground ger in size.
porcelain (75.8 MPa). l This procedure cannot be applied in ceramics that do
b. Compressive strength: Porcelains have good com- not contain Na1 ions.
pressive strength 331 MPa (48 000 psi) and hardness.
c. Low tensile, shear and flexure strength
2. Modulus of elasticity: Porcelain has a high modulus of Thermal Tempering
elasticity 69 GPa (10 3 l06 psi). l Sudden cooling of ceramic article results in solidification
3. Surface hardness: Porcelain is much harder than natu- of outer layer first which surrounds the soft molten core.
ral teeth (460 KHN). l Rapid cooling causes contraction introducing residual
4. Wear resistance: Porcelain is more resistant to wear compression stresses.
than natural teeth. Thus, it should not be placed oppo-
site natural teeth.
5. Thermal properties: Porcelain has low thermal con- Interruption of Crack Propagation
ductivity. l Another method of strengthening glass ceramics is to
Coefficient of thermal expansion: It is close to that of reinforce it with a dispersed phase of a different mate-
natural teeth (6.4–7.8 3 1026/°C). rial that is capable of hindering a crack from propagat-
6. Specific gravity: The true specific gravity of porcelain ing through the material.
is 2.242. The specific gravity of fired porcelain is usu- l Two different types of dispersions used to interrupt
ally less, because of the presence of air voids. It varies crack propagation are as follows:
from 2.2 to 2.3.
7. Dimensional stability: Porcelain is dimensionally sta- . Dispersion strengthening: By absorption of energy
1
ble after firing. by the dispersed tough particle from the crack and thus
8. Chemical stability: It is insoluble and impermeable to depleting its driving force for propagation.
oral fluids, i.e. it is chemically inert. For example: Alumina core porcelain with 90–95%
9. Aesthetic properties: The aesthetic qualities of porce- alumina, aluminous porcelain with 40–50% alumina
lain are excellent. It is able to match adjacent tooth
structure in translucence, colour and intensity. In addi- . Transformation toughening: By change of crystal
2
tion, attempts have also been made to match the fluo- structure under stress to absorb energy from the crack.
rescent property of natural teeth when placed under For example: Introduction of partially stabilized zirco-
ultraviolet light. nia into ceramics at high temperatures.
10. Biocompatibility: It is compatible with the oral tissues.
Q. 3. Classification and uses of dental porcelain
METHODS OF STRENGTHENING Ans. Classification of dental porcelain is as follows:
PORCELAIN 1. According to their firing temperature
Strengthening brittle materials is done by the following: a. High fusing: 1290–1370°C
1. Introduction of residual compressive stresses into the b. Medium fusing: 1095–1260°C
surface of the material c. Low fusing: 870–1065°C
2. Interruption of crack propagation through the material d. Ultra low fusing: , 850°C
2. According to use body and enamel porcelain is then condensed over it

a. Construction of artificial teeth and fired in the usual manner.
b. Fabrication of jacket crowns and inlays l When compared to metal ceramic crown aluminous
c. As veneers over cast metal restorations porcelain crowns are considered to be more
3. According to the method of firing aesthetic.
a. Air fired, i.e. at atmospheric pressure l Their strength is almost twice that of conventional
b. Vacuum fired, i.e. at reduced pressure porcelains, and is sufficient for use on anterior
4. According to application teeth. However for posterior teeth it is considered
a. Core porcelain inadequate.
b. Dentine or body porcelain l They are less expensive than metal ceramic crowns
c. Enamel porcelain and require less removal of tooth structure during

d. Glazes tooth preparation.
5. According to composition
a. Feldspathic Q. 5. Consideration for metal ceramics
b. Leucite-based Ans.
c. Lithia-based
d. Aluminous l Porcelains lack tensile and shear strength, but can resist
e. Pure alumina, silica, zirconia porcelains etc. only compressive stresses. To overcome this disadvan-
Uses of dental porcelain are as follows: tage the porcelain is fused directly to metal.
1. Single unit crowns l The bond between the porcelain and metal should be
a. Porcelain jacket crown (PJC) strong in order to avoid leakage between the two in the
b. Metal ceramic crown or porcelain fused to metal interface.
(PFM) l When porcelain is bonded to an alloy substructure it has
c. Castable glass ceramic crowns the advantage of a good fit of metal casting and aesthet-
2. Porcelain veneers for crowns and bridges ics of porcelain.
3. Artificial teeth l The alloys used for bonding with porcelain should have
4. Inlays and onlays the following properties:

5. Ceramic brackets used in orthodontia 1. Coefficient of thermal expansion of alloy should be
6. Implants, bioglasses, etc. close or nearly the same as that of porcelain.
2. The fusion temperature of the alloy should be higher
Q. 4. Aluminous porcelain than that of porcelain so that it does not melt or sag
Ans. at the firing temperature.
3. It should have a high modulus of elasticity to prevent
flexing of metal framework and hence avoiding frac-
ture of porcelain.
Aluminous Porcelains 4. It should be capable of forming a bond with porce-
l An alumina-reinforced porcelain was developed by lain. The composition should provide constituents
McLean in 1965. for oxide formation, which provide a chemical bond
l Its composition is similar to that of conventional porce- with porcelain. The alloy should be capable of wet-
lain except for the increased alumina content (40–50%). ting while porcelain is applied to it and hence aid in
The dispersed alumina crystals strengthen the porcelain mechanical bonding.
by interruption of crack propagation. The crack cannot 5. It should not contain copper or silver as they stain in
penetrate the alumina crystals as easily as it can the glass. the interface and discolour porcelain.
l Aluminous porcelain is used in the construction of the 6. It should have a high proportional limit, to avoid
core layer of the porcelain jacket crown. Conventional excess stress on the porcelain, which is brittle.
SHORT ANSWERS
Q. 1. Uses of dental porcelain b. Metal ceramic crown or porcelain fused to metal
Ans. (PFM)
c. Castable glass ceramic crowns
Uses of dental porcelain are as follows: 2. Porcelain veneers for crowns and bridges
1. Single unit crowns 3. Artificial teeth
a. Porcelain jacket crown (PJC) 4. Inlays and onlays
5 . Ceramic brackets used in orthodontia Ans.

6. Implants, bioglasses, etc
l Feldspar is a naturally occurring mineral and is a double
Q. 2. Composition of porcelain silicate of potassium and aluminium (K2O·Al2O36SiO2).
l It acts as a flux, matrix and surface glaze.
Or, l When it is mixed with metal oxides and fired at high
Composition of dental porcelain temperatures it can form a glass phase that is able to
Ans. soften and flow slightly. Because of this the porcelain
powder particles coalesce together.
Composition of dental porcelain is listed in Table 18.1. l The process by which the particles coalesce is called
sintering.
l It is the basic glass former. During firing feldspar fuses
TABLE 18.1 Composition of Porcelain
and acts as a matrix and binds silica and kaolin.
Feldspar 60–80 Basic glass former Q. 6. Castable ceramics or advantages of castable ceramics
Kaolin 3–5 Binder Ans. Advantages of castable ceramics or dicor glass ce-
ramic are as follows:
Quartz 15–25 Filler
1. Ease of fabrication
Aluminium 8–20 Glass former 2. Improved aesthetics
Boric oxide 2–7 Glass former and 3. Minimal processing shrinkage
flux 4. Good marginal fit
Oxides of Na, K 9–15 Fluxes (glass 5. Moderately high flexural strength
and Ca modifiers) 6. Low thermal expansion equal to that of tooth structure
Metallic pigments ,1 Colour matching 7. Minimal abrasiveness to tooth enamel
Q. 7. Types of glazes used in dental porcelain

Q. 3. Advances in dental ceramics Ans.
Ans. Recent advances in dental porcelains are as follows:
Types of glaze used in dental porcelain are as follows:
Three jacket crown porcelains have been introduced. 1. Overglaze
2. Self-glaze
1 . Magnesia core
2. Extrusion-moulded or injection-moulded aluminous Overglaze
core material l Overglazes are ceramic powders containing more glass
3. Fluoride–mica glass or castable ceramics modifiers with lower fusion temperatures.
l It may be applied to porcelain restoration after it has
Q. 4. Uses of glazing in dental porcelain
been fired. It imparts an impervious glossy surface to
Ans. In order to remove the surface cracks and improve the the restoration.
flexure strength following glazing methods are used: l The coefficient of thermal expansion of the overglaze
1. Autoglazing or self-glazing should be slightly lower than that of body porcelain.
2. Add on or extended glazing
Self-Glaze
Uses of Glazing l All the constituents of porcelain frit are completely
1. Porcelains are glazed in order to give a smooth and melted to form a single phase glass. Then the porcelain
glossy surface and to enhance aesthetics and help in is said to be self-glazed.
hygiene. l Its chemical durability is better than overglaze due to
2. The glaze powders are mixed with liquid, applied over higher fusion temperature.
the smoothened crown and fired at temperature lower
than that of body porcelain. Q. 8. Dicor
3. Strength of glazed porcelain is much more when com- Ans.
pared to unglazed porcelain. If the glaze is removed by
grinding the transverse strength reduces to half. 1. The first commercially available castable ceramic mate-
4. The glaze is also effective in reducing crack propagation. rial for dental use is Dicor.
2. Dicor was developed by corning glass works and mar-
Q. 5. Role of feldspar in porcelain keted by Dentsply International. Hence the name Dicor.
3. Dicor is a castable glass that is formed into an inlay, Q. 10. Aluminous porcelain
facial veneer, or full-crown restoration by a lost-wax
Ans.
casting process similar to that employed for metals.
4. It is not used nowadays because of 1. Aluminous porcelain is a ceramic composed of a glass
a. very low tensile strength and tends to fracture easily matrix phase and at least 35 vol% Al2O3.
in stress acting areas and 2. It gives strength and aesthetics to ceramic jacket
b. more amount of tooth material is removed as thick crown.
crowns are required.
Topic 19
Denture Base Resins

LONG ESSAYS
Q. 1. Classify denture base materials. Write composi- Liquid
tion and actions of each constitutent of heat-cured
acrylic. Add a note on porosity and its causes in dental Methyl methacrylate Plasticizes the polymer
acrylic resins. Dibutyl phthalate Plasticizer
Ans. Denture base materials are classified as follows: Glycol dimethacrylate (1–2%) Crosslinking agent
Hydroquinone (0.006%) Inhibitor

Denture Base Materials
Metallic (e.g. cobalt Nonmetallic (e.g. acrylic resins)
chromium)
Porosity
Gold alloys Vinyl resins 1 . Porosity is a processing error in acrylic resins.
2. Porosity may be of two types as follows:
Aluminium
a. Internal porosity
Stainless steel b. External porosity
3. Internal porosity
Denture Base Resins a. Is the form of voids or bubbles within the mass of the
polymerized acrylic.
Temporary (e.g. self-cure Permanent (e.g. heat-cured denture
acrylics) resins) b. It is usually not present on the surface of the denture.
It is confined to the thick portions of the denture base
Shellac base plate Light-cured resins
and it may not occur uniformly.
Base plate wax Pour type resins c. Mainly caused due to the vaporization of monomer
Injection-moulded resins when the temperature of the resin increases above
the boiling point of monomer (100.8°C) or very low
Metallic bases
molecular weight polymers.
d. Internal porosity can be avoided by using long and
COMPOSITION low temperature curing cycle.
e. It can be avoided by curing the dentures with excessive
Powder thickness using long, low temperature curing cycle.
4. External porosity
Poly(methyl methacrylate) and other (5%) Polymer powder
copolymers
a. It can occur due to two reasons as follows:
i. Lack of homogeneity
Benzoyl peroxide Initiator
ii. Lack of adequate pressure
Compounds of mercuric sulphide, Dyes
cadmium sulphide i. Lack of Homogeneity
Zinc or titanium oxide Opacifiers 1. If the dough is not homogenous at the time of polymer-
Dibutyl phthalate Plasticizer
ization the portions containing more monomer will
shrink more than the adjacent area.
Dyed organic filler and inorganic For aesthetics 2. This localized shrinkage results in voids. The resin ap-
particles like glass fibres or beads
pears white.
3. It can be avoided by using proper powder liquid ratio 2. Aesthetics of poly(methyl methacrylate) is acceptable.
and mixing it well. It is a clear transparent resin which can be pigmented
4. The mix is more homogenous in the dough stage, so or coloured easily to duplicate the oral tissue.
packing should be done in the dough stage. 3. The polymer has a density of 1.19 gm/cm3.
4. These materials are typically low in strength. They
ii. Lack of Adequate Pressure have adequate compressive and tensile strength for
1. Lack of pressure during polymerization or inadequate complete or partial denture applications.
amount of dough in the mould during final closure
Compressive strength 75 MPa
causes bubbles which are not spherical. The resin is
lighter in colour. Tensile strength 52 MPa
2. It can be avoided by using the required amount of
dough. Check for excess or flash during trail closure. 5. Impact strength is a measure of energy absorbed by a
Flash indicates adequate material. material when it is broken by a sudden blow. Ideally
denture base resins should have high impact strength
When porosity is present on the surface, to prevent breakage when it is accidentally dropped.
a . it makes the appearance of denture base unsightly. Addition of plasticizers increases the impact strength.
b. proper cleaning of the denture is not possible, so the 6. Acrylic resins are materials having low hardness. They
denture hygiene and thus, the oral hygiene suffers. can be easily scratched and abraded.
c. it weakens the denture base and the pores and areas of Heat-cured acrylic resin 18–20 KHN
stress concentration, thus, the denture warps as the
stresses relax. Self-cured acrylic resin 16–18 KHN
Q. 2. What are the denture base resins? Describe prop- 7. They have sufficient modulus of elasticity or stiffness
erties and fabrication techniques of heat-cured acrylic (2400 MPa) for use in complete and partial dentures.
denture base resins. 8. A well-processed acrylic resin denture has good di-
mensional stability. The processing shrinkage is bal-
Ans. Acrylic resins are derivatives of ethylene and contain anced by the expansion due to water sorption.
a vinyl group in their structural formula. The acrylic resins 9. Acrylic resins shrink during processing due to:
used in dentistry are the esters of a. thermal shrinkage on cooling and
b. polymerization shrinkage.
i. acrylic acid: CH25CHCOOH and
ii. methacrylic acid: CH25C(CH3)COOH.
Polymerization Shrinkage
95% of the dentures made today use one of the acrylic resins.
During polymerization, the density of the monomer changes
from 0.94 g/mL to 1.19 g/mL. This results in shrinkage in
PROPERTIES OF DENTURE RESINS the volume of monomer polymer dough.
The fit of the denture is not affected because the shrink-
Properties of Methyl Methacrylate Monomer age is uniformly distributed over all surfaces of the denture.
1. It is clear, transparent, volatile liquid at room tempera- The actual linear shrinkage observed is low.
ture.
Volume shrinkage 8%
2. It has a characteristic sweetish odour.
3. The physical properties of monomer are as follows: Linear shrinkage 0.53%
Melting point 48°C 10. Acrylic resins exhibit water sorption, they absorb
Boiling point 100°C water (0.6 mg/cm2) and expand. This partially com-
Density 0.945 g/mL at
pensates for its processing shrinkage. This process is
20°C reversible. Thus, on drying they lose water and
shrink.
Heat of polymerization 12.9 Kcal/mol
11. Acrylic is virtually insoluble in water and oral fluids.
Volume shrinkage during polymerization 21% They are soluble in ketones, esters, and aromatic and
chlorinated hydrocarbons, e.g. chloroform and ace-
tone. Alcohol causes crazing in some resins.
Properties of Poly(Methyl Methacrylate) 12. Thermal properties
1. The taste and odour of completely polymerized acrylic 1. Poly(methyl methacrylate) is chemically stable to
resin is tasteless and odourless. Poorly made dentures heat up to a point. It softens at 125°C. However,
with a high amount of porosity can absorb food and above this temperature, i.e. between 125°C and
bacteria, resulting in an unpleasant taste and odour. 200°C it begins to depolymerize.
2. Thermal conducitivity: They are poor conductors of injecting the resin under pressure. A sprue hole and a
heat and electricity. This is undesirable because pa- vent hold are formed in the gypsum mould.
tients wearing acrylic complete dentures often com- 3 . The soft resin is contained in the injector and is forced
plain that they cannot feel the temperature of food or into the mould space as needed. It is kept under pressure
liquids they ingest, thus reducing the pleasure. until it has hardened.
3. Coefficient of thermal expansion: These materials 4. No trial closures are required with this technique. There
have a high coefficient of thermal expansion is no difference in accuracy or physical properties as
(81 3 1026/°C). Addition of fillers reduces the co- compared to compression moulding technique.
efficient of expansion.
1 3. Heat-cured acrylic resins have good colour stability. Advantages
14. Completely polymerized acrylic resins are biocompat- 1. Dimensional accuracy
ible. True allergic reactions to acrylic resins are rarely 2. Low free monomer content
seen in the oral cavity. A true allergy to acrylic resin 3. Good impact strength
can be recognized by a patch test.
15. During the polymerization process the amount of re- Disadvantages
sidual monomer decreases first rapidly and then later 1. High cost of equipment
more slowly. In heat-cured acrylics before the start of 2. Difficult mould design problems
curing the residual monomer is 26.2%. In 1 h at 70°C 3. Less craze resistance
it decreases to 6.6% and at 100°C it is 0.29%. 4. Special flask is required
16. The adhesion of acrylic to metal and porcelain is poor,
and mechanical retention is required. Adhesion to plas-
tic denture teeth is good, i.e. chemical adhesion. c. Pour and Cure Fluid Resin Technique
17. Shelf life varies considerably. Acrylic resins dispensed as 1. This is a chemically activated resin similar in composi-
powder/liquid have the best shelf life. The gel type has a tion as cold cure denture base resin.
lower shelf life and has to be stored in a refrigerator. 2. On mixing it forms a thin dough which can be poured in
to mould space. Prepared in a special flask.
3. It is kept in a pressure chamber for 30–60 min for
Fabrication Techniques of Heat-Cured Acrylic
polymerization.
Denture Base Resins 4. Very minimum polishing is required and can be deliv-
Complete and partial dentures are usually fabricated by one ered in a short time to patient.
of the following techniques:
a. Compression moulding technique Advantages
b. Injection moulding technique 1. Simple and quick technique
c. Fluid resin technique 2. Minimum finishing and polishing
d. Visible light curing technique
Disadvantages
1. Large polymerization shrinkage
a. Compression Moulding Technique 2. Air entrapment
1. This is the most commonly used technique in the fabri- 3. Shifting of teeth in soft investment used and poor bond-
cation of heat activated acrylic resin dentures. ing of acrylic teeth to denture base
2. Steps involved in this technique are as follows: 4. High residual monomer and Lower mechanical prop-
a. Preparation of the waxed denture pattern erties
b. Preparation of the split mould
c. Application of separating medium d. Light Cure Denture Base Technique
d. Mixing of powder and liquid
e. Packing 1. This is a single component system supplied as sheet and
f. Curing rope forms in light proof pouches.
g. Cooling 2. Its composition is similar to composite resin.
h. Deflasking, finishing and polishing 3. A visible light of 468 nm wavelength is used as an acti-
vator and complete denture is cured in a light chamber
for 10 min.
b. Injection Moulding Technique
1. A special thermoplastic resin is available for this Disadvantages
technique. 1. Method is more complicated
2. This technique requires special equipment and special 2. Expensive
thermoplastic material. The mould space is filled by 3. No improvement of properties
Q. 3. Write in detail the composition, properties and uses the chamber to provide uniform exposure to the light
of denture base resins and add a note on light-activated source.
denture base resins.
Disadvantages
Ans.
1. The method is more complicated,
2. expensive and
3. no improvement of properties.
COMPOSITION
Q. 4. What are soft liners? Write the composition, prop-
Liquid erties and uses of tissue conditioners.
Methyl methacrylate Plasticizes the polymer Ans.

Glycol dimethacrylate (1–2%) Crosslinking agent SOFT OR RESILIENT DENTURE LINERS
Hydroquinone (0.006%) Inhibitor-prevents setting
Soft liners can be said to be of two types as follows:
1. Temporary soft liners (also known as tissue conditioners)
Powder 2. Permanent soft liners
a. Plasticized acrylic resin
Poly(methyl methacrylate) and other Polymer b. Vinyl resins
copolymers powder (5%) c. Silicone rubbers
Benzoyl peroxide Initiator 3. The purpose of the permanent soft liner is to protect
Compounds of mercuric sulphide, cadmium Dyes the soft tissue by acting as a cushion. They are used
sulphide when there is irritation of the mucosa, in areas of se-
vere undercut and congenital or acquired defects of
Zinc or titanium oxide Opacifiers
palate.
Dyed organic filler and inorganic particles like For aesthetics

glass fibres or beads
TISSUE CONDITIONERS
Tissue conditioners or temporary soft liners are materials
For properties of denture resins refer to above Long whose useful function is very short, generally a matter of a
Essay Q. 2 of the same topic. few days.
LIGHT-ACTIVATED DENTURE BASE RESINS Uses

1. They consist of 1. Relining of ill-fitting denture with tissue conditioner
a. a urethane dimethacrylate matrix with an acrylic allows the tissues to return to normal, at which a new
copolymer, denture can be made.
b. microfine silica fillers, and 2. As a impression material.
c. a camphorquinone-amine photo-initiator system
One such product is known as VLC triad. Composition
2. It is supplied in premixed sheets having a clay-like con- These are highly plasticized acrylic resins, supplied as a
sistency. It is provided in opaque light tight packages to powder and a liquid powder poly(ethyl methacrylate) or
avoid premature polymerization. one of its copolymers.
3. The denture base material is adapted to the cast while it Liquid aromatic ester (butyl phthalate, butyl glycolate)
is in a plastic state. The denture base can be polymer- in ethanol or an alcohol of high molecular weight.
ized without teeth and used as baseplate. The properties that make tissue conditioners effective
4. The teeth are added to the base with additional material are as follows:
and the anatomy is sculptured while the material is a. Viscous properties, which allow excellent adaptation to
still soft. the irritated denture-bearing mucosa over a period of
5. It is polymerized in a light chamber (curing unit) with several days and brings it back to health.
blue light of 400–500 nm from high intensity quartz— b. Elastic behaviour which cushions the tissues from the
halogen bulbs. The denture is rotated continuously in forces of mastication and bruxism.
Q. 5. What is copolymerization and name its advantages? –M – M – M – M – M - . . . - M – M – M – M - M –

Y Y
Ans.
Y Y
1. In addition polymerization reactions that have been Y Y
described, the macromolecule was formed by polymer- Y Y
ization of a single type of structural unit. . .
2. In order to improve the physical properties, it is often . .
advantageous to use two or more chemically different iii. Block type: In a block copolymer, n-identical monomer
monomers as starting materials. The polymers thus units occur in relatively long sequences along the main
formed may contain units of all the monomers origi- polymer chain.
nally present. Such a polymer is called a copolymer and . . . - M – M – M – M – . . . M – M – Y – Y – Y – . . .
its process of formation is known as copolymerization. -Y – Y – M – M - . . .
Types of Copolymers Application of Copolymerization

There are three different types of copolymers as follows: Copolymerization is used to alter the physical properties
i. Random type: In random type of copolymer the differ- of resins. Many useful resins are manufactured by copoly-
ent monomers are randomly distributed along the chain, merization.
such as 1. Small amounts of ethyl acrylate may be copolymerized
–M –M – M – M –Y– M – Y – M –Y –Y – M – with methyl methacrylate to alter the flexibility.
ii. Graft type: In graft copolymers, sequences of one of the 2. Block and graft polymers show improved impact strength.
monomers are grafted on to a backbone of the second In small amounts they modify the adhesive properties of
monomer species. resins as well as their surface characteristics.
SHORT ESSAYS
Q. 1. Denture reliners Advantages
Or, 1 . Less distortion due to room temperature curing.
2. These materials are used for relining resin dentures di-
Denture relining materials rectly in the mouth.
Ans.
Hard Liners
1. Denture reliners are polymeric material placed on the
tissue-contacting surface of a denture base to absorb 1 . These are same as that of denture base materials.
some of the energy produced by masticatory impact and 2. The materials used are either cold cure or heat-cured
to act as a type of shock absorber between the occlusal acrylics with compositions similar to denture base
surfaces of a denture and the underlying oral tissues. resins.
2. Reliners may be classified as follows: 3. They should chemically bond to old denture base and
a. Hard or soft retain dimensional stability.
b. Heat-cured or self-cured 4. Cold cure acrylic is usually preferred due to its (a)
c. Temporary or permanent simple technique, (b) less distortion and warpage and
d. Resin based or silicone based (c) adequate strength as a liner.
Heat-Cured Acrylic Resin Soft or Resilient Denture Liners

New resin is cured against the old denture by compression l Soft liners are of two types:
moulding technique. A low curing temperature is necessary 1. Temporary soft liners (also known as tissue condi-
for the relining process to avoid distortion of the denture. tioners)
2. Permanent soft liners, e.g. plasticized acrylic resin,
vinyl resins, silicone rubbers
Self-Cured Resins l The purpose of the permanent soft liner is to protect the
Self-cured resins may be used instead of heat-cured. soft tissue by acting as a cushion.
l They are used when there is irritation of the mucosa, Q. 3. Tissue conditioners
in areas of severe undercut and congenital or acquired
defects of palate. Ans.
l Tissue conditioners or short term resilient soft liners are

Q. 2. Separating medium
chemically activated polymeric materials that tend to
Ans. degrade more rapidly than heat activated resins.
l They are supplied as chemically cured, powder of poly-
methylmethacrylates or its higher copolymers. The

Applications of Separating Medium liquid has large molecular sized plasticizer like some
As the resin must not contact the gypsum surface while cur- aromatic esters such as butyl phthalate, butyl glycolate
ing a separating medium is used as follows: or dibutyl phthalates of about 50–80% in alcohol or
1. To prevent water from the mould entering into the ethanol.
l They can be formed directly in the patient’s mouth.
acrylic resin which may affect the rate of polymeriza-
l Disadvantages with tissue conditioners are as follows:
tion and colour resulting in crazing.
2. To prevent monomer penetrating into the mould mate- 1. Poor mechanical bonding
rial, causing plaster to adhere to the acrylic resin and 2. Dimensional instability
producing a rough surface. 3. No permanent resilience
3. Application of separation media helps in easier retrieval 4. Difficult to polish and poor hygiene
of the denture from the mould. 5. Decrease of strength of denture due to preparation of
relief space.
Various types of separating media used are as follows: l A new technique for soft liners has been recently
1. Tin foil evolved where a viscous silicone liquid is filled in an
2. Cellulose lacquers envelope of thin polyethylene film. This liner has an
3. Solution of alginate compounds advantage of continuous adaptation to the denture base.
4. Calcium oleate
5. Soft soaps Q. 4. Mixing stages of acrylic resins
6. Sodium silicate
Ans.
7. Starches
l Polymer powder is mixed with monomer liquid in the
Tin Foil ratio of 3:1 by weight or 2.5:1 by volume.
l The powder dissolves in the liquid and forms a dough
Tin foil was the material used earlier and was very effec- which is convenient for packing the mould under
tive. Its manipulation is time consuming and difficult. It has compression.
been largely replaced by other separating media known as l Physically five stages of mixing can be observed:
tin foil substitutes. 1. Wet–Sandy stage: The polymer gradually settles in to
the monomer, the liquid wets the powder particles and
the mix appears as fluid incoherent mass like wet sand.
Sodium Alginate Solution
2. Sticky stage: The monomer dissolves the polymer by
This is the most popular separating medium. It is water penetrating into it. The mix becomes sticky and
soluble. It reacts with the calcium of the plaster or stone to stringy like a cobweb if the mass is touched or held
form a film of insoluble calcium alginate. between the fingers.
Composition: Two percent sodium alginate in water, 3. Dough or gel stage: The monomer diffuses into the
glycerine, alcohol, sodium phosphate and preservatives polymer, the powder further dissolves forming a
homogenous soft dough like mass. The mass is plas-
tic, nonsticky and ready to be packed into the mould
Precautions to be Taken
at this stage.
1. Waxes or oil remaining on the mould surface will inter- 4. Rubbery stage: The monomer disappears by further
fere with the action of the separating medium. penetration into the polymer and evaporation.
2. Mould should be warm, not hot. Continuity of the film The mass is cohesive, rubber like and nonplastic in
will break if the mould is steaming hot. this stage. Packing should be accomplished before
3. Coating of medium left on the teeth will prevent bonding this stage.
of teeth with denture base. 5. Stiff stage: The mass becomes stiff.
Q. 5. Curing cycle of denture base resins

Application
Ans.
Separating media is applied using a brush, coating only the
plaster surfaces, and not the acrylic teeth. One or two coats l Curing cycle or polymerization cycle is the technical
may be applied. name for the heating process employed to control the
initial propagation of polymerization in the denture Q. 6. Advantages of acrylic resin as denture base material
mould.
Ans. Advantages of acrylic resin as denture base material
l The selection of curing cycle depends on the thickness
are as follows:
of the resin.
1. Less porosity of material
l Following are the recommended curing cycles:
2. Higher molecular weight
1. Heating the flask in water at 60–70°C for 9 h
3. Lower residual monomer content
2. Heating the flask at 65°C for 90 min, then boiling the
4. Material is strong
water for 1 h for adequate polymerization in thinner
5. Shows less distortion and less initial deformation
portions.
6. Less creep and quicker recovery
l Removing the flask from the water bath, bench cooling
7. Good colour stability and satisfactory aesthetic qualities:
it for 30 min, and placing it in cold tap water for 15 min
a. Biocompatible and hygienic
is satisfactory.
b. Simplicity in fabrication
SHORT NOTES
Q. 1. Porosity Their composition includes the following:
1. Alkaline compounds
Or,
2. Detergents
Porosity in dentures 3. Flavouring agents
4. Sodium perborate
Or, l When the powder is dissolved in water, the perborate
decomposes to form an alkaline peroxide solution.

Porosity and its effects in dental resins
Which in turn decomposes to liberate oxygen. The oxy-
Ans. gen bubbles then act mechanically to loosen the debris.
l Hypochlorite solutions are contraindicated in base
l Porosity is a processing error in acrylic resins. metal alloy dentures.
l Porosity may be of following two types:
1. Internal porosity Q. 3. Denture reliners
2. External porosity
Ans.
l Internal porosity:
l Is the form of voids or bubbles within the mass of the l Denture reliner is a polymeric material placed on the
polymerized acrylic. tissue contacting surface of a denture base to absorb
l Mainly caused due to the vaporization of monomer some of the energy produced by masticatory impact and
when the temperature of the resin increases above to act as a type of shock absorber between the occlusal
the boiling point of monomer (100.8°C) or very low surfaces of a denture and the underlying oral tissues.
molecular weight polymers. l Mainly three varieties of denture relining materials are
l Internal porosity can be avoided by using long and used as follows:
low temperature curing cycle. 1. Hard liners, e.g. usually cold cure acrylics
l External porosity: It can occur due to two reasons as 2. Soft resilient liners, e.g. polysilicones, polymer res-
follows: ins, highly plasticized polyvinyl chlorides, plasti-
1. Lack of homogeneity cized polyurethanes
2. Lack of adequate pressure 3. Short-term resilient liners or tissue conditioners, e.g.
l This is avoided by using the required amount of dough supplied as powder containing polymethylmethacry-
and distributing it correctly in the mould cavity. lates or its higher copolymers and liquid containing
aromatic esters such as butyl phthalate, butyl glyco-
Q. 2. Denture cleansers late or dibutyl phthalates
Ans.
Q. 4. Tissue conditioners
l Dentures are cleaned by either immersion in the agent Ans.
or by brushing with the cleanser.
l Several types of denture cleaning materials are used. l Tissue conditioners or a short term resilient soft liners
For example: Household cleansers, bleaches, vinegar, are chemically activated polymeric materials that tend
dentifrices, mild detergents, etc to degrade more rapidly than heat activated resins.
l The most common commercial denture cleansers are the l They are supplied as powder of polymethylmethacry-
immersion type, which are available as a powder or tablet. lates or its higher copolymers. The liquid has large
molecular sized plasticizer like some aromatic esters microfine silica fillers, and a photoinitiator system
such as butyl phthalate, butyl glycolate or dibutyl (camphorquinone amine photo initiator).
phthalates of about 50–80% in alcohol or ethanol. 2 . They are polymerized in a light chamber (curing unit)
l They can be formed directly in the patient’s mouth. with blue light of 400–500 nm from high intensity
l Disadvantages with tissue conditioners are as follows: quartz halogen bulbs. The denture is rotated continu-
1. Poor mechanical bonding ously in the chamber to provide uniform exposure to the
2. Dimensional instability light source.
3. No permanent resilience
4. Difficult to polish and poor hygiene Q. 7. Condensation polymerization resins
Q. 5. Cold cure acrylic or autopolymerizing resin Ans.
Ans. Condensation resins are of two types as follows:

l Those in which polymerization is accompanied by re-
l The chemically activated acrylic resins polymerize at peated elimination of small molecules with the forma-
room temperature. They are also known as self-curing tion of by products such as water, halogen acids, etc.
or cold-cured or autopolymerizing resins. l Those in which functions groups are repeated in poly-
l In cold-cured acrylic resins, the chemical initiator ben- mer chains, e.g. polyurethane
zoyl peroxide is activated by another chemical di- At present condensation resins are not widely used in
methyl-para toluidine which is present in the monomer. dentistry.
l Instead of heat as in heat-cured resins, the polymeriza-
tion is achieved at room temperature. Q. 8. Chemical stages in polymerization
Q. 6. Light-activated denture base resins Ans. There are four chemical stages in polymerization
which are as follows:
Ans. 1. Induction
2. Propagation
1. Light-activated denture base material consists of a ure-
3. Termination
thane dimethacrylate matrix with an acrylix copolymer,
4. Chain transfer
Topic 20
Dental Implants
SHORT ANSWER
Q. 1. Dental implant materials Currently, the vast majority of implant systems use tita-
Ans. nium in some form.
Materials used in dental implants are as follows:

Titanium
1. Metals
a. Stainless steel l The titanium is the most popular implant material in use
b. Cobalt–chromium–molybdenum based today. It has become the gold standard in implant mate-
c. Titanium and its alloys rials.
d. Surface-coated titanium l The most commonly used titanium products are pure Ti
2. Ceramics and titanium alloys, namely, Ti–6AL–4V and Ti–6AL–

a. Hydroxy apatite 4V extra low interstitial (ELI).
b. Bioglass l Commercially pure titanium comes in different grades
c. Aluminium oxide from CP grade I to CP grade IV.

3. Polymers and composites l Many other materials include vitallium, porcelain, high-
4. Others density aluminium oxide (alumina), sapphire (alpha

a. Gold, alumina), bioactive glass (Bioglass) and carbon and
b. Tantalum and carbon compound (C and SiC).
c. Carbon, etc.
Key Points to Remember

Introduction
l Father of dentistry: Pierre Fauchard
l Father of modern dentistry: GV Black
l List of some important American National Standards Institute / American Dental Association specifica-
tions dental material, instruments, and equipment are as follows:
S. No Title S. No Title
1 Dental amalgam alloy 20 Dental duplicating material
2 Gypsum-bonded casting investment for dental gold 21 Zinc silicophosphate cement
alloy
25 Dental gypsum products
3 Dental impression compound
26 Dental X-ray equipment
4 Dental inlay casting wax
27 Direct filling resins
5 Dental casting gold alloy
28 Endodontic files and reamers
6 Dental mercury
29 Hand instruments
7 Dental wrought gold wire alloy
30 Zinc oxide-eugenol restorative materials
8 Dental zinc phosphate cement
40 Dental implants
9 Dental silicate cement
A) Unalloyed titanium for dental implants
11 Dental agar impression material
B) Cast cobalt-chromium-molybdenum alloys for
12 Denture base polymers dental implants
13 Denture cold-curing repair resin 42 Phosphate-bonded investment
14 Dental base metal casting alloy 61 Zinc polycarboxylate cement
16 Dental impression paste zinc oxide - eugenol type 66 Glass ionomer cements
17 Denture base temporary relining resin 69 Dental ceramics
18 Dental alginate impression material 90 Rubber dams
19 Elastomeric dental impression materials
Physical properties of dental materials

l Colour: Colour is a sensation induced from light of varying wavelengths reaching the eye.
l Dimensions of colour
i. Hue: Dominant colour of an object.
ii. Value: Relative lightness or darkness of a colour.
iii. Chroma: Degree of saturation of a particular hue.
l These three parameters of colour when plotted in a 3-D graph it is called ‘Munsell colour coordinate
system’.
l Creep: Time dependent plastic strain of a material under a static load or constant stress is known as
creep.
l Hardness: Hardness is the ability to withstand permanent deformation in the form of indentation load.
l Metamerism: Phenomenon in which the colour of an object under one type of light appears to change
when illuminated by a different light source is known as metamerism.

l Rheology: Study of the deformation and flow characteristics of matter.
l Tarnish: Process by which a metal surface is dulled or discoloured when a reaction with a sulphide,
oxide, chloride or other chemical causes a thin film to form.
l Corrosion: Chemical or electrochemical in which a solid usually a metal is attacked by an environmen-
tal agent resulting in pavrtial or complete dissolution.

l Viscosity: Resistance of a fluid to flow.
Mechanical properties of dental materials

l Stress: Force per unit area within a structure subjected to an external force or pressure is known as stress.
l Shear stress: Ratio of force to the original cross-sectional area parallel to the direction of the force ap-
plied to a test specimen.
l Tensile stress: Ratio of tensile force to the original cross-sectional area perpendicular to the direction of
applied force.
l Compressive stress: Ratio of compressive force to cross-sectional area perpendicular to the axis of ap-
plied force.
l Strain: Change in length per unit initial length is known as strain.
l Elastic strain: Deformation that is recovered upon removal of an externally applied force or pressure.
l Plastic strain: Deformation that is not recoverable when the externally applied force is removed is
known as plastic strain.

l Poisson’s ratio: The ratio of lateral strain to axial strain is called Poisson’s ratio.
(Under tensile load, there is increase in length and as well as at the same time there is decrease in cross-
sectional area, this is known as lateral strain).
l Strength: Maximum stress that a structure can withstand without sustaining a specific amount of plastic
strain or stress at the point of fracture.
l Tensile strength: Tensile stress at the point of fracture.
l Yield strength: The stress at which a test specimen exhibits a specific amount of plastic strain.
l Compressive strength: Compressive stress within a compression test specimen at the point of fracture.
l Elastic modulus or Young’s modulus: Relative stiffness of a material.
Or
Ratio of elastic stress to elastic strain within the elastic limit (it is a measure of the rigidity or stiffness
of the material).
l Proportional limit: Maximum stress at which stress is directly proportional to strain and above which
plastic deformation occurs.

l Elastic limit: The maximum stress that a material can withstand without undergoing permanent
deformation.
l Resilience: The relative amount of elastic energy per unit volume released on unloading of a test
specimen.
l Ductility: Relative ability of a material to deform plastically under a tensile stress before it fractures.
l Malleability: Ability of a material to sustain considerable permanent deformation without rupture under
compression as in hammering or rolling into a sheet, e.g. gold, silver etc.

l Brittleness: Relative inability of a material to deform plastically.
l Toughness: Ability of a material to absorb elastic energy to deform plastically before fracturing.
l Hardness: Resistance of a material to plastic deformations typically measured under an indentation
load.
Hardness tests
Micro hardness tests Macro hardness tests

Knoop hardness test Brinell and Rockwell test
Impression materials
l Classification of impression materials
By setting mechanism By elasticity

Chemical reaction (Irreversible) Inelastic or rigid materials Elastic materials
Plaster of Paris Alginate hydrocolloid
Zinc oxide-eugenol Nonaqueous elastomers
Polysulphide
Polyether
Condensation silicone
Addition silicone
Thermally induced physical reaction (reversible) Compound wax Agar hydrocolloid
Gypsum products
l Different methods of manufacturing gypsum have produced different types of gypsum products as
follows :
i. Type I – Impression plaster
ii. Type II– Model plaster
iii. Type III – Dental stone
iv. Type IV – Die stone
v. Type V – High strength and high expansion die stones
Type of Gypsum Setting Time Setting Expansion W/P Ratio

i. Impression plaster 4 min 0.15 % 0.5-0.75
ii. Model plaster 12 min 0.30 % 0.45-0.50
iii. Dental stone or class I stone or hydrocal 12 min 0.20 % 0.28-0.30
iv. High strength dental stone or class II stone or 12 min 0.10% 0.22-0.24
improved stone or densite
v. Dental stone high strength and high expansion 12 min 0.30 % 0.18-0.22
Dental waxes
l Classification of dental waxes
According to Origin
i. Mineral wax ii. Plant wax iii. Insect wax iv. Animal wax
e.g: paraffin e.g: carnauba e.g: beeswax e.g: spermaceti
ceresin candelilla
According to Use
a. Pattern waxes b. Processing waxes c. Impression waxes

i. Inlay casting wax i. Boxing wax i. Corrective wax
ii. RPD casting wax ii. Utility wax ii. Bite registration wax
iii. Base plate wax iii. Sticky wax
Dental casting alloys casting investments and procedures
Functional classification of casting gold alloys
Type I Type II Type III Type IV

Soft Medium Hard Extra Hard
Uses of casting gold alloys

Type I (soft) –Small inlays
Type II (medium) –Inlays, three quarter crowns, pontics
Type III (hard) – Full crowns, short span bridges
Type IV (extra hard) – Long span bridges, clasps and partial denture framework.
l Summarising casting defects and dimensional errors in casting according to Coombe
Casting defects are classified by ‘Coombe’ as follows:
A. Distortion (dimensional errors)
B. Surface roughness
C. Porosity
D. Incomplete casting
E. Contamination of casting due to oxidation.
A. Dimensional errors in casting
Problem Cause Precaution

Casting too large Excessive expansion Use correct temperature and correct investment
Casting too small Too little mould expansion Heat the mould sufficiently
Distorted casting Distorted wax pattern Correct handling of wax
B. Rough surface on casting
Cause Precaution
Rough surface a) Investment breakdown Avoid overheating of mould and alloy
b) Air bubbles on wax (nodules l Correct use of wetting agent
on casting) l Correct vacuum investing
c) Weak surface of investment l Avoid too high investment water/powder ratio
l Avoid dilution of investment from too much wetting
agent
Fins on casting Cracking of investment l Avoid too rapid heating of investment
C. Porosity
Type of Porosity Cause Prevention

Suck back (localized shrinkage, l Shrinkage of molten alloy on l Use thick sprue
shrink spot porosity) cooling l Placing reservoir
l Irregular voids in casting l Flaring the point of attachment
l Thin sprue diameter l Attach sprue at thickest portion of
wax pattern
Back pressure l Escape of air is prevented due l Adjusting the sprue such that there
to bulk of investment is only 6mm (1/4 inch) distance
l Rounded margin in casting from casting ring to nearest part of
pattern
l Sufficient casting pressure
l Proper burnout
Pinhole, sub-surface, gaseous in- l Spherical voids in casting l Avoid overheating and prolonged
clusions l Due to rapid entry of alloy in heating
to the mould l Use long and thin sprue
Micro porosity l Rapid solidification shrinkage l Increase melting temperature
D. Incomplete casting
An incomplete casting may result when:
i. Insufficient alloy is used.
ii. Alloy not able to enter thin parts of mould.
iii. When mould is not heated to casting temperature.
iv. Premature solidification of alloy.
v. Sprues are blocked with foreign bodies.
vi. Back pressure due to gases in mould cavity.
vii. Low casting pressure.
viii. Alloy not sufficiently molten or fluid.
E. Contamination of casting
i. Due to oxidation when molten alloy is over heated.
ii. Use of oxidizing zone of the flame.
iii. Failure to use flux.
iv. Due to formation of sulphur compounds
Finishing and polishing materials
Commonly Used Agents Purpose

Pumice Smoothening of dentures, polishing of artificial teeth
Zinc oxide Polishing of amalgam restorations
Rouge Polishing of noble metal alloys
Zirconium silicate Prophylactic paste for polishing natural teeth
Chromic oxide Stainless steel
Tin oxide Metallic restorations
Corundum Smoothening of metal alloys

Bonding
Generations of Dentine bonding agents
1st generation Uses glycerol-phosphoric acid dimethacrylate

nd
2 generation Uses chloro substituted phosphate esters of various monomers
rd
3 generation Includes 3 step procedure, i.e. conditioning, priming and bonding
4th generation Relies on formation of hybrid layer. The steps of conditioning and priming are
combined and hence are called as self- etching primers
5th generation Steps 2 and 3 are combined
th
6 generation It is a single step procedure
All 3 solutions in one bottle
7th generation Fluoride releasing bonding agents
Restorative Resins
Classification of composites and their properties
Conventional composite It is the composite with largest filler particle size and high strength and hardness
l
Contains filler particles ranging in size of 8-12 micrometres

l
Less water sorption and coefficient of thermal expansion

l
Not easy to polish, results in rough surface that tends to retain stains
l
Micro-filled composite Contains smallest filler particle size ranging from 0.04–0.4 micrometres, with lowest
l
strength and hardness

Has highest thermal expansion coefficient and water sorption
l
Excellent aesthetics due to the increased smoothness

l
Small particle Contains filler particles ranging in size of 1-5 micro metres
l
It has the good surface smoothness like microfilled composites and improved physi-
l
cal properties like conventional composite

It has the highest compressive strength of all the composites
l
Hybrid composite It has filler particle size ranging from 0.6-1micro meters
l
It exhibits smooth finishing and better aesthetics than small particle composite, but
l
yet have similar physical properties
Dental cements
l Base: Layer of insulating, sometimes medicated cement, placed in the deep portion of the preparation
to protect pulpal tissue from thermal and chemical injury.
l Cavity liner: A thin layer of cement, e.g. calcium hydroxide suspension in an aqueous or resin carrier,
used for protection of the pulp is known as cavity liner, e.g. certain glass ionomer cements that are used
as an intermediate layer between tooth and composite restorative materials.
l Varnish: A solution of natural gum, synthetic resins or resins dissolved in a volatile solvent, such as
acetone, ether or chloroform.

l Luting agent: A viscous material placed between tooth structure and a prosthesis that hardens through
chemical reactions to firmly attach the prosthesis to the tooth structure.

l Restoration: Filling material or prosthesis used to restore or replace a tooth, a portion of a tooth, mul-
tiple teeth on other oral tissues.

Skinner’s classification of cements and their uses
Cement Principal Use Secondary Use

Zinc phosphate Luting agent for restorations and Intermediate restorations, thermal
orthodontic appliances insulating layers and root canal
restorations
Zinc phosphate with silver and Intermediate restorations
copper solutions
Zinc oxide- eugenol Temporary and intermediate restora- Root canal restorations, periodontal
tion, temporary and permanent luting pack
agent for restorations, thermal insulat-
ing bases and pulp capping agent
Polycarboxylate Luting agent for restorations and ther- Luting agent for orthodontic appli-
mal insulating bases ances and as intermediate restoration
Silicate Anterior restoration
Silicophosphate Luting agent for restorations Intermediate restorations, luting agent
for orthodontic appliances
Glass ionomer Coating for eroded areas, luting Pit and fissure sealant anterior
agent for restorations restorations
Thermal insulating layer
Resin Luting agent for restorations Temporary restorations
Calcium hydroxide Pulp capping agent and thermal

insulating layer
Dental Amalgam
l An amalgam is an alloy that contains mercury as one of its constituents.
l Composition of conventional (low copper) amalgams
Silver (65%): Increases expansion, increases strength and whitens the alloy
Tin (29%): Decreases expansion, strength as well as hardness and reduces tarnish and corrosion
resistance
Copper (,6%): Increases hardness, strength and expansion.
Zinc (,1%) : Scavenger/deoxidiser, increases the longevity of the restoration.
Classification of amalgam alloys
A) Based on copper content
i. Low copper – , 6%
ii. High copper – . 6%
l Admixed : 9 – 20%
l Single composition: 13–30%
B) Based on zinc content

l Zinc containing – Contains more than 0.01 % of zinc.
l Zinc free – Contains less than 0.01 % of zinc.
C) Based on alloy particle shape

l Lathe cut – Irregular shape
l Spherical and
l Admixed – Contain both lathe cut and spherical alloys.

Direct filling gold

Direct filling gold is a direct filling restorative material
Classification of direct filling gold
I. Foil
A) Sheet
i. Cohesive
ii. Noncohesive
B) Ropes
C) Cylinders
D) Laminated foil
E) Platinized foil
II. Electrolytic precipitate (crystalline gold)
A. Mat gold
B. Mat foil (mat gold plus gold foil)
C. Gold-calcium alloy
III. Granulated gold (encapsulated gold powder)
Dental Ceramics
An inorganic compound with nonmetallic properties typically consisting of oxygen and one or more metal-
lic or semi metallic elements that is formulated to produce the whole or the part of a ceramic based dental
prosthesis.
Classification of dental porcelain is as follows:
I. According to their firing temperature
a. High fusing – 1290 to 1370oC
b. Medium fusing – 1095 to 1260 oC
c. Low fusing – 870 to 1065 oC
d. Ultra low fusing – , 850 oC.
II. According to use
a. Construction of artificial teeth
b. Fabrication of jacket crowns and inlays
c. As veneers over cast metal restorations.
III. According to the method of firing
a. Air fired i.e. at atmospheric pressure
b. Vacuum fired i.e. at reduced pressure.
IV. According to application
a. Core porcelain
b. Dentine or body porcelain
c. Enamel porcelain
d. Glazes.
V. According to composition
a. Feldspathic
b. Leucite based
c. Lithia based
d. Aluminous
e. Pure alumina, silica, zirconia porcelains, etc.
Uses of dental porcelain are as follows:
i. Single unit crowns:
a. Porcelain jacket crown (PJC)
b. Metal ceramic crown or porcelain fused to metal (PFM)
c. Castable glass ceramic crowns.
ii. Porcelain veneers for crowns and bridges.
iii. Artificial teeth.
iv. Inlays and onlays.
v. Ceramic brackets used in orthodontia

vi. Implants, bioglasses etc.
Recent Porcelains
l Magnetic core
l Extrusion moulded or injection moulded aluminous core material
l Fluoride – mica glass or castable ceramics.
Denture base resins
Denture Base Resins
Temporary Permanent
E.g. Self-cure acrylics E.g. Heat cure denture resins
Shellac base plate Light cured resins
Base plate wax Pour type resins
Injection moulded resins
Metallic bases
Comparison of heat cured and self-cured resins
Property Heat Cured Resins Self-Cured Resins

Mode of activation Free radicals supplied by ap- Free radicals supplied by the chemical reaction
plication of heat between the initiator and the chemical activators
like tertiary amines and sulphide system
Degree of polymerization More polymerized Less polymerized
Molecular weight Usually high Less
Strength High Low
Polymerization shrinkage More, 0.5% Less, 0.3%
Residual monomer content Less and around 0.3 to 0.5% More and around 3 to 5%
Water sorption Less 0.21% More around 3 %
Porosity Less porous More porous
Colour stability More Less
Dimensional stability More Less
Colour stability Greater Poor
Biological compatibility Less irritating to the mucosa More irritating
Dental Implants
Classification of dental implants
Endosteal Subperiosteal Transosteal

l Root form l Unilateral l Staple
l Blade form l Bilateral l Single pins
l Ramus frame l Multiple pins

Section II
General Pathology
Topic 1 Cell Injury, Cell Death and Adaptations 109

Topic 2 Acute and Chronic Inflammation 120
Topic 3 Tissue Repair: Regeneration, Healing and Fibrosis 136
Topic 4 Haemodynamic Disorders, Thrombosis and Shock 141
Topic 5 Diseases of the Immune System 161
Topic 6 Neoplasia 170
Topic 7 Genetic and Paediatric Diseases 186
Topic 8 Environmental and Nutritional Disorders 187
Topic 9 Infections and Infestations 192
Topic 10 Heart and Blood Vessels 194
Topic 11 Haematopoietic and Lymphoid Systems 196
Topic 12 Lung 214
Topic 13 Diseases of Oral Cavity and Salivary Glands 215
Topic 14 Liver, Gallbladder and Biliary Tract 221
Topic 15 Male and Female Genital System 222
Topic 16 Endocrine System 222
Topic 17 Musculoskeletal System 224
Topic 18 Skin 227
Topic 19 Nervous System 229
Section II
General Pathology
Topic 1
Cell Injury, Cell Death and Adaptations

LONG ESSAYS
Q. 1. Define necrosis. Write different types of necrosis Pathology
and give examples.
l Grossly necrosed tissues look pale, firm and slightly
Or, swollen in early stages.
l They become more yellowish, softer and shrunken with
Classify necrosis and mention nuclear changes.
further progression of necrosis.
Ans.
Microscopic Examination
NECROSIS
l Microscopically the hallmark of the coagulative necro-
Necrosis is defined as focal death along with degradation of sis is the conversion of the normal cell into tombstones,
tissue by hydrolytic enzymes liberated by cell. i.e. normal outline of the cell is retained so that cell type
can still be recognized but their cytoplasmic and nuclear
Various types of necrosis are as follows: details are lost.
1. Coagulative necrosis: Necrosis seen in heart, kidney l The necrosed cells are swollen and appear more eosino-
and spleen philic than the normal cells.
2. Liquefaction necrosis: Necrosis seen in infarcts and l The denaturation of cellular proteins and enzymatic
abscess cavities digestion of the cell brings about these changes.
3. Caseous necrosis: Necrosis seen in centre of tubercu- l Eventually the necrosed focus is infiltrated by inflam-
lous foci matory cells and the dead cells are phagocytosed
4. Fat necrosis: Special type of cell death seen in pancreas leaving granular debris and fragments of cells.
and breast
5. Fibrinoid necrosis: Seen in peptic ulcers
Liquefaction (Colliquative) Necrosis
When necrosed cells and tissues are converted into
Coagulative Necrosis l
structureless fluids it is called as liquefactive necrosis,

l It is the most common type of necrosis usually seen in e.g. infarct of brain and abscess cavity.
heart, kidney and spleen. l It occurs commonly due to ischaemia and bacterial
l It occurs due to the irreversible cell injury, mostly from or fungal infections, due to degradation of tissues by
sudden cessation of blood flow and less commonly from action of powerful hydrolytic enzymes.
bacterial and chemical agents. l Nerve tissues become liquefied after necrosis because it
contains more of lipid and water which do not coagulate.

l The affected area is set with liquefied centre containing
Causes
necrotic debris.
l Ischaemia (sudden cessation of blood flow): Most common l Microscopically, liquefied tissue has no structure. The
l Bacterial infections: Diphtheria, bacillary dysentery cystic space contains necrotic debris and phagocytosed
l Chemical agents: Mercuric chloride material and macrophages.
109
l The cyst wall is formed by proliferation of capillar- Q. 2. Define and classify gangrene. Write about diagnosis
ies, inflammatory cells, glial cells in case of brain and management of wet gangrene.
and proliferating fibroblasts in case of abscess
Or,
cavity.
Define gangrene. Give an account of different varieties
of gangrenes with examples.
Caseous Necrosis
Ans.
l When the necrosed tissue is converted into soft cheese-
like mass it is called as caseous necrosis.
l Such necrosis occurs in case of granuloma production GANGRENE
by tuberculous infections. It combines features of both
l Gangrene is a form of necrosis of tissue with super-
coagulative and liquefactive necrosis.
added putrefaction. Here the necrosis is of coagulative
l Grossly, foci of caseous necrosis resemble dry cheese
type due to ischaemia.
and looks soft, granular and yellowish.
l There are three main forms of gangrene, i.e. dry, wet
l Microscopically, the central part of granuloma shows
and gas gangrene.
finely granular structure-less material which contains
fragments of cells and nucleic acids which give some-
what purple strain. Dry Gangrene
l This form of gangrene begins in the distal part of limb due
Fat Necrosis to ischaemia, e.g. dry gangrene in toes and feet due to arte-
riosclerosis especially in old patients, thromboangiitis oblit-
l Fat necrosis is a special form of cell death occurring due
erans (Buerger’s disease), Raynaud’s disease, trauma, etc.
to necrosis of fat cells or adipose tissue.
l The gangrene spreads slowly upwards until it reaches a point
l It commonly occurs in breast and pancreas.
where blood supply is adequate to keep the tissue viable.
l It is of two types as follows:
1. Traumatic fat necrosis: It occurs in breast due to

trauma in subcutaneous fat cells. Pathologic Changes
2. Acute pancreatic necrosis: This occurs due to the l The affected part grossly appears dry, shrunken and
release of pancreatic lipase from injured or in- dark black.
flamed tissues which digests the fat and results in l On microscopic examination the line of separation con-
pancreatitis. sists of inflammatory granulation tissue and it usually
l Fat necrosis grossly appears as yellowish white and firm
brings about complete separation.
deposits.
l Microscopically, the necrosed fat cells have cloudy
appearance with only faint outline left and the soap Wet Gangrene
takes light blue colour occupying fat globule and l This occurs in naturally moist tissues and organs like
identified as many granular clumps in tissue sections. the mouth, lungs, cervix, vulva, etc.
l Wet gangrene usually develops rapidly due to blockage
Fibrinoid Necrosis of venous and less commonly arterial blood flow from
thrombosis or embolism.
l This type of necrosis is characterized by deposition l Important clinical conditions included in wet gangrene
of fibrin-like material, e.g. peptic ulcer, immunologic are diabetic foot and bed sores.
tissue injury, arterioles in hypertension etc. l The affected part is stuffed with blood which favours
l Microscopically, fibrinoid necrosis is identified by the growth of putrefactive bacteria.
brightly eosinophilic, hyaline-like deposition in the l Systemic manifestations of septicaemia and finally
vessel wall or on the luminal surface of a peptic ulcer. death occurs due to absorption of toxic products formed
by bacteria.
Nuclear Changes in Necrosis
Pathologic Changes
The nuclear changes in necrosis are as follows:
1. Pyknosis: Condensation of nuclear chromatin l The affected part appears soft, swollen, putrid, rotten
2. Karyolysis: The basophilia of the chromatin may un- and dark.
dergo dissolution l Classic example is gangrene of bowel due to strangu-
3. Karyorrhexis: Fragmentation lated hernia, volvulus or intussusception.

Section | II General Pathology 111
l No clear line of demarcation between gangrenous l It is especially common in liver as it plays central role in
segment and viable tissue. fat metabolism, but it may occur in other nonfatty tissues
like heart, skeletal muscle, kidneys and other organs.
l Fatty change may be mild and reversible or severe and
Gas Gangrene
irreversible resulting in cell death.
l It is special form of wet gangrene caused by gas-form-
ing clostridia.
l It occurs in open contaminated wounds, especially in
Aetiology
muscles or as complication of operations. The commonest causes of fatty liver are as follows:
1. Excess alcohol consumption
Pathologic Changes 2. Starvation
3. Malnutrition
l The affected area is swollen, oedematous, painful and 4. Obesity
crepitant due to accumulation of gas bubbles in the tissues. 5. Diabetes mellitus
l The muscle fibres undergo coagulative necrosis with
6. Chronic illness, e.g. tuberculosis
liquefaction. The affected area becomes dark black and 7. Late pregnancy
foul smelling. 8. Reye’s syndrome
9. Hypoxia, e.g. cardiac failure, anaemia etc
Q. 3. Mention types of intracellular accumulations. Discuss
10. Hepatotoxins and certain drugs
pathogenesis and microscopic appearance of fatty liver.
Or,
Pathogenesis
Discuss the aetiopathogenesis and pathology of fatty
l In fatty liver accumulation of triglycerides can occur
liver and microscopic appearance of fatty liver.
due to following defects in normal fat metabolism.
l Increased entry of free acids into liver
Ans. l Increased synthesis of fatty acid by liver
l Intracellular accumulation of substances can occur l Decreased conversion of fatty acids into ketone bodies
within the cytoplasm or nucleus of the cell in abnormal l Increased glycerophosphate causing increased esterifi-
amounts resulting in cell injury. cation of fatty acids to triglycerides

l Reversible cell injury results from mild intracellular ac- l Decreased synthesis of lipid acceptor protein so
cumulations, while irreversible cell injury results from decreased formation of lipoprotein from triglycerides
more severe damage. l Block in the excretion of lipoprotein from liver into plasma
l Various types of intracellular accumulations are as follows:
1. Accumulation of constituents of normal cellular meta- Gross Appearance

bolic processes in excess. For example: Accumulation of
excessive amounts of lipids, proteins and carbohydrates Grossly, the fatty liver appears enlarged with a tens glistening
2. Accumulation of abnormal substances produced as a capsule and rounded margins. The cut surface bulges slightly
result of abnormal metabolism due to lack of some and is pale yellow in colour and greasy to touch Fig. 1.1.
enzymes, e.g. storage diseases
3. Accumulation of pigments both exogenous and
endogenous. For example:
a. Endogenous pigments: Melanin, lipofuscin and
haemoproteins like haemosiderin, haematin,
bilirubin and porphyrins
b. Exogenous pigments
Hepatic artery
i. Inhaled pigments like carbon, coal dust, silica
or stone dust, iron, asbestos and various other Portal vein
organic substances
ii. Ingested pigments like silver, lead and certain Central vein
cathartics Hepatocytes
iii. Injected pigments like India ink, cinnabar and Fat cell with
carbon peripherally
located nucleus
FATTY LIVER
l Fatty change or steatosis is the intracellular accumula-
tion of neutral fat within parenchymal cells. FIGURE 1.1 Microscopic appearance of fatty liver.
l Microscopic examination reveals numerous lipid vacu- l Sometimes, the hepatocytes laden with large lipid
oles in the cytoplasm of hepatocytes. vacuoles may rupture and coalesce to form fatty cysts.
l The vacuoles are initially small, i.e. microvesicular and Infrequently, lipogranulomas may appear.
are present around nucleus. With the progression of the l Fat in the tissues can be demonstrated by frozen section
process, the vacuoles become larger, i.e. macrovesicu- followed by fat stains like Sudan dyes, Oil red O and
lar, pushing the nucleus to the periphery of the cells. osmic acid.
SHORT ESSAYS
Q. 1. Characteristics of dry gangrene 2. Liquefaction necrosis: Necrosis seen in infarcts and
abscess cavities
Ans.
3. Caseous necrosis: Necrosis seen in centre of tubercu-
lous foci
GANGRENE 4. Fat necrosis: Special type of cell death seen in pancreas
and breast
l Gangrene is a form of necrosed tissue with superadded
putrefaction.
l The type of necrosis is coagulative due to ischaemia.
l There are three main forms of gangrene, i.e. dry, wet Coagulative Necrosis
and gas gangrene.
l It is the most common type of necrosis usually seen in
heart, kidney and spleen.
Dry Gangrene l It occurs due to the irreversible cell injury, mostly from
l This form of gangrene begins in the distal part of limb sudden cessation of blood flow and less commonly from
due to ischaemia, e.g. dry gangrene in toes and feet due bacterial and chemical agents.
to arteriosclerosis especially in old patients, thromboan-
giitis obliterans (Buerger’s disease), Raynaud’s disease,
Causes
trauma, etc.
l The gangrene spreads slowly upwards until it reaches a l Ischaemia (sudden cessation of blood flow): Most
point where blood supply is adequate to keep the tissue common
viable. l Bacterial infections: Diphtheria, bacillary dysentery
l Chemical agents: Mercuric chloride
Pathologic Changes
Pathology
l The affected part grossly appears dry, shrunken and
dark black. l Grossly necrosed tissues look pale, firm and slightly
l On microscopic examination the line of separation con- swollen in early stages.
sists of inflammatory granulation tissue and it usually l They become more yellowish, softer and shrunken with
brings about complete separation. further progression of necrosis.
Prognosis Microscopic Examination

l As bacteria fail to survive here it results in little septi- l Microscopically, the hallmark of the coagulative necrosis
caemia and has better prognosis. is the conversion of the normal cell into tombstones,
i.e. normal outline of the cell is retained so that cell type
Q. 2. Mention types of necrosis with examples and can still be recognized but their cytoplasmic and nuclear
describe briefly coagulative necrosis. details are lost.
l The necrosed cells are swollen and appear more eosino-
Ans.
philic than the normal.
l The denaturation of cellular proteins and enzymatic
NECROSIS digestion of the cell brings about these changes.
l Eventually the necrosed focus is infiltrated by inflam-
Necrosis is defined as focal death along with degradation of
tissue by hydrolytic enzymes liberated by cell. matory cells and the dead cells are phagocytosed
leaving granular debris and fragments of cells.
Various types of necrosis are as follows:
Q. 3. What is dystrophic calcification? Give two examples.
1. Coagulative necrosis: Necrosis seen in heart, kidney
and spleen Ans.
Pathological calcification or heterotopic calcification is the Microscopic Examination

deposition of calcium salts in tissues other than osteoid or
l Routine haematoxylin and eosin-stained sections
enamel.
show calcium salts as deeply basophilic, irregular and
granular clumps.
There are two types of pathologic calcification as follows:
l The deposits may be intracellular, extracellular or at
1. Dystrophic calcification
both locations.
2. Metastatic calcification
l Occasionally heterotopic bone formation or ossification
may occur.
DYSTROPHIC CALCIFICATION l The calcium salts are confirmed by special stains like
silver impregnation method of Von Kossa producing

Dystrophic calcification is a type of pathological calcifica-
black colour and alizarin red producing red staining.
tion which is characterized by deposition of the calcium
l They also give positive Prussian blue reaction due to
salts in tissues which are dead or degenerate but have nor-
diffuse or granular deposits of iron accompanying the
mal calcium metabolism and normal serum calcium levels.
pathological calcification.
Aetiology Q. 4. Wear and tear pigment

Dystrophic calcification may occur due to the following Ans.
reasons:
l Lipofuscin is also known as wear and tear pigment. It is
1. Calcification in dead tissue
a haemoprotein-derived pigment.
a. Caseous necrosis in tuberculosis (most common site
l Lipofuscin or lipochrome is yellowish-brown intracel-
for dystrophic calcification)
lular lipid pigment.
b. Liquefaction necrosis in chronic abscesses
l The pigment is found in atrophied cells of old age.
c. Fat necrosis
l It is seen in myocardial fibres, hepatocytes, Leydig cells
d. Infarcts
of testis and neurons in senile dementia.
e. Thrombi especially in veins (phleboliths)
l In heart muscle change is associated with wasting
f. Haematomas in the close vicinity of bones
of muscle and commonly referred to as brown atrophy.
g. Dead parasites like in hydatid cyst, schistosoma
l It is an example of residual bodies as it represents the
eggs, cysticercosis
collection of indigestible material in the lysosomes after
h. Calcification in breast cancer
autophagy.
i. Congenital toxoplasmosis
2. Calcification in degenerated tissues Q. 5. Metaplasia. What is it? Give examples.
a. Dense old scars
b. Atheromas (mainly in aorta and coronary arteries) Ans.
c. Monckeberg’s sclerosis (calcification in tunica
media) METAPLASIA
d. Stroma of tumours such as uterine fibroids, breast
cancer, thyroid adenoma, etc. l Meta means transformation and plasia means growth.
e. Calcifications in the walls of long standing cysts l Metaplasia is defined as reversible change of one
(epidermal and pilar cysts) type of epithelial or mesenchymal adult cells to another
f. Calcinosis cutis type of adult epithelial or mesenchymal cells usually in
g. Senile degenerative changes in costal, tracheal or response to abnormal stimulus.
bronchial cartilages, pineal gland in brain l Metaplasia is divided into following two types:
1. Epithelial
2. Mesenchymal
Pathogenesis
It is linked to the formation of normal hydroxyapatite in the
Epithelial Metaplasia
bone involving two phases as follows:
l Initiation phase: Here the calcium and phosphates begin l This is more common type. The metaplastic change
to accumulate intracellularly in the mitochondria or may be patchy or diffuse.
extracellularly in membrane-bound vesicles. l Some common types of epithelial metaplasia are as follows:
l Propagation phase: Here the minerals deposited in the
initiation phase are propagated to form mineral crystals.

Squamous Metaplasia
However, local alteration of pH in the necrotic tissue
and release of enzymes from the necrotic or degenerated There is transformation of various types of epithelium into
tissue are also implicated in the pathogenesis. squamous epithelium due to chronic irritation. For example:
l In bronchus (normally lined by stratified columnar c. Hypertrophy of skeletal muscle: Hypertrophied mus-
ciliated epithelium), in chronic smokers cles in athletes and manual labourers
l In gallbladder, in chronic cholecystitis d. Compensatory hypertrophy: It may occur in an organ
l In prostate, in chronic prostatitis when the contralateral organ is removed, e.g. after
l In renal pelvis and urinary bladder, in chronic infections nephrectomy on one side in young patients there is
and stones compensatory hypertrophy of kidney as well as
nephrons on other side.
Columnar Metaplasia
Q. 7. Define hyperplasia and give examples.
There is transformation of various epithelia into columnar
Ans.
epithelium. For example:
l Intestinal metaplasia in healed chronic gastric ulcer l Hyperplasia is an increase in the number of parenchy-
l In cervical erosion mal cells resulting in enlargement of the organ or
l Conversion of pseudostratified columnar epithelium in tissue.
chronic bronchitis and bronchiectasis to columnar type l Hyperplasia occurs due to increased recruitment of cells
from resting phase of the cell cycle to undergo mitosis,

Mesenchymal Metaplasia when stimulated.
l Hyperplasia persists as long as the stimulus is present.
There is transformation of one adult type of mesenchymal
tissue to another.
CAUSES
Osseous Metaplasia Hyperplasia may occur due to physiologic and pathologic
causes.
Osseous metaplasia is formation of bone in fibrous tissue,
cartilage and myeloid tissue. For example: 1. Physiologic hyperplasia: The two most common types
l In arterial wall, in old age (Monckeberg’s calcific
are as follows:
sclerosis) a. Hormonal hyperplasia
l In fibrous stroma of tumour
i. Hyperplasia of pregnant uterus
l In cartilage of larynx and bronchi in old age
ii. Hyperplasia of female breast during puberty,
l In soft tissues, in myositis ossificans
pregnancy and lactation
iii. Proliferative activity of normal endometrium
after normal menstrual cycle
Cartilaginous Metaplasia b. Compensatory hyperplasia
Occurs in healing of fracture where there is undue mobility. i. Regeneration of liver following partial hepatec-
tomy
ii. Regeneration of epidermis after skin abrasion
Q. 6. Hypertrophy. Define and give examples. 2. Pathologic hyperplasia: Due to excessive stimulation of
Ans. hormones or growth factors
i. Endometrial hyperplasia following oestrogen excess
Hypertrophy means an increase in size of parenchymal cells ii. Formation of skin warts from hyperplasia of
resulting in enlargement of the organ or tissue, without any epidermis due to HPV
change in the number of cells. iii. Formation of granulation tissue during healing of
wounds
AETIOLOGY Q. 8. Haemosiderosis
Hypertrophy is caused by increased functional demand Ans.
or by hormonal stimulation. It may be classified into the
following: l Haemosiderosis is caused due to excess haemosiderin
1. Physiologic hypertrophy: Enlarged size of uterus during production when there is increased breakdown of red
pregnancy cells or systemic overload of iron.
2. Pathologic hypertrophy: l Haemosiderin is ferric iron which is formed by aggre-
a. Hypertrophy of cardiac muscle: Systemic hyperten- gates of ferritin and is identifiable by light microscopy as
sion, aortic valve disease, mitral insufficiency golden yellow to brown granular pigment in the mono-
b. Hypertrophy of smooth muscle: Cardiac achalasia nuclear phagocytes of the bone marrow, spleen and liver.
(in oesophagus), pyloric stenosis (in stomach), intes- l Local haemosiderosis: This develops whenever there
tinal strictures, muscular arteries in hypertension is haemorrhage into the tissues. With lysis of cells
haemoglobin is liberated which is taken up by macro- i. Excessive intake of dietary iron: Bantu’s disease
phages where it is degraded and stored as haemosid- ii. Increased erythropoietic activity: Haemolytic
erin, e.g. changing colours of a bruise or a black eye. anaemia
l Systemic (generalized) haemosiderosis: Systemic over- iii. Excessive intestinal absorption of iron: Haemo-
load of iron results in generalized haemosiderosis. It chromatosis
may occur in two patterns as follows: b. Reticuloendothelial deposition occurs usually fol-
a. Parenchymatous deposition of haemosiderin: It oc- lowing repeated blood transfusions or after paren-
curs in parenchymal cells of liver, kidney, pancreas teral iron therapy in liver, spleen and bone marrow.
and heart due to following causes:
SHORT NOTES
Q. 1. Apoptosis DYSTROPHIC CALCIFICATION
Ans. l It is a type of pathologic calcification in which calcium
l Apoptosis means falling off or dropping off effect. salts are deposited in the dead or degenerating tissue of
l Apoptosis is a form of coordinated and internally pro- the body.
l It is not associated with increased level of serum
grammed cell death which is of significance in various
pathological and physiological conditions. calcium and is related to change in local environment.
l Characteristic morphological changes in apoptosis on
This is the most frequent type of pathological calcifica-
histologic and electron microscopic examination are as tion found in wide variety of tissues.
l In oral cavity areas of dystrophic calcification are found
follows:
l Shrinkage of cells with dense cytoplasm and almost
in gingiva, tongue, cheek and pulp.
l One of the most common intraoral dystrophic calcifica-
normal organelles
l Convolution of cell membrane with formation of
tion found in the pulp of the teeth is the pulp stone.
apoptotic bodies
l Chromatin condensation around the periphery of
METASTATIC CALCIFICATION
nucleus
l Involvement of single cell or clusters of cells in the l Abnormal deposition of calcium in the tissue due to
background of viable cells increase in amount of serum calcium is called meta-
l No acute inflammatory reaction static calcification.
l Phagocytosis of apoptotic bodies by macrophages l It occurs particularly in diseases like hyper-parathyroidism
which depletes the bone calcium and causes high level

Q. 2. Gas gangrene of blood calcium.
l Metastatic calcification also occurs in hyper-vitaminosis D.
Ans.
In this type of calcification deposit of calcium occurs
l Gas gangrene is a special form of wet gangrene caused in kidney, lung, gastric mucosa and media of blood
by gas-forming clostridia. vessels.
l It occurs in open contaminated wounds, especially in
muscles or as complication of operations.

CALCINOSIS
l Pathologic changes: The affected area is swollen, oede-
matous, painful and crepitant due to accumulation of gas l Abnormal deposition of calcium under the skin is also
bubbles in the tissues and it becomes dark black and foul known as calcinosis.
smelling. l There are two forms of calcinosis as follows:
1. Calcinosis circumscripta: It is circumscribed form.

Q. 3. Pathological calcification 2. Calcinosis universalis: It is generalized form and is
Ans. associated with scleroderma and dermatomyositis.
l Pathologic or heterotopic calcification is the abnormal Q. 4. Dystrophic calcification

deposition of the calcium salts in various tumours and Ans.
organs of the body other than osteoid and enamel.
l They are of three types as follows: Dystrophic calcification is a type of pathological calcifica-
1. Dystrophic calcification tion which is characterized by deposition of the calcium
2. Metastatic calcification salts in tissues which are dead or degenerated but have nor-
3. Calcinosis mal calcium metabolism and normal serum calcium levels.
AETIOLOGY Necrosis is defined as focal death along with degradation of

tissue by hydrolytic enzymes liberated by cell.
Dystrophic calcification may occur due to the following
reasons:
Various types of necrosis are as follows:
l Calcification in dead tissue: Caseous necrosis in tuber-
1. Coagulative necrosis: Necrosis seen in heart, kidney
culosis, liquefaction necrosis in chronic abscesses, fat
and spleen
necrosis infarcts, phleboliths, calcification in breast
2. Liquefaction necrosis: Necrosis seen in infarcts and
cancer, etc.
abscess cavity
l Calcification in degenerated tissues: Dense old scars,
3. Caseous necrosis: Necrosis seen in centre of tubercu-
atheromas (mainly in aorta and coronary arteries),
lous foci
stroma of tumours such as uterine fibroids, breast can-
4. Fat necrosis: Special type of cell death seen in pancreas
cer, thyroid adenoma, etc.
and breast
l Microscopic examination: Routine haematoxylin and
eosin-stained sections show calcium salts as deeply ba-
sophilic, irregular and granular clumps which may be Q. 8. Aetiology of cell injury
intracellular, extracellular or at both locations.
Ans.
Q. 5. Enumerate the differences between dystrophic and
metastatic calcification.
Cell injury may be defined as a variety of stresses a cell
Ans. encounters as a result of changes in internal and external
environment.
Dystrophic Calcification Metastatic Calcification
Causes of cell injury are as follows:
Calcium salts are Deposition of calcium in the
deposited in the dead normal tissues of the body.
1. Genetic causes
or degenerating tissues 2. Acquired causes
of the body. a. Hypoxia and ischaemia
Serum calcium levels are Increase in amount of serum
b. Physical agents
normal. calcium. c. Chemical agents
d. Microbial agents
Calcium metabolism is Deranged calcium metabolism
normal. e. Immunological agents
f. Nutritional derangements
Causes: Necrosis, Causes: Hyperparathyroidism, g. Psychological factors
infarcts, thrombi, old destructive bone lesions,
scars, atheromas, etc hypervitaminosis D, milk-alkali
syndrome, etc.
Q. 9. Free radical injury
Ans.
Q. 6. Hyaline change
l The free radical-mediated injury plays an important
Ans. role in situations like ionizing radiation by causing radi-
olysis of water, chemical toxicity, hyperoxia, cellular
l Hyaline is a descriptive histologic term for glassy aging, etc.
homogenous, eosinophilic appearance of material in l The three partially reduced intermediate species of
eosin and haematoxylin-stained sections. oxygen are generated between the reaction of O2 to H2O
l Hyaline changes are associated with pathological condi-
as shown below:
tions that may be intracellular or extracellular. 1. Superoxide (O22 )
l Intracellular hyaline changes are seen in epithelial cells
2. Hydrogen peroxide (H2O2)
as in hyaline droplets, in proximal tubular epithelial 3. Hydroxyl radical (OH2)
cells, in case of excess reabsorption of plasma protein, l The hydroxyl radical is the most reactive species. It may
Russell’s bodies representing excessive immunoglobu- produce membrane damage by following mechanisms:
lins, in the rough endoplasmic reticulum. 1. Lipid peroxidation
l Extracellular hyaline changes are seen in connective tis-
2. Oxidation of proteins
sues like hyaline degeneration, in leiomyomas, hyaline 3. DNA damage: Free radicals cause brakes in the
arteriosclerosis, in renal vessels, in hypertension. single strands of nuclear and mitochondrial DNA,
thus results in cell injury.
Q. 7. Types of necrosis with examples
4. Cytoskeletal damage: Reactive oxygen species are
Ans. also known to interact with cytoskeletal elements
and interfere in mitochondrial aerobic phosphoryla- yellowish, softer and shrunken with further progression
tion and thus cause ATP depletion. of necrosis.
l The antioxidants are used to inactivate the free radicals. l Microscopic examination: Microscopically the hallmark
of the coagulative necrosis is the conversion of the nor-

Q. 10. Reversible cell injury mal cell into tombstones, i.e. normal outline of the cell
Ans. is retained so that cell type can still be recognized, but
their cytoplasmic and nuclear details are lost.
l Cell injury may be defined as a variety of stresses a cell
encounters as a result of changes in internal and external Q. 12. Fatty degeneration
environment. Ans. Fatty changes or degeneration is the intracellular
l When the stress is mild to moderate, the injured cell may
accumulation of neutral fat within parenchymal cell.
recover and this is called reversible cell injury (Fig. 1.2).
l Pathogenesis l It is especially common in liver, heart, skeletal muscle
and kidney.
l Aetiology
Hypoxia/Ischaemia 1. Excess alcohol consumption
2. Starvation
Degeneration of cellular ATP
3. Malnutrition
4. Obesity
5. Diabetes mellitus
6. Chronic illness (tuberculosis)
Decreased Damaged sodium Decreased protein 7. Late pregnancy
intracellular pH pump synthesis
Q. 13. Define and classify gangrene.
Ans.
Ultrastructural or functional changes
l Gangrene is a form of necrosed tissue with superadded
Reversible cell injury putrefaction. The type of necrosis is coagulative due to
FIGURE 1.2 Reversible cell injury. ischaemia.
l There are three main forms of gangrene as follows:
1. Dry gangrene
Q. 11. Enumerate the types of necrosis and define the 2. Wet gangrene
coagulative necrosis. 3. Gas gangrene
Ans. Q. 14. Dry gangrene

Ans.
NECROSIS Dry gangrene usually begins in the distal part of limb due
l Necrosis is defined as focal death along with degrada- to ischaemia, e.g. in toes and feet due to arteriosclerosis.
tion of tissue by hydrolytic enzymes liberated by cell.
l Various types of necrosis are as follows: PATHOLOGIC CHANGES
1. Coagulative necrosis
2. Liquefaction necrosis l The affected part is dry, shrunken and dark black.
3. Caseous necrosis l The line of separation usually brings about complete
4. Fat necrosis separation.
l The line of separation consists of inflammatory granula-
5. Fibrinoid necrosis
tion tissue.
Coagulative Necrosis Q. 15. Hypertrophy and hyperplasia

l It is the most common type of necrosis usually seen in Ans.
heart, kidney and spleen caused by the irreversible cell
injury, mostly from sudden cessation of blood flow.
HYPERTROPHY
l Causes: Ischaemia, bacterial infections and chemical
agents Hypertrophy is an increase in size of parenchymal cells re-

l Pathology: Grossly necrosed tissues look pale, firm and sulting in enlargement of the organ or tissue, without any
slightly swollen in early stages. They become more change in the number of cells.
It is synthesized in melanocyte and dendritic cells and is

Causes l
stored in the form of cytoplasmic granules in the phago-

May be due to increased functional demand or by hormonal cytic cells called as melanophores.
stimulation. l Hyperpigmentation occurs during the following:
1. Addison’s disease
It may be classified into the following: 2. Chronic arsenic poisoning
1. Physiologic hypertrophy: Enlarged size of uterus during 3. Melanotic tumour
pregnancy l Hypopigmentation occurs during the following:
2. Pathologic hypertrophy: Hypertrophy of cardiac muscle, 1. Albinism
smooth muscle and skeletal muscles, compensatory hyper- 2. Leucoderma
trophy of organs when the contralateral organ is removed
Q. 18. Aetiology of fatty liver
HYPERPLASIA Ans. Fatty change or steatosis is the intracellular accumu-
lation of neutral fat within parenchymal cells.
Hyperplasia is an increase in the number of parenchymal
cells resulting in enlargement of the organ or tissue.
AETIOLOGY
Causes
The commonest causes of fatty liver are as follows:
May be due to physiologic and pathologic causes. 1. Excess alcohol consumption
1. Physiologic hyperplasia: The two most common types 2. Starvation
are as follows: 3. Malnutrition
a. Hormonal hyperplasia: Hyperplasia of pregnant 4. Obesity
uterus, hyperplasia of female breast during puberty, 5. Diabetes mellitus
pregnancy and lactation 6. Chronic illness (tuberculosis)
b. Compensatory hyperplasia: Regeneration of liver 7. Late pregnancy etc.
following hepatectomy, regeneration of epidermis
after skin abrasion Q. 19. Causes of ischaemia
2. Pathologic hyperplasia: Due to excessive stimulation of
Ans. Ischaemia is defined as deficient blood supply to part
hormones or growth factors
of a tissue. Ischaemia may be partial or complete.
a. Endometrial hyperplasia following oestrogen excess
b. Formation of skin warts from hyperplasia of epider-
mis due to HPV
CAUSES
Q. 16. Lipofuscin
Causes in the Heart
Ans.
l Inadequate cardiac output resulting from heart block,
l Lipofuscin is also known as wear and tear pigment. ventricular arrest and fibrillation may cause hypoxic
l Lipofuscin or lipochrome is yellowish-brown intra- injury to brain.
cellular lipid pigment found in atrophied cells of
old age.
Causes in the Arteries
l It is seen in myocardial fibres, hepatocytes, Leydig cells
of testis and neurons in senile dementia. l Luminal occlusion as in thrombosis and embolism
l In heart muscle change is associated with wasting of l Causes in arterial wall such as vasospasm, hypothermia,
muscle and commonly referred to as brown atrophy. ergotism, arteriosclerosis
l Outside pressure on an artery such as ligature, tourni-
Q. 17. Melanin pigment quet, tight plaster, bandages
Ans.
l Melanin is an endogenous pigment.

Causes in the Veins
l It is the brown black, nonhaemoglobin-derived pigment l Luminal occlusion such as in thrombosis of mesenteric
normally present in hair, skin, choroid of eye, meninges veins, cavernous sinus thrombosis
and adrenal medulla. l Causes in vessel wall as in varicose veins of leg
l Outside pressure on vein as in strangulated hernia— Q. 22. Hyperplasia

intussusceptions
Ans. Hyperplasia is an increase in the number of paren-
chymal cells resulting in enlargement of the organ or
Causes in the Microcirculation tissue.
l Luminal occlusion as in sickle cell anaemia, red cells
parasitized by malaria
l Causes in microvasculature wall such as vasculitis, e.g.
CAUSES
polyarthritis nodosa, frost bite injuring the vessel walls Hyperplasia may be due to physiologic and pathologic
l Outside pressure on microvasculature as in bed sores causes.
Q. 20. Atrophy 1. Physiologic hyperplasia: The two most common types

are as follows:
Ans. a. Hormonal hyperplasia: Hyperplasia of pregnant
Atrophy may be defined as the decrease in number and size uterus, hyperplasia of female breast during puberty,
of parenchymal cells of an organ or its parts which was pregnancy and lactation
once normal. b. Compensatory hyperplasia: Regeneration of liver
following hepatectomy, regeneration of epidermis
after skin abrasion
CAUSES 2. Pathologic hyperplasia: Due to excessive stimulation of
Atrophy may be caused due to the following: hormones or growth factors
1. Physiologic changes: Atrophy is a normal aging process a. Endometrial hyperplasia following oestrogen excess
in some tissues, which could be due to loss of endocrine b. Formation of skin warts from hyperplasia of epider-
stimulation or arteriosclerosis. mis due to HPV
a. Atrophy of lymphoid tissue in lymph nodes, appen-
dix and thymus Q. 23. Hypertrophy
b. Atrophy of gonads after menopause Ans.
2. Pathologic changes: They may be caused due to starva-
tion, ischaemic, disuse endocrine or pressure atrophy. l Hypertrophy is an increase in size of parenchymal cells
resulting in enlargement of the organ or tissue, without
Q. 21. Metaplasia any change in the number of cells.
l Causes: Hypertrophy is caused by increased functional
Ans.
demand or by hormonal stimulation. It may be classified
l Metaplasia is defined as reversible change of one into the following:
type of epithelial or mesenchymal adult cells to another 1. Physiologic hypertrophy: Enlarged size of uterus
type of adult epithelial or mesenchymal cells usually in during pregnancy
response to abnormal stimulus. 2. Pathologic hypertrophy: Hypertrophy of cardiac
l Metaplasia is of two types: epithelial and mesenchymal. muscle, smooth muscle and skeletal muscle
Q. 24. Antioxidants
EPITHELIAL METAPLASIA
Ans.
l This is more common type. The metaplastic change
may be patchy or diffuse. l Antioxidants are endogenous or exogenous substances
l Some common types of epithelial metaplasia are which inactivate the free radicals.
squamous metaplasia and columnar metaplasia. l These substances include the following:
1. Vitamin E, A and C
2. Sulfhydryl-containing compounds: Cysterine and
MESENCHYMAL METAPLASIA glutathione
l There is transformation of one adult type of mesenchy- 3. Serum proteins: Ceruloplasmin and transferrin
mal tissue into another. l Antioxidants also play a role in net effect of free radical
l Osseous metaplasia and cartilaginous metaplasia are injury as they influence the rate of elimination of free
common types of mesenchymal metaplasia. radicals.
Topic 2
Acute and Chronic Inflammation

LONG ESSAYS
Q. 1. Define inflammation. Describe the various vascu- Transient Vasoconstriction of Arterioles: Immediately
lar changes of inflammation. after the injury there is transient vasoconstriction of
arterioles lasting for about 3–5 s in minor injuries and for
Ans.
about 5 min in more severe injuries, after which normal
l Inflammation is defined as a protective response intended blood flow is restored.
to eliminate the initial cause of cell injury as well as ne-
Persistent Vasodilatation: Persistent vasodilatation fol-
crotic cells and tissues resulting from the original insult.
lows which involves mainly the arterioles and to a lesser
l It is a local response of living mammalian tissues to injury
extent venules and capillaries. This results in increased
due to any agent and is a body’s defence reaction in order
blood flow through the microvasculature that is respon-
to eliminate or limit the spread of injurious agents as well
sible for the warmth and the redness at the site of inflam-
as to remove the consequent necrosed cells and tissues.
mation. This state may last for about half an hour after
l The protective mission of inflammation is accomplished
injury.
by diluting, destroying or otherwise neutralizing harm-
ful agents like microbes and toxins. Rise in Local Hydrostatic Pressure: After vasodilatation,
l The agents that cause inflammation are as follows: there is rise in local hydrostatic pressure which results in
1. Physical agents: Heat, cold, radiation, mechanical transudation of fluid into the extracellular space. This is
trauma responsible for the swelling at the site of inflammation.
2. Chemical agents: Organic and inorganic poisons
3. Infective agents: Bacteria, viruses and their toxins Slowing or Stasis of Microcirculation: This occurs due
4. Immunological agents: Cell-mediated and antigen– to increased permeability of microvasculature that results in
antibody reactions increased concentration of RBCs and thereby increasing the
l Acute inflammation has two major components that can viscosity of blood.
be described as follows:
Margination or Peripheral Orientation of Leucocytes:
1. Vascular events
Stasis is followed by leukocytic margination or peripheral
2. Cellular events
orientation of leucocytes along the vascular endothelium.
l Vascular events or vascular changes constitute altera-
This is the first step in the journey of leucocytes through the
tions in vessel calibre resulting in vasodilation and in-
vascular wall into the interstitial tissue.
creased vascular permeability.
After sticking briefly to the vascular endothelium, the
l Cellular events include emigration of leucocytes espe-
leucocytes migrate through the gaps between the endothe-
cially PMNs from the microcirculation and accumulation
lial cells into the extravascular space. This phenomenon is
in the focus of injury (cellular recruitment and activation).
known as emigration.
l Vascular changes in inflammation are as follows:
1. Changes in vascular calibre and flow

2. Increased vascular permeability Increased Vascular Permeability
Pathogenesis
Changes in Vascular Calibre and Flow
Initially the escape of fluid is due to vasodilatation and
(Haemodynamic Changes) l
increased volume of blood flow results in consequent

l Alteration in microvasculature, i.e. capillaries, venules elevation of intravascular hydrostatic pressure, resulting
and arterioles is the first response to tissue injury. in movement of fluid from capillaries into the tissues,
l Changes in the blood vessels begin rapidly after infec- this fluid is called transudate and it contains little
tion or injury but may develop at variable rates depend- protein.
ing on the nature and severity of original inflammatory l Later the characteristic inflammatory oedema, exudates,
stimulus. appears by increased vascular permeability.
l Changes in the vascular flow and calibre of small blood l Increased vascular permeability occurs due to endothe-
vessels in the injured tissue takes place in a sequence of lial lining of the microvasculature becoming leaky.
events as follows: Then the intravascular osmotic pressure decreases and
osmotic pressure of interstitial fluid increases resulting many toxic mediators which may cause endothelial in-
in excessive outward flow of fluid into interstitial jury or detachment.
compartment which is the inflammatory exudate.
l The net result is outflow of water and ions into the ex- Leakage from New Blood Vessels
travascular tissues. Fluid accumulation in extravascular l The vessel sprouts formed during tissue repair remain
spaces is called oedema. leaky until proliferating endothelial cells mature suffi-
ciently to form intercellular junctions.
l Some of the factors that induce angiogenesis, e.g. vas-
Mechanisms Involved in Increased Vascular
cular endothelial growth factor (VEGF) directly induce
Permeability increased vascular permeability via transcytosis.
Several mechanisms contributing to increased vascular
permeability in acute inflammatory reactions are as Q. 2. Define inflammation. Discuss cellular events in
follows: acute inflammation.
1. Contraction of endothelial cells Ans.
2. Retraction of endothelial cells
3. Direct injury to endothelial cells l Inflammation is defined as a protective response intended
4. Leukocyte-mediated endothelial injury to eliminate the initial cause of cell injury as well as ne-
5. Leakage from new blood vessels crotic cells and tissues resulting from the original insult.
l It is a local response of living mammalian tissues to
Contraction of Endothelial Cells injury due to any agent.
l Endothelial cell contraction leading to intercellular gaps
in postcapillary venules is the most common cause of CELLULAR EVENTS IN ACUTE

increased vascular permeability.
l Endothelial cell contraction occurs rapidly after binding
INFLAMMATION
of chemical mediators to specific receptors is usually Cellular events in acute inflammation can be grouped under
short-lived (15–30 min) and is called the immediate two headings as follows:
transient response. 1. Leukocyte recruitment
2. Leukocyte activation
Retraction of Endothelial Cells
l A slower and more prolonged retraction of endothelial
Leukocyte Recruitment
cells resulting from changes in the cytoskeleton may be
induced by cytokines such as tumour necrosis factor The sequence of events in the recruitment of leucocytes
(TNF) and interleukin-1 (IL-1). The onset of response from vascular lumen to the extravascular space consists of
takes 4–6 h to develop after the initial trigger and per-
1. margination, adhesion to endothelium and rolling along
sists for 24 h or more.
vessel wall,
Direct Injury to Endothelial Cells 2. firm adhesion to endothelium,
3. transmigration between endothelial cells and
l Endothelial injury results in vascular leakage by causing
4. migration in interstitial tissues towards a chemotactic
endothelial cell necrosis and detachment. stimulus.
l It usually follows severe injuries like thermal injury,
certain bacterial infections. Exudation of leucocytes is the most important feature of

l The changes can affect entire microvasculature includ- acute inflammation which consists of escape of leucocytes
ing venules, capillaries and arterioles. from lumen of the microvasculature to the interstitial tissues.
l Increased permeability may begin immediately after the
injury and persist for several hours or days, it is known

Margination and Rolling
as immediate sustained response.
l Direct injury to endothelial cells may also induce a l Blood flow rate increases due to vasodilatation in acute
delayed prolonged leakage which begins after a delay of inflammation but subsequently there is slowing or stasis
2–12 h and lasts for several hours or even days. of blood stream.
For example, mild to moderate thermal injury, certain l This stasis changes the normal axial flow of blood which
bacterial toxins, X-ray or UV irradiation. consists of central cell stream of leucocytes and RBCs and
peripheral cell-free plasma layer closer to the vessel wall.
Leukocyte-Mediated Endothelial Injury l As the blood flows from capillaries into postcapillary
l It occurs as a consequence of leukocyte accumulation venules circulating cells are swept by laminar flow
along the vessel wall. The activated leucocytes release against the vessel wall.
l In addition, the smaller red blood cells tend to move l Diapedesis is responsible for haemorrhagic appearance
faster than the larger white blood cells. As a result, leu- to the inflammatory exudate.
cocytes are pushed out of central axial column and thus l The damaged basement membrane is repaired almost
have a better interaction with lining endothelial cells. immediately.

This process of leukocyte accumulation at the periphery l The dominant cells in the exudate are neutrophils in first
of vessels is called margination or pavementing. 6–24 h and are short-lived and replaced by monocytes
l Following the process of margination, leucocytes tum- and macrophages in next 24–48 h and they survive
ble on the endothelial surface, transiently sticking along much longer.
the way, it is a process called rolling.
l The weak and transient adhesions involved in rolling are
Chemotaxis
mediated by the selectin family of adhesion molecules.
l The three members of selectin family are as follows: l After extravasating from the blood, leucocytes migrate
1. P-selectin (CD62P): Present on endothelial cells and towards the sites of infection or injury along a chemical
platelets, gradient by a process called chemotaxis.
2. E-selectin (CD62E): Expressed on endothelial cells l Chemotaxis is the transmigration of leucocytes across
and several barriers of endothelium, basement membrane,

3. L-selectin (CD62L): Expressed on surface of most perivascular myofibroblasts and matrix to reach the in-
lymphocytes. terstitial tissue mediated by chemotactic factors.
l These chemotactic agents are also called as chemokines
and they carry specific receptors.

Adhesion and Transmigration l Both exogenous and endogenous substances can be
l The next step in the reaction of leucocytes is firm adhe- chemotactic for leucocytes including
sion to endothelial surfaces. 1. bacterial products, especially peptides with
l This adhesion is mediated by integrins expressed on N-formylmethionine termini,
leukocyte cell surfaces interacting with their ligands on 2. cytokines, especially those of the chemokine family,
endothelial cells. 3. components of the complement system particularly
l Integrins are normally expressed on leukocyte plasma C5a and
membrane in a low-affinity form and do not adhere to 4. products of the lipoxygenase pathway of arachidonic
their appropriate ligands until leucocytes are activated acid metabolism particularly leukotriene B4 (LTB4).
by chemokines. l These mediators are produced in response to infections
l Chemokines are chemoattractant cytokines that are and tissue damage and during immunologic reactions.
secreted by many cells at the site of inflammation and
are displayed bound to proteoglycans on the endothelial
surface.
Leukocyte Activation
l When the adherent leucocytes encounter the displayed Leucocytes must be activated to perform their functions
chemokines, the cells are activated and their integrins once they have been recruited to the site of infection or tis-
undergo conformational changes and cluster together, sue necrosis.
thus converting to a high affinity form. Leukocyte activation results in many enhanced functions like:
l The net result of cytokine stimulated increased integrin l Phagocytosis of particles, an early step in the elimina-
affinity and increased expression of ligands is stable at- tion of harmful substances.
tachment of leucocytes to endothelial cells at sites of l Production of substances that destroy phagocytosed
inflammation. microbes and remove dead tissues include lysosomal
enzymes and reactive oxygen and nitrogen species.
l Production of mediators that amplify the inflammatory
Transmigration
reaction, including arachidonic acid metabolites and
l After being arrested on endothelial surface, leucocytes cytokines.
migrate through the vessel wall primarily squeezing
between the cells at intercellular junctions. This move-
Phagocytosis
ment of leucocytes is called diapedesis, which occurs
mainly in the venules of the systemic vasculature and l Phagocytosis is the process of engulfment of solid
also in the capillaries of pulmonary circulation. particulate matter by the cells called as phagocytes.
l Then by secreting collagenases, the neutrophils damage l The main types of phagocytic cells are as follows:
the basement membrane locally and escape out into 1. Polymorphonuclear neutrophils: Also called as
the extravascular space. This phenomenon is known as microphages, they appear early in an acute inflam-
emigration or transmigration. matory response.
2. Macrophages: These are circulating monocytes and Killing or Degradation Stage

fixed tissue mononuclear phagocytes. l In this final stage, the microorganisms are killed by the
l Phagocytosis consists of following distinct but interre- antibacterial substances and digested or degraded by
lated steps: hydrolytic enzymes.
1. Recognition and attachment of the particles to the l The antibacterial substances act in one of the following
ingesting leukocyte ways:
2. Engulfment with subsequent formation of a phago- 1. Oxygen-dependent bactericidal mechanism
cytic vacuole l The mechanism of production of these oxygen
3. Secretion or degranulation stage metabolites is brought about by NADPH oxidase
4. Killing and degradation of the ingested material present in the cell membrane of phagosomes which
oxidizes NADPH and in the process converts oxygen
Recognition and Attachment Stage or Opsonization to superoxide ion (O2–).
l The microorganism to be phagocytosed and the –
l The superoxide ion (O2 ) is then converted by sponta-
phagocytic cell repel each other due to both having a neous dismutation into hydrogen peroxide.
negatively charged surface. l Here H2O2 is converted into hypochlorous acid, a
l To overcome this repulsion, the microorganism gets more potent bactericidal in presence of halides by the
coated with a naturally occurring factor in serum called enzyme myeloperoxidase (MPO) present in granules
opsonins and gets targeted for phagocytosis by a of neutrophils or monocytes or independent of it.
process called opsonization. 2. Myeloperoxidase (MPO)-independent killing
l The two main opsonins in the serum and their corre- l Mature macrophages lack the enzyme MPO and they
sponding receptors on the cell surface are as follows: carry out the bactericidal activity by producing OR
1. IgG opsonin and corresponding receptor is Fc or O2 from either Haber-Weiss reaction (in presence
fragment of immunoglobulin on the surface of of O2) or Fenton reaction (in presence of Fe21).
polymorphs and monocytes. l These reactive oxygen metabolites are particularly
2. C3b opsonins fragment of complement and corre- useful in eliminating the microbes that grow within
sponding receptor for C3b on the phagocytic cell the phagocytes, e.g. Mycobacterium tuberculosis,
surface. Histoplasma capsulatum.
3. Oxygen-independent bactericidal mechanism
Engulfment Stage l Some agents like lysosomal hydrolase, permeability
l Binding of opsonized particles triggers engulfment. increasing factors, defensins and cationic proteins
l The opsonized particle bound to the phagocyte sur- released from phagocytic cell granules do not require
face is engulfed by formation of cytoplasmic pseudo- oxygen for bactericidal activity.
pods around it and enveloping it in a phagocytic 4. Nitric acid mechanism
vacuole. l Nitric oxide (NO) produced by the endothelial cells
l Eventually the membrane of phagocytic vacuole breaks and activated macrophages seem to have fungicidal
from the cell surface so that membrane-lined phagocytic and antiparasitic action in animals.
vacuole lies free in the cytoplasm.
l This is converted into phagolysosome or phagosome on Q. 3. Discuss the role of chemical mediators in the
its fusion with the lysosomes of the cell. process of the inflammation.
Secretion or Degranulation Stage Or,

Classify chemical mediators of acute inflammation and
l The preformed granules stored in the polymorphonu-
discuss their role briefly.
clear neutrophils are discharged into the phagosome and
the extracellular environment. Ans.
l The specific secondary granules are discharged while l Chemical mediators of inflammation are also called
the azurophilic granules are fused with the phago- permeability factors or endogenous mediators of
somes. increased vascular permeability.
l The polymorphonuclear neutrophils synthesize and l These are a large and increasing number of endogenous
secrete numerous other products in addition to granules compounds which can enhance vascular permeability.
like l Mediators may be produced locally by cells at the site
1. enzymes (interleukin 2 and 6, TNF), of inflammation or they may be synthesized in the liver
2. arachidonic acid metabolites (prostaglandins, leu- and circulating in the plasma as inactive precursors that
kotrienes, platelet activating factor) and are activated at the site of inflammation.
3. oxygen metabolites (superoxide oxygen, hydrogen l Most mediators induce their effects by binding to
peroxide, hypochlorous acid). specific receptors on target cells.

l Mediators may stimulate target cells to release second- l Histamine is released from these cells by variety of
ary effector molecules. When two different mediators stimuli as given below:
have similar actions they amplify a particular response, l Physical injury, e.g. heat, cold, irradiation, trauma,
whereas when they have opposing effects they serve to irritant chemicals, immunologic reactions, etc.
control the response. l Anaphylatoxins like fragments of complement C3a
l The actions of most mediators are tightly regulated. and C5a, which increase vascular permeability and
Once activated and released from the cell, mediators cause oedema in tissues
quickly decay or inactivated by enzymes or eliminated l Leukocyte-derived histamine releasing proteins from
or they may be inhibited. neutrophils, monocytes and platelets

l They are broadly classified into two groups as follows: l Neuropeptides, e.g. substance P
1. Cell-derived mediators l Certain cytokines, e.g. interleukins 1 and 8
2. Plasma protein-derived mediators l The main actions of histamine are as follows:
l It causes vasodilation and is the principal mediator of
immediate phase of increased vascular permeability,

Cell-Derived Mediators inducing venular endothelial contraction and interen-
Major cell-derived mediators of inflammation are as dothelial gaps.
follows: l Soon after its release histamine is inactivated by
1. Vasoactive amines (histamine, 5-hydroxytryptamine) histaminase.

2. Arachidonic acid metabolites (eicosanoids)
a. Metabolites via cyclooxygenase pathway (prosta-
5-Hydroxytryptamine (5-HT) or Serotonin
glandins, thromboxane A2, prostacyclin)
b. Metabolites via lipoxygenase pathway (5-HETE, l It is also preformed vasoactive mediator, with effects
leukotrienes) similar to histamine but is a less potent mediator of
3. Platelet-activating factor increased vascular permeability and vasodilatation.
4. Cytokines (IL-1, TNF-a, TNF-b, IFN-g chemokines) l It is present in tissues like chromaffin, cells of GIT,
5. Reactive oxygen species spleen, nervous tissue, mast cells and platelets.
6. Nitric oxide
7. Lysomal enzymes
Arachidonic Acid Metabolites (Eicosanoids)
Arachidonic acid (AA) is a fatty acid that is derived either
Plasma Protein-Derived Mediators l
directly from diet or from the conversion of essential fatty

(Plasma Proteases) acids like linoleic acid to arachidonic acid.
These are products of three interrelated systems, i.e. the l Leucocytes, mast cells, endothelial cells and platelets are
complement, kinin and coagulation systems. the major sources of AA metabolites in inflammation.
The common plasma protein-derived mediators of in- l Products derived from the metabolism of AA affect a
flammation are as follows: variety of biological processes, including inflammation

1. Complement proteins, e.g. multiple breakdown products and haemostasis.
2. Coagulation proteins, e.g. activated factor XII l Arachidonic acid must be activated by stimuli or other
3. Kinins, e.g. produced by proteolytic cleavage of precursors mediators like C5a to form metabolites by one of the
following pathways:
1. Metabolites via cyclooxygenase pathway are prosta-
CELL-DERIVED MEDIATORS glandins, thromboxane A2, prostacyclin.
Vasoactive Amines 2. Metabolites via lipoxygenase pathway are
5-hydroxyeicosatetraenoic acid (5-HETE), leukotri-
Histamine and 5-hydroxytryptamine (5-HT) or serotonin enes.
are the two important pharmacologically active amines
that have role in early inflammatory response. Their
main effects are vasodilation and increased vascular Platelet-Activating Factor (PAF)
permeability. l It is originally named for its ability to aggregate platelets
and cause degranulation and is a phospholipid-derived
Histamine mediator with a broad-spectrum of inflammatory effects.
l It is generated from the membrane phospholipids of
l It is stored in the granules of mast cells, basophils and neutrophils, monocytes, basophils or mast cells, other
platelets. leucocytes, endothelial cells and platelets.
l Apart from its action on platelet aggregation and release Lysosomal Enzymes of Leucocytes
reaction, the actions of PAF as mediator of inflamma-
tion are as follows: l The inflammatory cells—neutrophils and monocytes,
1. Increased vascular permeability and vasodilation in which on release elaborate a variety of mediators of in-
low concentration and vasoconstriction otherwise flammation such as granules of neutrophils, monocytes
2. Chemotaxis and macrophages.
3. Enhanced leucocytes adhesion to endothelium l They play a role in microbial killing and tissue injury.
4. Leukocyte degranulation and oxidative burst

5. Stimulates the synthesis of other mediators espe- PLASMA PROTEIN-DERIVED MEDIATORS
cially eicosanoids (PLASMA PROTEASES)
l Circulating proteins of three interlinked systems. These
Cytokines are:
l They are polypeptide substances produced by activated 1. complement,
lymphocytes and monocytes. Usually act at short range, 2. kinin and
mediate multiple effects mainly in leukocyte recruit- 3. coagulation protein.
ment and migration. l They are involved in several aspects of the inflammatory
l The major cytokines in acute inflammation are TNF reaction.

and IL-1, as well as chemoattractant cytokines called
chemokines. Complement System
l The complement system consists of plasma proteins that
Actions play an important role in host defence, i.e. immunity.
l They induce endothelial effects in the form of increased l On activation by classic or alternate pathway yields
leukocyte adherence, thrombogenicity, elaboration of anaphylotoxins C3a, C4a, C5a and membrane attack
other cytokines, fibroblastic proliferation and acute complex (MAC) which cause release of histamine from
phase reactions. mast cells and basophils, increased vascular permeabil-
l They cause activation of macrophages and neutrophils. ity causing oedema in tissues.
l Activation of complement system by microbes or anti-
bodies leads to the generation of multiple breakdown

Reactive Oxygen Species (ROS) products, which are responsible for
l ROS are synthesized via the NADPH oxidase pathway 1. leukocyte chemotaxis,
and are released from neutrophils and macrophages that 2. opsonization,
are activated by microbes, immune complexes, cyto- 3. phagocytosis of microbes as well as other particles and
kines and a variety of other inflammatory stimuli. 4. cell killing.
l They play a role in microbial killing and tissue injury.
Kinins
Nitric Oxide (NO) l They are produced by proteolytic cleavage of precur-
l NO is a short-lived, soluble, free radical gas produced sors.
by many cell types and capable of mediating a variety l Kinin system activation leads
of functions. l They mediate vascular reaction and pain.
l NO is synthesized denovo from L-arginine, molecular l Bradykinin causes smooth muscle contraction, vasodi-
oxygen and NADPH by the enzyme nitric oxide synthase. latation, increased vascular permeability and pain.
l Macrophages produce nitric oxide during oxidation of
arginine by the action of NO synthase. Coagulation Proteins

l NO plays the following roles in inflammation:
1. Vasodilatation (relaxation of vascular smooth muscles) l Activated factor XII triggers the clotting, kinin and
2. Antagonism of all stages of platelet activation complement cascades and activates fibrinolytic system.
(adhesion, aggregation and degranulation)
3. Microbicidal or cytotoxic action in activated macro-
Clotting System
phages
4. Reduction of leukocyte recruitment at inflammatory l Factor XIIa initiates formation of fibrinogen which is
sites acted upon by thrombin to form fibrin and fibrinopeptides.
The fibrinopeptides result in increased vascular permea- Secondary Syphilis

bility, chemotaxis of leucocytes and anticoagulant activity.
l The cases of primary syphilis which are inadequately
treated develop into painless mucocutaneous lesions in
Fibrinolytic System 2–3 months after exposure.
l Mucocutaneous lesions may be in the form of mucus
l It is activated by plasminogen activator. Plasmin causes
patches of mouth, pharynx and vagina.
factor XII which stimulates the kinin system to generate
bradykinin.
l All these provide an evidence that many molecules are Tertiary Syphilis
involved in different aspects of inflammatory reaction
and they contribute to various components of acute l 2–3 years later following first exposure the tertiary
inflammation. lesion of syphilis appears.
l They are of two types as follows:
Q. 4. Describe briefly clinical stages and serological 1. Syphilitic gumma: Solitary, localized, rubbery lesion
diagnosis of syphilis. with central necrosis, seen in liver, testis, bone and
brain
Ans. 2. Diffuse lesions: The lesions appear following
widespread dissemination of spirochaetes in the
SYPHILIS body. Seen mainly in cardiovascular and nervous
systems.
l Syphilis is a venereal (sexually transmitted) disease l Lesions of tertiary syphilis are much less infective than
caused by spirochetes Treponema pallidum. other two stages.
l T. pallidum does not produce any endotoxin or exotoxin.
The pathogenesis of lesions appears to be due to host

immune response. Treponema infection is associated Diagnosis
with two important antibodies which are as follows: l Syphilis is diagnosed by direct demonstration of bacte-
1. The Wasserman antibodies ria within the lesions in primary and secondary stages or
2. The treponemal antibodies by serological tests in all the stages.
l Nontreponemal antibody tests (VDRL and RPR) are
Mode of Transmission directed against treponemal cell wall and crossreact

with host tissues. They are the first tests to become
1. Sexual intercourse: Lesion on glans penis, vulva, vagina positive and are widely used as screening tests. They
and cervix may be negative in the advanced stages of the disease.
2. Intimate person to person contract: Lesion on lips, l False positive nontreponemal antibody tests may occur
tongue or fingers in SLE, in drug addicts and during pregnancy.
3. Transfusion of infected blood l Treponemal antibody tests include
4. Materno-fetal transmission 1. fluorescent treponemal antibody absorption test (FTA),
2. microhaemagglutination assay for Treponema
Stages of Acquired Syphilis pallidum antibodies (TPHA) and
3. Treponema pallidum immobilization (TPI).
Depending upon the period after which lesion appears and These tests become positive within 4–6 weeks after infec-
type of lesion the stages of syphilis are as follows: tion but remain positive indefinitely.
1. Primary syphilis
2. Secondary syphilis Q. 5. Define granuloma. What are the causes, pathology
3. Tertiary syphilis and fate of granuloma?
Or,
Primary Syphilis
What is a granuloma? List common examples of chronic
l Typical lesion of primary syphilis is chancre which granulomatous diseases. Describe the evolution and fate
appears on genitals or at extragenital sites in 2–4 weeks of tubercle.
after exposure of infection.
l Initially the lesion is painless papule which ulcerates in
Ans.
centre.
l So a fully developed chancre is an indurated lesion with
central ulceration accompanied by regional lymphadenitis.

GRANULOMA
l The chancre heals without scarring even without l Granuloma is defined as a circumscribed tiny lesion,
treatment. about l mm in diameter composed predominantly of
collection of modified macrophages called epithelioid Q. 6. Write briefly about aetiopathogenesis of tubercu-
cells and rimmed at periphery by lymphoid cells. losis. Describe the complications of secondary pulmo-
l Chronic granulomatous inflammation is characterized nary tuberculosis.
by the formation of granulomas. For example:
Ans.
1. Tuberculosis
2. Syphilis
3. Leprosy
4. Fungal infection TUBERCULOSIS
Tuberculosis is a communicable chronic granulomatous
Evolution of Tubercle disease caused by Mycobacterium tuberculosis usually
involving lungs, but may affect any extrapulmonary organ
Entrance of Mycobacterium tuberculosis or tissue in the body.
Produce weak antigen Secondary Pulmonary Tuberculosis

l Secondary or postprimary or reactivation or chronic tu-
Activation of B and T cells
berculosis is the pattern of disease that arises in an indi-
vidual who has been previously exposed or sensitized
host when host immune defences are compromised and
Collection of macrophages usually manifest as cavitary lesions in the lung apices.
l The initial lesion in secondary pulmonary tuberculosis
is usually a small focus of consolidation, less than 2 cm

Macrophages undergo structural changes and form epithelioid cell in diameter, within 1–2 cm of the apical pleura.
l It occurs by haematogenous spread of infections from
primary complex to the apex of affected lung where the

Aggregation of epithelioid cells oxygen tension is high and favourable for growth of
aerobic tubercle bacilli.
l Such foci are sharply circumscribed, firm, grey-white
Tight cluster (hard tubercle)
to yellow areas that have a variable amount of central
caseation and peripheral fibrosis.
l In favourable cases, initial parenchymal focus under-
Soft cluster (soft tubercle) or granuloma
goes progressive fibrous encapsulation leaving only
Constituents of Granuloma fibrocalcific scars.
l Histologically active lesions show characteristic coales-
1 . Epithelioid cells cent tubercles with central caseation.
2. Lymphoid cells l Tubercle bacilli can be demonstrated by appropriate
3. Giant cells methods in early exudative and caseous phases of
4. Necrosis granuloma formation, it is usually impossible to find
5. Fibrosis them in the late, fibrocalcific stages.
l HIV is a well-known risk factor for development of
Fate of Granuloma recrudescence of active tuberculosis.

l The disease may progress and extend along several
Soft tubercle (granuloma) different pathways as follows:

1. Progressive pulmonary tuberculosis
2. Miliary pulmonary tuberculosis
Liquefaction and extends to the surrounding soft tissues 3. Endobronchial, endotracheal and laryngeal tuberculosis
4. Systemic miliary tuberculosis
5. Isolated organ tuberculosis
Discussing contents (pus) 6. Lymphadenitis especially in the cervical region (scrofula)
Cold abscess Fate of Secondary Pulmonary Tuberculosis

l Localized, apical, secondary pulmonary tuberculosis
Lesion surrounded by progressive fibrosis may heal with fibrosis either spontaneously or after
therapy or the disease may progress further.
l The lesions may coalesce together to form larger area of
Dystrophic calcification tuberculosis, which are as follows:

1. Fibrocaseous tuberculosis Tuberculous Caseous Pneumonia

2. Tuberculous caseous pneumonia
In an individual with high degree of hypersensitivity,
3. Miliary tuberculosis
secondary pulmonary tuberculosis may spread to rest of the
lung, producing caseous pneumonia.
Fibrocaseous Tuberculosis Systemic Miliary Tuberculosis
l The original area of tuberculosis pneumonia undergoes
l This is lymphohematogenous spread of tuberculous in-
massive central caseation necrosis.
fection. It ensues when infective foci in the lungs seed
l Tubercular cavity is spherical with thick fibrous wall,
the pulmonary venous return to the heart.
lined by yellowish, caseous, necrotic material and the
l The organisms subsequently disseminate through the
lumen is traversed by thrombosed blood vessel.
systemic arterial system. Almost every organ in the
l Around the wall of cavity foci of consolidation are seen.
body may be seeded.
The overlying pleura may also be thickened.
l The military lesions are millet seed sized (1 mm diam-
l Microscopically the wall of cavity shows eosinophilic,
eter), yellowish, firm areas.
granular, caseous material which may show foci of dys-
l Almost every organ in the body may be seeded. Lesions
trophic calcification.
resemble those in the lung.
l Tubercular granulomas consist of epithelioid cells,
l Miliary tuberculosis is most prominent in the liver, bone
Langhans giant cells and peripheral mantle of lym-
marrow, spleen, adrenals, meninges, kidneys, fallopian
phocytes and central caseation necrosis. The outer wall
tubes and epididymis.
of the cavity shows fibrosis.
l The spread may be extrapulmonary into liver, spleen,
Complications kidney, brain and bone marrow.

1. May produce haemoptysis.
Lymphadenitis
2. Extending to pleura produces bronchopleural fistula.
3. Tubercular empyema It is the most frequent form of extrapulmonary tuberculosis,
4. Thickened pleura usually occurring in the cervical region (scrofula).
SHORT ESSAYS
Q. 1. What are the types of exudation? Ans.
Ans. l Inflammation is defined as a protective response intended
to eliminate the initial cause of cell injury as well as ne-
l Increased vascular permeability allows the movement
crotic cells and tissues resulting from the original insult.
of protein-rich fluid and even cells into the interstitium;
l It is a local response of living mammalian tissues to injury
it is known as exudate.
due to any agent and is a body’s defence reaction in order
l The appearance of escaped plasma determines the mor-
to eliminate or limit the spread of injurious agents as well
phologic type of inflammation as given below:
as to remove the consequent necrosed cells and tissues.
1. Serous: when the fluid exudates resemble serum or is
watery, e.g. pleural effusion in tuberculosis, blister
formation in burns CARDINAL SIGNS OF INFLAMMATION
2. Fibrinous: when the fibrin content of the fluid exu-
The response is manifested as the cardinal signs of inflam-
date is high, e.g. in pneumococcal and rheumatic
mation which were given by the Roman writer Celsus in
pericarditis
first century AD. They are listed in Table 2.1.
3. Purulent or suppurative exudate is the formation
of creamy pus as seen in infection with pyogenic
bacteria e.g. abscess, acute appendicitis.
TABLE 2.1 Cardinal Signs of Inflammation
4. Haemorrhagic: where there is vascular damage,
e.g. acute haemorrhagic pneumonia in influenza Cardinal Sign Mechanism
5. Catarrhal: when the surface inflammation of the 1. Rubor (redness) Capillary dilatation
epithelium produces increased secretion of mucous,
2. Tumour (swelling) Infiltration
e.g. common cold
3. Calor (heat) Pyrogens
Q. 2. Define inflammation. What are the cardinal signs
4. Dolor (pain) Lymphokines
of inflammation?
These four cardinal signs of inflammation were named by the l The polymorphonuclear neutrophils synthesize and
Roman writer Celsus in first century AD. To these Virchow secrete numerous other products in addition to granules
later added the fifth sign functio laesa (loss of function). like enzymes, arachidonic acid metabolites and oxygen
metabolites.
Q. 3. Phagocytosis
Ans. Killing or Degradation Stage
l In this final stage, the microorganisms are killed by the
Phagocytosis is the process of engulfment of solid particu-
antibacterial substances and digested or degraded by
late matter by the cells called as phagocytes.
hydrolytic enzymes.
l The antibacterial substances act in one of the following
The main types of phagocytic cells are
ways:
1. polymorphonuclear neutrophils and
1. Oxygen-dependent bactericidal mechanism
2. macrophages.
2. Myeloperoxidase (MPO)-independent killing
Phagocytosis consists of following distinct but interrelated 3. Oxygen-independent bactericidal mechanism
steps: 4. Nitric acid mechanism
3. Recognition and attachment of the particles to the
ingesting leukocyte Q. 4. Classify and discuss chemical mediators of acute
4. Engulfment, with subsequent formation of a phagocytic inflammation.
vacuole Ans.
5. Secretion or degranulation stage
6. Killing and degradation of the ingested material l Chemical mediators are also called permeability fac-
tors or endogenous mediators of increased vascular
permeability; these are large and increasing number of
Recognition and Attachment Stage endogenous compounds which can enhance vascular
or Opsonization permeability.
l The microorganism to be phagocytosed and the phago- l The substances acting as chemical moderators of
cytic cell repel each other due to both having a negatively inflammation may be released from the cells, plasma or
charged surface. the damaged tissue itself. They are broadly classified
l To overcome this repulsion, the microorganisms get into two groups as follows:
coated with a naturally occurring factor in serum called 1. Mediators released by cells
opsonins and get targeted for phagocytosis by a process 2. Mediators originated from plasma
called opsonization.
l The two main opsonins in the serum and their corre-
CELL-DERIVED MEDIATORS
sponding receptors on the cell surface are: IgG opsonin
and C3b opsonins. 1 . Vascoactive amines (histamine, 5-hydroxytryptamine)
2. Arachidonic acid metabolites (eicosanoids)
a. Metabolites via cyclooxygenase pathway (prosta-
Engulfment Stage glandins, thromboxane A2, prostacyclin)
l Binding of opsonized particles triggers engulfment. b. Metabolites via lipoxygenase pathway (5-HETE,
l The opsonized particle bound to the phagocyte surface leukotrienes)
is engulfed by formation of cytoplasmic pseudopods 3. Lysomal components
around it and enveloping it in a phagocytic vacuole. 4. Platelet-activating factor
l The phagocytic vacuole is then converted into 5. Cytokines (IL-1, TNF-a, TNF-b, IFN-g chemokines)
phagolysosome or phagosome on its fusion with the 6. Nitric oxide and oxygen metabolites
lysosomes of the cell.
PLASMA PROTEIN-DERIVED MEDIATORS
Secretion or Degranulation Stage (PLASMA PROTEASES)
l The preformed granules stored in the polymorphonu- These are the products of:
clear neutrophils are discharged into the phagosome and 1. the kinin system,
the extracellular environment. 2. the clotting system,
l The specific secondary granules are discharged while the 3. the fibrinolytic system and
azurophilic granules are fused with the phagosomes. 4. the complement system.
l After injury the skin exhibits triple response or the red-

Q.5. Chemotaxis
line response. This is characterized by the following:
Ans. 1. Appearance of redline following stroking due to lo-
cal vasodilatation
l Chemotaxis is the transmigration of leucocytes across 2. Flare is the bright reddish appearance or flush
several barriers of endothelium, basement membrane, surrounding the redline.
perivascular myofibroblasts and matrix to reach the 3. Wheal is a swelling or oedema surrounding the red-
interstitial tissue mediated by chemotactic factors. line that occurs due to transudation of fluid into the
l The concept of chemotaxis can be illustrated by
extravascular space.
Boyden’s chamber experiment.
l Here a millipore filter separates the leukocyte suspen-
sion from the test solution containing chemotactic agent Altered Vascular Permeability
in a tissue culture chamber. Increased vascular permeability is seen during inflammation.
l It is observed that the leucocytes migrate through the
pores of filter towards the chemotactic agent.

l These chemotactic agents are also called as chemokines
CELLULAR EVENTS IN ACUTE
and they carry specific receptors. INFLAMMATION
l Some of the potent chemokines are as follows:
Cellular events in acute inflammation can be grouped under
1. Leukotriene B4 two headings as listed in Table 2.2.
2. Platelet factor 4
3. Components of complement system TABLE 2.2 Cellular Events in Acute Inflammation
4. Cytokines, particularly IL-8
Exudation of Leucocytes Phagocytosis
5. Soluble bacterial products
6. Monocyte chemoattractant protein Change in the formed Attachment stage or
7. Chemotactic factor for CD41 T cells elements of the blood opsonization
8. Exotoxin chemotactic for eosinophils Adhesion or rolling Engulfment stage
Emigration Secretion or degranulation
Q.6. Discuss the vascular and cellular events of in- stage
flammation.
Chemotaxis Killing or degradation stage
Ans.
Q. 7. Classify leprosy. Describe the pathology of tuber-

VASCULAR CHANGES IN INFLAMMATION culoid leprosy.
l Alteration in microvasculature, i.e. capillaries, venules, l Leprosy or Hansen’s disease is a slow communicable
and arterioles is the first response to tissue injury. disease caused by Mycobacterium leprae.
l It takes place as changes in the haemodynamic state and l It can be classified into two types based on the resis-
in vascular permeability. tance offered as follows:

1. Lepromatous leprosy (represents low resistance)
2. Tuberculoid leprosy (represents high resistance)
Haemodynamic Changes l According to Ridley and Jopplings Classification,
l It is the earliest sign of inflammation, that results from leprosy is classified into seven types as follows:
changes in the vascular flow and calibre of small blood 1. TT: Tuberculoid polar
vessels in the injured tissue. 2. BT: Borderline tuberculoid
l It takes place as a sequence of events as follows: 3. TI: Tuberculoid indefinite
1. Transient vasoconstriction of arterioles 4. BB: Mid borderline
2. Persistent vasodilatation of arterioles, venules and 5. LI: Lepromatous indefinite
capillaries 6. BL: Borderline lepromatous
3. Rise in local hydrostatic pressure 7. LL: Lepromatous polar
4. Slowing or stasis of microcirculation l Tuberculoid leprosy is characterized by asymmetrical
5. Stasis is followed by leukocytic margination or skin lesions that are hypopigmented and erythematous
peripheral orientation of leucocytes along the vascu- macular.
lar endothelium l Nerve involvement is with distinct sensory distribution.
l After sticking briefly to the vascular endothelium, the l Histopathology involves hard tuberculi similar to granu-
leucocytes migrate through the gap between the endothe- lomatous lesions eroding the basal layer of epidermis.
lial cells into the extravascular space. This is known as l Tissue reaction: Acid fast bacilli in macrophages,
emigration. noncaseating granulomas

Q. 8. What is Ghon’s complex? Thoracic Actinomycosis

Ans. l The infection in the lungs is due to aspiration of organ-
ism from oral cavity or extension of infection from ab-
l Primary tuberculosis or Ghon’s complex or childhood dominal or hepatic lesions.
tuberculosis is the infection of an individual who has l Abdominal actinomycosis: The abdominal infection re-
not been previously infected or immunized. sults from swallowing of organisms from oral cavity or
l Mode of transmission
extension from thoracic cavity.
1. Usually direct by inhalation of air-borne organisms l Pelvic actinomycosis: Actinomycosis infection in the
2. By exposure to contaminated secretions of infected pelvis occurs as a complication of intrauterine contra-
persons ceptive devices.
3. By drinking milk contaminated with Mycobacterium
bovis
l The most commonly involved tissues for primary com- Lab Diagnosis of Actinomycosis
plex are lung and hilar lymph nodes. l The inflammatory reaction is a granuloma with central
l Primary complex or Ghon’s complex in lungs consist of
suppuration. There is formation of abscess in the centre
three components as follows: of lesions and chronic inflammatory cells, giant cells
1. Pulmonary component: Lesion in the lung is primary and fibroblasts are seen at periphery.
focus or Ghon’s focus. It is 1–1.5 cm solitary area l The centre of each abscess contains bacterial colony
of grey-white inflammatory consolidation. Tubercle sulphur granule characterized by radiating filaments
bacilli, either free or within phagocytes drain to with hyaline, eosinophilic, club-like representatives of
the regional lymph nodes, which often caseate. secreted immunoglobins.
This combination of parenchymal lesion and nodal l Bacterial stains reveal the organisms as nonacid, fast,
involvement is referred to as Ghon’s complex. Gram-positive filaments.
2. Lymphatic vessel component: The lymphatics drain-
ing the lung lesion consists of phagocytes containing Q. 10. Differences between transudates and exudates
bacilli and may develop beaded, miliary tubercles
along the path of hilar lymph nodes. Ans. Differences between transudates and exudates are
3. Lymph node component: This consists of enlarged given in Table 2.3.
hilar and tracheobronchial lymph nodes in the area
drained. The affected lymph nodes are matted and TABLE 2.3 Differences between Transudates and Exudates
show caseation necrosis.
Point of
Q. 9. Write briefly on actinomycosis. Difference Transudates Exudates
Ans. Definition Filtrate of blood Oedema of

plasma without inflamed tissue
l Actinomycosis is a chronic suppurative disease caused changes in endothe- associated with
lial permeability, e.g. increased vascular
by anaerobic bacteria Actinomycetes israelii.
oedema in conges- permeability,
l The infection is always endogenous in origin. The
tive cardiac failure e.g. pus
organisms invade, proliferate and disseminate in favour-
Character Noninflammatory Inflammatory
able conditions. type of oedema type of oedema
l Based on anatomical location of lesions, actinomycosis
is of following types: Protein content Low: Less than High: 2.5–3.5 g/dL;
1 g/dL; mainly high content of fi-
1. Cervicofacial actinomycosis albumin, low brinogen and other
2. Thoracic actinomycosis fibrinogen, hence coagulation factors,
3. Abdominal actinomycosis no tendency to hence readily coag-
4. Pelvic actinomycosis coagulate ulates
Glucose content Same as in Low: Less
plasma than 60 mg/dL
Cervicofacial Actinomycosis
Specific gravity Low: Less High: More
l This is the commonest form, the infection enters from than 1.015 than 1.018
tonsils, carious teeth, periodontal disease or trauma pH . 7.3 (basic) , 7.3 (acidic)
following tooth extraction.
l Initially, a firm swelling develops in lower jaw. In time, the
LDH Low High
mass breaks down and abscesses and sinuses are formed. Cells Few cells, mainly Many cells,
l The discharging pus contains typical tiny yellow sul- mesothelial cells including
phur granules. The infection may extend into adjoining and cellular debris inflammatory and
parenchymal cells
tissues as well as destroy bone.
Q. 11. Mention varieties of inflammation. l The outcome of acute inflammation may be removal of
the exudate with restoration of normal tissue architec-
Ans. ture, transition to chronic inflammation or extensive
Inflammation is defined as a local response of living mam- destruction of the tissue resulting in scarring.
malian tissue to injury due to any agent. It is a body’s
defence reaction in order to eliminate or limit the spread of Chronic Inflammation
injurious agent as well as to remove consequent necrosed
cells and tissues. l Chronic inflammation is inflammation of prolonged
duration about weeks to months to years in which active
inflammation, tissue injury and healing proceed simul-
TYPES OF INFLAMMATION taneously, e.g. tuberculosis, leprosy, fungal infection,
Depending on the host immune levels and duration of re- schistosomiasis.
l Chronic inflammation is characterized by the following:
sponse, inflammation can be classified as acute and chronic.
1. Infiltration with mononuclear cells including macro-
phages, lymphocytes and plasma cells
Acute Inflammation 2. Tissue destruction, largely induced by the products
l Acute inflammation is a rapid response to injury or mi- of the inflammatory cells
crobes and other foreign substances that is designed to 3. Repair, involving new vessel proliferation, i.e. an-
deliver leucocytes and plasma proteins to sites of injury. giogenesis and fibrosis.
SHORT NOTES
Q. 1. Chemotaxis 2. Engulfment stage
3. Secretion stage
Ans.
4. Degradation stage
l Chemotaxis is defined as the transmigration of leucocytes
across several barriers of endothelium, basement mem- Q. 3. Lymphokines
brane, perivascular myofibroblasts and matrix to reach Ans.
the interstitial tissue mediated by chemotactic factors.
l The concept of chemotaxis can be illustrated by l Activated lymphocytes are known as lymphokines.
Boyden’s chamber experiment. l They produce cytokines which are polypeptide sub-
l The chemotactic agents are also called as chemokines stances that act on self cells producing them or on other
and they carry specific receptors. cells and act as mediators of inflammation.
l Some of the potent chemokines are as follows:
1. Leukotriene B4 Q. 4. Signs of inflammation

2. Platelet factor 4 (PF4) Ans.
3. Components of complement system (C5a)
4. Cytokines, particularly IL-8 l Inflammation is defined as a protective response intended
5. Soluble bacterial products to eliminate the initial cause of cell injury as well as
6. Monocyte chemoattractant protein (MCP-1) necrotic cells and tissues resulting from the original
7. Chemotactic factor for CD41 T cells insult.
8. Exotoxin chemotactic for eosinophils l Cardinal signs of inflammation are given in Table 2.4.
Q. 2. Phagocytosis TABLE 2.4 Cardinal Signs of Inflammation

Ans. Cardinal Signs Mechanism
l Phagocytosis is the process of engulfment of solid 1. Rubor (redness) Capillary dilatation

particulate matter by the cells called as phagocytes. 2. Tumour (swelling) Infiltration
l The two main types of phagocytic cells are as follows:
3. Calor (heat) Pyrogens
1. Polymorphonuclear neutrophils (microphages): They
appear early in an acute inflammatory response. 4. Dolor (pain) Lymphokines
2. Macrophages: These are circulating monocytes and
fixed tissue mononuclear phagocytes. l These four cardinal signs of inflammation were named
l Both these types share a common process of phagocyto- by the Roman writer Celsus in first century AD.
sis involving four steps as follows: l To these Virchow later added the fifth sign known as
1. Attachment stage functio laesa (loss of function).
Q. 5. Vascular phenomenon in inflammation l Stimuli or substances inducing acute inflammation,

e.g. heat, cold, irradiation, trauma, irritant chemicals,
Ans. immunologic reactions, etc.
l Anaphylatoxins like fragments of complement C3a and
C5a, which increase vascular permeability and cause

VASCULAR CHANGES IN INFLAMMATION oedema in tissues
l Histamine releasing factors from neutrophils, mono-
l Alteration in microvasculature, i.e. capillaries, venules
and arterioles, is the first response to tissue injury. cytes and platelets
l Neuropeptides such as substance P
l It takes place as changes in the haemodynamic state and
l Interleukins
in vascular permeability.
The main actions of histamine are vasodilation, in-
creased vascular permeability, itching and pain. Stimula-
Haemodynamic Changes tion of mast cells and basophils also releases products
l It is the earliest sign of inflammation, that results from of arachidonic acid metabolism including the release of
changes in the vascular flow and calibre of small blood slow reacting substances of anaphylaxis which consists of
vessels in the injured tissue. various leukotrienes.
l It takes place as a sequence of events as follows:
Q. 7. Exudate
1. Transient vasoconstriction of arterioles
2. Persistent vasodilatation of arterioles, venules and Ans.
capillaries
3. Rise in local hydrostatic pressure l Exudate is defined as oedema of inflamed tissue associ-
4. Slowing or stasis of microcirculation ated with increased vascular permeability, e.g. pus.
l The oedematous fluid consists of primarily high protein
5. Stasis is followed by leukocytic margination or pe-
ripheral orientation of leucocytes along the vascular content—2.5–3.5 g/dL, inflammatory cells and paren-
endothelium. chymal cells.
l It readily coagulates due to high fibrinogen and other
l After sticking briefly to the vascular endothelium, the
leucocytes migrate through the gap between the endo- coagulation factors.
l It has a pH less than 7.3 and a high specific gravity more
thelial cells into the extravascular space, this is known
as emigration. than 1.018.
l It has low glucose content less than 60 mg/dL.
l After injury the skin exhibits triple response or the red-
line response. This is characterized by the following:

Q. 8. Gumma
1. Appearance of redline following stroking due to lo-
cal vasodilatation Ans.
2. Flare is the bright reddish appearance or flush sur-
rounding the redline. l The syphilitic gumma is a lesion caused due to tertiary
3. Wheal is a swelling or oedema surrounding the red- syphilis.
l It is a solitary, localized rubbery lesion with central
line that occurs due to transudation of fluid into the
extravascular space. necrosis. Seen in organs like liver, testis, bone and brain
associated with scarring of hepatic parenchyma.
l Histologically the structure of gumma shows the fol-
Altered Vascular Permeability lowing:
Increased vascular permeability is seen during inflammation. 1. Central coagulative necrosis resembling caseation
but is less destructive so that outlines of necrosed
Q. 6. Mention the role of histamine in inflammation. cells can still be faintly seen.
2. Surrounding zone of palisaded macrophages with
Ans. lymphocytes, plasma cells, giant cells and fibroblasts.
Two important pharmacologically active amines that
Q. 9. Granuloma
have role in early inflammatory response are histamine and
5-hydroxytryptamine (5-HT) or serotonin. Ans.
l Granuloma is defined as circumscribed, tiny, lesion,

HISTAMINE about 1 nm in diameter, composed predominantly of
It is stored in the granules of mast cells, basophils and collection of modified macrophages called epitheli-
platelets. Histamine is released from these cells by various oid cells and rimmed at the periphery by lymphoid
agents as follows: cells.
l Besides the presence of epithelioid cells and lymphoid l It can be classified into two types based on the resis-
cells, granuloma have giant cells, necrosis and fibrosis. tance offered as follows:
1. Lepromatous leprosy—representing low resistance
Q. 10. Actinomycosis 2. Tuberculoid leprosy representing high resistance
l Lepromatous leprosy is characterized by multiple
Ans.
symmetrical skin lesions that are hypopigmented and
l Actinomycosis is a chronic suppurative disease caused erythematous maculopapular or nodular.
by anaerobic bacteria Actinomycetes israelii. l Nerve involvement is present with less severe sensory
l The infection is always endogenous in origin. The distribution.

organisms invade, proliferate and disseminate in favour- l Histopathology involves collection of foamy macro-
able conditions. phages or lepra cells in the dermis separated from epi-
l Based on anatomical location of lesions, actinomycosis dermis by a clear zone.
is of following types:
1. Cervicofacial actinomycosis Q. 13. Pathological lesions of syphilis
2. Thoracic actinomycosis Ans. Pathological lesions of syphilis are primary, second-
3. Abdominal actinomycosis ary and tertiary depending upon the period after which
4. Pelvic actinomycosis lesion appear and type of lesions.
Of all the types, cervicofacial actinomycosis is the com-
monest form.
l Lab diagnosis of actinomycosis
Primary Syphilis
1. The inflammatory reaction is a granuloma with cen-
tral suppuration. l Typical lesion is chancre.
2. The centre of each abscess contains bacterial colony l This appears on genitals or at extragenital sites in
sulphur granule characterized by radiating filaments. 2–4 weeks after exposure of infection.
3. Bacterial stains reveal the organisms as nonacid, l Initially the lesion is painless papules which ulcerate in
fast, Gram-positive filaments. centre. So a fully developed chancre is an indurated lesion.

l The chancre heals without scarring even without
Q. 11. Congenital syphilis treatment.
Ans.
Secondary Syphilis
l Treponema pallidum may be transmitted across the pla-
centa from the infected mother to the fetus at any time l Inadequately treated patients of primary syphilis develops
during pregnancy. Congenital syphilis may develop in mucocutaneous lesions and are painless in 2–3 months
fetus of more than 16 weeks gestation. after exposure.
l The likelihood of maternal transmission is high during l Mucocutaneous lesions may be in form of mucus
the early stages, i.e. primary and secondary stages of the patches of mouth, pharynx and vagina.
disease, when spirochetes are most numerous.
l Manifestations of congenital syphilis include still birth,
Tertiary Syphilis
infantile syphilis and late (tardive) congenital syphilis.
l Infantile syphilis manifests at birth or within first few l About 2–3 years following first exposure, tertiary lesion
months of life. Affected infants present with chronic of syphilis appears.
rhinitis (snuffles) and mucocutaneous lesions. l They are of two types as follows:
l Late (tardive) congenital syphilis refers to cases of un- 1. Syphilitic gumma: Solitary, localized, rubbery lesion
treated congenital syphilis of more than 2 years. Classic with central necrosis, seen in liver, testis, bone and
manifestations include the Hutchinson triad, notched brain
central incisors, interstitial keratitis with blindness and l Diffuse lesions: The lesions appear following wide-
deafness from eighth cranial nerve injury. spread dissemination of spirochaetes in the body. Seen
mainly in cardiovascular and nervous systems.
Q. 12. Lepromatous leprosy l Lesions of tertiary syphilis are much less infective than
other two stages.

Ans.
Q. 14. Chronic granulomatous inflammation
l Leprosy is a slow communicable disease caused by
Mycobacterium leprae. Ans.
Granuloma is defined as a circumscribed tiny lesion, about Primary complex

1 mm in diameter composed predominantly of collection of
Or,
modified macrophages called epithelioid cells and rimmed
at periphery by lymphoid cells. Primary tuberculosis
Examples of granulomatous inflammation:
Ans.
1. Tuberculosis
2. Syphilis l Primary tuberculosis or Ghon’s complex or childhood
3. Leprosy tuberculosis is the infection of an individual who has
4. Fungal infection not been previously infected or immunized.
l The most commonly involved tissues for primary com-
Q. 15. Cellular events in acute inflammation plex are lung and hilar lymph nodes.
Ans. l Primary complex or Ghon’s complex in lungs consists
of three components as follows:

Cellular events in acute inflammation can be grouped under 1. Pulmonary component
two headings as given in Table 2.5. 2. Lymphatic vessel component
3. Lymph node component
TABLE 2.5 Cellular Events in Acute Inflammation l The pulmonary component exhibits a lesion in the lung
known as primary focus or Ghon’s focus. It is 1–1.5 cm

Exudation of Leucocytes Phagocytosis
solitary area of grey-white inflammatory consolidation.
Change in the formed Attachment stage or l Tubercle bacilli, either free or within phagocytes drain
elements of the blood opsonization
to the regional lymph nodes, which often caseate. This
Adhesion or rolling Engulfment stage combination of parenchymal lesion and nodal involve-
Emigration Secretion or degranulation ment is referred to as Ghon’s complex.
stage
Q. 18. Oral manifestations of syphilis
Chemotaxis Killing or degradation stage
Ans.
Q. 16. What is tuberculoid granuloma? Give three l Oral lesions occur in the secondary syphilis known as
examples. mucous patches, on tongue, gingiva, etc. or as a split
papule on lips, which are highly infectious.
Ans. l Tertiary or late syphilis or gumma is a granuloma with
central necrosis, noninfectious and most common on the

l Tuberculoid granuloma is defined as circumscribed,
tongue and palate.
tiny lesion, about 1 nm in diameter, composed pre-
l Palatal perforation by ulcer after vigorous antibiotic use
dominantly of collection of modified macrophages
is known as Herxheimer reaction.
called epithelioid cells and rimmed at the periphery by
l Atrophic or interstitial glossitis is most characteristic lesion
lymphoid cells.
and has malignant potential to squamous cell carcinoma.
l Tissue response in tuberculosis represents classical
l In congenital or prenatal syphilis, most constant finding
example of chronic granulomatous inflammation in
is relatively short roots of mandibular permanent first
humans.
molars, short maxilla, Hutchinson’s triad (teeth, eye or
l It is caused by Mycobacterium tuberculosis that has five
ear involved), hypoplasia of incisors and molars, i.e.
pathogenic strains: hominis, bovis, avium, murine and
notched screwdriver-shaped incisors and Mulberry/
cold-blooded vertebrate strain.
Moon’s/Fournier’s molars.
l Its special characteristics are tuberculosis granuloma
l Treatment: Penicillin is the drug of choice.
with central caseation necrosis; acid-fast bacilli. It can
be diagnosed by the following: Q. 19. Chronic inflammation
1. Acid-fast (Ziehl-Neelsen) staining
2. Fluorescent dye methods Ans.
3. Culture of organism
l Chronic inflammation is inflammation of prolonged
4. Guinea pig inoculation
duration about weeks to months to years in which active
Q. 17. Ghon’s complex inflammation, tissue injury and healing proceed simul-
taneously, e.g. tuberculosis, leprosy, fungal infection,
Or, schistosomiasis.
l Chronic inflammation is characterized by the following: l Morphologically different cells are seen in chronic
1. Infiltration with mononuclear cells including macro- inflammation and tumours.
phages, lymphocytes and plasma cells
2. Tissue destruction, largely induced by the products
of the inflammatory cells Giant Cells in Inflammation
3. Repair, involving new vessel proliferation, i.e. an- l Foreign body giant cells: Chronic infective granuloma,
giogenesis and fibrosis leprosy and tuberculosis
l Langhans giant cells: Sarcoidosis and tuberculosis
Q. 20. Tuberculoid type of leprosy l Touton’s giant cells: Xanthoma
Ans. l Aschoff’s giant cells: Rheumatic nodules
l Leprosy is a slow communicable disease caused by

Mycobacterium leprae. Giant Cells in Tumours
l It can be classified into two types based on the resis-
l Anaplastic cancer giant cells—seen in carcinoma of
tance offered as follows:
liver and various soft tissue sarcomas
1. Lepromatous leprosy—representing low resistance
l Reed-Sternberg cells: Hodgkin’s lymphoma
2. Tuberculoid leprosy—representing high resistance
l Giant cell tumour of bone—uniform distribution of
l Tuberculoid leprosy is characterized by asymmetrical skin
osteoclastic giant cells spread in the stroma
lesions that are hypopigmented and erythematous macular.
Nerve involvement is with distinct sensory distribution. Q. 23. Lepra reaction
l Histopathology involves hard tuberculi similar to granu-
lomatous lesions eroding the basal layer of epidermis. Ans.
Q. 21. Chancre Lepra reaction is the reaction seen in leprosy patients.

There are two types of lepra reactions as follows:
Ans. Borderline reactions: The polar forms of leprosy do not
undergo any change in clinical and histopathological pic-
l Chancre is a typical lesion of primary syphilis which
ture. The borderline patients are unstable and the condition
appears on the genitals or extragenital sites in 2–4
may upgrade or degrade according to the patient’s immune
weeks after exposure to infection.
status.
l Initially the lesion is a painless papule which ulcerates
in the centre. 1. Upgrading reaction: This is characterized by in-

l So a fully developed chancre is an indurated lesion with creased cell-mediated immunity and is seen in lepro-
central ulceration accompanied by regional lymphadenitis. matous leprosy patients who upgrade to tuberculous
l The chancre heals without scarring even without treatment. type.
2. Downgrading reaction: This is characterized by low-
Q. 22. Giant cells ered cell-mediated immunity and is seen in tuberculous
Ans. leprosy patients who degrade to lepromatous type.
l Giant cells are normally seen in cells like osteoclasts of bone,
trophoblasts in placenta, megakaryocytes in bone marrow. Erythema nodosum leprosum (ENL) reaction: This
l In chronic inflammation when the macrophages fail
reaction occurs in lepromatous patients after treatment.
to deal with particles to be removed, they fuse together It is characterized by tender cutaneous nodules, fever,
to form multinucleated giant cells. iridocyclitis, synovitis and lymph node involvement.
Topic 3
Tissue Repair: Regeneration,

Healing and Fibrosis
LONG ESSAYS
Q. 1. Describe the healing of a fracture. Enumerate the Define healing. Mention types of wound healing. Describe
causes for nonhealing of fracture. healing of a fracture and factors influencing the same.
Or, Or,
Describe the stages in healing of a fracture. Mention five 2. Osseous callus formation
factors that can cause delayed healing. l The procallus acts as a scaffolding on which osseous
callus composed of lamellar bone is formed.

Ans.
l The new formation of blood vessels and osteoblasts
l Healing can be defined as the body response to injury in is by laying down osteoid which is calcified and
an attempt to restore normal structure and function. laminar bone is formed by developing Haversian
l Healing can take place by repair or regeneration or
system concentrically around the blood vessels.
l External callus consists of new tissue which forms
sometimes both.
l Types of wound healing are as follows:
around the outside of the two fragments of bone. Internal
1. Healing by primary intention (primary union) callus is the new tissue arising from the marrow cavity.
l The periosteum is an important structure in callus
2. Healing by secondary intention (secondary union)
l Healing of fracture or repairing of bone occurs by callus
formation and ultimate healing of the fracture.
formation. It depends upon the 3 Remodelling of the callus
l The external and internal calluses which unite the
1. trauma of the fracture,
2. whether the fracture is complete or incomplete, two fragments of bone must be remodelled because
3. whether the fracture is simple (closed), comminuted there is always an overabundance of new bone pro-
(splintering of bone), or compound (communicating duced to strengthen the healing site.
l During the formation of lamellar bone, osteoblastic
to skin surface).
l Healing of fractures may take place by two ways as
laying and osteoclastic removal are taking place
follows: remodelling the united bone ends, which after some-
1. Healing by primary union time is indistinguishable from normal bone.
l It occurs in special situations when the ends of
fractures are approximated as is done by applica- GENERAL FACTORS AFFECTING THE

tion of compression clamps. HEALING OF ORAL WOUNDS
l Bony union takes place with the formation of med-
ullary callus without periosteal callus formation. Local Factors

2. Healing by secondary union l Infection: It is the most important factor acting locally.
l It is the more common type of fracture healing. Severe bacterial infection delays the process of wound
Though it is continuous, it takes place in three steps. healing.
The process of secondary bone union is described in fol- l Blood supply: Poor blood supply to wound shows
lowing three steps: delayed healing. Injuries to face heal quickly due to rich
1. Procallus formation blood supply while injury to leg having poor blood
l Haematoma formation: It occurs due to extravasa- supply heals slowly.
tion blood from the disruption of blood vessels, fill- l Foreign bodies: Various foreign bodies including suture
ing the area surrounding fracture site. interfere with healing and cause intense inflammatory
l Local inflammatory response: Occurs at the site of reaction and infection and delays healing.
injury with exudation of fibres, polymorphs and l Immobilization is important in healing process. If wound
macrophages. fragments of necrosed bone are scav- is in an area subjected to constant movements so that
enged by macrophages and osteoclasts. the formation of new connective tissue is continuously
l In growth of granulation tissue: It begins with neo- disrupted, delayed wound healing results.
vascularization and proliferation of mesenchymal l Exposure to ionizing radiation: It delays granulation
cells from periosteum and endosteum. tissue formation.
l A soft callus is formed which joints the ends of frac- l Exposure to UV light: It facilitates healing.
ture bone. This callus is composed of woven bone l Type, size and location of injury: They determine whether
and cartilage. healing takes place by resolution or organization.
l The cells of inner layers of periosteum have osteogenic
potential and lay down collagen as well as osteoid

matrix in the granulation tissue. The osteoid undergoes
Systemic Factors
calcification and is called woven bone callus. l Age: Wound healing is rapid in young and somewhat
l The subperiosteal osteoblasts may form cartilage at slow in aged, due to poor blood supply to injured area
fracture site. in latter age group.
l This stage is called provisional callus or procallus l Nutrition: Deficiency of constituents like protein, vita-
formation. min C and zinc delays the wound healing.
l Systemic infection delays wound healing. l The migrating epithelial cells separate the underly-
l Administration of glucocorticoids has anti-inflammatory ing viable dermis from overlying necrotic material
effect. and clot, forming scale which is cast off.
l Uncontrolled diabetes is more proven to develop infec- l The basal cells from the margins continue to divide. By
tions and hence delay in healing. fifth day a multilayered new epidermis is formed which
l Haematological abnormalities like defect of neutrophil is differentiated into superficial and deeper layers.
functions, neutropenia and bleeding disorders slow the 4 . Organization
process of wound healing. l By the third day, fibroblasts also invade the wound
area. By fifth day new collagen fibrils start forming

Q. 2. Describe the healing of wound by primary union. which dominate till healing is completed.
Mention the differences between primary and l In 4 weeks, the scar tissue with scanty cellular and
secondary union. vascular elements, a few inflammatory cells and epi-
Or, thelial surface is formed.
5. Suture tracks
Define repair. Discuss factors which influence the pro- l Each suture track is a separate wound and incites the
cess of repair. Describe briefly healing by secondary same phenomena as in healing of the primary
union. wound, i.e. filling the space with haemorrhage some
Or, inflammatory cell reaction, epithelial cell prolifera-
tion along the suture track from both the margins,
Define repair and regeneration. Describe differences fibroblastic proliferation and formation of young
between primary healing and secondary healing. collagen.
l When sutures are removed around seventh day, much
Ans.
of epithelialized suture track is avulsed and the
l Repair is a form of healing where healing takes place by remaining epithelial tissues in track are absorbed.
proliferation of connective tissue elements resulting in l However, sometimes the suture track gets infected,
fibrosis and scarring. or the epithelial cells may persist in the track
l Regeneration is a form of healing where healing takes (implantation or epidermal cysts).
place by proliferation of parenchymal cells and usu-
ally results in complete restoration of the original
tissues. SECONDARY INTENTION
l Wound healing can take place in two ways as follows:
l Healing by secondary intention occurs in open wounds
1. Healing by primary intention (primary union) with large tissue defect, and at times infected and
2. Healing by secondary intention (secondary union) having extensive loss of cells and tissue.
l Secondary union takes place from base upwards and
PRIMARY HEALING margins inward. It is slow and results in a scar.

l Secondary union takes place in the following steps:
Primary healing takes place in wounds which
1. Initial haemorrhages where the wound space gets
l are surgically incised, filled with fibrin and blood clot which dries.
l have clean edges approximated by surgical sutures, 2. Inflammatory phase that occurs within 24 h with ap-
l are uninfected and pearance of polymorphs from the wound margin.
l do not have much loss of cells and tissues. 3. By third day macrophages appear which clear off the
debris.
The following events occur in healing of wounds by 4. Epithelial changes where epithelial cells proliferate
primary intention: from the wound margins and migrate in the form of
1. Haemorrhage: Immediately after injury, the space be- epithelial spurs till re-epithelialization occurs and
tween approximated surfaces of incised wound is filled the gap is closed completely.
with blood which then clots and seals the wound and 5. But proliferation cells do not cover the gap till
prevents dehydration and infection. granulation tissue from the base starts filling the
2. Acute inflammatory response: It occurs within 24 h with wound space.
appearance of polymorphs from the margins of incision 6. Granulation tissue forms the main bulk of secondary
by third day, polymorphs are replaced by macrophages healing. It is formed by proliferating fibroblasts and
which clear off the debris. neovascularization.
3. Epithelial changes 7. Wound contraction takes place due to action of
l From the both cut margins the basal cells of epider- myofibroblasts present in the granulation tissue.
mis start proliferating in the form of epithelial spurs The wound tissue formed contracts to one-third to
and marginating towards incisional space. one-fourth of its original size.
8. Presence of infection delays healing process by Primary Healing Secondary Healing

release of bacterial toxins which provoke necrosis,
Edges of wound are Edges of wound are not
suppuration and thrombosis. approximated by surgical approximated by surgical
Differences between primary and secondary healing are sutures sutures
listed in Table 3.1. Takes place in surgically Takes place in infected and
incised wounds large wounds caused due to
any form of injury
TABLE 3.1 Differences between Primary and Secondary
Scar formation is neat and Scar formation is ugly and large
Healing small
Primary Healing Secondary Healing There is no granulation It forms the main bulk of
Wound is clean and Wound is open with large tissue formation secondary healing
uninfected tissue defect and at times Healing takes place from Healing takes place from base
infected margins inward upwards besides from margins
There is not much loss of There is extensive loss of cells inward
cells and tissues and tissues Healing is rapid Healing is slow
SHORT ESSAYS
Q. 1. Granulation tissue Fibrous Tissue Formation
Ans. l New fibroblasts originate from fibrocytes and by miotic
division of fibroblasts.
l Granulation tissue is a newly proliferated tissue that is l Some of these are myofibroblasts, i.e. they have charac-
formed during healing of a wound by secondary intention. teristics of smooth muscle cells.
l Granulation tissue is formed by proliferation of fibro-
l The fibrils begin to appear by about sixth day.
blasts and neovascularization from the adjoining viable l The number of new fibroblasts and blood vessels
elements. It is deep red, granular and very fragile. decrease and more and more collagen is formed as
l It takes place in three phases as follows:
maturation advances.
1. Phase of inflammation: The acute inflammatory re- l This results in the formation of inactive looking scar
sponse occurrence with the exudation of plasma, known as cicatrization.
neutrophils and some monocytes within 24 h. The
blood clot forms at the site of trauma, after injury. Q. 2. Complications of wound healing
2. Phase of clearance: Necrotic tissue, debris and
RBCs are removed from the site by the proteolytic Ans.
enzymes liberated from neutrophils, autolytic en- During wound healing, complications can occur which may
zymes from dead tissue cells and phagocytic activity slow down the process.
of macrophages.
3. Phase of ingrowth of granulation tissue: This phase
consists of two main processes: angiogenesis and Some common complications of wound healing are as
fibrous tissue formation as described below. follows:
1. Infection: Severe infections of wound delays wound
healing.
2. Implantation (epidermal) cyst: Persistence of epithelial
ANGIOGENESIS (NEOVASCULARIZATION) cells in the wound after healing results in formation of
l New blood vessels are formed at the site of injury by implantation or epidermal cyst.
proliferation of endothelial cells from the margins of 3. Pigmentation: Sometimes healed wounds may have a
severed blood vessels. rust-like colour due to staining with haemosiderin.
l Initially these are solid buds, within few hours they Some coloured pigments may be left behind during
develop a lumen and start carrying blood. healing that impart colour.
l They are leaky in the beginning but soon differentiate 4. Deficient scar formation: This may occur due to inade-
into muscular arterioles, thin-walled venules and true quate formation of granulation tissue.
capillaries. 5. Incisional hernia: A weak scar, especially after lapa-
l This process is influenced by the following: rotomy, may be the site for bursting open of the wound
1. Endothelial cells growth factor: Positive from an incisional hernia.
2. Type IV collagen and other components of matrix: 6. Hypertrophied scars and keloid formation: At times
Negative scar formation is ugly and painful. Excessive formation
of collagen in healing may result in keloid formation. l Foreign bodies: Various foreign bodies including suture
Hypertrophied scars are confined to the borders of the interfere with healing and cause intense inflammatory
initial wound while keloids are claw-like or tumour-like reaction and infection and delays healing.
projections of the connective tissue. l Immobilization is important in healing process. If wound
7 . Excessive contraction: An exaggeration of wound is in an area subjected to constant movements so that the
contraction may result in formation of contractures or formation of new connective tissue is continuously dis-
cicatrization. rupted, delayed wound healing results.
8. Neoplasia: Rarely scar may be the site of development l Exposure to ionizing radiation: It delays granulation
of carcinoma later, e.g. squamous cell carcinoma in tissue formation.
Marjolin’s ulcer, i.e. the scar following burns on skin. l Exposure to UV light: It facilitates healing.
l Type, size and location of injury: They determine whether

Q. 3. Describe the factors delaying wound healing. healing takes place by resolution or organization.
Ans.
General factors delaying the healing of oral wounds are as

SYSTEMIC FACTORS
follows: l Age: Wound healing is rapid in young and somewhat
1. Local factors slow in aged, due to poor blood supply to injured area
2. Systemic factors in latter age group.
l Nutrition: Deficiency of constituents like protein,
vitamin C and zinc delays the wound healing.

LOCAL FACTORS
l Systemic infection delays wound healing.
l Infection: It is the most important factor acting locally. l Administration of glucocorticoids has anti-inflamma-
Severe bacterial infection delays the process of wound tory effect.
healing. l Uncontrolled diabetes is more proven to develop
l Blood supply: Poor blood supply to wound shows infections and hence delay in healing.
delayed healing. Injuries to face heal quickly due to l Haematological abnormalities like defect of neutrophil
rich blood supply while injury to leg having poor blood functions, and neutropenia and bleeding disorders slow
supply heals slowly. the process of wound healing.
SHORT NOTES
Q. 1. Fracture healing l Granulation tissue is a newly proliferated tissue that is
Ans. formed during healing of a wound by secondary intention.
l Granulation tissue is formed by proliferation of fibro-
l Healing can be defined as the body response to injury in blasts and neovascularization from the adjoining via-
an attempt to restore normal structure and function. ble elements. It is deep red in colour, granular and
l Healing of fractures may take place by two ways as follows: very fragile.
1. Healing by primary union l Formation of granulation tissue takes place in three
2. Healing by secondary union phases as follows:

l Healing by primary union occurs in special situations 1. Phase of inflammation
when the ends of fractures are approximated as is done 2. Phase of clearance
by application of compression clamps. Bony union 3. Phase of ingrowth of granulation tissue
takes place with the formation of medullary callus
without periosteal callus formation. Q. 3. Healing by secondary intention
l Healing by secondary union is the more common type
Ans.
of fracture healing. Though it is continuous, it takes
place in following three steps: l Healing by secondary intention occurs in a wound
1. Procallus formation 1. open with large tissue defect and at times infected.
2. Osseous callus formation 2. having extensive loss of cells and tissue.
3. Remodelling of the callus 3. which has not been approximated by surgical sutures
but has been left open.
Q. 2. Granulation tissue
l Secondary union takes place from base upward and mar-
Ans. gins inward. It is slow and results in a scar formation.

l Secondary union takes place in the following steps: Q. 4. Sequential stages in wound healing by first inten-
1. Initial haemorrhage, where the wound space gets tion or primary union.
filled with fibrin and blood clot.
Ans.
2. Inflammatory phase occurs within 24 h with appear-
ance of polymorphs. l Primary healing takes place in clean and uninfected and
3. Epithelial changes, where epithelial cells prolifer- surgically incised wounds whose edges are approxi-
ate from the wound margins and migrate in mated by sutures.
the form of epithelial spurs till re-epithelialization l Sequential stages in wound healing by first intention or
occurs. primary union are as follows:
4. Granulation tissue forms the main bulk of secondary 1. Initial haemorrhage
healing. It is formed by proliferating fibroblasts and 2. Acute inflammatory response
neovascularization. 3. Epithelial changes
5. Wound contraction occurs due to action of myofibro- 4. Organization
blasts present in the granulation tissue. 5. Suture tracks
Topic 4
Haemodynamic Disorders, Thrombosis

and Shock
LONG ESSAYS
Q. 1. Define oedema. Describe aetiopathogenesis of 2. Subcutaneous oedema is of two types
oedema.
Ans.
Oedema may be defined as abnormal and excessive accu- a. Pitting oedema (It produces de- b. Nonpitting or solid oedema
mulation of fluid in interstitial tissue spaces and serous pression on momentary pressure (It does not produce depression.)
cavities. of finger on oedema.) Example: Myxoedema, elephan-
tiasis
3. Depending on oedema fluid, oedema are of two types

Types of Oedema
1. Three main types of oedema

a. Transudative oedema b. Exudative oedema
(It is made up of filtrate of blood (It is made of oedema of
plasma.) inflammatory tissue.)
Example: Cardiac and renal oedema Example: Inflammatory oedema
a. Localized b. Generalized c. Special
(in the organ or limb) (anasarca or dropsy) Example: Pulmo-
MECHANISM OF OEDEMA
Example: Inflamma- Example: Systemic in distri- nary, cerebral
tory, lymphatic, toxic, bution especially noticeable l Oedema is the result of an increase in the forces that
allergic in the subcutaneous tissue, tend to move fluids from intravascular compartment to
e.g. renal, cardiac, nutritional the interstitial space.
l The following six mechanisms may be operating singly Example

or in combination to produce oedema:
1 . Removal of axillary lymph nodes in radical mastectomy
1. Decreased plasma oncotic pressure
2. Outside pressure on the abdominal or thoracic duct by
2. Increased capillary hydrostatic pressure
tumours or effusions
3. Lymphatic obstruction
3. Inflammation of the lymphatics as seen in filariasis
4. Tissue factors
4. Occlusion of lymphatic channels by the malignant cells
5. Increased capillary permeability
6. Sodium and water retention
Tissue Factors
Decreased Plasma Oncotic Pressure
l Oncotic pressure of interstitial space and tissue tension
l The plasma oncotic pressure exerted by the total amount and the forces acting in the interstitial space are quite
of plasma proteins tends to draw fluid into the vessels small and insignificant.
normally. l However, they can cause oedema when oncotic pressure
l A fall in the total plasma protein level or hypoprotein- of interstitial fluid is elevated due to increased vascular
aemia less than 5 g/dL lowers plasma oncotic pressure permeability and inadequate removal of proteins by
and thus it cannot effectively counteract the hydrostatic lymphatics.
pressure of blood. This results in increased outward
movement of fluid from the capillary wall and de-
creased inward movement of fluid from the interstitial
Increased Capillary Permeability
space causing oedema. l An intact capillary endothelium acts as semipermeable
l Albumin exerts highest oncotic pressure (four times than membrane permitting free flow of water and crystalloids
globulin) and thus hypoalbuminaemia (level , 2.5 g/dL) only and allowing only minimal passage of tissue
often results in oedema. proteins.
l Hypoproteinaemia usually produces generalized oedema. l However, the capillary endothelium may be injured
l Example: by various capillary poisons such as toxins and their
l Oedema of renal disease: nephrotic syndrome, acute products, histamine, anoxia, venoms, certain drugs and
glomerulonephritis chemicals.
l Ascites of liver disease: cirrhosis l In such cases there is development of gaps between the
endothelial cells increasing the capillary permeability to

plasma proteins. Thus, oncotic pressure of plasma is
Increased Capillary Hydrostatic Pressure
reduced and that of interstitial fluid is elevated, conse-
l Capillary hydrostatic pressure is the force that normally quently producing oedema.
tends to drive fluid through the capillary wall into inter-
stitial space by counteracting the force of plasma Examples:
oncotic pressure. 1. Generalized oedema in systemic infections, poisonings,
l Usually the hydrostatic pressure at venular end of capil- certain drugs and chemicals, anaphylaxis and anoxia.
laries is low (12 mg of Hg) allowing the return of inter- 2. Localized oedema such as
stitial fluid. a. inflammatory oedema: infections, allergic reactions,
l A rise in the hydrostatic pressure at the venular end to a insect bite, irritant drugs and chemicals
level more than the plasma oncotic pressure results in b. angioneurotic oedema involves face, trunk, lips, larynx,
minimal or no reabsorption of fluid at the venular end pharynx and lungs
consequently leading to oedema.
l Example
Sodium and Water Retention
1. Oedema of cardiac disease: congestive cardiac
failure, constrictive pericarditis Excessive retention and decreased renal excretion of
2. Passive congestion: mechanical obstruction due to sodium and water occur in response to hypovolaemia
thrombosis of veins of lower limbs, varicosities, through the following mechanisms:
pressure by uterus, tumours
Intrinsic Renal Mechanism
Lymphatic Obstruction l It is activated in response to sudden reduction in the ef-
l Normally the interstitial fluid in the tissue spaces fective arterial blood volume as in severe haemorrhage.
escapes through lymphatics and thus obstruction to l Hypovolaemia stimulates atrial baroreceptors located in
outflow of the lymphatics causes localized oedema and carotid sinus and aortic arch. They in turn send sympa-
is known as lymphoedema. thetic outflow via the vasomotor centre in the brain.
This leads to renal ischaemia producing reduction in Pathogenesis

GFR, decrease in urinary sodium excretion and conse-
quently retaining sodium in the body. Oedema in Nephrotic Syndrome
l Nephrotic syndrome is characterized by persistent and
Extrarenal Mechanism heavy proteinuria resulting in hypoalbuminaemia.
l This reduces plasma oncotic pressure so much that it
l Sodium retaining hormone aldosterone, by the renin an cannot counteract the effect of hydrostatic pressure of
giotensin system is mainly concerned with this mechanism. blood.
l Low concentration of sodium in the tubules stimulates l Thus there is increased outward flow of fluid from the
renin released by the granular cells of JG apparatus. capillaries and decreased inward flow of fluid from
l Renin then stimulates angiotensinogen and thus initiat- the interstitial space resulting in oedema (nephrotic
ing a cascade of events leading finally to production of oedema).
angiotensin II.
l Angiotensin II then stimulates the adrenal cortex to
secrete aldosterone which increases the sodium reab- Oedema in Glomerulonephritis

sorption from the renal tubules. l Glomerular diseases like acute diffuse glomerulone-
phritis and rapid progressive glomerulonephritis
ADH Mechanism produce oedema (nephritic oedema) due to excessive
reabsorption of sodium and water in the renal tubules
l Sodium retention leads to secondary water retention via rennin–angiotensin–aldosterone mechanism.
under the influence of ADH or vasopressin.
l ADH stored in neurohypophysis is released by in-
creased plasma sodium concentration and hypovolae- Oedema in Acute Tubular Injury
mia. Thus, all these three mechanisms lead to excessive l Acute tubular injury by shock or toxic chemicals causes
retention of sodium and water and their decreased renal loss of selective reabsorption and concentration of the
excretion in response to hypovolaemia and lowered glomerular filtrate by the renal tubules.
sodium concentration in the renal tubules. l This results in increased reabsorption of water and thus
Examples: oedema results.

1. Oedema of cardiac disease: Congestive cardiac failure
2. Ascites of liver disease: Cirrhosis CARDIAC OEDEMA
3. Oedema of renal disease: Nephrotic syndrome, glo-
merulonephritis Aetiology
Q. 2. Define oedema. Mention the different important In right-sided and congestive cardiac failure the generalized
types of oedema and their cause. oedema develops.
Ans. Pathogenesis of cardiac oedema is explained by following

hypothesis:
Oedema may be defined as abnormal and excessive accu-
1. Hypovolaemia caused due to reduced cardiac output
mulation of fluid in the interstitial tissue spaces and serous
stimulates intrinsic renal and extrarenal hormonal
cavities.
(renin–angiotensin–aldosterone) mechanisms as well as
ADH secretion, resulting in sodium and water retention
The different important types of oedema are as follows:
and oedema.
1. Renal oedema
2. Back pressure hypothesis: Due to heart failure, there
2. Cardiac oedema
is elevated central venous pressure. This is transmit-
3. Pulmonary oedema
ted to venous end of capillaries and this in turn raises
4. Cerebral oedema
the capillary hydrostatic pressure and results in tran-
sudation.
RENAL OEDEMA 3. Chronic hypoxia may injure the capillary wall causing
increased capillary permeability and leads to oedema.
Aetiology This is called forward pressure hypothesis. But this is
l Nephrotic syndrome not well accepted.
l Glomerulonephritis 4. Cardiac oedema is characteristically dependent oe-
l Acute tubular necrosis dema.
PULMONARY OEDEMA Cytotoxic Oedema

Pulmonary oedema develops from left heart failure. There is l Fluid accumulation is intracellular.
fluid accumulation not only in tissue spaces but also in the l Underlying mechanism is disturbance in cellular osmo-
pulmonary alveoli. It causes serious functional impairment. regulation.
Pathogenesis Example: Acute hypoxia with some chemicals, purulent

meningitis
Pulmonary oedema can result from either elevation of pulmo-
nary hydrostatic pressure or increased capillary permeability.
Interstitial Oedema
Elevation of pulmonary hydrostatic pressure l Occurs when excessive fluid crosses the ependymal lin-
l Increase in hydrostatic pressure of pulmonary capillar-
ing of ventricles and accumulates in periventricular
ies and the resulting imbalance between pulmonary white matter.
hydrostatic pressure and plasma oncotic pressure causes
excess fluid to move into interstitium. Example: Noncommunicating hydrocephalus
l As the draining capacity of lymphatics is exceeded, in-
terstitial oedema develops. Q. 3. What are the differences between an exudate and
l This, combined with prolonged elevation of hydrostatic a transudate?
pressure, causes alveolar lining cells to break and alveo-
lar oedema results. Ans. The major differences between exudate and transu-
l This mechanism is seen in left heart failure, mitral ste-
date are listed in Table 4.1.
nosis and thyrotoxicosis.
Increased capillary permeability TABLE 4.1 Differences between Exudate and Transudate
The alveolocapillary membrane may be damaged causing
increased vascular permeability so that excess fluid and Parameter Exudate Transudate
plasma proteins leak out, initially into interstitium and sub- Definition Exudate is defined Transudate is
sequently into alveoli. as oedema of defined as filtrate
Example: Fulminant pulmonary infections, inhalation inflamed tissue of blood plasma
associated with without changes
of ototoxic substances and radiation injury.
increased vascular in endothelial
permeability permeability
Acute high altitude oedema
Character Inflammatory type Noninflammatory
Individuals climbing to high altitude without waiting for of oedema oedema
acclimatization to set in suffer from this.
The anoxic damage to pulmonary vessels seems to be Protein High (.3 g/dL): Low (, 3 g/dL):
content due to high content especially albumin,
underlying mechanism. of fibrinogen and low fibrinogen, has
other coagulation no tendency to
factors it readily coagulate
CEREBRAL OEDEMA coagulates
In brain the function of fluid electrolyte is performed Glucose Low in neoplasms Same as in blood
by blood brain barrier located at the endothelial cells of and infections
capillaries. Specific High (. 1.018) Low (, 1.015)
gravity
Cerebral oedema is of three types as follows:
pH , 7.3 .7.3
1. Vasogenic oedema
2. Cytotoxic oedema LDH High Low
3. Interstitial oedema Effusion . 0.6 , 0.6
LDH/
serum
Vasogenic Oedema LDH ratio
l It results from increased filtration pressure or increased Cells Many cells Few cells, mainly
capillary permeability. (inflammatory as mesothelial cells
well as parenchyma) and cellular debris
l It is prominent around infarcts, brain abscess.
Q. 4. Define shock. Discuss types, pathogenesis and Reduced Effective Circulating Volume
pathology of shock.
It may result either
Ans. l by actual loss of blood volume as in hypovolaemic
shock or
Shock is defined as clinical state of cardiovascular collapse l by decreased cardiac output without actual loss of blood
characterized by as in cardiogenic and septic shock.
l an acute reduction of effective circulating blood volume.
l an inadequate perfusion of cells and tissues.

Tissue Anoxia
TYPES OF SHOCK Following reduction in effective circulating blood volume
there is decreased venous return to the heart resulting in
1 . Hypovolaemic shock
decreased cardiac output. This leads to tissue anoxia and
2. Septic shock
shock ensues.
3. Cardiogenic shock
The sequence of events in pathogenesis of shock are as
Hypovolaemic Shock follows:
Reduction in blood volume induces hypovolaemic shock.
Decreased effective circulatory blood volume
Causes
Decreased venous return
l Severe haemorrhage: Trauma, surgery
l Fluid loss: Burns, crush injury, dehydration due to
persistent vomiting and severe diarrhoea Decreased cardiac output
Septic Shock
Decreased blood flow
Severe bacterial infections or septicaemia induce septic shock.
a. Gram-negative septicaemia (endotoxic shock): In-
fections due to E. coli, Klebsiella and Pseudomonas Decreased supply of oxygen
cause endotoxic shock.
b. Gram-positive septicaemia (exotoxic shock): Infec-
Anoxia
tions due to streptococci and pneumococci cause
exotoxic shock and is less common.
Shock
Cardiogenic Shock
Acute circulatory failure with sudden fall in cardiac output STAGES OF SHOCK
from acute diseases of heart without actual reduction of
blood volume causes cardiogenic shock. Deterioration of the circulation in shock is a progressive
phenomenon and can be divided into following three stages
This may be due to (Table 4.2):
1. deficient emptying, e.g. myocardial infarction, rupture 1. Initial nonprogressive stage: During this stage reflex
of heart and cardiac arrhythmias. compensatory mechanisms are activated and perfusion
2. deficient filling, e.g. cardiac tamponade from haemo- of vital organs is maintained.
pericardium. 2. Progressive stage: This stage is characterized by tissue
3. obstruction to outflow, e.g. pulmonary embolism, ball hypoperfusion and onset of worsening circulatory and
valve thrombus. metabolic imbalances.
3. Irreversible stage: It sets in after the body has incurred
cellular and tissue injury so severe that even if the
PATHOGENESIS haemodynamic defects are corrected survival is not
There are two basic features in the pathogenesis of shock. possible.
TABLE 4.2 Stages of Shock . Heart in Shock

2
Stages Pathogenesis Effects There are two important morphogenic changes in heart in
all types of shock.
Initial Baroreceptor Tachycardia
nonprogressive a. Haemorrhage and necrosis: There may be small and
stage large ischaemic areas or infarcts particularly located in
Catecholamine Peripheral subpericardial and subendocardial regions.
release vasoconstriction b. Zonal lesions: There are opaque transverse contraction
Renin-angiotensin Cool clammy bands in myocytes near intercalated disc.
activation skin
3. Shock Lung
ADH release Renal conservation
of fluid l Due to dual blood supply lungs are not affected by
Sympathetic
hypovolaemic shock but are affected by septic shock.
stimulation The lungs become heavy and wet.
l Changes of adult respiratory distress syndrome are
Progressive ARDS Decreased
stage urinary output seen which include congestion, interstitial and alveolar
oedema, lymphocyte infiltration and fibrin and platelet
Anaerobic DIC
thrombi in microvasculature.
glycolysis
Lactic acidosis Mental confusion 4. Shock Kidney
Impaired Decreased l Irreversible renal injury is one of the important compli-
vasomotor cardiac output cations of shock.
response l Tubular lesions are seen referred to as acute tubular
Irreversible Persistent Brain: Death necrosis.

stage vasoconstriction l The end result is generally anuria and death.
Vasodilatation Lungs: ARDS

and vascular 5. Adrenal Changes in Shock
permeability l Adrenal shows stress syndrome which includes release
Myocardial Heart: Focal of aldosterone, glucocorticoid and catecholamines like

ischaemia myocardial adrenaline.
necrosis l In severe shock, adrenal haemorrhage can occur.
Cerebral Kidney: ATN

ischaemia 6. Liver in Shock: Due to hypoxia vasodepression mate-
rial is released which causes vasodilatation, focal necrosis,
TNF Liver: Necrosis
fatty liver and impaired liver functions.
Hypercoagulability Intestine: Necrosis
7. Haemorrhagic Gastroenteropathy: Hypoperfusion
may result in mucosal and mural infarctions of alimentary
tract called haemorrhagic gastroenteropathy.
PATHOLOGY OF SHOCK Various other organs like lymph nodes, spleen and
pancreas may also show foci of necrosis in shock.
Shock is characterized by the multisystem failure.
The morphogenic changes in shock are due to hypoxia Q. 5. Define shock. What are the factors responsible for
resulting in degeneration and necrosis. irreversible shock?
Predominant morphologic complications in shock are as
Ans.
follows:
When the shock is so severe that in spite of compensatory
1. Hypoxic Encephalopathy mechanisms and despite therapy and control of aetiologic
l Altered state of consciousness may be produced by agent, no recovery takes place it is called decompensated or
cerebral ischaemia in compensated shock. irreversible shock.
l In prolonged shock and cardiac arrest brain suffers from
severe ischaemic damage with loss of cortical functions, Its effects include the following:
coma and a vegetative state. 1. Progressive fall in blood pressure
l Dead and dying nerve cells are replaced by gliosis. 2. Severe metabolic acidosis due to anaerobic glycolysis
3 . Respiratory distress Q. 6. Define a thrombus. Mention the types and discuss

4. Ischaemic cell death of brain, heart and kidneys the fate of thrombus.
Ans.
Factors responsible for irreversible shock are as follows
with tissue anoxia occupying the central role: l The thrombus is the solid mass in circulation from the
1. Persistence of vasoconstriction: Persistence of vasocon- constituents of flowing blood. The thrombi can de-
striction can cause anoxia of tissues and organs like the velop anywhere in the cardiovascular system, i.e.
liver, spleen, kidney and intestine. The postcapillary cardiac chambers, on valves or in arteries, veins or
venular constriction contributing to anoxia is particu- capillaries.
larly significant. l The size and shape of thrombus depend on the site of
2. Vasodilatation and increased vascular permeability: Vaso- origin and the cause.
dilatation results in peripheral pooling of blood while l Thrombus may occur in heart, arteries, veins and
increased vascular permeability causes escape of fluid capillaries.
from circulation into the interstitial tissues, both of which
further deteriorates the effective circulating blood volume. Various types of thrombi are as follows:
3. Myocardial ischaemia: Persistently reduced blood flow 1. Mural thrombi
to myocardium causes coronary insufficiency and myo- l Thrombi occurring in the heart chambers or in the
cardial ischaemia due to release of myocardial depres- aortic lumen are known as mural thrombi.
sant factor. This results in depression of cardiac function, l Abnormal myocardial contraction or endomyocar-
reduced cardiac output and decreased blood flow. dial injury promotes cardiac mural thrombi.
4. Cerebral ischaemia: This causes depression of vasomotor 2. Arterial thrombi
centre. This results in vasodilatation and peripheral pool- l They are frequently occlusive and are produced by
ing of blood, thus reducing venous return to the heart. platelet and coagulation activation.
5. Vasodepressor material (VDM): VDM is a substance l They are typically a friable meshwork of platelets,
produced by the spleen and skeletal muscle and is fibrin, erythrocytes and degenerating leucocytes,
normally inactivated in the liver. In severe hypoxia as in which give greyish or white colour to it.
irreversible shock the mechanism of inactivation is l They are white or pale in colour and form where
damaged so that its blood levels rise. VDM causes blood flow is fast such as artery or in the heart.
peripheral vasodilatation, resulting in deterioration of l Microscopically distinct lines of Zahn composed of
the circulation. platelets, fibrin with entangled red and white blood cells
6. Tumour necrosis factor: In septic shock bacterial are seen.
products activate monocyte–macrophage cell system. 3. Venous thrombi
This causes release of substances like prostaglandin, l Venous thrombosis is also known as phlebothrombo-
leukotrienes, platelet activating factor and interleukins. sis and is almost invariably occlusive and the throm-
These substances have been implicated in producing bus can create a long cast of the lumen.
irreversible endotoxic shock. l Because these thrombi are formed in the sluggish
7. Intestinal factor: Haemorrhagic necrosis of intestinal venous circulation, they also tend to contain more
tract occurs from vasoconstriction. This results in loss enmeshed erythrocytes and are therefore called red
of blood and plasma into the intestine reducing the or stasis thrombi.
effective circulating blood volume. l The veins of lower extremities are most commonly af-
8. Bacterial factor: Prolonged anoxic injury to the reticu- fected; however they may occur in the upper extremities.
loendothelial organs like liver and spleen impairs l Microscopically distinct lines of Zahn with more
the normal antibacterial defence mechanism of these abundant red blood cells are seen.
organs. Result is release of undetoxified endotoxins 4. Postmortem thrombi: They are gelatinous with dark red
derived from intestinal bacteria into the circulation. dependent portion where red cells have settled by gravity
This causes further vasoconstriction and its harmful and a yellow chicken fat supernatant and they are usually
effects. not attached to the underlying wall.
9. Hypercoagulability of blood: In prolonged shock exces- 5. Vegetation: Thrombi occurring on the heart valves
sive accumulation of lactic acid in the blood enhances are called vegetations. Bacterial or fungal blood-borne
the release of catecholamines into the circulation. These infections can cause valve damage, leading to large
cause release of clot promoting factor, thromboplastin thrombotic masses. Sterile vegetations can also develop
and platelet aggregator. Excess lactic acid can also on noninfected valves in hypercoagulable state, so
cause endothelial injury and thus initiate thrombosis. called nonbacterial thrombotic endocarditis.
Fate of Thrombus l Capillary channels are eventually formed and to a limited

extent can create conduits along the length of thrombus and
The thrombi undergo some combination of the following thereby re-establish the continuity of the original lumen.
four events if a patient survives the initial thrombosis: l Recanalization can potentially convert a thrombus into
1. Propagation a vascularized mass of connective tissue that is eventu-
2. Embolization ally incorporated into the vessel wall and remains as
4. Dissolution subendothelial swelling. This fibrosed thrombus may
5. Organization also undergo hyalinization and calcification.
l Sometimes instead of organizing, the centre of a throm-
Propagation bus undergoes enzymatic digestion, due to release of ly-

sosomal enzymes from trapped leucocytes and platelets.
l Thrombi accumulate additional platelets and fibrin,
eventually causing vessel obstruction. Q. 7. Define embolism. Give an account of various types
l The thrombus may enlarge in size due to more and more of emboli.
deposition from the constituents of flowing blood and
ultimately cause obstruction of vessels. Ans.
l Embolism is the process of partial or complete occlu-

Embolization sion of some part of cardiovascular system by the
impaction of some mass (embolus) transported to the
l Thrombi dislodge or fragment and are transported else- site through the blood stream.
where in the vasculature. l The great majority of emboli represent some part or
l An embolus is a detached intravascular solid, liquid or
whole of a dislodged thrombus, hence it is commonly
gaseous mass that is carried by the blood to a site distant known as thromboembolism.
from its point of origin. l Embolization can be produced by various types of
l They produce effects according to the site of lodgment.
embolic material which include
l Around 99% of all emboli represent some part of a dis-
l droplets of fat,
lodged thrombus, hence the term thromboembolism. l undissolved air or gas bubbles,
l atherosclerotic debris (cholesterol emboli),
Dissolution l tumour fragments,
l bits of bone marrow amniotic fluid, etc.

l Dissolution is the result of fibrinolytic activation, which
leads to rapid shrinkage and even total lysis of recent Emboli are of various types as follows:
thrombi. 1. Depending upon the matter in the emboli
l The fibrinolytic system is activated by thrombus, with a. Solid, e.g. detached thrombi
consequent release of plasmin which dissolves the b. Liquid, e.g. fat globules
thrombus completely resulting in resolution. c. Gaseous, e.g. air
l Small venous thrombi are completely lysed but not 2. Depending upon whether infected or not
large thrombi. With older thrombi, extensive fibrin po- a. Bland, when sterile
lymerization renders the thrombus substantially more b. Septic, when infected
resistant to proteolysis and lysis is ineffectual. 3. Depending on the source of emboli
l This process can be accentuated by administration of a. Cardiac emboli
thrombolytic substances like urokinase, streptokinase b. Arterial emboli
especially in the early stage when fibrin is in monomeric c. Venous emboli
form. d. Lymphatic emboli
4. Depending upon the flow of blood
a. Paradoxical embolism: An embolus which is carried
Organization and Recanalization from the venous side of the circulation to the arterial
Thrombi induce inflammation and fibrosis (organization). side or vice versa
These can eventually recanalize, i.e. re-establish some degree b. Retrograde emboli: An embolus which travels against
of flow or they can be incorporated into a thickened vessel wall. the flow of blood is called retrograde embolus.
If a thrombus is not removed it undergoes organization as
follows:
l Older thrombi become organized by the ingrowth of
TYPES OF EMBOLISM
endothelial cells, smooth muscle cells and fibroblasts Some of the important types of embolism are as discussed
into the fibrin-rich clot. below:
Systemic Thromboembolism Air Embolism

A detached thrombus or part of thrombus constitute It occurs when air is introduced into venous or arterial cir-
the most important type of embolism. They may arise in culation. Gas bubbles within the circulation can obstruct
arterial or venous circulation (Table 4.3). vascular flow.
Venous air embolism: air may be sucked into systemic
veins under the following conditions:
TABLE 4.3 Comparison between Arterial and Venous i. Operations on head and neck and trauma
Embolism ii. Obstetrical operations and trauma
Arterial Emboli Venous Emboli iii. Intravenous infusion of blood and fluids
Sources
iv. Angiography
within the heart Thrombi in veins of Arterial air embolism: entry of air into pulmonary veins
l mural thrombi in left atrium or lower legs, in pelvic
ventricle veins, in cavernous
or its tributaries may occur in the following conditions:
l vegetations in mitral or aortic sinus and thrombi in i. Cardiothoracic surgery and trauma
valve and prosthetic valves right side of heart. ii. Paradoxical air embolism
within arteries iii. Arteriography
l atherosclerotic plaques Generally more than 100 mL of air is required to pro-
l aortic aneurysms
duce a clinical effect; bubbles can coalesce to form frothy
Arterial emboli may lead to The most significant masses sufficiently large to occlude major vessels.
l infarction, effect of venous
l myocardial infarction, emboli is pulmonary
l gangrene and embolism. Decompression Sickness
l sudden death.
l It is a specialized form of gas embolism and is also
known as Caisson disease. It occurs when individuals
are exposed to sudden changes in atmospheric pressure.
Fat Embolism l May appear in deep sea and scuba divers, in underwater
l Fat embolism usually arises following some severe construction workers and in individuals in unpressur-
trauma with fracture to long bones. ized aircraft that ascend rapidly to high altitudes.
l Various traumatic and nontraumatic causes of fat l Pathogenesis: It is produced when the individual decom-
embolism are as follows: presses suddenly either from high atmospheric pressure to
a. Traumatic causes normal level or from normal to low atmospheric pressure.
i. trauma to long bones (common cause of fat l Clinical effects are of two types: acute and chronic.
embolism) and
Acute form
ii. trauma to soft tissue, e.g. laceration of adipose
l The formation of minute gas bubbles within the skeletal
tissue.
muscles and supporting tissues in and about the joints
b. Nontraumatic causes
creates what is known as the bends.
i. extensive burns,
l In the lungs oedema, haemorrhages and focal atelectasis
ii. diabetes mellitus and
or emphysema may appear, sometimes leading to
iii. pancreatitis.
sudden respiratory distress called the chokes.
l Among 90% of traumatic fat embolism cases only 1%
of individuals manifest clinical signs or symptoms Chronic form is due to foci of ischaemic necrosis through-
known as fat embolism syndrome. out the body, especially the skeletal system.
l Fat embolism syndrome is characterized by pulmonary The features of chronic form include the following:
insufficiency, neurological symptoms, anaemia and l Avascular necrosis of bones, e.g. head of femur, tibia, etc.
thrombocytopenia. l Neurological symptoms like paraesthesias and paraplegia
l Petechial skin rash is common. Fat embolism syndrome l Lung involvement eliciting dyspnoea, nonproductive
is fatal in about 10% of cases. cough and chest pain

l Skin manifestations like itching, erythema, cyanosis
and oedema
Gas Embolism l Other organs like liver and pancreas may show lipid
Air, nitrogen and other gases can produce bubbles within vacuoles in their parenchymal cells
the circulation and obstruct the blood vessels. Two main Treatment of gas embolism consists of placing the
forms of gas embolism are air embolism and decompres- individual in a compression chamber where the baromet-
sion sickness. ric pressure may be raised. This speeds the solution of
the gas bubbles and permits slow decompression of the Aetiopathogenesis

individual.
Three primary influences on thrombus formation are called
Virchow’s triad.
Amniotic Fluid Embolism
1. Endothelial injury: Stasis or turbulence of blood flow or
l It is a grave but fortunately uncommon complication of alteration in normal flow of blood
labour and the immediate postpartum period. 2. Hypercoagulability of blood
l The onset is characterized by sudden severe dyspnoea,
cyanosis and hypotensive shock, followed by seizures

and coma.
Endothelial Injury
l The underlying cause is entry of amniotic fluid into l An intact endothelium by virtue of its functions main-
the maternal circulation via a tear in the placental mem- tains normal blood flow.
branes and rupture of uterine veins. l Endothelial injury is of major significance in the forma-
l It has a mortality rate in excess of 20–40%. tion of arterial thrombi and thrombi of the heart.
l Conditions and factors which cause endothelial injury
and predispose to thrombogenesis are as follows:

Atheroembolism
1. Endocardial injury in MI, myocarditis, cardiac
Atheromatous plaques especially from aorta, may get surgery, prosthetic valves
eroded which are then lodged in medium-sized and small- 2. Ulcerated plaques in advanced atherosclerosis
sized arteries. 3. Arterial diseases
4. Diabetes mellitus
5. Endogenous chemical agents like hypercholesterol-
Tumour embolism
aemia, homocystinuria and endotoxins
Malignant tumour cells invade the local blood vessels and l Physical loss of endothelium by vascular injury leads to
may form tumour emboli to be lodged elsewhere, produc- exposure of the subendothelial ECM, adhesion of platelets,
ing metastatic tumour deposits. release of tissue factors, and local depletion of PGI2 and
plasminogen activators which are thrombogenic and play
an important role in initiating haemostasis and thrombosis.
Miscellaneous Emboli
l Endothelium need not be denuded or physically dis-
Various other endogenous and exogenous substances may rupted to contribute to the development of thrombosis,
act as emboli. They are as follows: any perturbation in the dynamic balance of the pro-
1. Fragments of tissue thrombotic and antithrombotic activities of endothelium
2. Placental fragments can influence local clotting events.
3. Red cell aggregates l Significant endothelial dysfunction may occur with
4. Bacteria hypertension, turbulent flow over scarred valves or by
5. Parasites the action of bacterial endotoxins.
6. Barium emboli following enema l The dysfunction of endothelium may elaborate greater
7. Foreign bodies, e.g. needles, talc, sutures, bullets, cath- amounts of procoagulant factors like platelet adhesion
eters, etc molecules, tissue factor, plasminogen activator inhibi-
tors or may synthesize fewer anticoagulant effectors
Q. 8. Define thrombosis. Discuss the pathogenesis of like thrombomodulin, PGI2, t-PA.
thrombus.
Alteration of Blood Flow
Ans.
l Normal blood flow is laminar, where the most rapidly
moving central stream consists of leucocytes and red

cells, slow moving adjacent stream contains platelets
THROMBOSIS and the most slow moving cell-free or clear zone of
l Thrombosis is the process of formation of solid mass in plasma is close to endothelial layer.
circulation from the constituents of flowing blood. The l Turbulence in the blood flow contributes to arterial and
mass itself is called as thrombus. cardiac thrombosis by causing endothelial injury or

l The thrombi can develop anywhere in the cardiovascu- dysfunction as well as by forming countercurrents and
lar system, i.e. cardiac chambers, on valves or in local pockets of stasis.
arteries, veins or capillaries. l Stasis of the blood flow is a major contributor to
l The size and shape of thrombus depend on the site of the development of venous thrombi even in absence of
origin and the cause. endothelial injury.
l This is because, in turbulence and stasis, the normal 2. Individuals with such mutations have a significantly
axial flow of blood is disturbed causing platelets to increased frequency of venous thrombosis in setting of
come in contact with the endothelium. Moreover, turbu- other acquired risk factors.
lence may actually injure the endothelium resulting in
deposition of platelets and fibrin. Even the inhibitors of Secondary (Acquired) Hypercoagulable States
coagulation fail to reach the site of thrombus resulting
in enlargement of thrombus size. High Risk for Thrombosis
l Stasis and turbulence therefore l Prolonged bed rest or immobilization
1. disrupt laminar flow and bring the platelets into l Myocardial infarction
close contact with the endothelial layer, l Atrial fibrillation
2. prevent dilution of activated clotting factors by l Cancer
fresh flowing blood, l Prosthetic cardiac valves
3. retard the inflow of clotting factor inhibitors and l Disseminated intravascular coagulation
permit the build-up of thrombi and
4. promote endothelial cell activation, resulting in Low Risk for Thrombosis
local thrombosis, leukocyte adhesion, etc. l Cardiomyopathy
l Turbulence and stasis contribute to thrombosis in several l Nephrotic syndrome
clinical conditions like ulcerated atherosclerotic plaques, l Hyperoestrogen states (pregnancy)
aneurysms, acute myocardial infarction, mitral valve l Oral contraceptive use
stenosis, hyperviscosity syndromes like polycythemia. l Sickle cell anaemia
l Smoking
Hypercoagulability of Blood Unlike hereditary disorders, the pathogenesis of

acquired thrombotic diatheses is frequently multifactorial
l Hypercoagulability of blood is loosely defined as any and is more complicated.
alteration of coagulation pathways that predisposes to Hypercoagulability is associated with oral contracep-
thrombosis. tive use and the hyperoestrogenic state of pregnancy prob-
l It is brought about by following changes in the blood ably related to increased hepatic synthesis of antithrombin
composition: III. In disseminated cancers, release of procoagulant
l Increase in coagulation factors like fibrinogen, pro- tumour products predisposes to thrombosis. Smoking
thrombin, factor VIIa, VIIIa and Xa and obesity promote hypercoagulability by unknown
l Increase in platelet count and their adhesiveness mechanisms.
l Decreased levels of coagulation inhibitors like anti- Thrombi may propagate, resolve, become organized or
thrombin III, fibrin split products embolize. Thrombosis causes tissue injury by local vascular
l The hypercoagulability of blood is divided into primary occlusion or by distal embolization.
(genetic) or secondary (acquired) disorders.
Q. 9. Define infarction. Describe the pathology of infarct.
Primary (Genetic) Hypercoagulable States Ans.
Most Common
l Infarction is the process of tissue necrosis resulting
l Mutations in factor V gene (factor V Leiden) from some form of circulatory insufficiency.
l Mutations in prothrombin gene l Infarcts are areas of ischaemic, usually coagulative
l Mutations in methyltetrahydrofolate gene necrosis caused by occlusion of arterial supply or less
commonly by venous drainage.
Less Common
l Antithrombin III deficiency
l Protein C deficiency Aetiology

l Protein S deficiency Most commonly, infarcts are caused by the following:
Affected patients typically present with venous throm- 1. Interrupted blood supply called ischaemic necrosis
bosis and recurrent thromboembolism in adolescence or 2. Less commonly venous obstruction
early adult life. 3. Sudden, complete and continuous occlusion by throm-
Although inherited disorders are uncommon causes of bosis or embolism
significant hypercoagulable states on their own, collectively
they are significant for two reasons as follows: Factors that influence development of an infarct are as
1. Mutations can be coinherited and resulting risk of a follows:
thrombotic diathesis is synergistic. 1. Nature of the vascular supply
2 . The rate of development of the occlusion l The infarct due to arterial occlusion is pale while those
3. Vulnerability to hypoxia due to venous obstruction is haemorrhagic.
4. Oxygen content of the blood l Usually all infarcts are poorly defined and slightly
haemorrhagic. Margins of both types of infarcts tend to

become better defined with time by a narrow rim of
Pathogenesis congestion attributable to inflammation at the edge of
l Localized hyperaemia occurs immediately after isch- the lesion.
aemia. Within few hours, the affected part becomes l The recent infarcts are generally slightly elevated over
swollen because of oedema and haemorrhage. the surface while the old infarcts are shrunken and de-
l Early changes are cloudy swelling and degeneration. pressed under the surface of the organ.
Progressive autolysis of necrotic tissue and haemolysis
Histologic characteristics of infarction
of red cells follow.
l The pathognomonic or dominant histologic characteris-
l An acute inflammatory reaction and hyperaemia appear
tic of infarction is ischaemic coagulative necrosis of the
in the surrounding tissue. Blood pigments are deposited
affected area. It generally contains some amount of
in the infarct.
haemorrhage.
l There is progressive ingrowth of granulation tissue.
l At the periphery there is inflammatory reaction pre-
Finally the infarct is replaced by fibrous scar.
dominated by neutrophils initially but subsequently
even macrophages and fibroblasts appear.
Morphology l Eventually most infarcts are ultimately replaced by
Infarcts are classified as follows: fibrous scar tissue, which at times may show calcifica-
1. On the basis of their colour tion. The brain is an exception to these generalizations.
a. Red (haemorrhagic) Ischaemic tissue injury in CNS results in liquefactive
b. White (anaemic) necrosis.
2. On the basis of presence or absence of microbial infection
Q. 10. Describe morphology and microscopic structure
a. Septic
of cardiac infarction.
b. Bland
Ans.
Red (haemorrhagic) infarcts occur
l with venous occlusion. The sequence of morphologic changes in all myocardial
l usually in loose tissues such as lung that allows blood to infarcts is as follows:
collect in the infracted zone. 1. Within first 6–12 h no striking gross changes are
l in tissues with dual circulations such as lungs and small discernible in old infarcts except that the affected
intestine permitting flow of blood from an unobstructed myocardium is slightly paler and dry than normal.
parallel supply into a necrotic area. 2. By about 24 h due to stagnation of blood the infarct
l in tissues that were previously congested because of develops cyanotic, red purple blotchy areas of haemor-
sluggish venous outflow. rhage.
l when the flow is re-established to a site of previous arte- 3. In the next 48–72 h the infarct becomes more well
rial occlusion and necrosis. defined and develops a yellow border due to neutro-
White (anaemic) infarcts occur with arterial occlusions philic infiltration.
or in solid organs like heart, spleen and kidney where the 4. In 3–7 days the infarct has hyperaemic border while the
solidity of the tissue limits the amount of haemorrhage that centre is yellow and soft.
can seep into the area of ischaemic necrosis from adjoining 5. By a period of 10 days the periphery of the infarct
capillary beds. appears reddish purple due to growth of granulation
Septic infarcts occur when bacterial vegetations from tissue.
heart valves embolize or when microbes seed an area of 6. The infracted area is replaced by a thin grey-white hard
necrotic tissue. In such cases the infarct is converted to an shrunken fibrous scar by the end of 6 weeks and is well
abscess, with correspondingly great inflammatory response. developed in about 2–3 months.
Microscopically the changes of cardiac infarct are as

Gross Appearance
follows:
All infarcts tend to be usually wedge shaped, the apex 1. First week
pointing towards the occluded vessel and the wide base on l Under routine light microscopy within the first 6 h no
the surface of the organ. detectable histologic change is observed.
l After 6 h there is appearance of some oedema fluid of proliferation of capillaries and fibroblasts from the
between the myocardial fibres and the muscle fibres margins of the infarct.
at the margin of the infarct show vacuolar degenera- 2 . Second week
tion termed as myocytolysis. l Most of the necrosed muscle at the periphery is re-
l By 12 h coagulative necrosis of the myocardial fibres moved by 10th day. The fibrovascular reaction at the
sets in and neutrophils begin to appear at the margin margins is more prominent. Many pigmented macro-
of the infarct and is characterized by loss of striations phages containing haemosiderin and lipofuscin are
and intense eosinophilic hyaline appearance and may seen.
show nuclear changes like karyolysis, pyknosis and l Most of necrosed muscle in small infarcts is removed
karyorrhexis. and newly laid collagen fibres replace the periphery

l Coagulative necrosis progresses further during the of the infarct by the end of second week.
first 24 h and there is slight neutrophilic infiltrate at 3. Third week: Necrosed muscle fibres from large infarcts
the margins. continue to be removed and are replaced by ingrowth of
l During the first 24–48 h, coagulative necrosis is new collagen fibres.
complete with loss of nuclei. The neutrophilic 4. Fourth to sixth week: There is increase in collagenous
infiltrate is well developed and extends centrally into connective tissue, decreased vascularity, fewer macro-
the interstitium. phages, lymphocytes and plasma cells by the end of
l In 3–7 days, neutrophils are necrosed and slowly 6 weeks resulting in a contracted fibrocollagenic scar
disappear. The process of resorption of necrosed with diminished vascularity.
muscle fibres begins. Simultaneously there is onset
SHORT ESSAYS
Q. 1. What are the types of exudation? Describe the Formation of an abscess
sequelae of pyogenic abscess.
l When the pyogenic bacteria causing acute inflammation
Ans. results in severe tissue necrosis, the process progresses
to suppuration.
l Initially there is intense neutrophilic infiltration and
EXUDATION
subsequently pus is formed as mixture of neutrophils,
Exudate is the inflammatory oedema which is protein rich bacteria, fragments of necrotic tissue, cell debris and
with a specific gravity usually greater than 1.020. fibrin. This results in formation of an abscess.
Various types of exudates are as follows:

1. Serous exudate: when fluid exudate resembles serum or
Sequelae of pyogenic abscess
is watery, e.g. pleural effusion in tuberculosis, blister 1. Drainage: Most common sequelae of abscess is drain-
formation in burns, etc. age. Abscess may be discharged to the surface due to
2. Fibrinous exudate: when fibrin content is high in the fluid increased pressure inside or may require drainage by a
exudates, e.g. pneumococcal and rheumatic pericarditis surgeon.
3. Purulent or suppurative exudates: formation of creamy 2. Healing by fibrous scarring: Since there is associated
pus as in infection with pyogenic bacteria, e.g. abscess, tissue destruction, resolution does not occur. Healing
acute appendicitis, etc. takes place by fibrous scarring.
4. Haemorrhagic exudate: when there is vascular damage, 3. Calcification: The abscess if not drained, may get
e.g. acute haemorrhagic pneumonia in influenza organized by dense fibrous tissue and in time gets
5. Catarrhal exudate: when there is increased mucous con- calcified.
tent in the fluid exudates, e.g. common cold.
Q.2. Define oedema and mention types of oedema.
Pyogenic Abscess Ans.
The formation of an acute inflammatory cavity filled with Oedema may be defined as abnormal and excessive accu-
pus by pyogenic bacteria is termed as pyogenic abscess. mulation of fluid in interstitial tissue spaces and serous
It is a form of acute inflammation. cavities.
Types of Oedema Shock is defined as clinical state of cardiovascular collapse

characterized by an acute reduction of effective circulating
A. Three main types of oedema blood volume and an inadequate perfusion of cells and tissues.
Types of shock:
1. Hypovolaemic shock
2. Septic shock
3. Cardiogenic shock
i. Localized ii. Generalized iii. Special Hypovolaemic shock: Reduction in blood volume induces
(in the organ or limb) (anasarca or dropsy) Example: Pulmo- hypovolaemic shock
Example: Inflamma- Example: Systemic in distri- nary, cerebral
tory, lymphatic, toxic, bution especially noticeable Causes
allergic in the subcutaneous tissue, l Severe haemorrhage: Trauma, surgery
e.g. renal, cardiac, nutritional l Fluid loss: Bums, crush injury, dehydration due to
persistent vomiting and severe diarrhoea.

B. Subcutaneous oedema is of two types
Septic shock: Severe bacterial infections or septicaemia
induce septic shock.
a. Gram-negative septicaemia (endotoxic shock): Infec-
i. Pitting oedema (It produces de- ii. Nonpitting or solid oedema tions due to E. coli, Klebsiella and Pseudomonas causes
pression on momentary pressure (It does not produce depression.) endotoxic shock.
of finger on oedema.) Example: Myxoedema, elephan- b. Gram-positive septicaemia (exotoxic shock): Infections
tiasis due to streptococci and pneumococci causes exotoxic
shock and is less common.
C. Depending on oedema fluid, oedema are of two types
Cardiogenic shock: Acute circulatory failure with sudden
fall in cardiac output from acute diseases of heart without
actual reduction of blood volume causes cardiogenic shock.
This may be due to
i. Transudative oedema ii. Exudative oedema
l deficient emptying, e.g. myocardial infarction, rupture
(It is made up of filtrate of blood (It is made of oedema of
of heart and cardiac arrhythmias.
plasma.) inflammatory tissue.)
l deficient filling, e.g. cardiac tamponade from haemo-
Example: Cardiac and renal oedema Example: Inflammatory oedema
pericardium.
l obstruction to outflow, e.g. pulmonary embolism, ball
valve thrombus.
Q. 3. Irreversible shock
Ans. The factors responsible for irreversibility of shock Q. 5. Fate of thrombus
are the following with tissue anoxia occupying the central Ans. The thrombus is the solid mass in circulation from the
role. constituents of flowing blood.
● Persistent vasoconstriction The thrombi can develop anywhere in the cardiovascu-
● Vasodilatation and vascular permeability lar system, i.e. cardiac chambers, on valves or in arteries,
● Myocardial ischaemia veins or capillaries.
● Cerebral ischaemia
● Tumour necrosis factor (TNF)
● Hypercoagulability FATE OF THROMBUS
The thrombi undergo some combination of the following
The predominant morphologic complications are as follows: four events if a patient survives the initial thrombosis:
● Brain: Death
1. Propagation
● Lungs: ARDS
2. Embolization
● Heart: Focal myocardial necrosis
3. Dissolution
● Kidney: ATN
4. Organization
● Liver: Necrosis
● Intestine: Necrosis
Propagation
Q. 4. Classification of shock
l Thrombi accumulate additional platelets and fibrin,
Ans. eventually causing vessel obstruction.
l The thrombus may enlarge in size due to more and more Two main forms of gas embolism are: air embolism and
deposition from the constituents of flowing blood and decompression sickness.
ultimately cause obstruction of vessels.
Air Embolism
Embolization l It occurs when air is introduced into venous or arterial
l Thrombi dislodge or fragment and are transported else- circulation. Gas bubbles within the circulation can
where in the vasculature. obstruct vascular flow.
l An embolus is a detached intravascular solid, liquid or l Air may enter the circulation during obstetrical opera-
gaseous mass that is carried by the blood to a site distant tions or as a consequence of trauma to the chest wall.
from its point of origin. l Generally more than 100 mL of air is required to
l They produce effects according to the site of lodgment. produce a clinical effect; bubbles can coalesce to
form frothy masses sufficiently large to occlude major
vessels.
Dissolution
Dissolution is the result of fibrinolytic activation, which
Decompression Sickness
l
leads to rapid shrinkage and even total lysis of recent

thrombi. l It is a specialized form of gas embolism and is also
l The fibrinolytic system is activated by thrombus, with known as Caisson disease. It occurs when individuals
consequent release of plasmin which dissolves the are exposed to sudden changes in atmospheric pressure.
thrombus completely resulting in resolution. l May appear in deep sea and scuba divers, in underwater
construction workers and in individuals in unpressur-

ized aircraft that ascend rapidly to high altitudes.
Organization and Recanalization l Clinical effects are of two types: acute and chronic.
Thrombi induce inflammation and fibrosis (organization). These

can eventually recanalize, i.e. re-establish some degree of flow, Acute Form
or they can be incorporated into a thickened vessel wall.
If a thrombus is not removed it undergoes organization l The formation of minute gas bubbles within the skeletal
as follows: muscles and supporting tissues in and about the joints
l Older thrombi become organized by the ingrowth of creates what is known as the bends.
endothelial cells, smooth muscle cells and fibroblasts l In the lungs oedema, haemorrhages and focal atelectasis
into the fibrin rich clot. or emphysema may appear, sometimes leading to
l Capillary channels are eventually formed and thereby sudden respiratory distress called the chokes.
re-establish the continuity of the original lumen.
l Recanalization can potentially convert a thrombus into
Chronic Form
a vascularized mass of connective tissue that is eventu-
ally incorporated into the vessel wall and remains as l This is due to foci of ischaemic necrosis throughout
subendothelial swelling. the body, especially the skeletal system resulting in
l This fibrosed thrombus may also undergo hyalinization avascular necrosis of bones, neurological symptoms
and calcification. like paraesthesias and paraplegia and lung involve-
ment eliciting dyspnoea, nonproductive cough and
Q. 6. Air emboli chest pain.
l Treatment of gas embolism consists of placing the indi-
Ans. Embolism is the process of partial or complete occlu-
vidual in a compression chamber where the barometric
sion of some part of cardiovascular system by the impac-
pressure may be raised. This speeds the solution of the
tion of some mass (embolus) transported to the site through
gas bubbles and permits slow decompression of the
the blood stream.
individual.
Emboli are of various types depending upon the matter
in the emboli as follows: Q. 7. Evolution of thrombus
1. Solid, e.g. detached thrombi Ans.
2. Liquid, e.g. fat globules
3. Gaseous, e.g. air l Thrombosis is the process of formation of solid mass in
circulation from the constituents of flowing blood. The
mass itself is called as thrombus.
Gas Embolism l The thrombi can develop anywhere in the cardiovascu-
Air, nitrogen and other gases can produce bubbles within lar system, i.e. cardiac chambers, on valves or in arter-
the circulation and obstruct the blood vessels. ies, veins or capillaries.
AETIOPATHOGENESIS Increase in platelet count and their adhesiveness

l
Decreased levels of coagulation inhibitors like anti-

l
Three primary influences on thrombus formation called
thrombin III, fibrin-split products
Virchow’s triad are as follows:
l The hypercoagulability of blood is divided into primary
1. Endothelial injury
(genetic) or secondary (acquired) disorders.
2. Stasis or turbulence of blood flow or alteration in
normal flow of blood
3. Hypercoagulability of blood Primary (Genetic) Hypercoagulable States
l Mutations in factor V gene (factor V Leiden), mutations
Endothelial Injury in prothrombin gene and mutations in methyltetrahy-
drofolate gene are most common.
l An intact endothelium by virtue of its functions main- l Affected patients typically present with venous throm-
tains normal blood flow. bosis and recurrent thromboembolism in adolescence or
l Endothelial injury is of major significance in the forma-
early adult life.
tion of arterial thrombi and thrombi of the heart.
l Physical loss of endothelium by vascular injury leads to
exposure of the subendothelial ECM, adhesion of plate- Secondary (Acquired) Hypercoagulable States
lets, release of tissue factors, and local depletion of PGI2 l Prolonged bed rest or immobilization, myocardial
and plasminogen activators which are thrombogenic infarction, atrial fibrillation, cancer and dissemi-
and play an important role in initiating haemostasis and nated intravascular coagulation are high risk for
thrombosis. thrombosis.
l Endothelium need not be denuded or physically dis-
l Unlike hereditary disorders, the pathogenesis of ac-
rupted to contribute to the development of thrombosis, quired thrombotic diatheses is frequently multifactorial
any perturbation in the dynamic balance of the pro- and is more complicated.
thrombotic and antithrombotic activities of endothelium l Thrombi may propagate, resolve, become organized
can influence local clotting events. or embolize. Thrombosis causes tissue injury by local
vascular occlusion or by distal embolization.
Alteration of Blood Flow
Q. 8. Define the embolism and discuss the thromboem-
l Normal blood flow is laminar, where the most rapidly bolism.
moving central stream consists of leucocytes and red
cells, slow moving adjacent stream contain platelets and Ans.
the most slow moving cell-free or clear zone of plasma l Embolism is the process of partial or complete occlu-
is close to endothelial layer. sion of some part of cardiovascular system by the
l Turbulence in the blood flow contributes to arterial and
impaction of some mass (embolus) transported to the
cardiac thrombosis by causing endothelial injury or site through the blood stream.
dysfunction as well as by forming countercurrents and l The great majority of emboli represent some part or
local pockets of stasis. whole of a dislodged thrombus, hence it is commonly
l Stasis of the blood flow is a major contributor to the
known as thromboembolism.
development of venous thrombi even in absence of en-
dothelial injury. Emboli are of various types as follows:
l Turbulence and stasis contribute to thrombosis in sev-
1. Depending upon the matter in the emboli
eral clinical conditions like ulcerated atherosclerotic a. Solid, e.g. detached thrombi
plaques, aneurysms, acute myocardial infarction, mitral b. Liquid, e.g. fat globules
valve stenosis, hyperviscosity syndromes like polycy- c. Gaseous, e.g. air
themia. 2. Depending upon whether infected or not
a. Bland, when sterile
Hypercoagulability of Blood b. Septic, when infected
3. Depending on the source of emboli
l Hypercoagulability of blood is loosely defined as any a. Cardiac emboli
alteration of coagulation pathways that predisposes to b. Arterial emboli
thrombosis. c. Venous emboli
l It is brought about by following changes in the blood
d. Lymphatic emboli
composition: 4. Depending upon the flow of blood
l Increase in coagulation factors like fibrinogen,
a. Paradoxical embolism
prothrombin, factor VIIa, VIIIa and Xa b. Retrograde emboli
SYSTEMIC THROMBOEMBOLISM This may lead to ischaemic injury to brain.

2. Causes in the arteries: These are
A detached thrombus or part of thrombus constitute the
a. luminal occlusion such as due to
most important type of embolism. They may arise in
i. thrombosis,
arterial or venous circulation.
ii. embolism.
b. causes in the arterial wall such as
Arterial Emboli Venous Emboli i. vasospasm,
Sources ii. hypothermia,
within the heart Thrombi in veins of lower iii. arteriosclerosis,
l mural thrombi in left atrium legs, in pelvic veins, in iv. polyarteritis nodosa.
or ventricle cavernous sinus and c. Outside pressure on artery such as ligature tourni-
l vegetations in mitral or thrombi in right side of quet torsion tight bandages
aortic valve and prosthetic heart.
valves
3. Causes in the veins: Blockage of venous drainage may
within arteries lead to engorgement and obstruction to arterial supply
l atherosclerotic plaques resulting in ischaemia.
l aortic aneurysms
Arterial emboli may lead to The most significant effect Examples:

l infarction, of venous emboli is a. Luminal occlusion as in
l myocardial infarction, pulmonary embolism. i. thrombosis of mesenteric veins,
l gangrene and ii. cavernous sinus thrombosis.
l sudden death.
b. Causes in vessel wall: varicose veins of legs
c. Outside pressure on the vein
Q. 9. Mention the causes of ischaemia. i. strangulated hernia,
ii. intussusceptions.
Ans. Ischaemia is defined as deficient blood supply to a
d. Causes in the microcirculation
part of a tissue.
i. Luminal occlusion
l by red cells, e.g. in sickle cell anaemia,
l by white cells, e.g. in chronic myeloid

AETIOLOGY leukaemia,
Various causes of ischaemia are as follows: l by fibrin, e.g. defibrination syndrome,
1. Causes in the heart: Inadequate cardiac output may l by fat embolism.
result from ii. Causes in microvasculature wall such as

a. heart block, l vasculitis, e.g. arthus reaction and
b. ventricular arrest, l frost bite injuring wall of small blood vessels.
c. fibrillation. iii. Outside pressure on microvasculature as in

bedsores.
SHORT NOTES
Q. 1. Angioedema Ans. Oedema may be defined as abnormal and excessive
accumulation of fluid in interstitial tissue spaces and serous
Ans.
cavities.
l Angioedema is an autosomal dominant disorder which
manifests as a form of local anaphylaxis. TYPES OF OEDEMA
l It is characterized by laryngeal oedema, oedema of
eyelids, lips, tongue and trunk. Three main types of oedema

l The response is mediated by humoral antibodies of IgE
type or reagin antibodies.

l It involves the release of pharmacologically active
substances like histamine, serotonin, leukotrienes, pros- Localized Generalized Special

taglandins and platelet-activating factor. These act as (in the organ or limb) (anasarca or dropsy) Example: Pulmo-
anaphylactic mediators and are responsible for changes Example: Inflamma- Example: Systemic in distri- nary, cerebral
associated with angioedema. tory, lymphatic, toxic, bution especially noticeable
allergic in the subcutaneous tissue
Q. 2. Define and mention the types of oedema. (renal, cardiac, nutritional)
Q. 3. Mechanism of oedema TABLE 4.4 Differences between Exudate and Transudate
Ans. Parameter Exudate Transudate

Definition Exudate is defined Transudate is
l Oedema is extravasation of fluid from vessels into inter- as oedema of defined as
stitial spaces. The fluid may be protein rich (exudates) inflamed tissue noninflammatory
or protein poor (transudate). associated with filtrate of blood
l Oedema results from any of the following conditions: increased vascular plasma without
permeability. changes in
1. Increased hydrostatic pressure
endothelial
2. Decreased colloid osmotic pressure permeability.
3. Lymphatic obstruction that impairs interstitial fluid
Protein High (.3 g/dL) Low (, 3 g/dL)
clearance
content
4. Primary renal sodium retention
5. Increased vascular permeability Specific High (. 1.018) Low(, 1.015)
gravity
Q. 4. Pulmonary oedema pH , 7.3 . 7.3
Ans. Cells Many cells Few cells, mainly

(inflammatory as well mesothelial cells
Pulmonary oedema develops from left heart failure. There as parenchyma) and cellular debris
is fluid accumulation not only in tissue spaces but also
in the pulmonary alveoli. It causes serious functional im-
pairment.
RENAL OEDEMA
PATHOGENESIS
Pulmonary oedema can result from either Aetiology
l elevation of pulmonary hydrostatic pressure or 1 . Nephrotic syndrome
l increased capillary permeability. 2. Glomerulonephritis
Elevation of pulmonary hydrostatic pressure: Increase in 3. Acute tubular necrosis
hydrostatic pressure of pulmonary capillaries and the re-
sulting imbalance between pulmonary hydrostatic pressure
and plasma oncotic pressure causes excess fluid to move Pathogenesis
into interstitium resulting in interstitial oedema. 1. Oedema in nephrotic syndrome: Nephrotic syndrome is
Increased capillary permeability: The alveolocapillary characterized by persistent and heavy proteinuria result-
membrane may be damaged causing increased vascular ing in hypoalbuminaemia. This reduces plasma oncotic
permeability so that excess fluid and plasma proteins leak pressure and there is increased outward flow of fluid
out, initially into interstitium and subsequently into alveoli. from the capillaries and decreased inward flow of fluid
Acute high altitude oedema: Individuals climbing to high from the interstitial space resulting in oedema known as
altitude without waiting for acclimatization to set in suffer nephrotic oedema.
from this. 2. Oedema in glomerulonephritis: Glomerular diseases
The anoxic damage to pulmonary vessels seems to be like acute diffuse glomerulonephritis produce oedema
underlying mechanism. (nephritic oedema) due to excessive reabsorption of
sodium and water in the renal tubules via rennin–
Q. 5. Differences between transudate and exudate angiotensin–aldosterone mechanism.
Ans. 3. Oedema in acute tubular injury: Acute tubular injury by
shock or toxic chemicals causes loss of selective reab-
The major differences between exudate and transudate are sorption and concentration of the glomerular filtrate by
listed in Table 4.4. the renal tubules. This results in increased reabsorption
of water and thus oedema results.
Q. 6. Renal oedema
Ans. Q. 7. Types of exudates
Ans.
Oedema may be defined as abnormal and excessive accu-
mulation of fluid in the interstitial tissue spaces and serous Exudate is the inflammatory oedema which is protein rich
cavities. with a specific gravity usually greater than 1.020.
Various types of exudates are as follows: 2. Septic shock: Severe bacterial infections or septicaemia
1. Serous exudates, e.g. blister formation in burns induce septic shock.
2. Fibrinous exudates, e.g. pneumococcal and rheumatic Gram-negative septicaemia causes endotoxic shock and
pericarditis Gram-positive septicaemia causes exotoxic shock.
3. Purulent or suppurative exudates, e.g. abscess 3. Cardiogenic shock: Acute circulatory failure with
4. Haemorrhagic exudates, e.g. acute haemorrhagic pneu- sudden fall in cardiac output from acute diseases of
monia in influenza heart without actual reduction of blood volume.
5. Catarrhal exudate, e.g. common cold
Q. 10. Anaphylactic shock
Q. 8. Nutmeg liver
Ans.
Ans. Nutmeg liver is the chronic venous congestion of
the liver due to chronic dilation of veins and capillaries of Anaphylaxis is a state of rapidly developing immune re-
the liver. sponse to an antigen to which the individual is previously
sensitized. Anaphylactic shock develops due to vasodilata-
tion and peripheral pooling of blood.
Aetiology
l Right heart failure
PATHOGENESIS
l Occlusion of inferior vena cava and hepatic vein l IgE antibodies sensitize basophils of peripheral blood or
mast cells of tissue leading to release of anaphylactic
Pathology: The liver is enlarged and tender. The capsule of
mediators like histamine, serotonin, VIP and chemotac-
the liver is tense.
tic factors of anaphylaxis.
Gross appearance: On cut section, it shows characteristic l The effects produced are increased vascular permeabil-
nutmeg liver due to red and yellow mottled appearance ity, smooth muscle contraction, early vasoconstriction
corresponding to congested centre of lobules and fatty followed by vasodilatation and shock.
peripheral zone respectively. l Increased vascular permeability and vasodilatation
leads to peripheral pooling of blood. This results in re-

duction of effective circulating volume and shock, e.g.
systemic anaphylaxis due to administration of antisera
l The centrilobular zone shows marked changes of con- drugs like penicillin.
gestion due to severe hypoxia. The central veins and
adjoining sinusoids are distended and filled with blood. Clinical features of systemic anaphylaxis include itching,
l Lobular haemorrhagic necrosis results from degeneration erythema, contraction of respiratory bronchioles, pulmo-
of hepatocytes in centrilobular region. In long-standing nary oedema, shock and death.
cases cardiac cirrhosis may result from fine centrilobular
fibrosis and regeneration of hepatocytes. Q. 11. Mechanism of shock in burns
l The peripheral zone of the lobule is less severely
Ans.
affected by chronic hypoxia and shows some fatty
change in hepatocytes. Reduction in blood volume due to fluid loss in burns
induces hypovolaemic shock.
Q. 9. Types of shock
Ans. There are two basic features in the pathogenesis of shock as
follows:
Shock is defined as clinical state of cardiovascular collapse a. Reduced effective circulating volume resulting from
characterized by either
l an acute reduction of effective circulating blood volume i. by actual loss of blood volume as in hypovolaemic
and shock or
l an inadequate perfusion of cells and tissues. ii. by decreased cardiac output without actual loss of
blood as in cardiogenic and septic shock.
Various types of shock are as follows: b. Tissue anoxia: Following reduction in effective circulat-
1. Hypovolaemic shock: Reduction in blood volume ing blood volume there is decreased venous return to the
induces hypovolaemic shock. heart resulting in decreased cardiac output. This leads to
Causes: Severe haemorrhage and fluid loss tissue anoxia and shock ensues.
Q. 12. Describe stages in shock. l Various traumatic and nontraumatic causes of fat embo-
Ans. lism are as follows:
1. Traumatic causes: trauma to long bones and soft
tissue
STAGES OF SHOCK 2. Nontraumatic causes: extensive burns, diabetes
mellitus and pancreatitis
Deterioration of the circulation in shock is a progressive l Fat embolism syndrome is characterized by pulmo-
phenomenon and can be divided into following three stages: nary insufficiency, neurological symptoms, anae
1. Initial nonprogressive stage: During this stage reflex mia and thrombocytopenia. Petechial skin rash is
compensatory mechanisms are activated and perfusion common.
of vital organs is maintained.
2. Progressive stage: This stage is characterized by tissue Q. 15. Caisson’s disease
hypoperfusion and onset of worsening circulatory and
metabolic imbalances. Ans.
3. Irreversible stage: It sets in after the body has incurred l Decompression sickness is a specialized form of gas
cellular and tissue injury so severe that even if the haemo- embolism and is also known as Caisson’s disease.
dynamic defects are corrected survival is not possible. l It occurs when individuals are exposed to sudden
changes in atmospheric pressure. As seen in deep sea

Q. 13. Mention various types of embolism.
and scuba divers, in underwater construction workers
Ans. and in individuals in unpressurized aircraft that ascend
rapidly to high altitudes.
Embolism is the process of partial or complete obstruction l Pathogenesis: It is produced when the individual
of some part of cardiovascular system by any mass carried decompresses suddenly either from high atmospheric
in circulation. The mass is called as embolus. pressure to normal level or from normal to low atmo-
spheric pressure.
Emboli are of various types as follows: l Clinical effects: Formation of minute gas bubbles
1. Depending upon the matter in the emboli within the skeletal muscles and supporting tissues in
a. Solid, e.g. detached thrombi and about the joints creates what is known as the
b. Liquid, e.g. fat globules bends. In the lungs oedema, haemorrhages and focal
c. Gaseous, e.g. air atelectasis or emphysema may appear, sometimes
2. Depending upon whether infected or not leading to sudden respiratory distress called the
a. Bland, when sterile chokes.
b. Septic, when infected l Treatment of gas embolism consists of placing the indi-
3. Depending on the source of emboli vidual in a compression chamber which permits slow
a. Cardiac emboli decompression of the individual.
b. Arterial emboli
c. Venous emboli Q. 16. Fate of thrombus
d. Lymphatic emboli
4. Depending upon the flow of blood Ans.
a. Paradoxical embolism: An embolus which is carried Thrombosis is the process of formation of solid mass in
from the venous side of the circulation to the arterial circulation from the constituents of flowing blood. The
side or vice versa mass itself is called as thrombus.
b. Retrograde emboli: An emboli which travels against
the flow of blood is called retrograde embolus. The fate of thrombus includes the following:
1. Propagation
Q. 14. Fat embolism
2. Embolization
Ans. 3. Dissolution
4. Organization
l Embolism is the process of partial or complete obstruc-
tion of some part of the cardiovascular system by any Propagation: Thrombi accumulate additional platelets and
mass carried in the circulation. fibrin, eventually causing vessel obstruction.
l Fat embolism is the obstruction to the arterioles and
capillaries by the fat globule. Embolization: An embolus is a detached intravascular solid,

l Fat embolism usually arises following some severe
liquid or gaseous mass that is carried by the blood to a site
trauma with fracture to long bones. distant from its point of origin.
Dissolution: Dissolution is the result of fibrinolytic activa- MORPHOLOGY

tion, which leads to rapid shrinkage and even total lysis of
Infarcts are classified as follows:
recent thrombi.
1. On the basis of their colour
a. Red (haemorrhagic)
Organization and recanalization: Thrombi induce inflam-
b. White (anaemic)
mation and fibrosis, i.e. organization. These can eventually
2. On the basis of presence or absence of microbial
recanalize, i.e. re-establish some degree of flow, or they can
infection
be incorporated into a thickened vessel wall.
a. Septic
Q. 17. Infarct b. Bland
Ans. Gross appearance: All infarcts tend to be usually wedge

shaped, the apex pointing towards the occluded vessel and
Infarct is an area of ischaemic, usually coagulative necrosis
the wide base on the surface of the organ.
caused by occlusion of arterial supply or less commonly by
venous drainage.
Histologic characteristics of infarction: The pathognomonic
or dominant histologic characteristic of infarction is isch-
AETIOLOGY aemic coagulative necrosis of the affected area. It generally
contains some amount of haemorrhage.
Most commonly, infarcts are caused by interrupted blood
supply called ischaemic necrosis and less commonly by
venous obstruction.
Topic 5
Diseases of the Immune System

LONG ESSAYS
Q. 1. Define hypersensitive reaction. Explain type IV b. Atopy
hypersensitive reaction. c. Antibody-mediated cell damage
d. Arthus phenomenon
Ans. e. Serum sickness
l Hypersensitivity or allergy is defined as state of exag- 2 . Delayed hypersensitivity (T cell-mediated)
gerated immune response to the antigen, which may a. Infection (tuberculin) type
lead to tissue damage, disease or even death following b. Contact dermatitis type
contact with specific antigens.
l The lesions of hypersensitivity, i.e. immunologic tissue
Coombs and Gell (1963) classified hypersensitivity
injury are produced due to interaction between antigen reactions into following four types based on different
and product of immune responses. mechanisms of pathogenesis:
1. Type I (anaphylactic, IgE or regain dependant type)
2. Type II (cytotoxic or cell stimulating)
CLASSIFICATION OF HYPERSENSITIVITY 3. Type III (immune complex or toxic complex disease)
Based on the time required for a sensitized host to develop 4. Type IV (delayed or cell-mediated hypersensitivity)
clinical reactions on re-exposure to the antigen hypersensi-
tivity is classified into following types: This classification is now widely used.
1. Immediate hypersensitivity
2. Delayed hypersensitivity
Immediate Type
They are subdivided into several distinct clinical types as l In this type, on administration of antigen the reaction
follows: occurs immediately.
1. Immediate hypersensitivity (B cell or antibody-mediated) l The immune response in this type is mediated by the
a. Anaphylaxis humoral antibodies.

It is of three types as follows: typical inflammatory reaction reaching a peak in 48–72

1. Type I: Anaphylactic atopic reaction, e.g. systemic ana- h after which it subsides slowly.
phylaxis or local anaphylaxis l Other examples of delayed hypersensitivity are as
2. Type II: Cytologic reaction, e.g. erythroblastosis fetalis, follows:

leucopenia 1. Tuberculosis
3. Type III: Immune complex reaction, e.g. arthritis and 2. Tuberculoid leprosy
skin diseases 3. Typhoid fever
4. Contact dermatitis
5. Graft rejection
Delayed Type
l It is also known as type IV hypersensitivity reaction. Q. 2. Define hypersensitivity. Classify with suitable
l In it, the reaction is slower and develops within 24–48 h examples the hypersensitivity reactions.
and the effect is prolonged. It is mediated by cellular
Ans.
response type IV reaction, e.g. tuberculosis and typhoid.
l Hypersensitivity or allergy is defined as state of exag-
Mechanism of Type IV Hypersensitivity Reaction gerated immune response to the antigen, which may
lead to tissue damage, disease or even death following
l Delayed hypersensitivity or type IV hypersensitivity con- contact with specific antigens.
stitutes one aspect of cell-mediated immune response. l The lesions of hypersensitivity, i.e. immunologic tissue
l The reaction is induced by sensitized T cells which on con- injury are produced due to interaction between antigen
tact with specific antigen release cytokines that cause bio- and product of immune responses.
logical effects on leucocytes, macrophages and tissue cells.
l It is provoked by specific antigens, evolving slowly and Coombs and Gell (1963) classified hypersensitivity reac-
consists of a mixed cellular reaction involving lympho- tions into following four types based on different mecha-
cytes and macrophages in particular. nisms of pathogenesis as follows:
l Delayed hypersensitivity can be transferred by lympho- 1. Type I (anaphylactic, IgE or regain dependant type)
cytes or the transfer factor. 2. Type II (cytotoxic or cell stimulating)
l The reactions are of two types as follows: 3. Type III (immune complex or toxic complex disease)
1. The tuberculin (infection ) type 4. Type IV (delayed or cell-mediated hypersensitivity)
2. The contact dermatitis type This classification is now widely used.
Depending upon the rapidity and duration of immune
Classical Delayed Type Hypersensitivity (DTH) response two distinct forms of hypersensitivity reaction are
there: immediate type and delayed type.
l This is mediated by specifically sensitized CD41 T cell
subpopulation on contact with antigen.
l These cells possess surface receptors which bind to IMMEDIATE TYPE
antigen resulting in cell injury characterized by slow l In this type, on administration of antigen the reaction
developing inflammatory response, e.g. tuberculin occurs immediately. The immune response in this type
reaction and typhoid fever. is mediated by the humoral antibodies.
l It is of three types as follows:
Direct T cell-Mediated Toxicity 1. Type I (anaphylactic or atopic reaction) hypersensi-

tivity, e.g. systemic anaphylaxis or local anaphylaxis
l CD81 subpopulation of T lymphocytes are cytotoxic 2. Type II (antibody-mediated) hypersensitivity, e.g.
T cells and are generated in response to antigen like cytologic reactions
virus infected cells and tumour cells. 3. Type III (immune complex reaction) hypersensitivity
l These cells possess surface receptors which bind to the
antigen and release lymphokines which cause biological

effects in leucocytes, macrophages and tissue cells. Type I (Anaphylactic or Atopic Reaction)
l There is cell injury characterized by slowly developing Hypersensitivity
inflammatory response and hence the name delayed
hypersensitivity. 1. Systemic anaphylaxis
l Tuberculin reaction is a classical example of delayed a. Administration of antisera
hypersensitivity. On intradermal injection of tuberculo- b. Administration of drugs
protein an unsensitized individual develops no response, c. Sting by wasp or bee
but in a person who has developed cell-mediated im- 2. Local anaphylaxis
munity to tuberculoprotein due to BCG vaccination or a. Hay fever
previous tuberculous infection, the person develops a b. Bronchial asthma
c. Food allergy l These complexes are then deposited to different tissue

d. Angioedema sites containing basement membrane exposed to circu-
lating blood.
l Following deposition of antigen antibody complexes in
Type II (Antibody-Mediated) tissues, there is acute inflammatory reaction and activa-
Hypersensitivity: Cytologic Reactions tion of complement system with elaboration of chemo-
l The cytotoxic reactions are defined as those reactions tactic factors, vasoactive amines and anaphylatoxins,
which cause injury to cell by combining humoral anti- e.g. arthritis and skin diseases.
bodies with cell surface antigens, blood cells are affected
commonly, e.g. erythroblastosis fetalis, leukopenia. DELAYED TYPE
T-Cell-Mediated (Type IV) Hypersensitivity
Mechanism
l Here, the reaction is slower and develops within 24–48 h
Cytotoxic antibodies to blood cells
l The mechanism involves direct cytolysis of blood cells response type IV reaction, e.g. tuberculosis and typhoid.
by combining cell surface antigen with IgG or IgM. l Tuberculin reaction is a classical example of delayed hy-
l The complement system is activated resulting in injury persensitivity. On intradermal injection of tuberculopro-
to cell membrane, e.g. autoimmune haemolytic anae- tein an unsensitized individual develops no response, but
mia, erythroblastosis fetalis and leukopenia. in a person who has developed cell-mediated immunity to
Cytotoxic antibodies to tissue components tuberculoprotein due to BCG vaccination or previous tu-
l Cellular injury may be brought about by antibodies reacting berculous infection, the person develops a typical inflam-
with some components of tissue cells in certain diseases, matory reaction reaching a peak in 48–72 h after which it
e.g. Graves’ disease, myasthenia gravis, male sterility. subsides slowly.
Antibody-dependent cell-mediated cytotoxicity l Other examples of delayed hypersensitivity are as
l Cytotoxicity is mediated by leucocytes like monocytes, follows:

neutrophils, eosinophils and NK cells. 1. Tuberculosis
l The cellular injury occurs by lysis of antibody-coated 2. Tuberculoid leprosy
target cells through Fc receptors on leucocytes. 3. Typhoid fever
l The antibody involved is IgG and the target cells killed 4. Contact dermatitis
are tumour cells, parasites.
Q. 3. Define amyloidosis. Discuss in detail the aetio-
pathogenesis and amyloidosis of kidney. Add a note on
Type III Hypersensitivity (Immune Complex its staining characteristics.
Reaction)
Ans.
Mechanism
l The type III reaction results from formation of immune
complexes by direct antigen–antibody combination as a AMYLOIDOSIS
result of which complement system gets activated caus- Amyloidosis is fundamentally a disorder of protein misfold-
ing cell injury. ing. It is a condition associated with a number of inherited
l Type III reactions are of two types as follows: and inflammatory disorders in which extracellular deposits
1. Local Arthus reaction: It is localized inflammatory of fibrillar proteins are responsible for tissue damage and
reaction, usually an immune complex vasculitis of functional compromise.
skin in an individual with circulating antibody. In it
fibrinoid necrosis is caused, e.g. injection of antiteta-
nus serum and Farmer’s lung. Aetiopathogenesis of Amyloidosis
2. Systemic reaction: Circulating immune complex The deposition of these misfolded proteins may result from
disease or serum sickness. the following:
1. Excessive production of proteins that are prone to
The steps involved in cell injury by circulating immune misfolding and aggregation
complexes are as follows: 2. Mutations that produce proteins that cannot fold prop-
l After antigen is introduced in circulation, it initiates erly and tend to aggregate
formation of antibodies which react with antigen to 3. Defective or incomplete proteolytic degradation of
undergo antigen–antibody reactions. extracellular proteins
Production of abnormal amounts of protein occurs as 3. if excretion of protein is impaired, e.g. associated
follows (Fig. 5.1): with long-term dialysis.
l A mutation may give rise to a form of protein that has
a tendency to fold improperly and form aggregates,

e.g. hereditary amyloidosis.
Stimulus Unknown carcinogen Chronic inflammation l Limited proteolysis may generate a protein that forms
amyloid fibrils, e.g. amyloidosis associated with

Alzheimer’s disease.
Monoclonal B lym- Macrophage activation
phocyte proliferation Amyloid is not a structurally homogenous protein, although
it always has the same morphologic appearance. Of the
Interleukin 1 and 6 more than 20 biochemically distinct forms of proteins,
three are most common. They are as follows:
1. The amyloid light chain (AL) protein: It is produced by
Plasma cells Liver cells plasma cells and is made up of complete immunoglobu-
lin (Ig) light chains, the amino-terminal fragments of
light chains or both.
Soluble precursor Immunoglobulin SAA protein 2. The amyloid-associated (AA) fibril is a unique nonim-
misfolded protein light chains munoglobulin protein derived from a larger 12-kd se-
Limited Limited rum precursor called serum amyloid associated (SAA)
proteolysis proteolysis protein that is synthesized in the liver. The production of
this protein is increased in inflammatory states as part of
Insoluble fibrils AL protein AL protein the acute phase response; therefore this form of amyloi-
FIGURE 5.1 Pathogenesis of amyloidosis (production of ab- dosis is associated with chronic inflammatory disorders.
normal amounts of protein). 3. Ab amyloid is found in cerebral lesions of Alzheimer’s
disease.
Production of normal amounts of mutant protein, e.g.
Several other proteins have been found in amyloid deposits
transthyretin occurs as follows (Fig. 5.2):
which are as follows:
1. Transthyretin (TTR): It is so named as it is a normal
serum protein that binds and transports thyroxine and
retinol. Mutations in the gene encoding transthyretin
Stimulus Mutation
result in production of a protein that aggregates and
form amyloid deposits. The resultant diseases are called
Soluble precursor
familial amyloid polyneuropathies.
Mutant transthyretin
misfolded protein 2. b2-microglobulin: It is a component of the MHC class I
molecules and a normal serum protein identified as the
Aggregation
amyloid fibril subunit (A b2m) in amyloidosis that compli-
Insoluble fibrils ATTR protein cates the course of patients on long term haemodialysis.
Amyloid deposits derived from diverse precursors like hor-
FIGURE 5.2 Pathogenesis of amyloidosis (production of nor- mones (procalcitonin) and keratin have also been reported.
mal amount of mutant protein).
Amyloidosis of Kidney
Several factors as described above may contribute to the
l Amyloidosis may be localized or systemic.
aggregation of certain proteins and the formation of fibrils
l Since the pattern of organ involvement in different
that deposit in extracellular tissues.
clinical forms of amyloidosis is variable, each major
l The protein may have a tendency to form aggregates of organ involvement is described separately as below.
misfolded forms when its concentration reaches abnor- l Amyloidosis of kidney is the most common and most
mally high levels. This may happen serious involvement in the disease.
1. as an individual ages, e.g. senile amyloidosis. l Grossly, the kidney may appear unchanged normal sized,
2. when its production is increased, e.g. chronic inflam- or it may be abnormally enlarged or terminally con-
matory states. stricted due to ischaemic effect in long-standing diseases.
l Cut section appears grey, pale, waxy and translucent. Staining Characteristics of Amyloid
l Microscopically, amyloid deposition occurs primarily
The oldest stain used to demonstrate amyloid is Lugol’s
in the glomeruli, it may involve peritubular tissues and
iodine which imparts mahogany brown colour to the
the wall of arteriole.
amyloid deposited area which turns violet on addition of
dilute sulphuric acid.
In the Glomeruli
Other special stains used to distinguish and confirm amy-
l The deposition occurs in basement membrane and pro- loid deposits are as follows:
duce terminal narrowing and distortion of glomerular 1. Haematoxylin and eosin: With these stains the amyloid
capillary tuft. appears as homogenous, structureless, and eosino-
l This release in increase of permeability of glomerular
philic hyaline material especially in relation to blood
capillaries to macromolecule causes proteinuria and vessels.
nephrotic syndrome. 2. Rosaniline dyes or metachromatic stains
l They use the metachromatic property of the amyloid,
In the Tubules i.e. the dye changes colour on reaction with amyloid.
l The stains are methyl violet and crystal violet which
l Amyloid deposits close to tubular epithelial basement impart rose pink colour to the amyloid deposits.
membrane. 3. Congo red and polarized light
l Amyloid deposits may further extend into intertubular l The most commonly used staining technique uses
connective tissue and inwards to produce degenerative dye Congo red. All types of amyloid have special
changes. affinity for Congo red stain which can be used on
l In vascular involvement they affect the wall of arterioles both gross specimens and microscopic sections. It is
and venules, producing narrowing of their lumina and also used for in vivo test.
consequent ischaemic effects. l It is used to distinguish between AL and AA
amyloid.
l Congo red stains amyloid in orange colour which
Gross Appearance
shows apple green birefringence when viewed under
l The affected organ is usually enlarged, pale and polarized light due to cross-pleated sheet configura-
rubbery. tion of amyloid fibrils.
l Cut surface appears grey with a waxy and firm consis- l A prior treatment with permanganate keeps the
tency and translucent parenchyma stains positive with primary amyloid or AL amyloid congophilic,
iodine test. i.e. Congo red positive but the secondary amyloid or
AA amyloid turns negative.
4. Fluorescent stains: Fluorescent stains like thioflavin
Microscopic Examination S or T binds to amyloid and fluorescent yellow under
l The deposits of amyloid are found in the extracellular ultraviolet light.
locations. 5. Sulphated alcian blue: It imparts blue-green colour to
l Initially in the walls of small vessels producing micro- amyloid positive areas.
scopic changes and effects. 6. Immunohistochemical stains: AA, AL and ATTR types
l Later the deposits are in large amounts causing macro- of amyloid can be distinguished by specific immunohis-
scopic changes and effects of pressure atrophy. tochemical staining.
SHORT ESSAYS
Q. 1. Classification of amyloidosis called amyloid having common morphological, struc-
tural and staining properties but with variable protein
Ans.
composition.
Amyloidosis is a group of diseases characterized by ex- Classification of amyloidosis is listed in Table 5.1.
tracellular deposition of fibrillar proteinaceous substance
TABLE 5.1 Classification of Amyloidosis Q. 2. Anaphylaxis

Major Chemically Ans.
Clinicopatho- Fibril Related
logic Type of Associated Protein Precursor Organs
Amyloidosis Diseases Type Protein Involved
ANAPHYLAXIS
1. Systemic (generalized) amyloidosis l The type I hypersensitivity is a B cell-mediated immedi-
ate hypersensitivity reaction. It is known as anaphylac-
a. Primary Multiple AL Immuno- Heart,
amyloidosis myeloma globulin bowel, tic atopic reaction.
(immunocyte and other light skin, l Anaphylaxis is defined as state of rapidly developing
dyscrasias monoclonal chains, skeletal immune response to an antigen to which individual is
with B cell chiefly g muscle previously sensitized.
amyloidosis) proliferations type
b. Secondary Chronic AA SAA Liver,
amyloidosis inflammatory spleen, Mechanism
(reactive conditions kidney,
l The response is mediated by humoral antibodies of
systemic adrenals
amyloidosis) IgE type.
l Antibodies are fixed on the surface of tissue cells, i.e.
c. Haemodialy- Chronic Ab2M b2 micro- Synovium,
sis associated renal failure globulin joints,
mast cells and basophils in a sensitized individual.
amyloidosis tendons l The antigen combines with the cell-fixed antibody, lead-
sheaths ing to release of pharmacologically active substances,

2. Hereditary or familial amyloidosis
i.e. vasoactive amines called as anaphylactic mediators
which produce the clinical reaction, e.g. histamine,
a. Familial _ AA SAA Liver,
serotonin, platelet activating factor, etc.
Mediterra- spleen,
l The effects of these agents are as follows:
nean fever kidney,
adrenals l Increased vascular permeability
l Smooth muscle contraction

b. Familial _ ATTR Transthy Heart
l Early vasoconstriction followed by vasodilatation
amyloidotic retin
neuropathies l Shock
(hereditary l Increased gastric secretion
polyneuropa- l Increased nasal and lacrimal secretion
thies)
l It occurs in two forms as follows:
c. Senile Senility ATTR Transthy Heart l The acute, potentially fatal systemic form called
amyloidosis retin anaphylaxis.
3. Localized amyloidosis l The chronic or recurrent, nonfatal typically localized
a. Senile Alzheimer’s Ab APP Cerebral

form called atopy.
cerebral disease blood The clinical examples of anaphylaxis are as follows:
vessels, 1. Systemic anaphylaxis
cerebral a. Administration of antisera
plagues b. Administration of drugs
b. Endocrine c. Sting by wasp or bee
i. Medullary Medullary A cal Calcitonin Thyroid 2. Local anaphylaxis
carcinoma carcinoma a. Hay fever
of thyroid of thyroid b. Bronchial asthma
ii. Islets of Diabetes AIAPP Islet Islets c. Food allergy
Langerhans type II amyloid of Langer- d. Angioedema
peptide hans
c. Isolated AANF Atrial Heart

Q. 3. Microscopy of amyloidosis of the spleen
atrial natriuretic Or,
amyloidosis factor Microscopy of sago spleen
Ans.
AMYLOIDOSIS OF THE SPLEEN and are deposited in body tissues, which activate the
complement system.
l The amyloidosis of the spleen may cause moderate to
l The resulting complement fragments attract poly-
marked splenomegaly.
morphonuclear leucocytes and platelets causing
l For some unknown reasons one of the following two
inflammation and tissue injury.
patterns of deposition are seen:
l Types: Two typical type III reactions are as follows:
1. Sago spleen
1. Arthus reaction (localized)
2. Lardaceous spleen
2. Serum sickness (generalized)
Sago Spleen
Arthus Reaction
l Sago spleen is a type of secondary or reactive amyloi-
It is a localized form of type III hypersensitivity. When an
dosis of the spleen. Splenomegaly is not marked.
antigen is injected subcutaneously or intradermally in an
l It occurs as a complication of chronic infections or
animal in which there were repeated administration of the
noninfectious inflammatory conditions associated with
same antigen previously, there occurs intense local oedema
tissue destruction.
and haemorrhage which reaches peak in 3–6 h. This is
l On gross appearance cut surface shows characteristic
called as Arthus reaction.
translucent pale and waxy nodules resembling tapioca-
like granules, i.e. sago grains, hence the name sago
spleen. Serum Sickness
l Microscopic appearance: The amyloid deposit begins
in the walls of the arterioles of the white pulp and may It is a systemic form of type III hypersensitivity, which
subsequently replace the follicles. appears 7–12 days following a single injection of a high
l In advanced cases histologically the entire follicle may
concentration of foreign serum such as diphtheria antitoxin.
be replaced. The clinical syndrome consists of fever, lymphadenopathy,
splenomegaly, arthritis, glomerulonephritis, endocarditis, vas-
culitis, urticarial rashes, abdominal pain, nausea and vomiting.
Lardaceous Spleen
Q. 5. Write in brief about immunoglobulins.
l Here histologically the amyloid deposit appears to spare
the follicles and instead involves the walls of splenic Ans.
sinuses and connective tissue framework of the red
pulp. l Immunoglobulin is defined as a protein of animal origin
l On gross examination of cut surface of the spleen,
endowed with known antibody activity.
l Immunoglobulins are synthesized by plasma cells and
fusion of the early deposit gives rise to large, map-like
areas of amyloidosis, creating what is designated as the also by lymphocytes.
l All antibodies are immunoglobulins but all immuno-
lardaceous spleen.
globulins may not be antibodies.
Q. 4. Write briefly on type III hypersensitivity. Various classes of immunoglobulins are as follows:
Ans.
l Type III hypersensitivity is also called as immune com- IgG

plex or toxic complex disease. It is a type of humoral l It is the major serum immunoglobulin comprising 80% of
antibody-mediated hypersensitivity reaction. the total immunoglobulins and distributed almost equally
l Here the tissue damage is caused by Ag–Ab complexes.
between intravascular and extravascular compartments.
They precipitate in and around small blood vessels, l It is the only maternal immunoglobulin that passes
causing damage to cells secondarily or on membranes, across the placenta and provides passive immunity to
interfering with their function. the newborn.
l Pathogenesis
l It is considered as general purpose antibody protective
l When an antigen combines with its corresponding
against infectious agents that are active in blood and
antibody, Ag–Ab complex is formed. tissues. The process of suppressing homologous anti-
l Normally these immune complexes are removed by the
body synthesis by a feedback process is utilized in
reticulo-endothelial system whereas reticulo-epithelial isoimmunization of women by the administration of
(RE) cells are inefficient to remove smaller complexes anti-Rh (D) IgG during delivery.
formed in antigen excess which occasionally persists
IgA l IgD may function as mutually interacting antigen receptor

for the control of leukocyte activation and suppression.
l It is the fast-moving alpha globulin and the second
most abundant class of immunoglobulins, constituting
10–13% of serum immunoglobulins. IgE
l Its normal serum level is 0.6–4.2 mg/mL with half-life
l IgE is chiefly produced in the linings of the respiratory
of 6–8 days. and intestinal tracts.
l It is reaginic antibody responsible for anaphylactic type
1. serum IgA of hypersensitive reaction and is mostly extravascular in
2. secretory IgA distribution.
l It is found in high concentration in colostrum, tear, bile,
l It has affinity for surface of tissue cells preferably mast
saliva, intestinal and nasal secretions. It promotes cells and mediates the Prausnitz-Kustner reaction.
phagocytosis and intracellular killing of organisms. l A trace amounts of IgE, i.e. few nanograms (ng) per
millilitre (mL) are present in normal serum but in atopic

IgM or type I allergic conditions like asthma, hay fever and
eczema the levels of IgE are greatly elevated.
l It is also known as macroglobulin. It appears to be l Physiological role of IgE are as follows:
spherical shape. IgM is mostly intravascular in distribu- 1. Protection against pathogens by release of inflamma-
tion about 80%. tory mediators through mast cell degranulation.
l It is not transported across the placenta and hence its 2. Has special role in defence against helmenthic
detection in fetus or newborn indicates intrauterine infections.
infections like syphilis, rubella, HIV infection and toxo- l Functions of immunoglobulins are as follows:
plasmosis. 1. Complement activation
2. Opsonization resulting in phagocytosis
3. Prevention of microbial attachment to the host cells
IgD
4. Neutralization of toxins
l It resembles IgG structurally and is mostly intravascular. 5. Restriction of motility of microorganisms
SHORT NOTES
Q. 1. Atopy Q. 2. B lymphocytes
Ans. Ans.
l Atopy is a form of type I hypersensitivity naturally l B lymphocyte precursors, pro-B cells during embryonic
occurring in human beings with familial distribution, life develop in fetal liver and afterwards continuously
e.g. hay fever and asthma. throughout life in the bone marrow.
l Features of atopy l When viewed under scanning microscope B cells have
l Atopy shows marked familial distribution and the an extensively filamentous surface, with numerous
inheritance is probably linked to MHC genotype. microvilli.
l The antigens commonly involved are characteristically l B cells have immunoglobulins on their surface. Each
inhalants or ingestants. Some are contact allergens. B cell approximately carries about 105 identical Ig mol-
l The artificial induction of atopy is difficult. Atopic ecules on its surface. The surface Ig on a B cell will
sensitization is developed spontaneously following have only single antigen specificity; therefore it serves
natural contact with atopens. as the antigen recognition unit.
l Atopy is IgE-mediated hypersensitivity reaction. l B cells produce antibody-mediated immune response by
l The antigen–antibody complex stimulates the release specific differentiation and proliferation of plasma cells
of mediators that are responsible for the manifesta- which produce antigen specific antibodies.
tions of the atopy.
l Manifestations of atopy are usually determined by the Q. 3. Cell-mediated immunity
portal of entry, i.e. conjunctivitis, rhinitis, broncho-
Ans.
spasm, GI symptoms and dermatitis following exposure
through eyes, nose, respiratory tract, intestines and skin l The cell-mediated immunity is also known as type IV
respectively. hypersensitivity reaction.
l In it, the reaction is slower and develops within 24–48 h Mechanism

l The response is mediated by humoral antibodies of
response type IV reaction, e.g. tuberculosis and typhoid.
IgE type.
l Tuberculin reaction is a classical example of delayed
l IgE antibodies sensitize basophils of peripheral blood
hypersensitivity. On intradermal injection of tuberculo-
of mast cells of tissue leading to release of pharmaco-
protein an unsensitized individual develops no response,
logically active substances called as anaphylactic me-
but in a person who has developed cell-mediated im-
diators, e.g. histamine, serotonin, platelet activating
munity to tuberculoprotein due to BCG vaccination
factor, etc.
or previous tuberculous infection, the person develops
l The effects of these agents are (a) increased vascular
a typical inflammatory reaction reaching a peak in
permeability, (b) smooth muscle contraction, (c) early
48–72 h after which it subsides slowly.
vasoconstriction followed by vasodilatation, shock,
l Other examples of delayed hypersensitivity are as
increased gastric secretion, (d) increased nasal and lacri-
follows:
mal secretion.
1. Tuberculosis
l The clinical examples of anaphylaxis are of two types as
2. Tuberculoid leprosy
follows:
3. Typhoid fever
1. Systemic anaphylaxis: Administration of antisera,
4. Contact dermatitis
administration of drugs, sting by wasp or bee
Q. 4. Routes of transmission of HIV 2. Local anaphylaxis: Hay fever, bronchial asthma,
food allergy, angioedema
Ans. HIV is a retrovirus that causes AIDS in human
beings. Q. 6. Define amyloidosis.
Ans.
ROUTES OF TRANSMISSION OF HIV
Amyloidosis is a group of diseases characterized by ex-
The viruses are present in the body fluids like blood, lymph
tracellular deposition of fibrillar proteinaceous substance
and genital fluids and get transmitted when a healthy individ-
called amyloid having common morphological, struc-
ual’s body fluids come in contact with an affected individual.
tural and staining properties but with variable protein
1. Sexual contact: Spread of HIV by sexual contact is the composition.
most common form of transmission.
2. Parenteral transmission: It is the next most common
GROSS APPEARANCE
mode of transmission seen in
a. intravenous drug abusers by sharing needles, sy- l The affected organ is usually enlarged, pale and
ringes, etc. rubbery.
b. haemophilics who have received large amounts of l Cut surface shows firm, waxy and translucent paren-
factor VIII concentrates. chyma staining positive with iodine test.

c. recipients of blood and blood products.
d. Perinatal transmission: It is also called vertical
MICROSCOPIC EXAMINATION
transmission.
3. Infected mothers can transmit HIV to the newborn l The deposits of amyloid are found in the extracellular
during pregnancy transplacentally or in immediate locations.
postpartum period through contamination with maternal l Initially in the walls of small vessels producing micro-
blood, infected amniotic fluid or breast milk. scopic changes and effects.
l Later the deposits are in large amounts causing macro-
Q. 5. Type I hypersensitivity reaction scopic changes and effects of pressure atrophy.
Ans.
Q.7. Sago spleen
TYPE I HYPERSENSITIVITY REACTION Ans.
l The type I hypersensitivity reaction is immediate reac- l Sago spleen is a type of secondary or reactive amyloi-
tion. It is known as anaphylactic atopic reaction. dosis of the spleen. Splenomegaly is not marked.
l Anaphylaxis is defined as state of rapidly developing l It occurs as a complication of chronic infections or
immune response to an antigen to which individual is noninfectious inflammatory conditions associated with
previously sensitized. tissue destruction.
l Gross appearance: Cut surface shows characteristic The oldest stain used to demonstrate amyloid is Lugol’s
translucent, pale and waxy nodules resembling tapioca- iodine which imparts mahogany brown colour to the amy-
like granules, i.e. sago grains; hence the name sago loid deposited area which turns violet on addition of dilute
spleen. sulphuric acid.
l Microscopic appearance: The amyloid deposit begins in Other special stains used to distinguish and confirm
the walls of the arterioles of the white pulp and may amyloid deposits are listed in Table 5.2.
subsequently replace the follicles.
l Fibril protein contains AA amyloid.
TABLE 5.2 Special Stains of Amyloid
l In advanced cases histologically the entire follicle may
be replaced. Special Stain Appearance

1. Haematoxylin and eosin Pink, amorphous and hyaline
Q. 8. Amyloidosis of liver
2. Rosaniline dyes or Rose pink colour is imparted
Ans. metachromatic stains to the amyloid deposits
l Amyloidosis of liver constitutes half of the cases of 3. Congo red and polar- Pink-red on light microscope,
ized light red-green birefringence under
systemic amyloidosis. polarized light
l Normal liver function is usually preserved in spite of
quite severe involvement of the liver. 4. Fluorescent stains Fluorescent under UV light
(thioflavin S or T)
l Grossly the deposits may be inapparent and cause
moderate to marked hepatomegaly. 5. Sulphated alcian blue Blue-green

l Histologically amyloid appears first in the space of 6. Immunohistochemical Positive immunoreactivity
disse (the space between hepatocytes and sinusoidal stains
endothelial cells), then progressively encroaches on
adjacent hepatic parenchymal cells and sinusoids.
l As time progresses deformity, pressure atrophy and
Q. 10. Lymphokines
disappearance of hepatocytes occur, causing total re-
placement of liver parenchyma by amyloid. Vascular Ans.
involvement and Kupffer cell depositions are frequent.
l Lymphocytes can be activated by contact with antigen.
Q. 9. Special stains of amyloid Activated lymphocytes produce lymphokines.
l One of the lymphokines IFN-g is a major stimulator of
Or, monocytes and macrophages.
l They produce cytokines which are polypeptide sub-
Special stains for demonstrating amyloid
stances that act on self cells producing them or on other
Ans. cells and act as mediators of inflammation.
Topic 6
Neoplasia
LONG ESSAYS
Q. 1. Define neoplasia. Give the differences between CLASSIFICATION OF TUMOURS

benign and malignant tumours. Benign Tumours
Benin tumours are generally spherical or ovoid in shape.
Ans.
They are encapsulated or well circumscribed, freely mov-
Neoplasia means new growth. According to Willis it is able, more often firm and uniform, unless secondary
defined as an abnormal mass of tissue the growth of which changes like haemorrhage or infarction supervene. They
exceeds and is uncoordinated with that of the normal remain localized and cannot spread to other sites and are
tissues and persists in the same excessive manner after the amenable to local surgical removal and the patient gener-
cessation of the stimuli which evoked the change. ally survives.
Malignant Tumours Features Benign Malignant

They are usually irregular in shape, poorly circumscribed Local invasion Not present but Usually present
and can invade and destroy adjacent structures. Secondary often compresses tumour, infiltrates
changes like haemorrhage, infarction and ulceration are the surrounding and invades the
tissues adjacent tissues
seen. Malignant tumours are also known as cancer. They
can metastasize (spread to distant sites) to cause death. Metastasis Absent Frequently present
Malignant tumours of epithelial origin are called as Prognosis Good prognosis, Death by local and
carcinomas while malignant mesenchymal tumours are only few local metastatic compli-
called as sarcomas. complications cations is usual.
The differences between benign and malignant tumours
are listed in Table 6.1.
Q. 2. Define neoplasia. Classify tumours. Discuss the
TABLE 6.1 Differences between Benign and Malignant modes of spread of malignant tumours.
Tumours
Ans.
Features Benign Malignant
Gross macroscopic features Neoplasia means new growth. According to Willis it is
defined as an abnormal mass of tissue, the growth of which
Boundaries Encapsulated or Poorly circum-
well-circumscribed scribed and
exceeds and is uncoordinated with that of the normal
with well-defined irregular with ill- tissues and persists in the same excessive manner after the
boundaries defined boundaries cessation of the stimuli which evoked the change.
Surrounding tis- Often compressed Usually invaded According to tissue of origin, tumours are classified as
sue and destroyed listed in Table 6.2.
Size Usually small and Often large
limited
Secondary Occurs less often Occurs more often TABLE 6.2 Classification of Tumours Based on Tissue of
changes Origin
Microscopic features Tissue of Origin Benign Malignant
Pattern Usually resembles Often poor resem- Tumours composed of one parenchymal cell type
the tissue of origin blance to tissue of
very closely origin Connective tissue Fibroma Fibrosarcoma
and derivatives
Basal polarity Retained Often lost
Lipoma Liposarcoma
Pleomorphism Usually not exhib- Often exhibited
ited Chondroma Chondrosarcoma
Nucleocytoplas- Normal Increased Osteoma Osteogenic

mic ratio sarcoma
Anisonucleosis Not present Generally present Endothelial and related tissues

Blood vessels Haemangioma Angiosarcoma
Hyperchromatism Absent Often present
Lymph vessels Lymphangioma Lymphangiosar-
Mitoses May be present but Mitotic figures coma
are always typical increased and are
mitosis generally atypical Synovium Meningioma Synovial
and abnormal sarcoma
Tumour giant May be present but Present with Mesothelium Mesothelioma

cells without clear atypia nuclear atypia Brain coverings Invasive
Cytoplasm May show normal Normal cytoplas- meningioma
constituents mic elements are Blood cells and related cells
reduced or lost
Haemopoietic Leukaemiae
Function Usually well May be retained,
cells
maintained are lost or
becomes abnormal Lymphoid tissue Lymphomas
Growth rate Usually slow Usually rapid Muscle
Continued
TABLE 6.2 Classification of Tumours Based on Tissue of Local Invasion or Direct Spread
Origin—cont’d
l The malignant tumours invade via the route of least
Tissue of Origin Benign Malignant resistance, as most cancers recognize no anatomic
Smooth Leiomyoma Leiomyosarcoma boundaries.
l Often, cancers extend through tissue spaces, permeate
Striated Rhabdomyoma Rhabdomyosar-
coma lymphatics, blood vessels, perineural spaces and
may penetrate a bone by growing through nutrient
Tumours of epithelial origin
Stratified squa- Squamous cell Squamous cell foramina.
mous epithelium papilloma or epidermoid l More commonly, the tumours invade thin wall capillar-
carcinoma ies and veins than thick walled arteries.
Transitional Transitional Transitional cell
epithelium, cell papilloma, carcinoma,
urinary tract urothelial urothelial
Metastasis or Distant Spread
epithelium papilloma carcinoma l The term metastasis denotes the development of sec-
Glandular epithe- Adenoma, Adenocarci- ondary implants discontinuous with the primary tumour
lium (epithelial papilloma, noma, papillary possibly in remote tissues.
lining of glands cystadenoma carcinoma,
l Metastasis is defined as spread of tumour by invasion in
or ducts) cystadenocarci-
noma such a way that discontinuous secondary tumour mass
formed at the site of lodgment.
Basal cell layer of Basal cell
l Malignant neoplasms may spread to distant sites by one
skin or adnexa carcinoma
of the following pathways:
Respiratory Bronchial Bronchogenic 1. Lymphatic spread
passages adenoma carcinoma
2. Haematogenous spread
Renal epithelium Renal tubular Renal cell 3. Seeding within body cavities and by other routes
adenoma carcinoma
Liver cells or Liver cell Hepatocellular
hepatocytes adenoma carcinoma
Lymphatic Spread
Placental Hydatidiform Choriocarci- l Lymphatic spread is more typical of carcinomas. They
epithelium mole noma usually metastasize through lymphatic route.
l The involvement of lymph nodes by malignant cells is
Testicular epithe- Seminoma,
lium (germ cells) embryonal of two forms, i.e. lymphatic permeation and lymphatic
carcinoma emboli.
Tumours of Nevus Malignant l Walls of lymphatics are invaded by cancer cells and
melanocytes melanoma may form a continuous growth in the lymphatic channel

Tumours of more than one neoplastic cell type—mixed
called lymphatic permeation or may detach to form tu-
tumours usually derived from one germ cell layer mour emboli to the draining lymph node.
l Generally, regional lymph nodes draining tumour are
Salivary glands Pleomorphic ad- malignant mixed
enoma (mixed tumour of sali- invariably involved producing regional metastasis, e.g.
tumour of salivary gland carcinoma breast to axillary lymph node, carcinoma
vary glands) thyroid to lateral cervical lymph nodes.
l Retrograde metastasis due to obstruction of lymphatics
Renal anlage Wilms’ tumour
by tumour cells is seen at unusual sites like metastasis of
Tumours of more than one neoplastic cell type—derived from
more than one germ cell layer—teratogenous
carcinoma of prostate to supraclavicular lymph nodes.
l Virchow’s lymph node is nodal metastasis preferentially
Totipotent cells in Mature teratoma, Immature to supraclavicular lymph node from cancers of abdomi-
gonads or in em- dermoid cyst teratoma, terato-
nal organs, e.g. cancer stomach, colon and gallbladder.
bryonic rests carcinoma
l Sometimes the cancer cells appear to traverse the lym-
phatic channels within the immediately proximate

nodes to be trapped in subsequent lymph nodes produc-
ing so- called skip metastasis.
SPREAD OF MALIGNANT TUMOURS
Generally, spread of malignant tumours is by two ways as
follows:
Haematogenous spread
1. Local invasion or direct spread l It is the most-feared consequence of a cancer and this is
2. Metastasis or distant spread the most-favoured pathway for sarcomas.
l The common site for blood-borne metastasis are lung, l Malignant neoplasms are characterized by a wide range
breast, thyroid, kidney, liver, prostate and ovary. of parenchymal cell differentiation, from surprisingly
l Systemic veins drain blood into venae cava from limb, well-differentiated to completely undifferentiated.
head and neck, cancers of these sites metastasize to lungs. Between the two extremes lie tumours referred to as
l Portal veins drain blood from bowel, spleen and liver, tu- moderately well differentiated. For example, well-
mours of these organs frequently has secondaries in liver. differentiated adenocarcinomas of thyroid contain
l Cancer cell readily invade the thin walls of capillaries normal appearing follicles.
and veins than arteries which are thick walled and l The better the differentiation of the cell, the more
contain invasion-resistant elastic tissue. completely it retains the functional capabilities found
l The tumour embolus may occlude a small vessel in the in its normal counterparts.
microcirculation, extend through the vessel wall and l Malignant neoplasms that are composed of undifferen-
then establish a metastasis at the new site of lodgment. tiated cells are said to be anaplastic. Lack of differen-
tiation or anaplasia is considered as a hallmark of
malignancy.
Various Other Routes l The term anaplasia literally means to form backwards.
1. Transcoelomic spread: Some of the cancers invade through It implies dedifferentiation or loss of the structural and
the serosal layer of coelomic cavity so that tumour frag- functional differentiation of normal cells. Anaplastic
ments or cluster of tumour cells detach and get implanted cells display marked pleomorphism.
elsewhere, peritoneal cavity is involved most often. l The inference is that benign tumours resemble the tis-
For example: Carcinoma of stomach seeding to both ova- sue of origin and are well differentiated; malignant
ries, carcinoma of ovary spread to entire peritoneal cavity tumours are poorly or completely undifferentiated or
2. Along epithelium lined surfaces: Intact epithelium and anaplastic.
mucus layer are quite resistant to penetration of tumour
cells, thus this route of spread is unusual. A few malig- Rate of Growth
nant tumours may spread through Fallopian tube from
the endometrium to ovaries or vice versa bronchus into l The benign tumours usually exhibit progressive
alveoli. and slow growth, may come to a standstill or regress;
3. Spread via CSF: Some of the malignant tumours may mitotic figures are rare and normal.
spread by release of tumour fragments and tumour cells l Rate of growth in malignant tumours is erratic and may
into CSF. be slow to rapid.

For example: Malignant tumour of ependyma and lepto- l The malignant tumour cells have increased mitotic rate
meninges and slower death rate, i.e. cancer cells do not follow
4. Implantation: Rarely, tumour cells may be implanted to normal control in cell cycle and are immortal.
a distant site by surgeon’s scalpel, needles, sutures or l Secondly the rate of growth of malignant tumours
may be implanted by direct contact such as transfer of is directly proportional to degree of differentiation.
carcinoma of lower lips to the opposing upper lip, etc. Mitotic figures may be numerous and abnormal.
Q. 3. Explain the characteristics of benign and malig-

nant tumours. Clinical and Gross Features
Ans. The characteristics of malignancy are as follows: l Secondary changes like haemorrhage, infarction and
1. Differentiation and anaplasia ulceration are seen more often in malignant tumours.
l The malignant tumours are irregular in shape, poorly
2. Rate of growth
3. Clinical and gross features circumscribed and extend into adjacent tissues.
4. Microscopic features
5. Local invasion or direct spread Microscopic Features
6. Metastasis or distant spread
l The malignant tumours have poor resemblance to
origin.
Differentiation and Anaplasia l Basal polarity is lost.
l Differentiation of parenchymal cells refers to the extent l Pleomorphism is present.
to which they resemble their normal forebears morpho- l Nucleocytoplasmic ratio is increased.
logically and functionally. l Anisonucleosis is generally present.
l Benign neoplasms are composed of well-differentiated l Hyperchromatism and abnormal mitotic figures are seen.
cells that closely resemble their normal counterparts. l Tumour giant cells are present with nuclear atyphia.
For example: A lipoma is made up of mature fat cells. l The function may be retained or lost or abnormal.
Local Invasion Features Benign Malignant

l Usually cohesive and expansile, well-demarcated Microscopic features
masses that do not invade or infiltrate the surrounding Pattern Usually resembles Often poor
normal tissues. the tissue of origin resemblance to
very closely tissue of origin
l Malignant tumours are locally invasive, infiltrate the
surrounding normal tissues. Basal polarity Retained Often lost

l Tumours invade via routes of least resistance, though even- Pleomorphism Usually not Often exhibited
tually most cancers recognize no anatomic boundaries. exhibited
l The cancers extend through tissue space, permeate Nucleocytoplas- Normal Increased
lymphatics, blood vessels, perineural spaces and may mic ratio
penetrate the bone by going through nutrient foramina. Anisonucleosis Not present Generally present
Hyperchromatism Absent Often present
Metastasis or Distant Spread Mitoses May be present but Mitotic figures
l Benign tumours do not exhibit metastasis. are always typical increased and are
mitosis generally atypical
l Malignant tumours frequently exhibit metastasis; the
and abnormal
larger and less differentiated the primary, the more
likely are metastases. Tumour giant May be present but Present with
cells without nuclear nuclear atypia
l Lymphatic spread: In general carcinomas metastasize
atypia
by lymphatic route. Virchow’s lymph node is nodal
metastasis to supraclavicular lymph node from cancers Cytoplasm May show normal Normal cytoplasmic
constituents elements are
of abdominal organ. reduced or lost
l Haematogenous spread: It is common root for sarcomas
but certain carcinomas also spread by this mode. The Function Usually well May be retained,
maintained are lost or becomes
common sites are lung, breast, thyroid, kidney, liver, abnormal
prostate and ovary.
Growth rate Usually slow Usually rapid
l Spread along body cavities and natural passages: The
routes of distant spread are transcoelom, epithelial lined Local invasion Not present but Usually present
surfaces, CSF and implantation. often compresses tumour, infiltrates
the surrounding and invades the
tissues. adjacent tissues
Q. 4. Discuss differences between benign and malignant
tumours. Add a note on paraneoplastic syndrome. Metastasis Absent Frequently
present
Ans.
Prognosis Good prognosis, Death by local and
Neoplasia is defined as a mass of tissue that is formed as a only few local com- metastatic compli-
plications cations is usual.
result of abnormal, excessive, uncoordinated, autonomous,
purposeless proliferation of cells.
The differences between benign and malignant tumours
are listed in Table 6.3.
PARANEOPLASTIC SYNDROMES
TABLE 6.3 Differences between Benign and Malignant Paraneoplastic syndromes are symptom complexes that
Tumours occur in patients with cancer and that cannot be readily
explained by local or distant spread of the tumour or by
Features Benign Malignant
elaboration of hormones indigenous to the tissue of origin
Gross macroscopic features of tumour.
Boundaries Encapsulated or Poorly circum-
They appear in 10–15% of patients with cancer and it is
well-circumscribed scribed and irregular
with well-defined with ill-defined important to recognize them for the following reasons:
boundaries boundaries 1. They may represent the earliest manifestation of an
occult neoplasm.
Surrounding Often compressed Usually invaded and
tissue destroyed 2. In affected patients, they may represent significant
clinical problems and may even be lethal.
Size Usually small and Often large
limited
3. They may mimic metastatic disease and confound
treatment.
Secondary Occurs less often Occurs more often The paraneoplastic syndromes are diverse and are
changes
associated with many different tumours.
Endocrinopathies (Endocrine Syndromes) Dermatologic Disorders (Cutaneous

Syndrome)
Clinical Major Forms of Causing
Syndromes Underlying Cancer Mechanism
Cushing Small cell carcinoma ACTH or
syndrome of lung, pancreatic ACTH-like
carcinoma, neural substance Acanthosis Gastric carcinoma, Immunologic
tumours nigricans lung carcinoma, secretion of
uterine carcinoma epidermal growth
Hypercalcaemia Squamous cell carci- Parathyroid
factor
noma of lung, breast hormone-
carcinoma, renal related protein, Dermatomyositis Bronchogenic breast Immunologic
carcinoma, adult TGF-a, TNF, carcinoma
T-cell leukaemia IL-1
Hypoglycaemia Fibrosarcoma, other Insulin or

mesenchymal sarco- insulin-like Others
mas, hepatocellular substance
Renal syndromes: Nephrotic syndrome seen in various
carcinoma
cancers due to tumour antigens, immune complexes, etc.
Elaboration of hormones or hormone-like substances Q. 5. Define carcinogenesis. Write briefly about carcino-
by cancer cells of nonendocrine origin is called ectopic genic agents. Discuss the chemical carcinogenesis.
hormone production.
Ans. Carcinogenesis means mechanism of induction of
tumour. Agents which can induce tumours are called as
Nerve and Muscle Syndrome carcinogens.
(Neuromyopathic Syndromes)
Three classes of carcinogenic agents are identified as
This is probably mediated by immunologic mechanisms. follows:
Some of the changes are peripheral neuropathy, myasthenia 1. Chemical carcinogens
gravis syndrome. 2. Physical carcinogens or radiant energy
3. Microbial agents or biological carcinogens
Syndromes Underlying Cancer Mechanism CHEMICAL CARCINOGENS
Myasthenia Bronchogenic carci- Immunologic
noma
l Chemical carcinogens have highly reactive electrophile
groups that directly damage DNA leading to mutations
Disorders of Breast carcinoma and eventually cancer.
central and pe-
l Human carcinogens include direct acting, indirect
ripheral nervous
system acting and promoters or agents that cause pathologic
hyperplasias of liver, endometrium, etc.
Effects on osseous, joints and soft tissues: hypertrophic
osteoarthropathy and clubbing of fingers in case of bron- Classification of chemical carcinogens depending upon the
chiogenic carcinoma mode of action is as follows:
1. Initiator carcinogens
2. Promoter carcinogens
Haematologic and Vascular Syndrome
Clinical Major Forms of Causing Initiator Carcinogens
They can initiate the process of neoplastic transformation.
Venous thrombosis Pancreatic carci- Tumour products
a. Direct-acting carcinogens: They do not require meta-
(Trousseau phe- noma, broncho- (mucins that acti-
nomenon) genic carcinoma, vate clotting) bolic activation.
other cancers i. Alkylating agents: Anticancer drugs, b-propiolac-
Nonbacterial Advanced cancers Hypercoagulability
tone, dimethyl sulphate, diepoxybutane
thrombotic endo- ii. Acylating agents: Acetyl imidazole, dimethylcarba-
carditis myl chloride
Anaemia Thymic neoplasms Unknown
b. Indirect-acting agents (procarcinogens): They require
metabolic activation.
i. Polycyclic and heterocyclic aromatic hydrocarbons: Stages in Chemical Carcinogenesis

Benzanthracenes, benzopyrene
Induction of tumour by a chemical substance or carcinogen
ii. Aromatic amines, amides and azo dyes: Naphthyl-
is called chemical carcinogenesis. Basic mechanism of
amine (b-naphthylamine), benzidine and azo dyes
chemical carcinogenesis is by induction of mutation in the
like 2-acetylaminofluorene, dimethylaminoazoben-
proto-oncogenes and antioncogenes.
zene (butter yellow)
iii. Naturally occurring products: Chemical derived
There are two distinct sequential stages in chemical carci-
from plants and microbial sources, i.e. aflatoxin B1,
nogenesis as follows:
griseofulvin, cycasin, actinomycin D and betel nuts
1. Initiation of carcinogenesis
iv. Others: Nitrosamines or nitrosamides in gastric
2. Promotion of carcinogenesis
carcinoma, arsenic in epidermal hyperplasia, insec-
ticides, fungicides, etc
Initiation of Carcinogenesis
Promoter Carcinogens l It is the first step in the carcinogenesis which pro-
duces a change which is sudden, irreversible and per-
Chemicals which promote further clonal proliferation
manent. It requires a single dose of carcinogen for
and expansion of initiated cells, e.g. phorbol esters, phenols
short time but the large dose for longer duration is
and certain hormones like oestrogen, contraceptive hor-
more effective.
mones, etc.
l Chemical carcinogens acting as initiators can be grouped
into direct-acting carcinogens and indirect-acting pro-

PHYSICAL CARCINOGENS carcinogens.
l The stages in conversion of a target cell into an initiated
Radiation Carcinogens cell are as follows:
l UV light, X–rays, etc. cause cancer by damage to DNA 1. Metabolic activation: Most carcinogens are activated
resulting in mutagenesis. chiefly by the mixed oxidases of the cytochrome
l Ionizing radiation damages the DNA of the cell by p450 system located in the microsomal component
directly altering the cellular DNA resulting in mutagen- of the endoplasmic reticulum or in the nucleus. It can
esis, dislodging ions from water and other molecules of be affected by the genetic and environmental influ-
the cell and result in formation of highly reactive free ences or stimulated by drugs like phenobarbital.
radicals that bring about the damage. However this stage is bypassed by the directly-acting
carcinogens.
2. Reactive electrophiles: Chemical carcinogens have
Nonradiation Carcinogens highly reactive electrophile groups that directly
By injury, mechanical trauma and burns induce carcinogenesis, damage DNA leading to mutations and eventually
e.g. mechanical injury (stones, scars), asbestosis and implants. cancer. The chemical carcinogens both direct and
indirect acting become electron deficient and bind to
electron-rich portion of other cell molecules like
BIOLOGICAL CARCINOGENS DNA, RNA and other proteins.
3. Target molecules: Primary target of the electrophile
They are chiefly viruses while others are parasites, fungus
is DNA and produces mutagenesis, although any
and bacteria.
gene may be the target of chemical carcinogens. The
l Viral carcinogens may be oncogenic viruses associated commonly mutated oncogenes and tumour suppres-
with neoplasm. sors such as RAS and p53 are important targets
l DNA oncogenic viruses, e.g. herpes virus, adeno virus, of chemical carcinogens. If the change in the DNA is
pox virus. DNA oncogenic viruses have direct access to not repaired by some cellular enzymes like in
the host cell nucleus and are incorporated to the genome xeroderma pigmentosa, then the cell becomes the
of the host cell DNA. initiated cell.
l RNA oncogenic viruses, e.g. acute transforming virus 4. Initiated cell: The unrepaired damage produced in
(leukaemia sarcoma virus), slow transforming and the DNA of the cell becomes permanent only if
hepatitis C virus. the altered cell undergoes at least one cycle of
proliferation. This results in transferring the
change to the next progeny of cells so that the
Chemical Carcinogenesis DNA damage becomes permanent and irreversible
Induction of tumour by a chemical substance or carcinogen making it vulnerable to the action of promoters of
is called chemical carcinogenesis. carcinogenesis.
Promotion of Carcinogenesis such as RAS, subsequent application of promoters leads

to clonal expansion of initiated (mutated) cells.
l It is the stage in the chemical carcinogenesis brought
l Being forced to proliferate, the initiated clone of cells
about by promoters of carcinogenesis.
accumulates additional mutations, developing eventu-
l Promoters are the chemical substances which lack
ally into a malignant tumour.
intrinsic carcinogenic potential but helps in further pro-
l The concept that sustained cell proliferation increases
liferation of initiated carcinogenesis, e.g. phorbol esters,
the risk of mutagenesis and hence neoplastic transfor-
hormones, phenols and drugs.
mation, is also applicable to human carcinogenesis, e.g.
l Although the effects of tumour promoters are pleiotro-
pathological hyperplasia of endometrium and increased
pic, induction of cell proliferation is a sine qua non of
regenerative activity that accompanies chronic liver cell
tumour promotion.
injury are associated with the development of cancer in
l It is more likely that while the application of an initiator
these organs.
may cause the mutational activation of an oncogene
SHORT ESSAYS
Q. 1. Metaplasia Q. 2. Describe the features of malignant cells. Name the
pathways of spread of malignant tumours.
Ans.
Ans.
Metaplasia is defined as a reversible change of one type of
epithelial or mesenchymal adult cells to another type of Features of malignant cells are as follows:
adult epithelial or mesenchymal cells usually in response to l The malignant tumours have poor resemblance to origin.
abnormal stimuli and often reverts back to normal on re- Basal polarity is lost.
moval of stimulus. l Pleomorphism and anisonucleosis is present. Tumour
Metaplasia is broadly divided into the following: giant cells are present with nuclear atypia. Nucleocyto-
1. Epithelial metaplasia plasmic ratio is increased.
2. Mesenchymal metaplasia l Hyperchromatism and abnormal mitotic figures are
seen.
l Chromosomal abnormalities are invariably present.
Epithelial Metaplasia l The function may be retained or lost or abnormal.
l More common and may be patchy or diffuse.

Results in replacement by stronger but less specialized
l
PATHWAYS OF SPREAD OF MALIGNANT
epithelium resulting in deprivation of protective mucus
secretion and hence more prone to infection. TUMOURS
For example: Generally, spread of malignant tumours is by two ways as
1. Squamous metaplasia: It occurs due to chronic irritation follows:
that may be mechanical, chemical or infective in origin. 1. Local invasion or direct spread
Usually seen in bronchus in chronic smokers and in 2. Metastasis or distant spread
uterine endocervix in prolapse of uterus and in old age.
2. Columnar metaplasia: Seen in intestinal metaplasia in
healed chronic gastric ulcer and in chronic bronchitis Local Invasion or Direct Spread
and bronchiectasis conversion of pseudostratified co- l The malignant tumours invade via the route of least
lumnar into columnar type. resistance, as most cancers recognize no anatomic
boundaries.
l Often, cancers extend through tissue spaces, perme-
Mesenchymal Metaplasia
ate lymphatics, blood vessels, perineural spaces and
1. Osseous metaplasia: Formation of bone in fibrous tis- may penetrate a bone by growing through nutrient
sue, cartilage and myxoid tissue as seen in: foramina.
a. arterial wall in old age,
b. cartilage of larynx and bronchi in elderly people and
c. scar of chronic inflammation of prolonged duration. Metastasis or Distant Spread
2. Cartilaginous metaplasia: In healing of fractures carti- The term metastasis denotes the development of secondary
laginous metaplasia may occur where there is undue implants discontinuous with the primary tumour possibly in
mobility. remote tissues.
Malignant neoplasms may spread to distant sites by one of 1. TNM system (T: primary tumour, N: regional lymph
the following pathways: node involvement, M: metastases)
1. Lymphatic spread 2. AJC (American Joint Committee) system
2. Haematogenous spread l The both systems take into account following three
3. Seeding within body cavities and by other routes criteria for staging any neoplasm:
1. Size of primary tumour
Lymphatic Spread 2. Nodal involvement
3. Metastasis
l Lymphatic spread is more typical of carcinomas. They
usually metastasize through lymphatic route. TNM Staging
l Generally, regional lymph nodes draining tumour are
l It was developed by Union Internationale Centre
invariably involved producing regional metastasis, e.g. Cancer, Geneva (UICC).
carcinoma breast to axillary lymph node, carcinoma l It indicates the three components of staging.
thyroid to lateral cervical lymph nodes. l T: Describes increasing size of primary tumour.
l Sometimes the cancer cells appear to traverse the lym-
l N: Indicates progressively advancing regional node
phatic channels within the immediately proximate involvement.
nodes to be trapped in subsequent lymph nodes produc- l M: Reflects absence or presence of distant metastases.
ing so- called skip metastasis. l For each of the components, numbers are given to
indicate the extent of involvement.

Haematogenous Spread l T0 to T4: In situ to largest and most extensive
primary tumour
l It is the most feared consequence of a cancer and this is
l N0 to N3: No nodal involvement to widespread
the most favoured pathway for sarcomas.
lymph node involvement
l The common site for blood-borne metastasis are lung,
l M0 to M2: No metastasis to disseminated haematog-
breast, thyroid, kidney, liver, prostate and ovary.
enous metastases
Various Other Routes

AJC System
l Transcoelomic spread: Some of the cancers invade
through the serosal layer of coelomic cavity, e.g. carci- Cancers are divided into stages 0 to 4, incorporating the
noma of stomach seeding to both ovaries, carcinoma of size of primary lesions and presence of nodal spread and of
ovary spread to entire peritoneal cavity. distant metastases. The staging of cancer has proved to be
l Along epithelium lined surfaces: Intact epithelium and of great clinical value as compared to grading.
mucus layer are quite resistant to penetration of tumour
cells, thus this route of spread is unusual. Q. 4. Characteristics of malignancy
l Spread via CSF: Some of the malignant tumours may Ans.
spread by release of tumour fragments and tumour
cells into CSF, e.g. malignant tumour of ependyma
and leptomeninges. The characteristics of malignancy are follows:
l Implantation: Rarely, tumour cells may be implanted to
1. Rate of growth
a distant site by surgeon’s scalpel, needles, sutures or 2. Clinical and gross features
may be implanted by direct contact such as transfer of 3. Microscopic features
carcinoma of lower lips to the opposing upper lip, etc. 4. Local invasion or direct spread
5. Metastasis or distant spread
Q. 3. Staging of cancer
Ans. Rate of Growth
l The malignant tumour cells have increased mitotic rate
and slower death rate, i.e. cancer cells do not follow
STAGING OF CANCER normal control in cell cycle and are immortal.
l Staging of cancer is determined by surgical exploration l Secondly the rate of growth of malignant tumours is
or imaging and is based on the size, local and regional directly proportional to degree of differentiation.
lymph node spread and distant metastasis.
l Staging is a system to determine the prognosis and
Clinical and Gross Features
choice of treatment of a malignant cancer.
l The important systems of staging which currently in use l Secondary changes like haemorrhage, infarction and
are as follows: ulceration are seen more often.
l The malignant tumours are irregular in shape, poorly Features Benign Malignant
circumscribed and extend into adjacent tissue.
Basal polarity Retained Often lost
Pleomorphism Usually not exhib- Often exhibited
Microscopic Features ited
l The malignant tumours have poor resemblance to Nucleocytoplasmic Normal Increased
origin. ratio
l Basal polarity is lost. Anisonucleosis Not present Generally
l Pleomorphism is present. Hyperchromatism and abnor- present
mal mitotic figures are seen. Cytoplasm May show normal Normal
l Nucleocytoplasmic ratio is increased. Anisonucleosis is constituents cytoplasmic
generally present. elements are
l Tumour giant cells are present with nuclear atypia.
reduced or lost
l The function may be retained or lost or abnormal. Function Usually well May be re-
maintained tained, are
lost or becomes
Local Invasion abnormal
l Tumours invade via routes of least resistance though Local invasion Not present Usually present
eventually most cancers recognize no anatomic bound- Metastasis Absent Frequently
aries. present
l The cancers extend through tissue space, permeate
Prognosis Good prognosis Death by local
lymphatics, blood vessels, perineural spaces and may only few local and metastatic
penetrate the bone by going through nutrient foramina. complications complications is
usual.
Metastasis or Distant Spread Q. 6. Teratoma

l Lymphatic spread: In general carcinomas metastasize
Ans.
by lymphatic route.
l Haematogenous spread: It is common root for sarco- l Teratoma is a neoplasm characterized by the presence
mas. The common sites are lung, breast, thyroid, kidney, of cells representing all the three germ layers—
liver, prostate and ovary. endoderm, mesoderm and ectoderm.
l Spread along body cavities and natural passages: The l They are most commonly seen in testis and ovaries.
routes of distant spread are transcoelom, epithelial lined l Grossly tetratomas exhibit following features:
surfaces, CSF and implantation. l Most testicular teratomas are large grey-white masses
causing enlargement of the involved testis.

Q. 5. Differences between benign and malignant l Cut surface shows characteristic variegated appear-
tumours ance, grey-white solid areas, cystic and honeycombed
Ans. The differences between benign and malignant tumours areas and foci of cartilage and bone.
are listed in Table 6.4. l Ovarian teratomas are benign and cystic and have
predominant ectodermal elements, often termed

TABLE 6.4 Differences between Benign and Malignant clinically as dermoid cyst.
Tumours l Benign cystic teratoma is a unilocular cyst 10–15 cm
diameter usually lined by skin and hence the name.

Features Benign Malignant The cyst is filled with paste-like sebaceous secretions
Growth rate Usually slow Usually rapid and desquamated keratin admixed with masses of hair.
Boundaries Encapsulated or Poorly circum- l Teratomas are classified into three types as follows:
well-circumscribed scribed and 1. Mature teratoma

with well-defined irregular with 2. Immature teratoma
boundaries ill-defined 3. Teratoma with malignant transformation
boundaries
Mitotic activity Low High Microscopically the above three categories have different
appearances.
Surrounding tissue Often compressed Usually invaded
and destroyed
Pattern of resem- Usually resembles Often poor
Mature Teratoma
blance the tissue of origin resemblance to l Mature testicular teratoma is composed of a disorderly
very closely tissue of origin
mixture of well-differentiated structures like cartilage,
smooth muscle, intestinal and respiratory epithelium, b. Asbestosis

mucous glands, neural tissue, fat and bone. c. Implants
l The commonest germ cell tumour and indeed the com-
monest ovarian tumour is the benign or mature cystic

CARCINOGENESIS BY IONIZING
teratoma (dermoid cyst). In mature ovarian teratoma, the
most prominent feature is the lining of cyst wall by RADIATION
stratified squamous epithelium and its adnexal structures l Ionizing radiation of all kinds like X-ray, alpha rays,
such as sweat glands, sebaceous glands and hair follicles. beta rays, and gamma rays, radioactive isotopes, protons
and neutrons are carcinogenic in man.
l The increased risk is with higher dose and with high
Immature Teratoma
linear energy transfers such as in neutrons and alpha
l In contrast to the mature cystic type, teratomas may rays than with low linear energy transfer as in X-rays
also be predominantly solid and composed of immature and gamma rays.
tissues similar to those in the early embryo.
l It is composed of incompletely differentiated and prim-
itive tissues along with some mature elements. Primitive Mechanism

tissues commonly present are poorly formed cartilage, l The oncogenic properties of ionizing radiation are
mesenchyme, neural tissue, etc. related to its mutagenic effect.
l Ionizing radiation causes chromosome breakage, trans-
Teratoma with Malignant Transformation locations less frequently point mutations, leading to
genetic damage and carcinogenesis.
l This is an extremely rare form with tissue elements l Ionizing radiation damages the DNA of the cell by
showing malignant transformation. Such change directly altering the cellular DNA resulting in muta-
resembles morphologically with typical malignancies genesis.
in other organs and tissues. l The effect depends upon the type of radiation dose, dose
rate and various host factors such as age, individual

Q. 7. Mention the types of physical carcinogens. Discuss susceptibility, immune competence, hormonal influ-
about injury caused by ionizing radiation. ences and type of cells irradiated.
Ans. l Most frequently radiation induced cancers are leukae-
mia (all forms except CLL), skin cancer, breast cancer,

Physical carcinogens are classified as follows: lung cancer, etc.
1. Radiation agents l Ionizing radiation rays induce the formation of pyrimi-
a. Ultraviolet light dine dimers within DNA, leading to mutations. There-
b. Ionizing radiations fore UV rays can give rise to squamous cell carcinomas
2. Nonradiation agents and melanomas of the skin.
a. Mechanical injury (stones, scars)
SHORT NOTES
Q. 1. Oncogenes For example: Rat sarcoma virus oncogene or r-RAS is
carried in bladder cancer, pancreatic adenocarcinoma,
Ans.
cholangiocarcinoma.
l Mutant versions of proto-oncogenes that function au- 2. Chromosomal translocation: Transfer of a portion of
tonomously without a requirement for normal growth one chromosome to another is implicated in the patho-
promoting signals are known as oncogenes. genesis of leukaemiae and lymphomas.
l A normal gene or proto-oncogene is converted or acti- For example:
vated to oncogene by a. Philadelphia chromosome, c-ABL proto-oncogene is
1. Change in the structure of the gene translocated from chromosome 9 to 22 and is seen in
2. Change in the regulation of gene expression 95% cases of CML.
b. c-MYC proto-oncogene is translocated from chromo-
Several ways by which oncogenes are activated are as some 8 to 14 in 75% cases of Burkitt’s lymphoma.
follows: 3. Gene amplification: It is the increase in the number of
1. Point mutation and deletion: Mutation of viral oncogene copies of a gene due to chromosomal alteration.
sequence increases the tumorigenic ability of acute For example: Neuroblastoma having n-MYC HSR
transforming retroviruses. region and ERB-B in breast and ovarian cancer.
Q. 2. Chemical carcinogens Metastasis or Distant Spread

Ans. Metastasis is defined as spread of tumour by invasion in
such a way that discontinuous secondary tumour mass
Chemical carcinogens have highly reactive electrophile
formed at the site of lodgment. Cancers may spread to
groups that directly damage DNA leading to mutations and
distant sites by following pathways:
eventually cancer.
1. Lymphatic spread
2. Haematogenous spread
Classification of chemical carcinogens depending upon the
3. Other routes
mode of action is as follows:
1. Initiator carcinogens
2. Promoter carcinogens Lymphatic Spread
l Usually carcinomas metastasize by lymphatic route.
Initiator Carcinogens l Generally, regional lymph nodes draining tumour are
invariably involved producing regional metastasis, e.g.
They can initiate the process of neoplastic transformation.
carcinoma breast to axillary lymph node, carcinoma
thyroid to lateral cervical lymph nodes.
They are of two types as follows:
1. Direct-acting carcinogens
2. Indirect-acting agents (procarcinogens) Haematogenous Spread
l This is common route for sarcomas.
Direct-acting carcinogens: They do not require meta-
l The common site for blood-borne metastasis are lung,
bolic activation, e.g. alkylating agents and acylating
breast, thyroid, kidney, liver, prostate and ovary.
agents.
Indirect-acting agents (procarcinogens): They require
Other Routes
metabolic activation.
1 . Transcoelomic spread
For example:
2. Along epithelium lined surfaces
l Polycyclic and heterocyclic aromatic hydrocarbons
3. Spread via CSF
l Aromatic amines, amides and azo dyes
4. Implantation
l Naturally occurring products
Q. 4. Burkitt’s lymphoma
Promoter Carcinogens Ans.
Chemicals which promote further clonal proliferation and l Burkitt’s lymphoma is a distinctive type of B-cell
expansion of initiated cells, e.g. phorbol esters, phenols and lymphoma caused by Epstein-Barr virus (EBV)
certain hormones like oestrogen, contraceptive hormones, etc. infection.
l Three subgroups of Burkitt’s lymphoma are recognized
Q. 3. Spread of malignant tumours
as follows:
Ans. 1. African endemic
2. Sporadic
Generally, spread of malignant tumours is by two ways as 3. Immunodeficiency associated
follows: l It is endemic in paraequitorial Africa and New
1. Local invasion or direct spread Guinea and occurs much less commonly in other
2. Metastasis or distant spread regions.
l The disease affects children and adolescents, and is
Local Invasion or Direct Spread associated with Epstein-Barr virus (EBV) infection and
malaria.
l The malignant tumours invade via the route of least l It involves extranodal sites, particularly the jaw, gastro-
resistance, though eventually more cancers recognize intestinal tract and gonads.
no anatomic boundaries. l The histological appearances are distinctive, with tightly
l Often, cancers extend through tissue spaces, permeate packed lymphoblasts interspersed with phagocytic
lymphatics, blood vessels, perineural spaces and may macrophages which impart a starry-sky appearance to
penetrate a bone by growing through nutrient foramina. histological sections.
Q. 5. Virus-related human tumours and examples 2. Submucosal fibrosis due to excess consumption of
chillies
Ans.
3. Poor orodental hygiene
l Viruses were first indicated as carcinogenic agents 4. Nutritional deficiencies
through the experiments of Rous in 1911 and Shope in 5. Exposure to sunlight
1932. 6. Exposure to radiation
l 20% of all human cancers worldwide are believed to 7. Plummer-Vinson syndrome
have virus association. Tumours associated with viruses
tend to be more common in youth. Preferential Sites
l Immunosuppression favours viral oncogenesis. Viruses
implicated in human carcinogenesis include Epstein- Lips (commonly lower), tongue, floor of the mouth and
Barr virus (Burkitt’s lymphoma) and human papilloma buccal mucosa
virus (cervical cancer).
l Oncogenic viral genome is directly incorporated into
Q. 7. Tumour markers
host cell DNA. Ans.
l Oncogenic RNA viral genome is transcribed into DNA
by reverse transcriptase prior to incorporation (onco- l Tumour markers are biochemical assays of products
genic retrovirus). elaborated by tumour cells in blood or other body
l Oncogenic viruses implicated in human tumours are as fluids.
follows: l These methods lack sensitivity as well as specificity and
can be used
l as an adjunct to diagnosis arrived at by other
Viruses Tumours
methods.
Human papilloma virus Common wart (squamous cell
l for prognostic and therapeutic purposes.
papilloma)
Cervical cancer l Important tumour markers and cancers producing them
are given below.

Epstein-Barr virus Burkitt’s lymphoma
Nasopharyngeal carcinoma
Hepatitis B and C virus Liver cell carcinoma Markers Cancers
Alpha fetoprotein (AFP) Hepatocellular carcinoma
Human herpes virus Kaposi’s sarcoma
and malignant teratoma
B-cell lymphoma
Monoclonal immunoglobu- Multiple myeloma
lin, Bence-Jones protein
There are few human cancers where aetiological role of
viruses is established by epidemiological and serological Prostate acid phosphatase Prostatic carcinoma
evidence. Calcitonin Medullary carcinoma of
thyroid
Q. 6. Aetiology of oral cancer
Peptide hormones (insulin, Apudomas (other than
Ans. gastrin) carcinoids and phaeochromo-
cytomas)
Squamous cell carcinoma or epidermoid carcinoma com- Vanillyl mandelic acid (VMA) Phaeochromocytoma
prises 90% of all malignant oral cavity tumours.
Q. 8. Paraneoplastic syndrome
AETIOLOGY
Ans.
Chief Factors
l Paraneoplastic syndromes are symptom complexes that
1 . Tobacco smoking and tobacco chewing occur in patients with cancer and that cannot be readily
2. Chronic alcohol consumption explained by local or distant spread of the tumour or
3. Human papilloma virus infection particularly HPV by elaboration of hormones indigenous to the tissue of
origin of tumour.
l They appear in 10–15% of patients with cancer.
Other Associated Factors
l The paraneoplastic syndromes are diverse and are
1. Chronic irritation from ill-fitting denture or jagged associated with many different tumours as shown
teeth below.
Endocrinopathies (Endocrine Syndromes)

Keratin
Major Forms of Underlying
Clinical Syndromes Cancer
Cushing syndrome Small cell carcinoma of lung Downward
proliferation
Hypercalcaemia Squamous cell carcinoma of lung
Keratin
Nerve and muscle syndrome (neuromyopathic syndromes):
Myasthenia in case of bronchogenic carcinoma Epithelial pearl
Effects on osseous joints and soft tissues: Hypertrophic Inflammatory

cells
osteoarthropathy and clubbing of fingers in case of bron-
chiogenic carcinoma
FIGURE 6.1 Squamous cell carcinoma.
Dermatologic disorders (cutaneous syndrome): Acantho-
sis nigricans as seen in case of gastric carcinoma and lung Clinical Features
carcinoma
l Most common locations are: the face, pinna of ears,
Others: Renal syndromes like nephrotic syndrome seen in vari- back of hands and mucocutaneous junctions.
ous cancers due to tumour antigens, immune complexes, etc. l Squamous cell carcinoma in situ appears as sharply
defined, red, scaling plaques.

Q. 9. Fibroma
l More advanced invasive lesions are nodular, show vari-
Ans. able scale and may ulcerate.

l Likelihood of metastasis is related to the thickness of
Fibroma is benign tumour of fibrous connective tissue. True the lesion and degree of invasion into the subcutis.
fibromas are uncommon in soft tissues. Combination of soft l Mucosal squamous cell carcinomas are generally much
fibrous growth with other mesenchymal tissue elements are more aggressive.
more frequent.
Macroscopically squamous cell carcinoma can have one of
Three types of fibroma are distinguished as follows: the following two patterns:
1. Fibroma durum: It is a benign often pedunculated and 1. An ulcerated growth with elevated and indurated margin
well-circumscribed tumour occurring on body surfaces is commonly seen.
and mucous membranes, composed of fully-matured 2. A raised fungating or polypoid verrucous lesion without
and richly collagenous fibrous connective tissue. ulceration.
2. Fibrolipoma or soft fibroma: It is composed of mixture
of mature fibrous connective tissue and adult fat. Microscopically the features are as follows:
3. Elastofibroma: A rare fibrous tumour located in the sub- l There is irregular downward proliferation of epidermal
scapular region. It is characterized by association of cells into the dermis. The mass of epidermal cells show
collagen bundles and branching elastic fibres. atypical features like variation in cell size and shape,
nuclear hyperchromatism, absence of intercellular
Q. 10. Squamous cell carcinoma (epithelioma) bridges, individual cell keratinization and occurrence of
atypical mitotic figures.
Ans.
l Higher grades of squamous carcinomas have highly
Squamous cell carcinoma (Fig. 6.1) is a malignant epi- atypical cells.

thelial tumour most commonly arising on sun-exposed
parts of skin or mucous membrane lined by squamous Q. 11. Rodent ulcer
epithelium. Or,
Various predisposing factors include the following: Describe aetiology, gross and microscopic picture of
1. UV light exposure basal cell carcinoma.
2. Solar keratosis Ans.
3. Old burn scars
4. Ionizing radiation Basal cell carcinoma or rodent ulcer (Fig. 6.2), the most
5. Chewing betel nuts and tobacco (in the case of cancer of common human cancer, is a locally invasive, slow-growing
oral cavity). tumour of middle aged that rarely metastasizes.
Stratified
Stratified squamous squamous
keratinized epithelium epithelium
Dense connective
tissue Malignant
pigment
Radiating arrangement Collagen

fibre
of small epithelial cells
Giant cells
FIGURE 6.2 Basal cell carcinoma.
Aetiology Melanocytes
l Lightly-pigmented white-skinned people subject to FIGURE 6.3 Malignant melanoma.
strong sunlight exposure
l Immunosuppression
l The aetiology is unknown but key role is of excessive
l Individuals with inherited defects in DNA repair
exposure to sunlight.
l The common sites are trunk, legs face, soles, palm and
Common Sites nail beds.
l Clinically it appears as a flat or slightly elevated naevus
l Basal cell carcinoma exclusively occurs on hairy skin.
with variegated pigmentation, irregular borders and of
l In 90% cases, most common location is face, usually
late undergone secondary changes of ulceration, bleed-
above a line joining lobe of the ear and the angle of the
ing and increase in size.
mouth.
l Microscopically, there is marked junctional activity
at epidermo-dermal junction and growth downwards

Pathology into dermis, melanin may be present or absent
without any prognostic influence. Some amount
Gross Appearance
of inflammatory infiltrate is present in invasive
Two common patterns are seen as follows: melanomas.
1. Multifocal growths arising from epidermis (superficial l Metastatic spread of malignant melanoma is very com-
type) mon and occurs via blood and lymphatics.

2. A noduloulcerative pattern in which a slow-growing
small nodule undergoes central ulceration with pearly, Q. 13. Oral squamous cell carcinoma
rolled margins. Ans.
The tumour enlarges in size by burrowing and by de-
stroying the tissues locally like a rodent and hence the name Squamous cell carcinoma or epidermoid carcinoma com-
rodent ulcer. prises 90% of all malignant tumours of oral cavity.
Microscopic Examination Aetiology

l Proliferation of basaloid cells is the most characteristic l Tobacco smoking and tobacco chewing
feature. l Chronic alcohol consumption
l These cells may be seen arranged in solid masses, l Human papilloma virus infection particularly HPV 16,
strands and nests of tumour cells in morphea pattern, 18 and 11

keratotic masses, cystic changes with sebaceous differ- l Chronic irritation from ill-fitting denture or jagged teeth
entiation. l Oral submucous fibrosis
These tumours are usually treated with complete local l Exposure to radiation
excision. l Plummer-Vinson syndrome
Q. 12. Malignant melanoma

Clinical Features
Ans.
l Squamous cell carcinoma has peak incidence in the age
Malignant melanoma or melanocarcinoma (Fig. 6.3) arising group of 40–45 years with definite male preponderance.
from melanocytes is one of the most rapidly spreading l The intraoral carcinomas are detected late and thus have
tumours of skin. poor prognosis except papillary type.

Common Sites 1. Papova virus: It is responsible for skin warts (squamous

cell papillomas) and invasive cervical cancer
l Lips (commonly lower), tongue, anterior floor of mouth,
2. Herpes virus: Epstein-Barr virus (EBV)—Burkitt’s lym-
buccal mucosa in the region of alveolar lingual sulcus
phoma) and human herpes virus 8 (HHV8)—Kaposi’s
sarcoma
Types 3. Adenovirus: causes upper respiratory tract infections
and pharyngitis
1 . Ulcerative type (most frequent type)
4. Poxvirus: They cause molluscum contagiosum
2. Papillary or verrucous type
5. Hepadna virus: Hepatitis B virus (hepatocellular carcinoma)
3. Nodular type
4. Scirrhous type
RNA Oncogenic Viruses
Microscopic Features These are retroviruses. Based on their ability to transform
l It ranges from well-differentiated keratinizing carci- target cells into neoplastic cells, these viruses are classified
noma to highly undifferentiated neoplasm. Surrounding as follows.
areas of lesion shows changes of epithelial dysplasia. 1. Acute transforming virus (leukaemia–sarcoma virus—
leukaemiae, sarcoma)
Q. 14. Carcinoma in situ 2. Slow transforming virus (mouse mammary tumour
virus—breast cancer)
Ans. 3. Human T-cell lymphotrophic virus (HTLV-1—adult
l If the epithelial dysplasia is extensive so as to involve T-cell leukaemia)
the entire thickness of the epithelium, the lesion is 4. Hepatitis C virus (HCV—hepatocellular carcinoma)
called carcinoma in situ.
Q. 16. Lab diagnosis of cancer
l Epithelial dysplasia is characterized by following
cellular, proliferative and cytologic changes: Ans.

1. Hyperplasia of epithelial layers
2. Disorderly arrangements of cells from basal layer to The different methods of lab diagnosis of cancer are as
the surface layer follows:
3. Loss of basal polarity 1. Histological methods: Diagnosis by these methods are
4. Cellular and nuclear pleomorphism made on the basis of cytological features of benign and
5. Increased nucleocytoplasmic ratio malignant tumours.
6. Nuclear hyperchromatism 2. Cytological methods: Two methods are employed.
7. Increased mitotic activity a. Exfoliative cytology—study of cells shed into body
l Dysplastic changes often occur due to chronic irritation
cavities, e. g. papanicolaou smear
or prolonged inflammation and they may disappear on b. Fine-needle aspiration cytology (FNAC)—study of
removal of the inciting stimulus. cells by putting a fine needle introduced under vacuum
l However, in a proportion of cases, it progresses to
3. Histochemistry and cytochemistry: These help in identify-
carcinoma in situ or invasive carcinoma, e.g. uterine ing the chemical composition of cells, their constituents
cervix, respiratory tract. and products by special staining methods, e.g. periodic
acid-Schiff for basement membrane and collagen.
Q. 15. Oncogenic viruses 4. Immunohistochemistry: This is an immunological
method of recognizing a cell by one or more of its spe-
Ans. cific components (antigens). Fluorescent dyes are used
l Oncogenic viruses are associated with neoplasms. to detect antigen antibody complex, e.g. 1 keratins help
l Based on their nucleic acid content the oncogenic in identifying carcinomas.
viruses divided into two groups as follows: 5. Electron microscopy: Some general features of malig-
1. DNA viruses nant cells identified by electron microscope are
2. RNA viruses a. cell junctions—their presence and type, and
b. nucleoli—size and density.
6. Tumour markers: Two important tumour markers are
DNA Oncogenic Viruses (a) alpha fetoprotein for hepatocellular carcinoma and (b)
DNA Oncogenic viruses have direct access to the host carcinoembryonic antigen for cancers of bowel, pancreas.
cell nucleus and are incorporated to the genome of the 7. Modern aids in tumour diagnosis are as follows:
host cell DNA. a. Flow cytometry
l In situ hybridization
DNA oncogenic viruses are classified into five subgroups l Molecular diagnostic techniques
as follows: l DNA microassay analysis of tumours
Topic 7
Genetic and Paediatric Diseases

SHORT ESSAY
Q. 1. Down’s syndrome 7. Oral findings include deficient maxilla with class
III relation of occlusion, open mouth, large tongue and
Ans.
caries free teeth due to excessive salivation.
Down’s syndrome or trisomy 21 or mongolism affects The overall prognosis for individuals with Down’s syndrome
approximately 1 in 1000 births. has improved remarkably in the recent past due to better
control of infections.
Aetiology
Q. 2. Chromosome mutation
1. The maternal age has a strong influence on the inci-
dence of Down’s syndrome, the incidence increases Ans.
with the maternal age. l The term mutation refers to permanent change in the
2. Nondisjunction of chromosome 21 during an early stage DNA. The genetic disorders arising from chromosomal
of embryogenesis. aberrations include disorders that are consequence of
numeric or structural abnormalities in the chromosomes.
Clinical Features l Some of the general features of chromosomal disorders
and some specific examples of diseases involving

It exhibits following characteristic clinical features: changes in the karyotype are as follows:
1. Epicanthal folds and flat facial profile, slanting eyes 1. Chromosomal disorders resulting from mutations
producing a mongoloid appearance. may be associated with absence i.e. deletion or
2. Mental retardation mainly due to trisomy 21. monosomy, excess i.e. trisomy, or abnormal rear-
3. The hands are short with a transverse simian palmar rangements i.e. translocation of chromosomes.
crease. There are also abnormalities of ears, trunk, 2. In general the loss of chromosomal material
pelvis and phalanges. produces more severe defects than does the gain of
4. Congenital malformations are common and quite chromosomal material.
disabling. 3. The excess chromosomal material may result from a
5. Cardiac malformations and serious infections are the complete chromosome as in trisomy or from part of
important causes of morbidity and mortality associated a chromosome as in Robertsonian translocation.
with this syndrome in early childhood. 4. Imbalances of sex chromosomes are tolerated much
6. The chromosomal imbalance in some undefined man- better than the similar imbalances of autosomes.
ner, also increases the risk of developing acute leukae- 5. Most of the times chromosomal disorders result
miae especially megakaryocytic leukaemia in these from de novo changes. An uncommon but important
persons. exception to this principle is exhibited by the trans-
location form of Down’s syndrome.
SHORT NOTES
Q. 1. Gaucher’s disease glucosylceramide in the mononuclear phagocytic cells
and their transformation into so-called Gaucher’s cells.
Ans.
3 . In the most common type I variant or classical form,
1. Gaucher’s disease is an autosomal recessive disorder, a affected phagocytes become enlarged (Gaucher’s cells)
storage disease due to defective lipid metabolism. and accumulate in the liver, spleen, bone marrow
2. Gaucher’s disease results from mutation in the gene that and lymph nodes manifesting as hepatosplenomegaly,
encodes glucosylceramidase. The deficient activity of lymphadenopathy, pancytopenia or thrombocytopenia
glucosylceramidase that normally cleaves the glucose secondary to hypersplenism, bone erosion, bone pains
residue from ceramide, leads to an accumulation of and pathological fractures.
4 . Type II or infantile form: Progressive involvement of CNS. a. Tay-Sachs disease caused due to inability to metabo-
5. Type III or juvenile form: Systemic involvement of lize GM2 gangliosides due to lack of lysosomal
spleen, liver, bone marrow and lymph node and progres- hexosaminidase.
sive involvement of CNS. b. Niemann-Pick disease types A and B are caused due
to deficiency of sphingomyelinase.
Q. 2. Niemann-Pick disease c. Niemann-Pick disease type C is caused due to defect
Ans. in cholesterol transport and resultant accumulation
of cholesterol and gangliosides in the nervous
1. Niemann-Pick disease is an autosomal recessive disor- system.
der due to disturbance of sphingomyelin metabolism. d. Gaucher’s disease results from lack of the lysosomal
2. It is caused due to deficiency of the enzyme sphingomy- enzyme glucosylceramidase which leads to an
elinase or deficiency of an activator protein. accumulation of glucosylceramide in the mononu-
3. Pathognomonic cells are present known as Niemann- clear phagocytic cells.
Pick cells in RE system. e. Myopathies due to inborn errors of metabolism
4. Niemann-Pick cell is a macrophage which contains include disorders of glycogen synthesis and degra-
sphingomyelin and cholesterol stored in lysosomes. It is dation.
somewhat smaller and has foamy and vacuolated cyto-
plasm staining positively with fat stains. It is found Q. 4. What is erythroblastosis fetalis?
widely in spleen, liver, lymph nodes, bone marrow, Ans.
lungs, bowel and brain.
1. In hydrops fetalis associated with fetal anaemia, both
Q. 3. Inborn errors of metabolism fetus and placenta are characteristically pale. In most
Ans. There are several variants of inborn errors of metabo- cases liver and spleen are enlarged from cardiac failure
lism caused due to mutations in enzyme proteins. They are and congestion.
as follows: 2. Additionally the bone marrow shows compensatory
1. Phenylketonuria—an autosomal recessive disorder hyperplasia of erythroid precursors and extramedullary
caused due to lack of enzyme phenylalanine hydroxylase hemopoiesis is present in the liver, spleen and possibly
and consequent inability to metabolize phenylalanine. kidneys, lungs and even heart.
2. Galactosaemia caused due to inherited lack of galactose- 3. The increased hematopoietic activity accounts for the
1-phosphate uridyltransferase causing accumulation of presence of large number of immature red cells including
galactose-1-phosphate and its metabolites in tissues. reticulocytes, normoblasts and erythroblasts in the pe-
3. Various lysosomal storage diseases like the following: ripheral circulation is known as erythroblastosis fetalis.
Topic 8
Environmental and Nutritional Disorders

LONG ESSAY
Q. 1. Classify vitamins. Discuss the role of vitamin D in
rickets and their clinical features.
VITAMIN D
l Vitamin D or calcitriol is a fat-soluble vitamin.
Ans.
l Vitamin D is commonly referred to as the antirachitic
A vitamin is defined as an organic substance not made by the vitamin. A variety of biochemical analogues have simi-
body, which is soluble in either fat or water and is ordinarily lar activity, e.g. vitamin D2 (ergocalciferol) and vitamin
needed only in minute quantities to act as a cofactor in a variety D3 (cholecalciferol).
21
of metabolic reactions. Vitamin D acts more like a hormone. l The hydroxylated cholecalciferols control Ca ions
concentration.
Vitamins are classified as follows: l Vitamin D exerts its major influence by combining with
1. Fat-soluble vitamins: A, D, E, K nonhistone proteins in the nuclei of intestinal epithelial

2. Water-soluble vitamins: B and C cells.
l Commonly rickets refer to any disorder in the vitamin be buckled inwards by pressure, with the release of the
D–calcium–phosphorus axis which results in hypomin- pressure, elastic recoil snaps the bones back into their
eralized bone matrix, but such a defect may result from original positions is known as craniotabes.
a number of aetiologies, hence a variety of forms of l An excess of osteoid produces frontal bossing and a
rickets exist. squared and box-like appearance to the head.
l Deformation of the chest results from overgrowth of
General manifestations of vitamin D deficiency are as
cartilage or osteoid tissue at the costochondral junction,
follows:
producing rachitic rosary.
l The inward pull at the margin of the diaphragm creates
Deficiency of vitamin D results in the following:
the Harrison’s groove, girdling the thoracic cavity at the
1. Rickets in children
lower margin of the rib cage.
2. Osteomalacia in adults
l Pigeon chest deformity is the anterior protrusion of
sternum due to action of respiratory muscles.
VITAMIN D DEFICIENT RICKETS l Bowing of legs occur in ambulatory children due to
weak bones of lower legs and knock knees due to
l The term rickets is derived from the old English word
enlarged ends of femur tibia and fibula.
wrickken which means to twist.
l Lumbar lordosis due to involvement of spine and pelvis
l Rickets is a clinical disorder seen in growing children
from 6 months to 2 years of age due to deficiency of

vitamin D. Biochemical Changes
The pathogenic mechanism of rickets is as follows: l Low levels of 25-hydroxy vitamin D and 1,25-dihydroxy
l The basic derangement in both rickets and osteomalacia vitamin D, active metabolites of vitamin D
is an excess of unmineralized matrix. l Normal or slightly low plasma calcium levels, low
l The changes that occur in the growing bones of children plasma phosphatase levels and raised plasma alkaline
with rickets are mostly complicated by inadequate phosphatase due to osteoblastic activity.
provisional calcification of epiphyseal cartilage and
deranging endochondral bone growth.
OSTEOMALACIA
The following sequence of events ensues in rickets:
1. Endochondral ossification in long tubular bones l Osteomalacia is the adult manifestation of the vitamin D
l Overgrowth of epiphyseal cartilage due to prolifera- deficiency characterized by failure of mineralization of
tion of cartilage cells at the epiphyses followed the osteoid matrix.
l In adults lack of vitamin D deranges the normal bone
by inadequate provisional calcification or mineral-
ization. remodelling that occurs throughout the life.
l The newly formed osteoid matrix laid down by osteo-
l Persistence and overgrowth of epiphyseal cartilage,
deposition of osteoid matrix on inadequately miner- blasts is inadequately mineralized, thus producing
alized cartilage resulting in enlargement and lateral the excess of persistent osteoid that is characteristic of
expansion of the osteochondral junction. osteomalacia.
l Although the contours of the bone are not affected, the
l Deformation of the skeleton due to loss of structural
rigidity of the developing bones. bone is weak and vulnerable to gross fractures or micro-
l Irregular overgrowth of small blood vessels in disor- fractures especially affecting vertebral bodies and femo-
ganized and weak bone. ral necks.
l Other clinical features include muscular weakness, vague
2. Intramembranous ossification in flat bones
l Mesenchymal cells differentiate into osteoblasts with bony pains, fractures following trivial trauma and Loos-
laying down of osteoid matrix which fails to get miner’s zones or pseudofractures at weak places in bones.
l Biochemical changes: Normal or low serum calcium
eralized resulting in soft and weak flat bones.
levels, lowered plasma phosphate levels and raised se-
rum alkaline phosphatase due to increased osteoblastic
Clinical Features activity
l The gross skeletal changes depend on the severity of the
rachitic process, its duration and in particular the VITAMIN D RESISTANT RICKETS
stresses to which individual bones are subjected.
l Craniotabes is the earliest bony lesion occurring due to l It is also known as refractory rickets or phosphate
small round unossified areas in the membranous bones diabetes.
of the skull. l Results in hypophosphatemia and hyperphosphaturia.
l During nonambulatory stage of infancy, the head and Does not respond to usual doses of vitamin D.
chest sustains greatest stresses. The softened occipital l Oral manifestations
bones may become flattened and the parietal bones can l Retarded dental eruption
l Pulp horns elongated often reaching DEJ convert 25-hydroxycholecalciferol to the active form
l Periapical involvement of grossly normal appearing of vitamin D.
deciduous or permanent teeth l Dramatic increase in faecal calcium excretion and nega-
l Multiple gingival fistulas tive N2 balance, secondary hyperparathyroidism may

l Lamina dura poorly defined cause osteitis fibrosa cystic.
l Irregular or abnormal alveolar bone and cementum l Renal rickets or renal osteodystrophy is seen in patients
with chronic renal failure. Renal rickets is mainly due to

decreased synthesis of calcitriol in kidney.
RENAL RICKETS l In rickets, the plasma calcitriol is decreased and alkaline
l It is also known as renal osteodystrophy. phosphatase activity is elevated.

l It is a painful crippling bone disease, due to inability
of kidneys to synthesize 1-alpha-hydroxylase and
SHORT ESSAYS
Q. 1. Pellagra l Widened and thickened osteoid seams and calcified
bone can be seen as unstained and black respectively
Ans.
in von Kossa’s stain.
l Niacin deficiency causes pellagra, i.e. rough skin. l Osteoclastic activity and fibrosis of marrow is increased.
l The cardinal manifestations of pellagra are referred to

as three Ds, i.e. dermatitis, diarrhoea and dementia and
Clinical Features
if not treated may lead to fourth D, i.e. death.
a. Dermatitis: Sunburn-like dermal rash on hands, legs l Muscular weakness and vague bony pains
and face which later turn black, crack and peal. l Fractures following trivial trauma
b. Diarrhoea: with enteritis, stomatitis, glossitis, sali- l Incomplete or greenstick fractures
vation, nausea and vomiting l Looser’s zones or pseudofractures at weak places in
c. Dementia: with hallucinations preceded by headache, bones
insomnia, poor memory, motor and sensory distur- Biochemical changes include normal or low serum cal-
bances cium levels, lowered plasma phosphate levels and raised
l Anaemia and hypoproteinaemia are common in pellagra. serum alkaline phosphatase due to increased osteoblastic
l Oral findings include the following: activity.
l Bald tongue of Sandwith
l Raw beefy tongue Investigations in vitamin D deficiency are as follows:

l The mucosa becomes fiery red and painful l Serum levels of active metabolites of vitamin D
l Profuse salivation (25-hydroxy vitamin D and 1,25-dihydroxy vitamin D)

l Chronic alcoholics are at high risk of developing l Plasma calcium and phosphate level
pellagra because in addition to dietary deficiency, niacin l Plasma alkaline phosphatase level
absorption is impaired in them.

Q. 3. Manifestations of vitamin A deficiency
Q. 2. Osteomalacia
Ans.
Or,
Microscopic picture of osteomalacia VITAMIN A DEFICIENCY

Ans. Nutritional deficiency of vitamin A is more common in
children.
Osteomalacia is the adult manifestation of the vitamin D
deficiency. Pathological changes in vitamin A deficiency are as follows:
Microscopic Picture of Osteomalacia Ocular Lesions

l It is characterized by failure of mineralization of the l Night blindness
osteoid matrix. l Xerophthalmia
l Widened and thickened osteoid seams and decreased l Keratomalacia due to infections of corneal ulcers
mineralization at the borders between osteoid and bone l Bitot’s spots are focal triangular areas of opacities due
can be seen as pink and basophilic respectively in Hand E to accumulation of keratinized epithelium.
stained smears. l Blindness due to infection, scarring and opacities
Cutaneous Lesions l Anaemia: It is common in scurvy and is most often

normocytic and normochromic type.
Xeroderma or toad-like appearance of skin because of
papular lesions due to follicular hyperkeratosis and keratin Q. 5. Define protein-energy malnutrition. Mention two
plugging in the sebaceous glands. differences between kwashiorkor and marasmus.
Ans.
Squamous Metaplasia
l Protein-energy malnutrition (PEM) is a serious, often
l Of respiratory epithelium predisposing to respiratory
lethal disease common in poor countries like Africa.
infections
l PEM presents as range of clinical syndromes, all char-
l Of pancreatic ductal epithelium leading to obstruction
acterized by inadequate dietary intake of proteins and
and cystic dilatation of pancreas
calories to meet the body needs. The two ends of the
l Of urothelium predisposing to pyelonephritis and renal
spectrum of syndromes are known as marasmus and
calculi
kwashiorkor.
l Progression of long-standing metaplasia to anaplasia
The differences between kwashiorkor and marasmus are
Q. 4. Scurvy listed in Table 8.1.
Ans.
l Vitamin C deficiency results in scurvy.
l The lesions and clinical manifestations of vitamin C TABLE 8.1 Differences between Kwashiorkor and
deficiency are seen more commonly in two extreme age Marasmus
groups, i.e. early childhood and geriatric patients.
Differentiating
The manifestations of vitamin C include the following: Points Kwashiorkor Marasmus
l Lesions in teeth and gums: Scurvy may interfere with 1. Deficiency of Protein and Protein intake
development of dentine. The gums are soft, swollen and calories
may bleed readily and get infected commonly. The 2. Weight of the 60% of normal 60–80% of
infected gums are known as scorbutic gingivitis. child for that normal
l Haemorrhagic diathesis: A marked tendency to bleed- age, height
ing is characteristic of scurvy. There may be haemor- and sex falls to
rhages of skin, mucus membrane, gums, muscle, joints 3. Protein Severe loss of the Depletion of the
and under periosteum. compartment visceral protein somatic protein
l Skeletal lesions: The most prominent change is effected compartment compartment
deranged formation of osteoid matrix and not deranged 4. Appearance Hypoalbuminaemia Emaciated
mineralization. Growing tubular bones and as well as results in increased appearance
flat bones are affected. fluid retention due to loss of
l Wound healing is delayed due to deranged collagen
giving rise to muscle and
oedematous subcutaneous fat
synthesis, poor preservation and maturation of fibro- appearance
blasts and localization of infections in the wounds.
SHORT NOTES
Q. 1. Manifestations of rickets and is characterized by muscle weakness, vague
bony pains, incomplete or greenstick fractures, frac-
Ans.
tures following trivial trauma.
l Rickets is due to deficiency of vitamin D. l Biochemical changes
l The primary defects in rickets are l Lower level of active metabolites of vitamin D
l interference with mineralization of bone and l Plasma calcium levels are slightly low or normal.
l deranged endochondral and intramembranous growth. l Plasma phosphate levels are lowered.
The disease exhibits following clinical characteristics: Q. 2. Scurvy

l Skeletal changes Ans.
l Craniotabes, bow legs, Harrison’s groove, pigeon
chest deformity and knock knees Scurvy is the deficiency state of vitamin C and is commonly
l Osteomalacia is adult counterpart of rickets in which seen in two extremes of life, i.e. early childhood and very
there is failure of mineralization of osteoid matrix old age.
Clinical features include the following: intrahepatic biliary obstruction, pancreatic insufficiency
l Marked tendency to bleeding due to deficiency of inter- and malabsorption syndrome.
cellular cement which holds together the cells of the l Bedridden patients or chronically ill patients
capillary endothelium.
l Skeletal changes are pronounced in growing children Q. 5. Vitamin B12
and are due to deranged formation of osteoid matrix. Ans.
l There is failure of resorption of mineralized cartilage
which projects under widened and irregular epiphyseal l Vitamin B12 is also known as extrinsic factor of Castle,
plate and is called as scorbutic rosary. cobalamine or antipernicious factor.
l Wound healing is delayed due to deranged collagen l Inadequate levels of vitamin B12 results in megaloblastic
synthesis. macrocytic anaemia.

l Anaemia is common in scurvy due to haemorrhagic l Principal neurologic lesions associated with vitamin B12
tendency, interference with formation of folic acid or deficiency are demyelination of the posterior and lateral
deranged iron metabolism. columns of the spinal cord, sometimes beginning in the
l Gums are soft and swollen, may bleed readily and get peripheral nerves.
infected commonly and there is interference with devel- l Oral manifestations include beefy red tongue with glos-
opment of dentine. There may be hyperkeratotic and sopyrosis, glossitis and glossodynia known as Hunter’s
follicular rash of skin. glossitis or Moeller’s glossitis, which is similar to bald
tongue of Sandwith seen in pellagra.
Q. 3. Enumerate the functions of vitamin C. l High doses of vitamin B12 can be used for treatment of
Ans. trigeminal neuralgia.
Vitamin C is also known as ascorbic acid or hexuronic acid. Q. 6. Oral manifestations of scurvy
Ans.
Functions of vitamin C are as follows:
l Plays a vital role in a variety of biosynthetic path- Scurvy is the deficiency state of vitamin C.
ways by accelerating hydroxylation and amidation
reactions. Oral manifestations of scurvy are as follows:
l The activation of prolyl and lysyl hydroxylases from l Atrophy and disorganization of odontoblasts and irregu-
inactive precursors, providing for hydroxylation of lar dentine formation

procollagen is the most clearly established function of l The pathognomonic sign is the swollen and spongy
vitamin C. gums, particularly the interdental papillae is involved

l It is required in hydroxylation of proline in collagen producing the appearance of scurvy buds.
synthesis. l In severe cases, haemorrhage in periodontal membranes
l It is required for H-transfer and maintenance of intracel- followed by loss of bone and loosening of teeth occurs.
lular oxidation reduction potential.
l Vitamin C has antioxidant properties. It can scavenge Q. 7. Clinical manifestations of kwashiorkor
free radicals directly and can act indirectly by regenerat- Ans. Kwashiorkor occurs when protein deprivation is rela-
ing the antioxidant form of vitamin E. tively greater than the reduction in total calories.
l It helps in iron uptake from GIT and is involved in
formation of folinic acid. Clinical manifestations of kwashiorkor are as follows:

l It is required for the normal development of ground l Usually occurs in children between 1 and 3 years when
substances in bone, dentine and other connective tis- they are completely weaned.
sues. l Marked protein deprivation is associated with severe
loss of visceral protein compartment, the resultant hy-

Q. 4. Causes of vitamin D deficiency poalbuminemia gives rise to generalized or dependent
Ans. oedema.
l Poor growth, enlarged fatty infiltration of liver and the
The causes of vitamin D deficiency are as follows: development of apathy, listlessness and loss of apatite.
l Strict vegetarians, chronic alcoholics l Hair changes include overall loss of colour or alternat-
l Inhabitants of polar region ing bands of pale and darker hair, fine texture and loss
l Covering the body from head to foot (purdah system) of firm attachment to the scalp.
l Liver and kidney diseases l Flaky paint dermatosis
l Malabsorption of lipids due to lack of bile salts such as l Associated micronutrient deficiency
Q. 8. Enumerate investigations required in vitamin D Q. 9. Enumerate oral manifestations of rickets.

deficiency.
Ans. Oral manifestations of vitamin D deficiency are as
Ans. follows:
l Delayed eruption of primary and permanent teeth
Investigations in vitamin D deficiency are as follows:
l Malalignment of the teeth in the jaws
l Serum levels of active metabolites of vitamin D
l Developmental anomalies of dentine and enamel and
(25-hydroxy vitamin D and 1,25-dihydroxy vitamin D)
higher caries index
l Plasma calcium and phosphate levels
l The teeth shows wide predentin zone with increased
l Plasma alkaline phosphatase levels
interglobular dentine.
The above investigations in vitamin D deficiency reveal the l The pulphorns are elongated and extend high, reaching
following: the dentinoenamel junction.

l Low levels of 25-hydroxy vitamin D and 1,25-dihydroxy l Lamina dura is poorly defined or irregular.
vitamin D, active metabolites of vitamin D. l Abnormal alveolar bone and cementum
l Normal or slightly low plasma calcium levels, low
plasma phosphatase levels and raised plasma alkaline

phosphatase due to osteoblastic activity.
Topic 9
Infections and Infestations

SHORT ESSAY
Q. 1. Lab diagnosis of enteric fever Faeces Culture
Ans. l Salmonellae are shed in faeces throughout the course
of disease and even in convalescence, hence faecal
Laboratory diagnosis of enteric fever is as follows: cultures are almost as valuable as blood cultures in
l Isolation of the bacteria from the patient
diagnosis.
l Demonstration of antibodies in the serum
l It becomes positive even in carriers.
l Demonstration of circulating typhoid bacillus antigen in
l Salmonella produce pale colonies on MacConkey and
blood or urine DCA media.
l General blood picture
l On Wilson-Blair medium salmonella produces jet black
colonies with metallic sheen due to production of H2S.

ISOLATION OF THE BACTERIA But Salmonella paratyphi A produces green colonies
due to absence of H2S production.
FROM THE PATIENT
l For isolation of bacteria specimen may be obtained
from blood, faeces, urine, aspirated duodenal fluid, bile,
Urine Culture
bone marrow or rose spots. l Salmonellae are shed in the urine irregularly and infre-
quently, hence they are less useful.
l It becomes positive only in second or third week in only
Blood Culture about 25% of cases.
l The blood culture yield as much as 90% positive results
in first week as bacteriaemia occurs early in the course
Duodenal Juice or Bile Culture
of the disease.
l Blood cultures rapidly become negative on treatment l These are cultured to detect chronic carriers on selective
with antibiotics. media.
DEMONSTRATION OF ANTIBODIES IN detecting protein, the outer membrane proteins of

SERUM (SEROLOGICAL TESTS) S. typhi.
Widal Test
DEMONSTRATION OF CIRCULATING
l It is an agglutination test which detects presence of se- ANTIGEN
rum agglutinins Hand O in the patient’s serum suffering
from enteric fever. l Antigens of the typhoid bacilli are consistently present
l In enteric fever antibodies to Salmonella start appearing in the blood and the urine of the patient in the early
in serum at the end of the first week and rises sharply stage of the disease.
during the third week. l These antigens can be demonstrated by the sensitized
l It is preferable to test two specimens of sera at an inter- staphylococcal coagglutination test. Cowen I strain of
val of 7–10 days to demonstrate a rising antibody titre. Staphylococcus aureus which contains protein A, is stabi-
l The antigens used in widal test are the O and H antigens lized with formaldehyde and coated with S. typhi antibody.
of Salmonella typhi and the H antigens of Salmonella 1% suspension of these cells is mixed with patient’s serum
paratyphi A and B. on a slide during the first week of the enteric fever. The
l The highest dilution of patient’s serum in respect to lymphoid antigen present in the serum of these patients
each salmonella antigen is read as the titre. combines with the antibody attached to the staphylococcal
l The agglutinin titre depends on the stage of the dis- cells producing visible agglutination within 2 min.
ease. Agglutinins usually start appearing by the end l The test is rapid, sensitive and specific but is not posi-
of the first week with sharp rise in second and third tive after first week of the disease.
weeks and the titre remains steady till the fourth l Other modes of detecting antigen are counterimmuno-
week after which it declines gradually. electrophoresis and ELISA.

l Demonstration of rising titre of four folds or greater
of both H and O agglutinins at an interval of 4–7 days GENERAL BLOOD PICTURE

is most important diagnostic criterion. A rising titre of
H or O antibodies between test done in the first week l General blood picture in enteric fever may show leuco-
and third week is highly significant. penia (leucocyte count 20,002,500 cells/mm3) with
l In a single test titre of 1:160 or above for O and 1:200 relative lymphocytosis.
or more for H signifies active infection.
l Carriers also give positive results for widal test.
Other Laboratory Tests
l Where bacteriological facilities are not available,
ELISA Test another valuable test is diazo test of urine.
l ELISA is a sensitive method of measuring antibody l If the test is positive, a red or pink-coloured froth
against the lipopolysaccharide of the salmonellae or develops on shaking the mixture.
SHORT NOTES
Q. 1. Amoebiasis Q. 2. Cysticercus cellulosae
Or, Ans.
Amoebic infection l Taenia solium, the adult tapeworm resides in the human
intestine and passes eggs in the human faeces which are
Ans. ingested by the pigs or infect vegetables.
l These eggs develop into larval stages in the host and
l Amoebiasis is caused by Entamoeba histolytica.
l It is the most common intestinal infection of the man, spread by blood to any site in the body and form cystic
particularly more common in the tropical and subtropi- larvae known as Cysticercus cellulosae.
l The infection caused by these larvae is known as cysti-
cal areas with poor sanitation.
l The lesions of amoebiasis include amoebic colitis,
cercosis, usually acquired by ingesting undercooked
amoeboma, amoebic liver abscess and spread to various pork measly port or uncooked contaminated vegetables
sites like peritoneum, lungs, heart, brain, etc. or by autoinfection.
Q. 3. Fungus affecting hair l Clostridial food poisoning: Infection with Clostridium

welchii occurs both by bacterial invasion and as well as
Ans.
by toxins.
l The superficial fungi like Microsporum, Trichophyton l A severe form of paralyzing illness caused by ingestion
and Epidermophyton spread by direct contact or by of Clostridium botulinum which produces neurotoxin is
fomites and infect tissues like skin, hair and nails. known as botulism.
l Tinea capitis is characterized by patchy alopecia l Salmonella food poisoning (salmonellosis): Caused by
affecting the scalp and eyebrows. food contaminated by Salmonella typhimurium or Sal-
l Tinea barbae is the acute folliculitis of the beard. monella enteritidis. Depletion of water and electrolytes
l The diagnosis of dermatophytosis is made by light might result in death.
microscopic examination of skin scrapings, fungal
culture and demonstration of fungus in tissue Q. 5. Rhinosporidiosis
secretions. Ans.
Q. 4. Bacterial food poisoning l Rhinosporidiosis is a chronic granulomatous disease
characterized by the development of friable polyps, usu-
Ans.
ally confined to the nose, mouth or eye, but rarely seen
l This is a form of acute bacterial illness that occurs on the genitalia or other mucous membranes.
following ingestion of food or water contaminated l Haematogenous dissemination may occur though the
with bacteria other than those that cause specific acute disease is generally confined to mucous membranes.
intestinal infections like typhoid, paratyphoid and l Causative agent is Rhinosporidium seeberi, a fungus.
cholera. l Pathogenesis: The mode of infection is not known
l Here the illness results from either bacterial invasion or though infection is believed to originate from stagnant
bacterial toxigenic effect on the bowel. water or aquatic life.
l Histologically the lesion is composed of large numbers
The commonest causes of bacterial food poisoning are as of fungal spherules embedded in a stroma of connective
follows: tissue and capillaries. The spherules are 10–200 µm in
l Staphylococcal food poisoning: It occurs due to libera- diameter and contain thousands of endospores.
tion of enterotoxins by the Staphylococcus aureus. A l The causative fungus Rhinosporidium seeberi has not
severe form of the illness is called pseudomembranous been cultivated in media, diagnosis is usually established
enterocolitis. by direct microscopy or histopathological examination.
Topic 10
Heart and Blood Vessels

SHORT ESSAYS
The macroscopic changes according to time after onset
Q. 1. Describe the gross macroscopic and microscopic of clinical symptoms are listed in Table 10.1.
features of myocardial infarction. TABLE 10.1 Macroscopic Features of Myocardial Infarction
Ans. Time after Onset of
Clinical Symptoms Macroscopic Changes
1. Infarction is ischaemic death of tissue within the living
Up to 18 h None
body. Only death of tissue due to restricted blood supply
is infarction. 24–48 h Pale oedematous muscle
2. The commonest and more serious form of myocardial 3–4 days Yellow rubbery centre with haemor-
infarction is a regional infarct. rhagic border
3. The overall shape of infarcts depends on the territory of 1–3 weeks Infracted area paler and thinner than
perfusion of the occluded blood supply. unaffected ventricle
4. Grossly most of the infarcts occur singly and vary in
3–6 weeks Silvery scar becoming tough and white
size from 4 to 10 cm.
The microscopic features according to time after onset b. Malignant hypertension

of clinical symptoms are listed in Table 10.2. 7. Essential or primary hypertension
TABLE 10.2 Microscopic Features of Myocardial Infarction Unknown aetiology. There is no evident cause; probably
multifactorial causes involve the following:
Time after Onset
a. Genetic susceptibility
of Clinical Symptoms Microscopic Changes
b. Excessive sympathetic nervous system activity
Up to 18 h None c. Abnormalities in Na/K cell membrane transport
24–48 h Oedema, acute inflammatory cell d. High salt intake
infiltration, necrosis of myocytes e. Abnormalities in rennin-angiotensin-aldosterone
3–4 days Obvious necrosis and inflamma- system
tion, early granulation tissue 8. Secondary hypertension
1–3 weeks Granulation tissue and then pro- It may result from several underlying conditions:
gressive fibrosis a. Renal disease
3–6 weeks Dense fibrosis i. Chronic renal failure
ii. Renal artery obstruction
iii. Acute glomerulonephritis
Q. 2. Hypertension b. Endocrine causes the following:
i. Cushing’s syndrome (hypersecretion of corticoste-
Ans. roids)
1. Hypertension may be defined as a sustained resting ii. Adrenal tumours which secrete aldosterone
blood pressure of more than 160/95 mm Hg, as accepted (Conn’s syndrome)
by most authorities since there is no universally agreed iii. Phaeochromocytoma (catecholamines)
definition of hypertension. c. Coarctation of aorta
2. Hypertension is the commonest cause of cardiac failure d. Drugs
in many societies and major risk factor for atherosclero- i. Especially corticosteroids
sis and cerebral haemorrhage, which are leading causes ii. Contraceptive pills
of death worldwide. iii. Some nonsteroidal anti-inflammatory drugs
3. Hypertension may be categorized as follows: 9. Benign hypertension
a. Mild: When diastolic pressure is between 95–104 a. It is indolent, often asymptomatic and discovered
mm Hg only during a routine medical examination. Here
b. Moderate: When diastolic pressure is between 105–14 there is a gradual organ damage.
mm Hg 10. Malignant hypertension
c. Severe: At diastolic pressure above 115 mm Hg a. It is a clinical and pathological syndrome character-
4. Border hypertension encompasses the range of blood ized by markedly raised diastolic blood pressure
pressure from 140/90 to 160/95 mm Hg. over 130–140 mm Hg and progressive renal disease.
5. Hypertension may be aetiologically classified as follows: b. Since most cases occur in patients with evidence of
a. Essential or primary hypertension previous benign hypertension, this is sometimes
b. Secondary hypertension known as accelerated hypertension.
6. Hypertension may be dynamically classified as follows: c. Here there is severe and often acute renal, retinal
a. Benign hypertension and cerebral damage.
SHORT NOTES
Q. 1. Hyperlipidaemia l Populations having hyperlipidaemia or hypercholester-
olaemia have high mortality rate from IHD.
Ans.
Dietary regulation and administration of cholesterol-lowering
l Hyperlipidaemia or hypercholesterolaemia is a major drugs have beneficial effect on reducing the risk of IHD.
risk factor for atherosclerosis.
l Individuals with hypercholesterolaemia due to various Q. 2. Atheromatous plaque
causes such as diabetes mellitus, myxoedema, nephritic
syndrome, von Gierke’s disease, xanthomatosis and Ans.
familial hypercholesterolaemia have increased risk of 1. The atheromas or atheromatous plaques or atheroscle-
developing atherosclerosis and ischaemic heart disease rotic plaques are initimal lesions that protrude into vas-
(IHD). cular lumina and are characteristic of atherosclerosis.
2. The major branches of aorta especially the iliac, the superficial luminal part of fibrous cap is covered by
femoral, carotid, coronary and cerebral arteries are endothelium and is composed of smooth muscle
often severely involved. cells, dense connective tissue and extracellular matrix
3. An atheromatous plaque consists of a raised lesion with a containing proteoglycans and collagen.
soft, yellow grumous core of lipid mainly cholesterol and 5 . Atheromatous plaques cause
cholesterol esters covered by a firm, white fibrous cap. a. obstruction of blood flow and
4. Microscopically the appearance varies based on the age b. weaken the underlying media and can themselves
of the lesion, but invariably it presents features such as rupture, causing acute catastrophic vessel thrombosis.
Topic 11
Haematopoietic and Lymphoid Systems

LONG ESSAYS
Q. 1. Define anaemia. Describe in detail aetiology, clini- d. Fish tapeworm (Diphyllobothrium latum) infestation
cal features, peripheral blood and bone marrow find-
ings in megaloblastic anaemia.
Important Causes of Folic Acid Deficiency
Ans.
1 . Decreased intake: Unbalanced diet and alcoholism
Anaemia is defined as haemoglobin concentration in blood 2. Increased demand: Pregnancy, infancy and haemolysis
below the lower limit of the normal range for age and sex 3. Decreased absorption: Sprue and celiac disease
of the individual. In an adult male 13 g/dL and for females 4. Drugs: Phenytoin, methotrexate, pyrimethamine and
11.5 g/dL is taken as the lower limit of the normal haemo- trimethoprim
globin range.
Clinical Manifestations
Pathology l The clinical manifestations are mainly due to involve-
It is caused by impaired DNA synthesis and is character- ment of haematological, gastrointestinal and nervous
ized by the distinctive abnormality in the haemopoietic systems.
precursors in bone marrow in which maturation of nucleus l Patients are anaemic and they may also have mild
is delayed related to cytoplasm. Defective DNA synthesis is jaundice due to raised plasma unconjugated bilirubin.
due to deficiency of vitamin B12 and folic acid. l Purpura is rare. Spleen may be enlarged.
l Anorexia, weight loss, diarrhoea, smooth and beefy
red tongue are important significant gastrointestinal

Aetiology manifestations.
Two principal causes of megaloblastic anaemia are l Neurological manifestations such as paraesthesia,
1. folate deficiency and sensory-motor paraparesis (subacute combined degen-

2. vitamin B12 deficiency. eration), forgetfulness, psychosis are found only in
cobalamin deficiency and may occur even in the
absence of anaemia.
Important Causes of Vitamin B12 (Cobalamin)
Deficiency
Laboratory Diagnosis of Megaloblastic
1 . Decreased intake: Vegetarians
Anaemia
2. Decreased absorption
a. Intrinsic factor deficiency: Pernicious anaemia and Laboratory diagnosis of the megaloblastic anaemia can be
postgastrectomy discussed under two headings as follows:
b. Diseases of terminal ilium: Sprue, Crohn’s disease 1. General laboratory investigations of anaemia
and intestinal resection 2. Special tests to establish the deficient nutrient either
c. Bacterial proliferation vitamin B12 or folic acid
General Laboratory Investigations sensitive, simple and more rapid than microbiological
assay.
Peripheral Smear
3. Schilling test (radioisotope absorption test): Schilling
l Haemoglobin (Hb) concentration test detects the deficiency of vitamin B12 and also
l MCV and MCH increases detects and distinguishes lack of intrinsic factor and
l MCHC decreases or remain normal malabsorption. The test is performed in three stages
l Reticulocyte count: is normal or less as follows:
l Red blood cells: Blood smear demonstrates anisocytosis,
poikilocytosis and presence of ovalocytes. 1. Stage I (without intrinsic factor)

l Oral dose of 0.5–2 mg of radioactively labelled
l Leucocytes: Total WBC count is less
l Thrombocytes: Giant platelets are present.

vitamin B12 (hot B12) is administered.
l A large dose of 4 mg of unlabelled vitamin B12
Bone Marrow Findings (cold B12) is administered parenterally after 2 h to
l Marrow cellularity: Hypercellular bone marrow with saturate the serum and the tissue binding sites.
decreased myeloid:erythroid ratio l Normally more than 7% of 1 mg or oral dose of
l Erythropoiesis: The erythroid hyperplasia is due to char- hot B12 is excreted in 24 h urine sample.
acteristic megaloblastic erythropoiesis. Megaloblasts are l A lower quantity of hot B12 is excreted in case of
abnormal, large, nucleated erythroid precursors, having deficiency of intrinsic factor.

nuclear cytoplasmic asynchrony. The nuclei are large, 2. Stage II (with intrinsic factor)
having fine, reticular and open chromatin. Abnormal l In the previous stage if the urinary excretion of hot
mitosis may be seen in megaloblasts. B12 is low, the test is repeated as in stage I with a high
l Marrow iron: Increase in the number and size of the
dose of intrinsic factor orally.
iron granules in erythroid precursors. Iron in reticulum l Interpretation: If the 24-hour urine excretion of
cells is increased. hot B12 is normal then it is interpreted that the
Biochemical Findings cause is deficiency of intrinsic factor. If the excre-
tion of hot B12 is still less then it is a case of perni-
l Rise in serum unconjugated bilirubin and LDH as a re-
cious anaemia.
sult of ineffective erythropoiesis causing marrow cell
breakdown. 3. Stage III (test for malabsorption of vitamin B12)
l Serum iron and ferritin may be normal or elevated. l Here the protein-bound vitamin B12 is used and the
urinary excretion of hot B12 is checked.

l Interpretation: A normal urinary excretion confirms
Special Tests for Causes of Specific Deficiency
the cause as the malabsorption.
These tests detect the deficiency of either vitamin B12 or
folic acid. Tests for Folate Deficiency
l The normal range of serum folate is 6–12 mg/mL.
1 . Tests for vitamin B12
l Values less than 4 mg/mL are considered diagnostic of
2. Tests for folate deficiency
folate deficiency.
Tests for Vitamin B12 It can be detected by the following:
l Normal serum level of vitamin B12 is 200–900 pg/mL. 1. Urinary excretion of FIGLU: On oral administration of
l Values less than 100 pg/mL indicate clinically deficient histidine, urinary excretion of FIGLU is increased in
stage. case of folate deficiency, as folic acid is required for
l The vitamin B12 deficiency can be established by the conversion of FIGLU to glutamic acid in catabolism of
following: histidine.
1. Microbiological assay: The serum sample to be 2. Serum folate assay
assayed is added to a medium containing all other a. Microbiological assay: The test is based on the prin-
essential growth factors required for a vitamin B12 ciple that the folic acid coenzyme, 5-methyl-THF is
dependent microorganism like Euglena gracilis, required for growth of Lactobacillus casei.
Lactobacillus leichmannii or Escherichia coli. The b. Radioassay: It is done by radioisotope dilution and is
medium is incubated and the growth is compared similar to serum B12 assay.
with the growth produced by a known amount of c. Red cell folate assay: Red cells contain 20–50 times
vitamin B12. more folate than serum and assay by microbiological
2. Radioassay: Assays of serum B12 by radioisotope and radioassay are more reliable indicator of tissue
dilution (RID) and radioimmunoassay (RIA) are more stores of folate than serum folate assay.
Q. 2. Define and classify anaemiae. Discuss about the IRON DEFICIENCY ANAEMIA (IDA)
clinical features, peripheral smear and bone marrow
l This is the most common form of anaemia worldwide.
study in iron deficiency anaemia.
l Iron is mainly available from a diet rich in, meat, liver,
Ans. beans and green vegetables.
l Milk is the poor source of iron.
Anaemia is described as haemoglobin concentration in l Daily iron requirement is 1 mg and 2 mg in females.
blood below the lower limit of the normal range for age and The absorption of iron is facilitated by the presence
sex of the individual. In an adult male 13 g/dL and for of acid in the stomach and vitamin C, while antacids,
females 11.5 g/dL is taken as the lower extreme of the calcium, phosphates and phytates decrease it.
normal haemoglobin range. l The most common cause of IDA is blood loss.
CLASSIFICATION OF ANAEMIA
Causes of Iron Deficiency Anaemia
Pathophysiologic Classification 1. Blood loss
Anaemia Due to Increased Blood Loss a. Acute blood loss: Accident and surgery
b. Chronic blood loss: Gastritis, peptic ulcer, hook-
1 . Acute post-haemorrhagic anaemia worm infestation, haemorrhoids and menstrual loss
2. Chronic blood loss 2. Increased demand: Infancy, adolescence and pregnancy
3. Malabsorption: Postgastrectomy, sprue and Crohn’s
Anaemia Due to Impaired Red Cell Function disease
4. Inadequate diet
1. Cytoplasmic maturation defect
a. Deficient haeme synthesis, i.e. iron deficiency anaemia
b. Defective globin synthesis, i.e. thalassaemic syndrome Clinical Features
2. Nuclear maturation defect, i.e. vitamin B12 or folic acid
General Symptoms
deficiency, e.g. megaloblastic anaemia
3. Defect in stem cell proliferation and differentiation l Anaemia patients with IDA may specifically have pago-
a. Aplastic anaemia phagia, i.e. craving for ice, cheilosis and spoon-shaped
b. Pure red cell aplasia nails (koilonychia).
4. Anaemia of chronic disorders l Additionally patient may complain of the following:
5. Bone marrow infiltration l Dysphagia due to formation of cricoid web (Plummer-
6. Congenital anaemia Vinson or Patterson-Kelly syndrome)

l Postcricoid web is a premalignant lesion.
l Splenomegaly is uncommon.
Haemolytic Anaemia
1 . Acquired or extracorpuscular
Investigations
2. Hereditary or intracorpuscular
l The general blood picture is microcytic hypochromic.
Serum iron and ferritin are low.
Morphologic Classification (Taking MCV,
l
l While total iron-binding capacity (TIBC) is increased.

MCH and MCHC into Consideration) l Transferrin saturation is below 16%.
1 . Normocytic l Bone marrow stains for iron reveal decreased or absent
2. Microcytic iron stores.
3. Macrocytic l Stool examination for parasites and occult blood is
4. Normochromic useful.
5. Hypochromic l Endoscopic and radiographic examination of gastroin-
testinal tract is needed to detect the source of bleeding.

The recent classification is based on reticulocyte index,
which is a measure of RBC production.
Lab Findings
l The reticulocyte index is increased (. 2.5%) due to
increase in erythropoiesis in haemolytic and haemor- Hematological Findings
rhagic anaemiae. Examination of peripheral blood picture
l A low reticulocyte index (, 2%) shows decreased
l Chromicity: Hypochromia of RBC central pallor in-
marrow production or maturation defects during creased anisochromia present
erythropoiesis.
l Size: Microcytic anisocytotic increased number of white blood cells in blood and/or
l Shape: Poikilocytosis often present, pear shaped tailed bone marrow.
variety of RBC, elliptical form common.
l Target cell: Present
CLASSIFICATION
l Reticulocytes: Present, either normal or reduced
l Osmotic fragility: Slightly decreased Leukaemiae are classified on the basis of cell types
l ESR: Seldom elevated predominantly involved into the following:
l Absolute value: MCV, MCH and MCHC are reduced. 1. Myeloid
2. Lymphoid
Bone Marrow Findings
And on basis of natural history of the disease into the
l Marrow cellularity: The marrow cellularity is increased following:
due to erythroid hypoplasia. 3. Acute
l Erythropoisis: Normoblastic erythropoiesis with pre- 4. Chronic
dominance of micronormoblasts.
l Marrow iron: Reduced reticuloendothelial iron stores
Acute Leukaemiae (Revised FAB
and absence of siderotic iron granules from developing
Classification)
normoblasts.
These are further classified depending upon the morphol-
ogy of the cells as follows:
Treatment
Oral Iron Therapy Acute Myeloblastic Leukaemia (AML)
l The drug of choice is ferrous sulphate 200 mg thrice a
day (elemental iron 60 mg thrice a day) orally. FAB Class Morphology Cytochemistry
l Taken in between meals.
M0: Minimally Blasts lack definite Myeloperoxidase
l About 15–20% patients may develop abdominal pain,
differentiated cytologic and negative
nausea, vomiting or constipation. AML cytochemical
l In such cases, the dose may be reduced or the salt is features but have
changed to ferrous gluconate or ferrous fumarate or myeloid lineage
carbonyl iron. antigens
l The treatment with oral iron is usually given for a long M1: AML Myeloblasts Myeloperoxidase
duration and is sustained for 6–12 months even after without predominate, positive
normalization of haemoglobin. maturation few if any granules
or Auer rods
M2: AML with Myeloblasts Myeloperoxidase
Parenteral Iron Therapy maturation with promyelocytes positive
predominate,
l Intravenous iron therapy: It is indicated when the pa- Auer rods may
tient is unable to tolerate oral iron, or has malabsorption be present
or the patient’s needs are relatively acute. Previously
M3: Acute Hypergranular Myeloperoxidase
used iron compound, iron dextran has been associated promyelocytic promyelocytes, 111
with the risk of anaphylaxis which is almost never seen leukaemia often with
with newer preparations like sodium ferric gluconate multiple Auer rods
and iron sucrose. per cell
l Red blood cell transfusion: Red cell transfusion is M4: Acute Mature cells of Nonspecific
indicated in patients with severe anaemia where cardio- myelomonocytic both myeloid esterase 1
respiratory conditions warrant immediate intervention leukaemia and monocytic
series in peripheral
or when there is continued and excessive blood loss.
blood myeloid
cells resemble M2
Q. 3. Classify leukaemia. Describe clinical picture, blood
and bone marrow findings in acute leukaemia. M5: Acute M5a: Poorly Nonspecific
monocytic differentiated esterase 11
Ans. leukaemia monoblasts
M5b: Differentiated
Leukaemiae are a group of disorders arising from malig- promonocytes
nant transformation of haematopoietic cells leading to and monocytes
FAB Class Morphology Cytochemistry Subtypes Includes

M6: Acute Erythroblasts pre- Erythroblasts: AML with characteristic AML with translocations
erythroleukaemia dominate, myelo- PAS 1 genetic abnormalities between chromosome 8 and
blasts and promyelo- Myeloblasts: 21 [t(8;21)], inversions in
cytes also increased Myeloperoxidase chromosome 16 [inv(16)], or
1 translocations between chromo-
some 15 and 17 [t(15;17)]
M7: Acute Pleomorphic Platelet
megakaryocytic undifferentiated peroxidase 1 AML with multilineage Patients who have had a prior my-
leukaemia blasts predominate dysplasia elodysplastic syndrome or
react with antiplatelet myeloproliferative disease that
antibodies transforms into AML
AML and MDS, therapy Patients who have had prior
related chemotherapy and/or radiation
Acute Lymphoblastic Leukaemia (ALL) and subsequently develop AML or
myelodysplastic syndrome
FAB Class Morphology Cytochemistry AML not otherwise Subtypes of AML that do not fall
L1: Homogenous small PAS6 categorized into the above categories
Childhood lymphoblasts, scanty Acid
Acute leukaemiae of Acute leukaemiae of ambiguous
ALL cytoplasm, regular round phosphatase6
ambiguous lineage lineage (also known as mixed
nuclei, inconspicuous
phenotype or biphenotypic
nucleoli
acute leukaemia) occur when
L2: Heterogenous lympho- PAS6 the leukaemic cells cannot be
Adult ALL blasts, variable amount Acid classified as either myeloid or
of cytoplasm irregular or phosphatase6 lymphoid cells, or where both
cleft nuclei, large nucleoli types of cells are present.
L3: Large homogenous, PAS2

Burkitt-type lymphoblasts, round Acid
Acute leukaemia is leukaemia characterized by predominant
ALL nuclei, prominent nucleoli, phosphatase2
cytoplasmic vacuolation undifferentiated leukocyte precursors or leukaemic blasts.
Chronic Leukaemiae CLINICAL FEATURES

a . Chronic myeloid leukaemia (CML) Due to Bone Marrow Failure
b. Chronic lymphocytic leukaemia (CLL) l Anaemia
c. Chronic eosinophilic leukaemia l Bleeding manifestations
d. Chronic basophilic leukaemia l Infections
e. Chronic monocytic leukaemia l Fever
f. Chronic neutrophilic leukaemia
g. Chronic lymphosarcoma cell leukaemia
h. Hairy cell leukaemia Due to Organ Infiltration
Of the above l Pain and tenderness of bones due to bone infarcts or
subperiosteal infiltrates
l a and b are main types, l Lymphadenopathy and tonsil enlargement
l c to g are less common variants and l Splenomegaly of moderate grade
l h is unusual variant. l Hepatomegaly due to leukaemic infiltration
l Leukaemic infiltration of kidney
l Gum hypertrophy due to infiltration of gingivae

WHO Classification of Acute Myeloid
l Chloroma or granulocytic sarcoma, a localized greenish
Leukaemia
coloured tumour of skin or orbit due to local infiltration
The World Health Organization (WHO) classification of of tissues by leukaemic cells
acute myeloid leukaemia attempts to be more clinically l Meningeal involvement manifesting as raised intracra-
useful and to produce more meaningful prognostic infor- nial pressure, headache, nausea and vomiting, blurring
mation than the FAB criteria. of vision and diplopia
l Testicular swelling and mediastinal compression The common chromosomal abnormalities in AML are as
follows:
l Aneuploidy: Hypo and hyperdiploid cell lines are found
LABORATORY DIAGNOSIS OF ACUTE
with equal frequency in AML.
MYELOID LEUKAEMIA
l Philadelphia chromosome [t (9;22)]: 25–30% cases of
Blood Picture AML in adults shows Philadelphia chromosome. It is

associated with poor prognosis.
Anaemia
l It is generally severe, progressive and normochromic in Cytochemistry
type.
l A moderate reticulocytosis up to 5% and few nucleated l Myeloperoxidase: Positive in immature myeloid cells
red cells may be present. containing granules and Auer rods, i.e. all forms
of AML from M1 to M6 but negative in M0 myelo-
blasts.
Thrombocytopenia l Sudan black: Positive in immature cells in AML
l Periodic acid schiff (PAS): Positive in erythroleukaemia

l Platelet count is , 50,000/µL.
l When platelet count is below 20,000/µL serious sponta- (M6)
l Nonspecific esterase: Positive in monocytic series
neous haemorrhagic episodes develop.
l Acute promyelocytic leukaemia (M3) may be associ- M4 and M5)
l Acid phosphatase: Diffuse reaction in monocytic cells
ated with a serious coagulation abnormality called
disseminated intravascular coagulation. (M4 and M5)
White Blood Cells Other Investigations

l In advanced cases WBC count is . 100,000/µL. 1. Serum muramidase: Serum levels of lysozyme, i.e.
l Majority of leucocytes in the peripheral blood are blasts
muramidase are elevated in myelomonocytic (M4) and
and there is often neutropenia due to marrow infiltration monocytic (M5) leukaemiae.
by leukaemic cells. 2. Serum uric acid: Serum uric acid level is frequently
l Some patients of myelodysplastic syndrome present
increased because of rapidly growing number of leukae-
with pancytopenia and have a few blasts are labelled mic cells.
subleukaemic leukaemia or have no blast are labelled as
Q. 4. Define leukaemia. Describe aetiology, clinical
aleukaemic leukaemia.
features and peripheral blood and bone marrow picture
of chronic myeloid leukaemia.
Bone Marrow Examination Ans.
l Cellularity: Typically the marrow is hypercellular with
Leukaemiae are a group of disorders arising from malig-
predominance of myeloblasts and promyelocytes. A dry
nant transformation of haematopoietic cells leading to
tap may also occur due to pancytopenia or adhesive
increased number of white blood cells in blood and/or
nature of leukaemic cells which are enmeshed in reticu-
bone marrow.
lin fibres.
l Leukaemic cells: Diagnosis of type of leukaemic cells is
done by routing Romanowsky stains and cytochemical CHRONIC MYELOID LEUKAEMIA (CML)
stains. Presence of at least 30% blasts in the bone mar-
Chronic myeloid leukaemia comprises one-fifth of all leukae-
row is the essential criteria for diagnosis of the acute
mia cases and usually seen in third and fourth decades of life.
leukaemia.
l Erythropoiesis
l Erythropoietic cells are reduced. Aetiology

l Dyserythropoiesis, megaloblastic features and ring
Chronic myeloid leukaemia (CML) is a type of myelopro-
sideroblasts are common.
liferative disorder. It occurs as a result of malignant trans-
l Megakaryocytes: They are usually reduced or absent.
formation of pluripotent stem cells leading to accumulation
l Cytogenetics: 75% cases show karyotypic abnormalities
of large number of immature leucocytes in the blood. The
in the dividing leukaemic cells.
underlying chromosomal abnormality in C is the Philadel- l Features of gout, visual disturbances, neurological mani-
phia chromosome (short 22) which results due to the recip- festations and priapism less commonly, lymph node en-
rocal translocation between chromosomes 9 and 22. largement, frequent infections, facial rash in juvenile CML
Genetic Factors Peripheral Blood of CML

High concordance rate is observed among identical twins if The peripheral blood findings are highly characteristic.
acute leukaemia develops in first year of life. There are l Leukocyte count is elevated often . 100,000 cells/µL.
families with excessive incidence of leukaemia which have l Circulating cells are predominantly neutrophils, meta-
been identified. myelocytes and myelocytes, but basophils and eosino-
phils are also prominent.
l A small portion of myeloblasts usually , 5% are seen.
Ionizing Radiation
l Typical finding is increased number of platelets
Radiation exposure is implicated in development of CML. (thrombocytosis).
Radiation exposure may be occupational, therapeutic, diag-
nostic or as in survivors of atomic bomb explosions.
Bone Marrow Picture
Hypercellular: As a result of hyperplasia of granulo-
Clinical Features l
cytic and megakaryocytic precursors

l Onset of CML is usually slow, and initial symptoms are l Myeloblasts are only slightly increased.
often nonspecific, e.g. easy fatigueability, weakness and l There is frequently an increase in the number of phago-
weight loss. cytes.
l The first symptom sometimes is dragging sensation in l Reduction in erythropoietic cells.
the abdomen, caused by extreme splenomegaly and is
characteristic of this condition.
l Weight loss, lassitude, anorexia, night sweats (hyperme-
Cytogenetics
tabolism), massive splenomegaly with acute pain in l Characteristic chromosomal abnormality called Phila-
case of splenic infarction, pallor, dyspnoea and tachy- delphia (Ph) chromosome formed by reciprocal translo-
cardia (anaemia) cation between part of long arm of chromosome 22 and
l Bleeding tendencies like easy bruising, epistaxis, men- that of chromosome 9 [t(9;22)] is usually seen in
orrhagia and haematomas 70–90% of the cases.
SHORT ESSAYS
Q. 1. Clinical features of anaemia 2. Central nervous system: Lack of concentration,
Ans. decreased memory, syncope, altered sensorium,
seizures
Anaemia is defined as a decrease in the level of haemoglo- 3. Cardiorespiratory: Palpitation, dyspnoea, angina, car-
bin below normal for that age and sex. The normal haemo- diomegaly, congestive heart failure, flow murmur
globin level varies from 14 to 16 g/dL in the adult male and 4. Gastrointestinal: Anorexia, nausea, distaste, stomatitis,
12 to 14 g/dL in the female. cheilosis, glossitis, dysphagia, malabsorption, hepato-
splenomegaly
5. Others: Loss of libido, impotence, menstrual abnor-
Clinical Features
malities
Patients who develop anaemia acutely such as following
massive bleeding may be highly symptomatic whereas those Q. 2. What is Leucocytosis? What are the causes?
with gradually developing anaemia may have mild symp- Ans.
toms. This is due to the development of various compensa-
tory mechanisms in order to improve tissue oxygenation. l Leucocytosis is an increase in the number of white
The symptoms and signs of anaemia are due to the anaemia cells and is common in a variety of reactive inflamma-
per se or due to conditions which have resulted in anaemia. tory states caused by microbial and nonmicrobial
stimuli.
Following are symptoms and signs due to anaemia itself: l This reactive leucocytosis may mimic leukaemia, such
1. General: Weakness, malaise, feverishness, tiredness, leukaemoid reactions must be distinguished from true
pallor, vertigo, tinnitus malignancies of the white cells.
Causes of Leucocytosis PERIPHERAL BLOOD PICTURE

Leucocytosis are relatively nonspecific and can be classi- OF CHRONIC MYELOID LEUKAEMIA
fied on the basis of particular white cell series affected (CML)
as follows: The peripheral blood findings are highly characteristic of
1. Neutrophilic leucocytosis CML.
a. Acute bacterial infections especially those caused l Leukocyte count is elevated often . 100,000 cells/µL.
by pyogenic organisms l Circulating cells are predominantly neutrophils, metamy-
b. Sterile inflammation caused by tissue necrosis elocytes and myelocytes, but basophils and eosinophils
(myocardial infarction, burns) are also prominent.
2. Eosinophilic leucocytosis (eosinophilia) A small portion of myeloblasts usually , 5% are seen.
a. Allergic disorders such as asthma, hay fever Typical finding is increased number of platelets (throm-
b. Allergic skin diseases, e.g. pemohigus, dermatitis bocytosis).
herpetiformis
c. Parasitic infestations
d. Drug reactions Bone Marrow Picture
e. Certain malignancies, e.g. Hodgkin’s disease and Hypercellular: As a result of hyperplasia of granulocytic
some non-Hodgkin’s lymphomas and megakaryocytic precursors.
f. Collagen vascular disorders and some vasculitides
3. Basophilic leucocytosis (basophilia): Rare, often indi- l Myeloblasts are only slightly increased.
cates CML l There is frequently an increase in the number of
4. Monocytosis phagocytes.
l Reduction in erythropoietic cells.
a. Chronic infections, e.g. tuberculosis
b. Bacterial endocarditis
Q. 5. Agranulocytosis
c. Rickettsiosis and malaria
d. Collagen vascular diseases, e.g. systemic lupus ery- Ans.
thematosus (SLE)
e. Inflammatory bowel diseases, e.g. ulcerative colitis l The term agranulocytosis is used to describe a state of
5. Lymphocytosis: Usually accompanies monocytosis in severe neutropenia.
l A reduction in the number of granulocytes in blood is
many disorders associated with
a. chronic immunologic stimulation, e.g. tuberculosis, known as neutropenia, when severe it is known as
brucellosis and agranulocytosis. Characteristically, the total white cell
b. viral infections, e.g. hepatitis A, cytomegalovirus, count is reduced to 1000 cells/µL and some times as few
Epstein-Barr virus, Bordetella pertussis infections. as 200–300 cells/µL.
Q. 3. Peripheral blood smear of vitamin B12 deficiency Causes

Ans. Neutropenia can occur in conditions where there is
The peripheral blood smear of vitamin B12 deficiency decreased production, increased destruction or excessive
exhibits following features: peripheral pooling of neutrophils.
l In the peripheral blood the earliest change is usually the
appearance of hypersegmented neutrophils. Important causes of neutropenia are as follows:

l Red blood cells: Blood smear demonstrates presence of
1. Drug induced: Anticancer drugs, antibiotics (sulphon-
large egg-shaped macro-ovalocytes, anisocytosis and amides, chloramphenicol), anticonvulsants (carbamaze-
poikilocytosis. pine) and antithyroid drugs
l The MCV is often greater than 10 fL (normal: 82–92 fL)
2. Haematological diseases: Aplastic anaemia, acute leukaemia,
l Though macrocytes appear hyperchromic, MCHC
myelofibrosis, tumour invasion and megaloblastic anaemia
decreases or remains normal. 3. Infections: Tuberculosis, typhoid, kala-azar, malaria,
l Hb concentration is less.
infectious mononucleosis and HN
l Reticulocyte count is normal or less.
4. Autoimmune: Systemic lupus erythematosus and Felty’s
l Leucocytes: Total WBC count is less.
syndrome
l Thrombocytes: Giant, misshapen platelets are present.
5. Congenital: Cyclic neutropenia
Q. 4. Peripheral blood and bone marrow picture of Clinical Manifestations

chronic myeloid leukaemia
l The manifestations depend on the severity and duration
Ans. of neutropenia and the type of illness.
l Initially patient develops malaise, chills and fever, with WHO Classification of Acute Myeloid Leukaemia
subsequent marked weakness and fatigueability. (AML)
l Infections constitute the major problem. They usually
present as ulcerating, necrotizing lesions of gingiva, Subtypes Includes

floor of the mouth, buccal mucosa, oropharynx and
AML with characteristic AML with translocations
other sites within oral cavity known as agranulocytic genetic abnormalities between chromosome 8 and
angina. Perirectal area, sinuses and lungs are also 21 [t(8;21)], inversions in
affected. chromosome 16 [inv(16)],
l Due to inability to mount a leukocyte response or translocations between
the lesions often show a massive growth of microor- chromosome 15 and 17
[t(15;17)]
ganisms.
l Common organisms responsible for infections are AML with multilineage Patients who have had a prior
Gram-negative Enteric bacilli, Pseudomonas, Staphylo- dysplasia myelodysplastic syndrome or
myeloproliferative disease that
coccus spp., Candida and Aspergillus. transforms into AML
l Lymphadenopathy and hepatosplenomegaly may be
AML and MDS, therapy Patients who have had prior
present.
related chemotherapy and/or radiation
and subsequently develop AML
or myelodysplastic syndrome
Investigations
AML not otherwise Subtypes of AML that do not
l Peripheral blood examination reveals the neutropenia categorized fall into the above categories
and also reveals the presence of any malignancies.
Acute leukaemiae of Acute leukaemiae of ambiguous
l Bone marrow examination is necessary to diagnose
ambiguous lineage lineage (also known as mixed
aplasia, infiltration and haematological malignancies. phenotype or biphenotypic
l Investigation for the presence of autoantibodies are acute leukaemia) occur when
needed. the leukaemic cells cannot be
classified as either myeloid or
lymphoid cells, or where both
Management types of cells are present.
l Patients with neutropenia and fever must be sent to the

hospital. Q. 7. Laboratory findings and peripheral blood picture
l Sample for culture should be taken and empirical of acute lymphatic leukaemia
parenteral broad-spectrum antibiotics must be started Ans.
immediately. Antifungal drugs are to be given if fever
does not respond to antibiotics. Diagnosis of acute leukaemia rests on identification of blast
l Neutrophil transfusion may help in severe infections. forms in the peripheral blood and bone marrow.
l In addition to removal of offending drug and control of Peripheral blood smear in acute lymphatic leukaemia
infections, treatment efforts may also include the ad- (ALL) shows the following:
ministration of growth factors like granulocyte colony- 1. Anaemia
stimulating factor (G-CSF), which stimulates neutrophil l It is generally severe, progressive and normochromic
production by the bone marrow. in type.
l A few nucleated red cells may be present.
Q. 6. WHO classification of acute myeloid leukaemia 2. Thrombocytopenia
l Platelet count is usually below 100,000 cells/µL.
Ans.
l Serious spontaneous haemorrhagic episodes develop
l Acute myeloid leukaemia is leukaemia characterized by when platelet count is below 20,000/µL.
predominant undifferentiated leucocyte precursors or 3. White blood cells: WBC count is variable, progressive
leukaemic blasts. rise in WBC count may exceed 100,000 cells/µL in
l The World Health Organization (WHO) classification advanced cases. In about 50% of patients it is less than
of acute myeloid leukaemia (AML) attempts to be 10,000 cells/µL.
more clinically useful and to produce more meaningful l However 25% cases at presentation shows reduced
prognostic information than the FAB criteria. count of 1000–4000/mL.
l Majority of leucocytes in the peripheral blood are

Decreased Platelet Survival
blasts and there is often neutropenia due to marrow
infiltration by leukaemic cells. Immunologic Destruction
The diagnosis can only be established by examining the 1. Autoimmune:
bone marrow. a. Immune thrombocytopenic purpura
In ALL, blasts compose more than 25% of the marrow b. Systemic lupus erythematosus (SLE)
cellularity. The nuclei of lymphoblasts in Wright-Giemsa- 2. Isoimmune: Posttransfusion and neonatal
stained preparations have somewhat coarse and clumped 3. Drug-associated: Quinidine, heparin, sulpha compounds
chromatin and one or two nucleoli. The cytoplasm of lym- 4. Infections: Infectious mononucleosis, HIV, cytomegalo-
phoblasts often contains large aggregates of periodic acid- virus infections
Schiff (PAS)-positive material.
Classification of ALL based on morphology of cells is Nonimmunologic Destruction
as follows: 1. Disseminated intravascular coagulation (DIC)
2. Thrombotic thrombocytopenic purpura
FAB Class Morphology Cytochemistry
3. Giant haemangiomas
L1: Homogenous small PAS 6 4. Microangiopathic haemolytic anaemias
Childhood lymphoblasts, scanty Acid
ALL cytoplasm, regular round phosphatase 6 Sequestration
nuclei, inconspicuous
nucleoli 1. Hypersplenism
L2: Heterogenous lympho- PAS 6 Dilutional
Adult ALL blasts, variable amount Acid
of cytoplasm irregular phosphatase 6 1. Human immunodeficiency virus (HIV)
or cleft nuclei, large
nucleoli
Clinical Features
L3: Large homogenous, PAS 2,
Burkitt-type lymphoblasts, round Acid l The usual manifestations are petechial haemorrhage,
ALL nuclei, prominent phosphatase 2 purpura, easy bruising, epistaxis and mucosal bleeding
nucleoli, cytoplasmic
such as menorrhagia in women, nasal bleeding, bleed-
vacuolation
ing from gums and haematuria.
l Intracranial haemorrhage is rare.
Q. 8. Thrombocytopenia
l Splenomegaly and hepatomegaly may also occur.
Ans.
Thrombocytopenia is defined as reduction in the peripheral Investigations

blood platelet count below the lower limit of normal range, l Low platelet counts, prolonged bleeding time, normal
i.e. below 150,000 cells/µL. coagulation profile and abnormal long clot retraction
Platelet counts in the range of 20,000–50,000 cells/µL time.
are associated with increased risk of posttraumatic bleeding
and spontaneous bleeding is evident when count falls below
20,000 cells/µL. Peripheral Blood Smear and Marrow Findings
l Platelet count is markedly reduced. Blood film shows
AETIOLOGY only occasional platelet which is often large in size.
l Bone marrow shows increased number of megakaryo-
Decreased Production of Platelets by Bone cytes.
Marrow l With sensitive technique antiplatelet IgG antibody can
1. Generalized disease of bone marrow be demonstrated on platelet surface.

a. Aplastic anaemia
b. Marrow infiltration: Leukaemia, disseminated cancer Treatment
2. Selective impairment of platelet production
a. Drug-induced: Alcohol, thiazides and cytotoxic drugs l Platelet transfusion
b. Infections: Measles and HIV l Treatment of the underlying cause
3. Ineffective megakaryopoiesis
Q. 9. Classical haemophilia
a. Megaloblastic anaemia
b. Paroxysmal nocturnal haemoglobinuria Ans.
HAEMOPHILIA oral mucosal bleed. These act as plasminogen activator

in oral tissue and results in clot formation.
l Haemophilia is a X-linked recessive disorder character- l EACA is given orally or of 100 mg/kg up to 10 g
ized by the deficiency of factor VIII (haemophilia A). initially followed by 1 mg/kg up to 5 g 6 hourly for
l Classical haemophilia or haemophilia A is the second
2–7 days. EACA can be used as a mouthwash.
most common hereditary coagulation disorder. Tranexamic acid in dosage of 0.5–1 g 8 hourly orally.
l This disorder is inherited as a sex-linked recessive
l In case of major oral surgery and extraction of perma-
trend, hence the disease manifests in males while nent teeth needs hospitalization and regular infusion of
females are carriers. VIII along with EACA.
Pathogenesis Q. 10. Von Willebrand’s disease
Haemophilia A is caused by quantitative reduction of factor Ans.

VIII in 90% of cases while 10% cases have normal or l Von Willebrand disease (vWD) is the most commonly
increased level of factor VIII but reduced activity. inherited haemostatic disorder, mainly inherited as an
autosomal dominant disorder.
l It occurs due to qualitative or quantitative defect in von
Clinical Manifestations
Willebrand factor (vWF).
l The clinical manifestation of haemophilia depends on l Von Willebrand factor (vWF) is a multimeric plasma
the severity of deficiency of the factor VIII. glycoprotein synthesized by megakaryocytes and endo-
l The bleeding is spontaneous in severe cases (factor VIII thelial cells. It serves two major functions as follows:
activity , 1 IU/dL), while it may occur after minor l Acts as a carrier protein for factor VIII.
trauma or surgery in moderate cases (factor VIII activity l Von Willebrand factor helps in adhesion of platelets
1–5 IU/dL). People with mild disease (factor VIII activ- to subendothelial collagen.
ity 5–40 IU/dL) rarely bleed spontaneously but can
bleed following severe trauma or surgery.
l Severe cases generally manifest in early childhood
Clinical Features
when the child starts crawling or walking whereas mild l In most cases, mild symptoms in the form of epistaxis,
and moderate cases may clinically manifest later in life. bleeding, menorrhagia and superficial bruises present.
l The bleeding occurs mainly in joints (haemarthrosis), l Gastrointestinal bleeding
muscles (haematoma), viscera or in retroperitoneum but l Excessive haemorrhage may be observed after dental
it can involve any organ system. extraction or surgery.
l Patients can also develop large calcified mass of blood
with inflammation that may be mistaken as tumour

(pseudotumour syndrome). Investigations
l Haematuria is also common in haemophilia. Intracra- l Prolonged bleeding time
nial and oropharyngeal bleeding may be fatal. l Normal platelet count
l Reduced vWF plasma levels and reduced factor VIII
Investigations activity
l Bleeding time and APTT are increased.
Activated partial thromboplastin time (APTT) is prolonged l The adhesion activity of vWF as measured by cofactor
whereas prothrombin time (PT), bleeding time and platelet assay is reduced.
count are within normal limits. Diagnosis is confirmed by
the assay of factor VIII or IX.
Treatment
Cryoprecipitate transfusion
Management l
l Factor VIII and vWF concentrate transfusion

l Specific therapy of haemophilia A includes administra- l Desmopressin
tion of factor VIII. l Bleeding episodes can be managed by giving vasopres-
l The dose and frequency of duration of factor VIII ad- sin (DDA VP) which increases the vWF levels.
ministration depends on severity of the bleeding. l Patients with persistent and severe bleeding are treated
l Cryoprecipitate in factor VIII, fibrinogen and von Will- with factor VIII concentrate that also contains consider-
ebrand factor (vWF) may benefit from desmopressin able amount of vWF. Cryoprecipitate (rich in I and
which increases factor VIII level to 2–3 folds. vWF) can be used alternatively.
l Antifibrinolytic agents like Epsilon-aminocaproic acid l Antifibrinolytic agent, e.g. tranexamic acid is useful in
(EACA) and tranexamic acid can be used in dental and conjunctive therapy during dental procedures.
Q. 11. What is the disseminated intravascular coagula- aggregation and adhesion with resultant deposition of
tion? Describe the aetiopathogenesis of the same. small thrombi and emboli throughout the microvas-
culature.
Ans.
3 . Consumption phase: The thrombolytic phase is fol-
Disseminated intravascular coagulation (DIC) is also termed lowed by a phase of consumption of coagulation factors
as defibrillar syndrome or consumption coagulopathy. and platelets.
It is a complex thrombo-haemorrhagic disorder (intra- 4. Secondary fibrinolysis: As a protective mechanism fibri-
vascular coagulation and haemorrhage). nolytic system is activated at the site of intravascular
coagulation. Secondary fibrinolysis causes breakdown
of fibrin resulting in formation of fibrin degradation
AETIOLOGY products (FDPs) in the circulation.
1. Massive tissue injury: In obstetrical syndromes, e.g. ab-
ruptio placentae, amniotic fluid embolism, retained dead Clinical Features
fetus, massive trauma, metastatic malignancies, surgery
2. Infections: Endotoxemia, septicaemia, malaria, certain l Bleeding, the most common manifestation
viral infection l Organ damage, due to ischaemia caused by widespread
3. Widespread endothelial damage: In aortic aneurysm, intravascular thrombosis such as kidney and brain
haemolytic-uraemic syndrome, severe burn l Less common manifestation includes microangiopathy,
4. Miscellaneous: Snake bite, shock, heat stroke, acute haemolytic anaemia and thrombosis in larger arteries
intravascular haemolysis and veins.
Pathogenesis Laboratory Diagnosis

The sequence of events in DIC are as follows: l Platelet count is low.
1. Activation of coagulation: The aetiological factors initi- l Blood film exhibits features of microangiopathic hae-
ating widespread activation of coagulation pathway by molytic anaemia.
release of tissue factors. l Prothrombin time, thrombin time and activated partial
2. Thrombotic phase: Endothelial damage from various thromboplastin time are prolonged.
thrombogenic stimuli causes generalized platelet l Plasma fibrinogen levels are reduced.
SHORT NOTES
Q.1. ESR 2. Inflammation: Rheumatoid arthritis, rheumatic fever,
other connective tissue disorders
Ans.
3. Neoplastic: Multiple myeloma, lymphoma, paraprotein-
If a sample of blood mixed with an anticoagulant is allowed aemiae
to stand in a vertical tube, the RBC settles down due to grav- 4. Miscellaneous: Aplastic anaemia, autoimmune disor-
ity (denser, specific gravity: 1.095) as compared to plasma ders, mixed connective tissue disorders
(specific gravity: 1.032) with a clear supernatant layer of
plasma. The rate at which the cells settle down is called ESR. Q. 2. Thalassaemia
Ans.
Methods of Estimation of ESR l Thalassaemiae are hereditary disorders characterized
There are two standard methods as follows: by quantitative abnormalities of globin chain synthesis,
1. Wintrobe’s and Landsberg’s method: ESR is measured i.e. reduced production of globin chains.
in undiluted blood in a haematocrit tube. l Reduction in alpha chain synthesis leads to alpha
2. Westergren’s method: ESR is measured in venous blood thalassaemia and that of beta chain leads to beta thal-
diluted accurately with 31.3 g/L trisodium citrate in the assaemia.
proportion of 1:4 (1 volume of 3.8% sodium citrate and l Beta thalassaemia major (Cooley’s anaemia) is a se-
4 volume of blood). vere disease and manifests in childhood. This condition

is transfusion dependent and generally fatal by 30 years
The conditions where ESR is markedly raised are as of age.
follows: l Beta thalassaemia minor is mild disease, nontransfu-
1. Infective: Tuberculosis, kala-azar, in most of the chronic sion dependent and patients can live full normal
infections lives.
Clinical Features l The diagnosis is confirmed by the bone marrow aspira-

tion and biopsy.
l The important clinical manifestations are anaemia,
l Chromosomal studies are done in children and younger
recurrent mild jaundice and hepatosplenomegaly.
adults to rule out inherited disorders like Fanconi’s
l The family history may be positive.
anaemia.
l Expansion of bones
l Iron overload due to repeated blood transfusion

Treatment
Laboratory Findings l Bone marrow transplantation is curative and the pre-
ferred mode of therapy in young patients , 40 years.
Tests such as l Immunosuppressive therapy
l haemoglobin electrophoresis, l Supportive therapy like packed red cell transfusion,
l decreased osmotic fragility, platelet concentrates

l amniocentesis and chorionic villi biopsy are performed l Granulocyte transfusion has also been used in over-
for prenatal diagnosis of inherited conditions like thal- whelming infections. Aseptic precautions must be
assaemia. observed to prevent infections.
Q. 4. Pernicious anaemia
Treatment
Ans.
l Supportive treatment in the form of packed cell transfu-
sion may be needed. However, repeated transfusion may l Pernicious anaemia is also known as Addisonian mega-
lead to iron overload which in turn may require treat- loblastic anaemia.
ment with chelating agents, deferoxamine. Folic acid, l Pathogenesis: An autoimmune reaction against gastric
5 mg daily is given to meet the increased demand. parietal cells causes atrophy of gastric mucosa.
l Bone marrow transplantation is curative in thalassaemia. l Microscopic examination reveals most characteristic
pathologic finding in pernicious anaemia, i.e. gastric

atrophy affecting the acid and pepsin-secreting portion
Q. 3. Aplastic anaemia of the stomach and sparing the antrum.
Ans. l About 2–3% of cases of pernicious anaemia develop
carcinoma of the stomach.

Aplastic anaemia is characterized by pancytopenia (anae-
mia, leukopenia and thrombocytopenia) and hypocellular
bone marrow.
Clinical Features
The clinical manifestations are mainly due to vitamin B12
deficiency.
Aetiology
l Anaemia
l Idiopathic
l Glossitis
l Secondary: Drugs (chloramphenicol, sulphonamides,
l Neurological abnormalities, gastrointestinal manifesta-
etc.), radiation, chemicals (DDT and benzene), viruses,
tions
pregnancy, paroxysmal nocturnal haemoglobinuria
l Congestive heart failure
(PNH)
l Haemorrhagic manifestations
l Inherited: Fanconi’s anaemia
Laboratory Findings
Clinical Features
l Hypergastrinaemia
l The common presentations are bleeding and symptoms
l Haematologic findings in blood and bone marrow are
of anaemia.
same as those of megaloblastic anaemia
l The excessive tendency to bleed is due to thrombocyto-
l Biochemical tests reveal serum bilirubin, LDH, hapto-
penia, presenting as easy bruising, epistaxis, gum bleed-
globin, ferritin and iron.
ing, heavy menstrual flow and petechiae.
l Schilling test is abnormal.
l Neutropenia may predispose patients to develop infec-
tions. Q. 5. PCV
Ans.
Investigations
PCV or haematocrit is the measure of volume percent of
l Peripheral blood smear shows normocytic or macro-
packed red cells in whole blood sample. Haematocrit
cytic anaemia, decreased granulocyte and platelet count.
literally means separation.
INDICATIONS Interpretation
l Anaemia An abnormal BT is usually the result of
l History of excessive blood loss
l To evaluate patient’s ability to tolerate GA and oral l abnormalities in the structure or ability of capillary
surgical procedures blood vessels to contract or
l abnormalities in the number or functional integrity of
Methods of estimation are as follows: the platelets.

l Using Wintrobe’s tube, blood is centrifuged for half an
hour at 3000 rpm. Q. 7. Thrombocytopenia

l Using capillary tube, blood is centrifuged at 12,500 rpm. Ans. Thrombocytopenia is defined as reduction in the
peripheral blood platelet count below the lower limit of
Observation normal range, i.e. below 150,000 cells/µL.
Three layers are observed after centrifugation.

l Plasma layer: Top most, clay yellow or straw coloured
Causes
l Buffy coat: Middle layer of WBC and platelets about
1 mm thick (platelets form a thin layer over WBC) l Decreased marrow production
l Column of RBC: Bottom layer l Aplastic anaemia
l Tumour infiltration
l Increased splenic sequestration
Interpretation l Hypersplenism
l Increased values of PCV indicates primary and second- l Increased peripheral destruction
ary polycythemia. l Circulating autoantibodies
l Decreased values of PCV indicates anaemia.
The following additional information is obtained from PCV Clinical Features

or haematocrit:
l Increased buffy coat: Indicates severe degree of leuco- l The usual manifestations are petechial haemorrhage,
cytosis or leukaemia. purpura, easy bruising, epistaxis and mucosal bleeding
l The colour of plasma layer are as follows: such as menorrhagia in women, nasal bleeding, bleed-
l Red colour indicates haemolysis. ing from gums and haematuria.
l Yellow colour indicates jaundice. l Splenomegaly and hepatomegaly may also occur.
l Cloudy or milky turbid indicates lipidaemia.
Q. 6. Bleeding time
Investigations
l Low platelet counts, prolonged bleeding time, normal
Ans.
coagulation profile and abnormal long clot retraction
l Bleeding time (BT) is defined as the time lapse between time
skin puncture and the arrest of bleeding.
l BT is the time from the onset of bleeding to the stop-
Peripheral Blood Smear and Marrow
page for bleeding. Bleeding stops due to the formation
of a temporary haemostatic plug.
Findings
l Procedure: Under aseptic conditions, give a deep finger l Platelet count is markedly reduced. Blood film shows
prick and note the time. Then remove the blood only occasional platelet which is often large in size.
drop every 15 s by a clotting paper (along the edges) l Bone marrow shows increased number of megakaryo-
at different spots till the bleeding stops. Count the num- cytes.
ber of spots and calculate BT as follows:
BT 5 Initial time 1 (number of spots 2 1) 3 15 s
Treatment
Platelet transfusion
Indications l
l Treatment of the underlying cause

l It is useful screening test in patients with a history of
prolonged bleeding.
l In patients with bleeding disorders before any surgical
Q. 8. Sickle cell anaemia
procedures Ans.
l Normal adult haemoglobin (HbA) is genetically altered Bone marrow findings in megaloblastic anaemia are as
to produce sickle haemoglobin (HbS). HbS is produced follows:
due to substitution of valine for glutamine at sixth 1. Marrow cellularity: Hypercellular bone marrow with
position of beta-globin chain. decreased myeloid:erythroid ratio
l In the heterozygous form or sickle cell trait, only 40% 2. Erythropoiesis: The erythroid hyperplasia is due to char-
of haemoglobin is HbS and the individual suffers from acteristic megaloblastic erythropoiesis. Megaloblasts are
sickling only under conditions of severe hypoxia. abnormal, large, nucleated erythroid precursors, having
l In homozygous form, nearly all the haemoglobin nuclear cytoplasmic asynchrony. The nuclei are large,
(100%) is HbS and the individual suffers from sickle having fine, reticular and open chromatin. Abnormal
cell anaemia. mitosis may be seen in megaloblasts.
3. Marrow iron: Increase in the number and size of the
Clinical Features iron granules in erythroid precursors. Iron in reticulum
cells is increased.
l Severe haemolytic anaemia
l Vaso-occlusive phenomena: During deoxygenation, the Q. 11. Blood picture in megaloblastic anaemia
RBC containing HbS change from biconcave disc shape
Ans.
to an elongated crescent-shaped or sickle-shaped cells.
These distorted cells block the blood circulation and Peripheral blood picture in megaloblastic anaemia exhibits
causes repeated vaso-occlusive episodes. following features:
l Constitutional symptoms: Impaired growth and devel- 1. Haemoglobin (Hb) concentration
opment, increased susceptibility to infections l MCV and MCH increase.
l Oral findings: Oral manifestations include generalized l MCHC decreases or remains normal.
osteoporosis, loss of trabeculation of the jaw bones with 2. Reticulocyte count is normal or less.
the appearance of large irregular spaces and morpho- 3. Red blood cells: Blood smear demonstrates anisocyto-
logic alterations in nuclei of oral epithelial cells. sis, poikilocytosis and presence of ovalocytes.
l Radiographic findings: Hair-on-end appearance on 4. Leucocytes: Total WBC count is less.
skull, tower-shaped skull, generalized osteoporosis, thin 5. Thrombocytes: Giant platelets are present.
cortices, enlarged medullary cavities
Q. 12. Peripheral blood smear in iron deficiency
anaemia
Laboratory Findings
Ans.
l Anaemia
l Sickle cells and target cells are seen on blood film. Peripheral blood picture in iron deficiency anaemia exhibits
l Positive sickling test following features:
l Chromicity: Hypochromia of RBC central pallor in-
Q. 9. Hereditary spherocytosis creased anisochromia present
Ans. l Size: Microcytic anisocytotic
l Shape: Poikilocytosis often present, pear-shaped tailed

l Hereditary spherocytosis is a common type of heredi- variety of RBC, elliptical form common
tary haemolytic anaemia in which red cell membrane is l Target cell: Present
abnormal. l Reticulocytes: Present, either normal or reduced
l It is inherited as autosomal dominant disorder. l Osmotic fragility: Slightly decreased
l Pathogenesis: Deficiency in the structural protein of the l Absolute values of MCV, MCH and MCHC are reduced.
red cell membrane spectrin
l Clinical features: Anaemia, jaundice, splenomegaly and Q. 13. Haemosiderin
pigmented gall stones
l Laboratory findings
Ans.
l Anaemia and reticulocytosis
l Haemosiderin is a haemoprotein, an important endoge-
l Blood film shows microspherocytes.
nous pigment derived from haemoglobin, cytochromes
l Osmotic fragility
and their breakdown products.
l Negative direct Coombs’ test
l It is a form of iron storage in the tissues and is formed
l Spontaneous autohaemolysis
by aggregates of ferritin.
l It is identifiable by light microscopy as golden yellow to
Q. 10. Bone marrow findings in megaloblastic anaemia
brown granular pigment in the mononuclear phagocytes
Ans. of the bone marrow, spleen and liver.
l Haemosiderin is ferric iron that can be demonstrated by l Thrombocytopenia

Prussian blue reaction. l Blood picture showing blasts and other primitive cells
l Bone marrow shows hypercellularity with blasts
l Haemosiderin deposition may result in the following:
1. Local haemosiderosis
2. Generalized haemosiderosis Treatment
3. Idiopathic haemochromatosis
l Local haemosiderosis develops whenever there is haem- l Chemotherapy with drugs like daunorubicin, cytosine
orrhage into the tissues. arabinoside, all transretinoic acid
l Allogenic BMT
l Systemic overload with iron may result in generalized
l Supportive therapy with blood transfusion, antibiotics
haemosiderosis in parenchymatous or reticuloendothe-
lial patterns.
Q. 16. Bone marrow findings in iron deficiency
l Idiopathic haemochromatosis is an autosomal dominant
anaemia
disease characterized by excessive absorption of iron. It
is associated with triad of pigmentary liver cirrhosis, Ans.
pancreatic damage and skin pigmentation.
Bone marrow findings in iron deficiency anaemia are as
Q. 14. Eosinophilia follows:
1. Marrow cellularity: The marrow cellularity is increased
Ans. due to erythroid hypoplasia.
An increase in the number of eosinophilic leucocytes is 2. Erythropoiesis: Normoblastic erythropoiesis with pre-
referred to as eosinophilia. dominance of micronormoblasts
3. Marrow iron: Reduced reticuloendothelial iron stores
The causes of eosinophilia are as follows: and absence of siderotic iron granules from developing
1. Allergic disorders: Bronchial asthma, urticaria, drug normoblasts
hypersensitivity
Q. 17. Chronic myeloid leukaemia
2. Parasitic infestations: Trichinosis, echinococcosis, intes-
tinal parasitism Ans.
3. Skin disease: Pemphigus, dermatitis herpetiformis,
erythema multiforme Chronic myeloid leukaemia is a malignant neoplastic trans-
4. Certain malignancies: Hodgkin’s disease and some formation of mature WBCs with a relatively indolent
non-Hodgkin’s lymphomas course. 90% have a positive Philadelphia chromosome, i.e.
5. Pulmonary infiltration with eosinophilia syndrome a 9:22 translocation.
6. Irradiation
7. Miscellaneous disorders: Sarcoidosis, rheumatoid arthri- Clinical Features
tis, polyarteritis nodosa
l Affects adults between 25 and 60 years of age.
Q. 15. Acute myeloid leukaemia l Tiredness and lethargy
l Weight loss
Ans. l Abdominal pain and fullness
l Massive splenomegaly
Acute myeloid leukaemia is a malignant neoplasm of the
l Pallor
haemopoietic stem cells of the myeloid series, character-
ized by the presence of immature cells called blasts.
Investigations
Clinical Features l Normochromic anaemia
l Common in the young and middle-aged individuals l Leucocytosis and thrombocytosis
l Bone marrow studies
l Abrupt onset of easy fatigueability, bleeding tendencies,
proneness to repeated infections
l Bony pain due to the infiltration of the marrow Treatment
l Central nervous system symptoms due to malignant in-
filtration like headache, visual blurring 1 . Allogenic bone marrow transplant

l Hepatosplenomegaly may be present. 2. Chemotherapy with busulphan, hydroxyurea
3. Interferons
Laboratory Investigations Q. 18. Blood picture in chronic myeloid leukaemia

l Anaemia and leucocytosis (WBC count of 50,000–100,000) Ans.
The blood picture in chronic myeloid leukaemia is as follows: Q. 21. Agranulocytosis

l Anaemia: It is normocytic normochromic.
Ans.
l Marked leucocytosis
l Myeloblasts do not exceed 10% of cells in peripheral The term agranulocytosis is used to describe a state of
blood. severe neutropenia.
l During accelerated phase rising leucocytosis associated
with thrombocytosis or thrombocytopenia and spleno-

megaly. Aetiology
l Platelet count may be normal or raised in half of the cases. l Most common causes are drugs.
l It may be also due to haematological diseases, infections,
Q. 19. Peripheral smear layer findings in acute lym- autoimmune (SLE) or congenital (cyclic) neutropenia.
phatic leukaemia l Basic defect is in arrest of cell maturation.
Ans.
Peripheral blood smear in acute lymphatic leukaemia Clinical Manifestations

(ALL) shows the following: l Initially patient develops malaise, chills and fever, with
1. Anaemia subsequent marked weakness and fatigueability.
2. Thrombocytopenia l Infections constitute the major problem. They usually
3. White blood cells present as ulcerating, necrotizing lesions of gingiva,
a. WBC count is variable, ranges from subnormal to floor of the mouth, buccal mucosa, oropharynx and other
markedly elevated values. sites within oral cavity known as agranulocytic angina.
b. Majority of leucocytes in the peripheral blood are Perirectal area, sinuses and lungs are also affected.
blasts and there is often neutropenia.
c. Due to marrow infiltration by leukaemic cells
d. Especially in ALL the smear cells in peripheral Lab Investigations
blood represent degenerated leucocytes. l WBC , 2000, complete absence of polymorphonuclear
leucocytes (PMN) or granulocytes.
Q. 20. Leukaemoid reaction l Investigation for the presence of autoantibodies.
Ans.
l Leukaemoid reaction is defined as the reactive excessive Management

leucocytosis in peripheral blood resembling that of l Empirical parenteral broad-spectrum antibiotics must
leukaemia in the subject who does not have leukaemia. be started immediately.
l Leukaemoid reaction may be myeloid or lymphoid. l Neutrophil transfusion may help in severe infections.
l In addition to removal of offending drug and control of
Myeloid Leukaemoid Reaction infections, treatment efforts may also include the
administration of growth factors like granulocyte
l The majority of leukaemoid reaction involves the granu- colony-stimulating factor (G-CSF), which stimulates
locyte series. neutrophil production by the bone marrow.
l It may occur in infection, intoxication, malignant
diseases, severe haemorrhages and severe haemolysis. Q. 22. Enumerate various causes of pancytopenia.
Ans.
Lymphoid Leukaemoid Reaction
Pancytopenia means occurrence of anaemia, leukopenia
l It is found in conditions such as infectious mononu- and thrombocytopenia together.
cleosis, whooping cough, chickenpox, measles and
tuberculosis. Causes of pancytopenia are as follows:
1. Aplastic anaemia
Lab Diagnosis 2. Pancytopenia with normal or increased marrow cellularity
a. Myelodysplastic syndromes
l Leucocytosis b. Hypersplenism
l Infective cases may show toxic granulation and Dohle c. Megaloblastic anaemia
bodies in the cytoplasm of neutrophils. 3. Paroxysmal nocturnal haemoglobinuria
4. Bone marrow infiltrations Clinical Features

a. Haematologic malignancies (leukaemiae, lympho-
mas, myelomas) l Seen in older adults.
b. Nonhaematologic metastatic malignancies l Important presentations are anaemia, bone pain and
c. Storage diseases infections.
d. Osteopetrosis l Pathological fractures are common.
l Patient may present with renal failure, spinal cord
Q. 23. Aetiology and clinical features of idiopathic compression.

thrombocytopenic purpura.
Ans. Investigations
Thrombocytopenia is defined as reduction in the peripheral l Bence-Jones proteins in urine
blood platelet count below the lower limit of normal range, l Reversal of serum albumin/globulin (A/G) ratio
i.e. below 150,000/µL. l Increase in total serum proteins to 8–16 g%
H/E: plasma cells with cart wheel or checkerboard pattern

Causes of Thrombocytopenic Purpura
l Impaired platelet production
Treatment
l Accelerated platelet destruction l The treatment of multiple myeloma includes radiother-
l Splenic sequestration: Splenomegaly apy, biphosphonates (pami zoledronate) and autologous
l Dilutional loss peripheral cell transplantation.
l Newer therapeutics include thalidomide and proteos-
ome inhibitors.
Clinical Features l Chemotherapeutic agents include melphalan, cyclo-
l The usual manifestations are petechial haemorrhage, phosphamide, doxorubicin, vincristine, dexamethasone.
easy brushing and mucosal bleeding such as menorrha-
gia in women, nasal bleeding, bleeding from gums and Q. 26. Prothrombin time (PT)
haematuria. Ans.
l Intracranial haemorrhage is rare.
l Splenomegaly and hepatomegaly may also occur. l Prothrombin time (PT) is the time in seconds that is re-
l Laboratory findings show markedly reduced platelet quired for fibrin mesh to form in a citrated or oxalated
count. plasma, where known amount of tissue thromboplastin
and calcium are added.
Q. 24. Burkitt’s lymphoma l PT is used as screening test in suspected clotting abnor-
malities.
Ans.
l It is used as an index of the degree of clotting abnor-
l Burkitt’s lymphoma is a rare type of non-Hodgkin’s malities in patients with deficiency of prothrombin and
lymphoma (NHL). factor VII, X as a result of liver disease, malabsorption
l Epstein-Barr virus (EBV) and HIV are associated with or coumarin therapy.
the development of Burkitt’s lymphoma.
l This is the most rapidly progressive tumour first
Q. 27. Rh factor
described in African children. Ans.
l Most patients present with lymphadenopathy and
abdominal mass. l Rh factor is an antigen present in the RBC. The antigen

l It has a tendency to metastasize to the CNS. was found in Rhesus monkey, so it was named as Rh fac-
l Treatment should be initiated promptly with intensive tor. There are many Rh antigens but D is more antigenic.
chemotherapy. Prophylactic chemotherapy is also given. l The persons having D antigen are called Rh positive and those
70–80% patients may be cured. without D antigen are Rh negative. Among Asian population,
85% of people are Rh-positive and 15% are Rh negative.
Q. 25. Multiple myeloma l Rh positive person can receive Rh-negative blood
without the risk of developing complications.

Ans.
l When Rh negative, mother carries Rh-positive fetus
Multiple myeloma is a malignant disease arising from neo- in two consecutive pregnancies then during second
plastic transformation of plasma cells of monoclonal origin. pregnancy erythroblastosis fetalis develops.
Topic 12
Lung
SHORT ESSAYS
Q. 1. Lab diagnosis of Corynebacterium diphtheriae in Toxigenicity is indicated by inflammatory reaction at
brief. the site of injection progressing to necrosis in 48–72 h in
the test animal and no change in the control animal.
Ans. Laboratory diagnosis of Corynebacterium diphthe-
riae consists of isolation of the bacteria and demonstration
of its toxicity. IN VITRO TESTS
Two swabs from the site of lesion, i.e. throat, nose or
larynx, one for smear and one for culture are as follows: Eleck’s Gel Precipitation Test
1. Bacteriological studies or isolation of the bacteria l Eleck’s test is an in vitro immunodiffusion test
a. Direct smear examination: Smears are stained by described by Bleck’s for demonstrating the toxigenicity
Albert’s stain show beaded slender rods in typical of the Corynebacterium diphtheriae.
Chinese letter pattern. l Procedure: A rectangular strip of filter paper impreg-
b. Culture nated with diphtheria antitoxin (1000 units/mL) is
i. Swabs are inoculated on Loeffler’s serum slope, placed on the surface of a 20% normal hoarse serum
tellurite agar and a plate of ordinary blood agar. agar in a Petri dish while the medium is still fluid. Then
ii. On Loeffler’s serum slope the growth appears in the surface is dried.
4–8 h but if negative reincubate for 24 h whereas l Once the agar is set narrow streaks of the test strains are
colonies on blood tellurite medium and blood made at right angle to the filter paper strip. A positive
agar appear in 36–48 h they should be incubated and negative control is set.
for at least 2 days before declaring no growth.
iii. Any growth on culture should be stained with The plate is incubated at 37°C for 24–48 h where the
methylene blue or Neisser or Albert stain which toxins produced diffuse in the agar.
shows metachromatic granules and typical Chinese l Interpretation: Toxigenic strains of C. diphtheriae pro-
letter pattern. duce arrowhead lines of precipitation where the
2. Demonstration of its toxicity by virulence tests bacterial toxin meets with the antitoxin in optimum
a. In vivo tests concentration.
i. Subcutaneous test l No precipitate is formed in the case of nontoxigenic
ii. Intracutaneous test strains.
b. In vitro tests
i. Elek’s gel precipitation test
ii. Tissue culture test Tissue Culture Test
l Toxigenicity of diphtheria bacilli is demonstrated by
IN VIVO TESTS incorporating the strains in the agar overlay of cell
culture monolayers. The toxins produced diffuse into
Subcutaneous test the cells below and kills them.
Growth from an overnight culture on Loeffler’s slope is emulsi-
fied in 2–4 mL broth and 0.8 mL of the emulsion is injected Q. 2. ARDS—describe causes and pathogenesis.
subcutaneously into two guinea pigs of which one is protected Ans.
with prior administration of 500 units of diphtheria antitoxin. If
the strain is virulent, then the unprotected animal dies in 4 days. l Adult respiratory distress syndrome (ARDS) is also
called as shock lung syndrome, diffuse alveolar damage,
acute alveolar injury, traumatic wet lungs and posttrau-
Intracutaneous Test matic respiratory insufficiency.
Broth emulsion is injected intracutaneously about 0.1 mL l Aetiology
into two guinea pigs where one is protected with 500 units l Shock due to sepsis, trauma, bums
of diphtheria antitoxin given the previous day and acts as a l Aspiration pneumonitis
control. However, other is given 50 units of antitoxin intra- l Drugs, e.g. salicylates, colchicine
peritoneally 4 h after the skin test, in order to prevent death. l Narcotic overdose
Infections especially diffuse pulmonary infection

l intravascular aggregation of neutrophils or by libera-
especially viral pneumonia tion of mediators of inflammation.
l Inflammation, e.g. pancreatitis l Pathology: Gross appearance of lungs is characteristi-
l Radiation cally stiff, congested and heavy.
l Fat embolism l Microscopic examination
l Inhalation of toxins and irritants, e.g. smoke, war
gases, nitrogen dioxide, metal fumes, etc. It reveals the following:

l Oxygen toxicity l Interstitial and intra-alveolar oedema
l Clinical features: Clinically it is characterized by sud- l Necrosis of alveolar epithelial cells with formation
den and severe respiratory distress, tachypnoea, tachy- of hyaline membranes, which chiefly composed of
cardia, cyanosis and severe hypoxaemia that fails to re- fibrin admixed with necrotic epithelial cells.
spond to oxygen therapy and assisted ventilation. l Congestion and intra-alveolar haemorrhages
l Pathogenesis: Basic initiating event in the pathogenesis l Changes of bronchopneumonia
of ARDS is diffuse damage to the alveocapillary wall l Interstitial fibrosis and regenerating flat alveolar
by anyone of the aetiological agent. The mechanism of epithelial cells lining the denuded alveoli in organiz-
damage may be by oxygen-derived free radicals, by ing stage.
SHORT NOTE
Q. 1. Lobar pneumonia 2. Red hepatization (early consolidation)
3. Grey hepatization (late consolidation)
Ans. Lobar pneumonia is an acute bacterial infection of a
4. Resolution
part of lobe, the entire lobe or even two lobes of one or both
l Clinical features
the lungs.
1. Symptoms: Shaking chills, fever, malaise with
l Aetiology pleuritic chest pain, dyspnoea and cough with expec-
l Streptococcus pneumoniae toration
l Staphylococcus aureus 2. Common physical findings: Fever, tachycardia and
l b-haemolytic streptococci tachypnoea
l Gram-negative bacteria like Haemophilus influenzae, 3. Marked-neutrophilic leucocytosis and blood cultures
Klebsiella pneumoniae, Pseudomonas, Proteus and are positive in about 30% of cases.
E. coli. 4. Chest X-ray may reveal consolidation.
l Morphology l Treatment
a. Response to antibiotics is usually rapid with clinical

Laennec’s original description divides lobar pneumonia improvement in 48–72 h after initiation of therapy.
into four sequential pathological phases as follows:
1. Stage of congestion (initial phase)
Topic 13
Diseases of Oral Cavity and Salivary Glands

SHORT ESSAYS
Q. 1. Epulis l They usually arise in young to middle-aged adults. It is
Ans. a nonpathological soft swelling of gums due to hyper-
emia that begins during middle trimester of pregnancy
l Epulis, also known as peripheral giant cell granuloma and subsides after delivery.
is an unusual inflammatory lesion of the gums which l Gross appearance
characteristically protrudes from the gingiva in close l The lesions are typically 1–1.5 cm hemispherical
relation to the teeth. masses covered by intact or ulcerated mucosa.
On cut section they appear grey to brown and are

l l Dysplastic type
indistinctive. l Shows irregular stratification of the epithelium, focal
l Microscopic examination areas of increased and abnormal mitotic figures, hy-

l Aggregation of multinucleate foreign body like giant perchromatism, pleomorphism, loss of polarity and
cells separated by scanty fibroangiomatous stroma. individual cell keratinization.
l There may be foci of haemosiderin deposits or an in- l Subepithelial tissue shows an inflammatory infiltrate
flammatory infiltrate secondary to mucosal ulceration. of lymphocytes and plasma cells.

l They should be differentiated from true central l Mild dysplasia reverts back to normal if offending aetio-
giant cell tumours and intraosseous reparative giant cell logical factor is removed, whereas severe dysplasia in-
granuloma. dicates progression to carcinoma.
l Treatment: Removal of underlying aetiology and surgical l Erythroplasia is a form of dysplastic leukoplakia where
excision. oepithelial atypia is marked and thus has higher risk of

developing into carcinoma.
Q. 2. Leukoplakia l If the epithelial dysplasia is extensive so as to involve the
entire thickness of the epithelium, the lesion is called car-

Or,
cinoma in situ which may progress to invasive carcinoma.
Leukoplakia of mouth
Ans. Treatment
The treatment of leukoplakia is aimed at the elimination of
Leukoplakia is a premalignant lesion of the oral cavity and
any recognizable irritating factors and includes following
is defined as a white patch or plaque on the oral mucosa
modalities:
. 5 mm in diameter, which neither can be rubbed off nor
can be classified into any other diagnosable disease. l Administration of vitamin A, vitamin B complex and
oestrogens
l X-ray therapy
Aetiology l Fulguration
l Smoking especially pipe and cigar smokers l Surgical excision
l Chronic friction, e.g. ill-fitting dentures or jagged teeth l Topical chemotherapy
l Local irritants like
l alcohol, Q. 3. Ameloblastoma
l very hot and spicy food and
Ans.
l beverages.
Ameloblastoma is the most common benign but locally
invasive epithelial odontogenic tumour.
Clinical Features
It occurs more frequently in males.
l
Pathogenesis
l Sites of predilection in descending order of frequency
are cheek mucosa, angle of mouth, alveolar mucosa, Ameloblastoma may be derived from the following:
tongue, lips, hard and soft palate and floor of the mouth. l Cell rest of enamel organ, either remnants of dental
lamina or remnants of Hertwig’s sheath, the epithelial

rest cells of Malassez.
Gross Appearance l Epithelial lining of a dentigerous cyst
l Lesion appears white, whitish yellow or red velvety of l Disturbance in the developing enamel organ
.5 mm in diameter. l Basal cell layer of the oral mucosa
l Has a variable appearance, usually circumscribed, slightly
elevated, smooth or wrinkled, speckled or nodular.

Clinical Features
l It usually occurs in individuals between 30–50 years
Histological Features with mean age of occurrence as 33 years.
l Microscopic examination reveals two types as follows: l The males are affected more commonly than females.
l Hyperkeratotic type l This lesion occurs in both the maxilla and mandible, but
l Dysplastic type the posterior mandible in the molar ramus is the most
l Hyperkeratotic type is characterized by an orderly common location.
and regular hyperplasia of squamous epithelium with l Clinically ameloblastoma presents as slowly enlarging,
hyperkeratosis on the surface. painless, ovoid and fusiform bony hard swelling of the jaw.
l Pain, paraesthesia and mobility of regional teeth are Q. 4. Vincent’s angina

present in some cases. Ans.
l Pathological fractures may occur in many affected
bones. Vincent’s infection primarily involves free gingival margin,

l Behaviour: Although it is not classified as a malignant the crest of free gingiva and the interdental papillae, when
lesion, it is extremely aggressive and infiltrative. such lesions spread to the soft palate and tonsillar areas it is
known as Vincent’s angina.
Radiographic Findings
Aetiology
l Radiolucent expansile multilocular or soap bubble
appearance of the bone l Vincent’s bacilli (fusiform bacilli) and Borrelia vincen-
tii are the causative organisms.
Pathology
Clinical Features
l Gross Appearance: The tumour is greyish white, usually
solid, sometimes cystic, replacing and expanding the l Vincent’s angina is a painful condition of the throat
affected bone. characterized by local ulceration of the tonsils, mouth
l Microscopic examination: Histologically the ameloblas- and pharynx.
toma shows neoplastic proliferation of odontogenic l It is one of the differential diagnosis of membrane over
epithelial cells mostly in following distinct patterns: the tonsil.

1. Follicular pattern (most common) l It may occur as an acute illness with diffuse involve-
l The neoplastic odontogenic epithelial cells prolif- ment of tissue or as chronic illness consisting of ulcer-
erate in the form of multiple discrete follicles and ation of tonsil.
islands within fibrous connective tissue stroma. l It is insidious in onset, with less fever and less discom-
l Structure of follicles is similar to enamel organ. fort in throat.

Each follicle-like structure is bordered on the l Membrane which usually forms over the tonsil, can be
periphery by the single layer of tall columnar easily removed revealing an irregular ulcer on the
cells resembling ameloblasts. The cells located at tonsil.
the centre of follicle are loosely arranged and
resemble stellate reticulum cells.
Treatment
l Microcyst formation is often observed inside these
follicles. l It is preferable to treat this condition conservatively in-

2. Plexiform pattern (second most common) stituting superficial cleansing of oral cavity in early
l This pattern of neoplastic cell proliferation forms acute stage of disease.
irregular plexiform masses or network of strands l In many cases prompt regression of disease results even
resembling fishnet-like pattern. without medication.

l Stroma is usually scanty and microcyst formation
occurs in the stroma. Q. 5. Pleomorphic adenoma

3. Acanthomatous pattern Ans.
l It is the squamous metaplasia within the islands
of tumour cells. Pleomorphic adenoma or mixed salivary tumour is the most

l Occasionally, epithelial or keratin pearls may be common tumour of major (60–75%) and minor (50%) sali-
observed. vary glands.
l Areas of calcification may be found in the meta-
plastic squamous epithelium.

Clinical Features
4. Basal cell pattern: It is similar to basal cell carcinoma.
5. Granular cell pattern: It is characterized by a marked l Parotid gland is the most common site of the pleomor-
transformation of the cytoplasm, usually of the phic adenoma.
stellate reticulum-like cells takes a very coarse l It is common in women and occurs more frequently in
granular eosinophilic appearance. fourth to sixth decades of life.

l Tumour is solitary and smooth surfaced but sometimes
may be nodular, painless and slow growing. It is often

Treatment located below and in front of ear.
l Complete surgical excision and long-term follow-up of l It does not show fixation either to the deeper tissues or
the patient to the overlying skin.

l The skin seldom ulcerates even though these tumours l The ductal cells are cuboidal or columnar and underly-
reach a fantastic size. ing myoepithelial cells may be polygonal or spindle
shaped resembling smooth muscle cells.
l Lumen of duct-like structures contain PAS positive
Pathology epithelial mucin.
Gross Appearance l Focal areas of squamous metaplasia and keratinization
may be present.
l It appears circumscribed, pseudoencapsulated, rounded, 2. Mesenchymal elements: These are loose connective
at times multilobulated, firm mass, 2–5 cm in diameter tissue and myxoid, mucoid and chondroid matrix
with bosselated surface, soft and mucoid consistency. which simulates cartilage.
l Cut surface is grey-white and bluish, semitranslucent,
usually solid but occasionally may show small cystic

spaces. Treatment
l Surgical excision is the accepted treatment for this tumour.
l The diverse histologic pattern of this neoplasm is one of Prognosis
its most characteristic features.
High rate of recurrence is due to
l It is characterized by pleomorphic or mixed appearance
where epithelial element is present in matrix of mucoid, l incomplete surgical removal due to proximity to facial
myxoid and chondroid tissue. nerve,
1. Epithelial component l pseudoencapsulation,
l It is the cells of ductal or myoepithelial origin arranged l implantation in the surgical field and
in various patterns like ducts, acini, tubules, sheets and l potential for malignant transformation.
strands.
SHORT NOTES
Q. 1. Leukoplakia Treatment
Ans. The treatment of leukoplakia is aimed at the elimination of
any recognizable irritating factors.
Leukoplakia is a premalignant lesion of the oral cavity and l Administration of vitamin A, vitamin B complex and
is defined as a white patch or plaque on the oral mucosa oestrogens
which cannot be rubbed off. l X-ray therapy, fulguration, surgical excision and topical
chemotherapy
Aetiology Q. 2. Dental caries
l Smoking, chronic friction from ill-fitting dentures or
Ans.
jagged teeth and local irritants like alcohol, very hot and
spicy food. l Dental caries is an infectious microbial disease of teeth
that results in localized dissolution and destruction of
calcified tissues.
Clinical Features
l It occurs more frequently in males. Aetiology
l Sites of predilection in descending order of frequency
are cheek mucosa, angle of mouth, alveolar mucosa, l Diet rich in carbohydrates which is soft and sticky
tongue, lips, hard and soft palate and floor of the mouth. l If the plaque is not removed it leads to tooth decay.
l Gross appearance
l Lesion appears white, whitish yellow or red velvety Pathologic Changes

of . 5 mm diameter.
l Has a variable appearance, usually circumscribed,
l Caries occur in areas of pits and fissures, mainly of
slightly elevated, smooth or wrinkled, speckled or molars and premolars where food retention occurs.
l Spread of caries in pit and fissures is rapid compared to
nodular.
l Microscopic examination reveals two types as follows:
smooth surface.
l Incipient caries lesion is smooth chalky white area of
l Hyperkeratotic type
l Dysplastic type
decalcification beneath the dental plaque.
l Recurrent caries occurs immediately near to the restora- l The lesion is characterized by necrosis of the marginal
tions due to leaky margins and improper removal of gingiva and may extend on to surrounding tissues
caries. of oral mucosa like lips and cheeks by gangrenous
l Arrested caries occurs only on occlusal surfaces and is necrosis.
an open cavity, the dentine gets burnished giving brown l The overlying skin becomes inflamed, oedematous and
stained polished appearance and hard which is known as finally necrotic, commencement of gangrene is noted by
eburnation of dentine. appearance of blackening of skin and extremely foul
l If untreated, caries leads to pulpitis and necrosis of the odour.
tooth. l Patients may have high temperature during the course of
the disease, suffer secondary infections and may die

from toxemia and pneumonia.
Caries Control Measures l Treatment: Although the disease is still serious, progno-
l Nutritional measures: Restrict carbohydrates, soft sticky sis is considerably better if antibiotics are administered
foods, decrease the frequency of eating promptly before the patient reaches the final stages
l Chemical measures of the disease. Any existing malnutrition should be
l Substances which alter the tooth surface or structure, immediately treated.
e.g. fluorides, chlorhexidine, biguanides, zinc chloride,
K-ferrocyanide, etc. Q. 5. Ameloblastoma
l Substances which interfere with carbohydrate degra-
Ans.
dation, e.g. vitamin K, sarcosides
l Mechanical measures Ameloblastoma is the most common benign but locally
l Brushing, flosssing, mouth rinsing (0.2% chlorhexi- invasive epithelial odontogenic tumour.
dine), fluoride mouthwashes
l Pit and fissure sealants, e.g. BIS-GMA, cyanoacry-
Pathogenesis
lates, etc
l Prophylactic odontotomy to make pit and fissures Ameloblastoma may be derived from the cell rest of enamel
self-cleansing organ, epithelial lining of a dentigerous cyst and basal cell
layer of the oral mucosa.
Q. 3. Oral candidiasis
Ans. Clinical Features
l Oral thrush or candidiasis is a most common opportu- l Age of occurrence: Between 30–50 years with mean age
nistic fungal infection caused by Candida albicans. of occurrence as 33 years.
l Oral thrush is characterized by the development of dis- l The males are affected more commonly than females.
crete creamy white patches on the mucosal surfaces of l It occurs in both the maxilla and mandible, but the
tongue or buccal mucosa. posterior mandible in the molar ramus is the most
l It occurs most frequently in bottle-fed infants, the old common location.
age and debilitated individuals. l Clinically ameloblastoma presents as slow enlarging,
l Various predisposing factors of candidiasis are impaired painless, bony hard swelling of the jaw.
immunity, prolonged use of oral contraceptives, long-
term antibiotic therapy, corticosteroid therapy, diabetes
Radiographic Findings
mellitus, obesity and pregnancy.
l For the treatment of oral thrush nystatin and metronida- l Radiolucent expansile multilocular or soap bubble
zole are useful. appearance of the bone
Q. 4. Cancrum oris
Pathology
Ans.
Histologically the ameloblastoma shows mostly the follow-
l Cancrum oris or noma or necrotizing stomatitis is an ing distinct patterns:
inflammatory disease of the oral cavity. l Follicular pattern (most common)
l It occurs more commonly in poorly nourished children l Plexiform pattern (second most common)
like in kwashiorkor, infectious diseases such as measles, l Acanthomatous pattern
immunodeficiencies and emotional stress. l Basal cell pattern
l It is a specific infection caused by Vincent’s organisms. l Granular cell pattern

Treatment l H/E: Always encapsulated, loose myxoid material is a

l Complete surgical excision and long-term follow-up of predominant feature. Cuboidal cells arranged in tubes
the patient or duct-like structures. Hyaline cells, i.e. modified
myoepithelial cells are commonly present.
Q. 6. Dentigerous cyst l The accepted treatment for this tumour is surgical
excision.
Ans.
Q. 8. Premalignant lesions
l Dentigerous cyst is said to originate by accumulation of
fluid between unerupted tooth crown and reduced Ans.
enamel epithelium (REE).
l It involves crown of impacted or unerupted tooth.
Premalignant lesions are a group of conditions which
l Most common site are third molars and maxillary
predispose to the subsequent development of cancer. For
canines, as these are mostly impacted teeth. example:
l Radiographically, it is usually a smooth unilocular
1. Carcinoma in situ
lesion, when a radiolucent area appears to project later- a. CIN of uterine cervix at the junction of ecto and
ally from the tooth crown, lateral dentigerous cyst is endocervix
suspected and when a radiolucent area surrounds b. Bowen’s disease of the skin
the crown of the involved tooth, the circumferential c. Actinic or solar keratosis
dentigerous cyst is described by Thoma. d. Oral leukoplakia
e. Intralobular and intraductal carcinoma of the breast
2. Some benign tumours
Histological Features of Dentigerous Cyst a. Multiple adenomas of the large intestine
l There are no characteristic histological microscopic b. Neurofibromatosis (von Recklinghausen’s disease)
features. 3. Miscellaneous
l Cyst wall is made up of a thin connective tissue. Lumen
a. Ulcerative colitis (long standing)
lined by stratified squamous epithelium. Connective b. Cirrhosis of liver
tissue contains islands of odontogenic epithelium and
Q. 9. Microscopic features of Warthin’s tumour
in inflammation. Rushton bodies are present. Content of
lumen is thin, watery yellow or straw coloured fluid, Ans.
occasionally blood tinged.
l Warthin’s tumour is also known as papillary cystadenoma
lymphomatosum. It is a type of monomorphic adenoma
Treatment and develops from parotid ductal epithelium present in the
l The large dentigerous cysts in young individuals are lymph nodes adjacent to or within parotid gland.
usually treated by marsupialization whereas smaller l It exhibits a definite predilection for men.
lesions can be surgically removed in their entirety. l Age of occurrence: Fourth to seventh decades of life
l The three potential complications that can arise follow-
ing incomplete surgical removal of the cyst are

1. ameloblastoma,
Pathology
2. epidermoid carcinoma and Gross appearance: The tumour is encapsulated, round or
3. mucoepidermoid carcinoma. oval with smooth surface. The cut section shows character-
istic slit-like or cystic spaces, containing chocolate-co-
Q. 7. Pleomorphic adenoma of salivary glands loured fluid and having papillary projections.
Ans.
l Pleomorphic adenoma is the most common tumour of Microscopic Examination

salivary glands and occurs usually in parotid gland. l Histologically, the tumour shows two components epi-
l It is often located below and in front of ear and is thelial parenchyma and lymphoid stroma.
not fixed to underlying tissues. The tumour is smooth, l As the name indicates the lesion is essentially an ade-
solitary but sometimes nodular, painless and slow noma exhibiting cyst formation with papillary projec-
growing. tions into cystic spaces and a lymphoid matrix showing
l Originates from myoepithelial and reserve cells of inter- germinal centres.
calated ducts.
1. Epithelial parenchyma l Immunologic abnormalities: Patients appear to have

l It is composed of glandular and cystic structures having an altered immune response directed against both
papillary arrangement and lined by characteristic nonpathogenic oral flora and host oral tissues.
eosinophilic epithelium. l Iron, vitamin B12 or folic acid deficiency
l The epithelial cells covering papillary projections are
columnar or cuboidal cells usually arranged in two Features of an Aphthous Ulcer

rows, although inner layer may be several cells thick.
2. Lymphoid stroma: Abundant lymphoid component l The aphthous ulcer begins as single or multiple superfi-
present under the epithelium in the form of promi- cial erosion covered by a grey membrane.
l It has a well-circumscribed margin surrounded by an
nent lymphoid tissue, often within germinal centres.
erythematous halo.
l Very painful and varies in size from 2 to 3 mm to over
Treatment 10 mm.
l The ulcers generally persist for 7–14 days and then heal
Surgical excision
gradually with little or no evidence of scarring.
l Anitschkow cells are histologically characteristic of
Q. 10. Aphthous ulcers
this ulcer.
Ans.
Aphthous ulcers are also known as canker sores. Treatment

No specific treatment, a tetracycline mouthwash 250 mg/ 5 mL
Aetiology used four times daily for 5–7 days produced good response
in 70% of the patients.
Numerous possible aetiologic factors suggested are as
follows: l Protection against pathogens by release of inflamma-
l Bacterial infection: Streptococcus sanguis, L-form of
tory mediators through mast cell degranulation
l Has special role in defence against helminthic
alpha-hemolytic streptococcus are causative agent of
the disease infections.
Topic 14
Liver, Gallbladder and Biliary Tract

SHORT NOTE
Q. 1. Idiopathic haemochromatosis organs like liver, pancreas, spleen, heart and endocrine
glands.
Ans.
l Tissue injury results from iron-laden lysosomes of pa-
l Idiopathic or primary haemochromatosis is an autoso- renchymal cells and lipid peroxidation of cell organelles
mal recessive disorder characterized by excessive ab- by excess iron.
sorption of iron associated with susceptible gene linked l It is associated with triad of pigmentary liver cirrhosis,
to HLA-A3 complex on chromosome 6. pancreatic damage resulting in diabetes mellitus and

l The excess iron in primary haemochromatosis is depos- skin pigmentation. Due to last two features the disease
ited mainly in the cytoplasm of parenchymal cells of is also termed as bronze diabetes.
Topic 15
Male and Female Genital System

SHORT ESSAY
Q. 1. Teratoma majority of ovarian teratomas and are benign and cystic
with predominant ectodermal elements often termed as
Ans.
dermoid cyst. Less than 1% of patients with dermoid
l Teratomas are the neoplasms of germ cell origin marked cyst develop malignant transformation.
by differentiation of totipotential germ cells into mature l Immature malignant teratoma: They are rare and
tissues representing all three germ layers: ectoderm, account for approximately 0.2% of ovarian tumours.
endoderm and mesoderm. l Monodermal or specialized teratoma: They are rare,
l Teratomas are further classified as follows: include two important examples: struma ovarii and
1. Benign (mature, adult) teratoma carcinoid tumour.
a. Benign cystic teratoma (dermoid cyst) 1. Struma ovarii is a teratoma composed exclusively
b. Benign solid teratoma of thyroid tissue recognizable grossly as well as
2. Malignant (immature) teratoma microscopically.
3. Monodermal or specialized teratoma 2. Carcinoid tumour is an ovarian teratoma arising
a. Struma ovarii from argentaffin cells of intestinal epithelium in the
b. Carcinoid tumour teratoma.
l Benign (mature, adult) teratoma: They constitute vast
SHORT NOTE
Q. 1. Define teratoma. tissues representing all three germ layers: ectoderm,
endoderm and mesoderm.
Ans.
l They are of three types: mature, immature and mono-
l Teratomas are the neoplasms of germ cell origin marked dermal.

by differentiation of totipotential germ cells into mature
Topic 16
Endocrine System
LONG ESSAY
Q. 1. Define and classify diabetes mellitus. Discuss com- a. Type I (insulin-dependent diabetes mellitus (IDDM))
plications of diabetes mellitus. b. Type II (noninsulin-dependent diabetes mellitus
(NIDDM))
Ans. Diabetes mellitus is a chronic disorder of carbohy-
i. Nonobese NIDDM
drate, fat and protein metabolism. A defective or deficient
ii. Obese NIDDM
insulin secretory response, which translates into impaired
iii. Maturity onset diabetes of the young (MODY)
glucose use is a characteristic feature of diabetes mellitus
2 . Secondary diabetes
resulting in hyperglycaemia.
a. Chronic pancreatitis
b. Post-pancreatectomy
c. Hormonal tumours (phaeochromocytoma, pituitary
CLASSIFICATION OF DIABETES MELLITUS tumours)
1. Primary (idiopathic) diabetes d. Drugs (corticosteroids)
e. Haemochromatosis Hyperosmolar Nonketotic Coma

f. Genetic disorders (lipodystrophy)
l Is usually a complication of type II diabetes caused by
severe dehydration resulting from sustained hypergly-
COMPLICATIONS OF DIABETES MELLITUS caemic diuresis.
l The loss of glucose in urine is so intense that the patient
l Complications of diabetes are seen in almost every
is unable to drink sufficient water to maintain urinary
tissue and organ of the body due to biochemical and
fluid loss.
structural alterations as a result of hyperglycaemia.
l The prominent clinical feature of central nervous
l The complications can be broadly divided into acute
system. Due to high viscosity of blood thrombotic and
metabolic complications and late systemic complica-
bleeding complications are frequent. The mortality rate
tions (Table 16.1).
is high.
TABLE 16.1 Complications of Diabetes Mellitus

Hypoglycaemia
Acute Metabolic Late Systemic
Complications Complications l Is seen in type I diabetes patients resulting from exces-
sive administration of insulin, missing a meal or due to
Diabetic ketoacidosis Atherosclerosis
stress.
Hyperosmolar nonketotic Diabetic microangiopathy l These episodes of hypoglycaemia may permanently
coma damage central nervous system and are therefore
Hypoglycaemia Diabetic nephropathy dangerous.
l These may result in worsening of diabetic control and
Diabetic neuropathy
rebound hyperglycaemia called as Somogyi’s effect.
Infections
Late Systemic Complications

Acute Metabolic Complications
Over a period of 15–20 years either type of diabetes
Diabetic ketoacidosis produces a number of systemic complications which are
l Is an exclusive complication of type I diabetes. It is responsible for morbidity and mortality.
developed in patients with severe insulin deficiency
combined with glucagon excess. Failure to take insulin Atherosclerosis
and exposure to stress are precipitating causes.
l Pathogenesis
l When compared to the general population development
of atheroma in diabetic patient is accelerated. The
Severe lack of insulin diabetics also have extensive lesions and often have
complicated plaques such as ulcerations, calcification
↓ causes
and thrombosis.
lipolysis in adipose tissue l Hyperlipidaemia, reduced HDL levels, nonenzymatic
↓releases glycosylation, increased platelet adhesiveness, obesity

free fatty acids into the circulation and associated hypertension are the possible contribu-
tory factors for this accelerated atherosclerosis.
↓ which are oxidized in liver to l The outcome of this complication is in form of early
ketone bodies (acetoacetic acid and hydroxybutyric acid) onset of coronary artery disease, silent myocardial
↓ infarction, cerebral stroke and gangrene of the toes
and feet.
Presence of glucagon accelerates this ketogenesis
Diabetic Microangiopathy
l As the ketogenesis continues unabated the excess
ketone bodies produced cannot be degraded by the l The thickening of the basement membrane of small
muscles and other tissues resulting in ketosis, which blood vessels and capillaries of different organs and
manifests as anorexia, nausea, vomiting, deep and fast tissues like skin, skeletal muscle, eye, kidney, etc. is due
breathing, mental confusion and coma. However, most to recurrent hyperglycaemia which causes increased
of the patients recover. glycosylation of haemoglobin and other proteins.
l Similar type of basement membrane-like material is 2. Vascular lesions such as hyaline arteriosclerosis of
also deposited in nonvascular tissues such as peripheral afferent and efferent arterioles and atheromas of renal
nerves, renal tubules and Bowman’s capsule. arteries
l Diabetic nephropathy is a common complication lead- 3. Diabetic pyelonephritis and necrotizing renal papillitis
ing to death in diabetes. 4. Tubular lesions or Armanni–Ebstein lesion
l Diabetic neuropathy affects all parts of the nervous
The four types of lesions seen are as follows: system. The basic pathological changes are segmen-
1. Diabetic glomerulosclerosis, which are diffused and tal demyelination, Schwann cell injury and axonal
nodular lesions of glomerulosclerosis damage.
SHORT NOTE
Q. 1. Thyrotoxicosis l Diaphoresis, i.e. excessive sweating is present.
l There is protrusion of eyes, exophthalmos with staring
Ans. Thyrotoxicosis is the syndrome resulting from in-
look.
creased levels of free thyroxin, i.e. T4 and T3.
Treatment
Symptoms The management of thyrotoxicosis consists of the following:
l Hyperactivity, irritability, heat intolerance and palpitations l General management: Advice the patient to take mental
l Fatigue and weakness and physical rest along with nutritious diet.
l Weight loss with increased appetite l Drug therapy:
1. Carbimazole is commonly used drug. It is started

with an initial dose of 30 mg/day, adjustment of
Signs doses is made when patient comes under control and
l Tachycardia is main sign which is present due to activa- maintenance dose is given, i.e. 10–20 mg/day.
tion of thyrocardiac component. 2. Potassium perchlorate 800 mg/day in divided doses.
l Systolic hypertension 3. Iodides are given, i.e. sodium or potassium iodide
l Presence of tremors, i.e. involuntary movement of 6–10 mg/day.
body parts is present. l Surgical treatment: Subtotal thyroidectomy
131
l Cardiac arrhythmias, i.e. atrial fibrillation and atrial l Radioiodine treatment: I is used and average effective
tachycardia develops. dose is 8–10 millicuries.
Topic 17
Musculoskeletal System
SHORT ESSAYS
Q. 1. Osteomyelitis
PYOGENIC OSTEOMYELITIS
Ans.
l Pyogenic or suppurative osteomyelitis is caused by
An infection of the bone is termed osteomyelitis. It is bacterial infections like Staphylococcus aureus, strepto-
the blood-borne infection of the bone arising from various cocci, E. coli, Pseudomonas.
systemic diseases such as enteric fever, actinomycosis, l The haematogenous pyogenic osteomyelitis occurs
mycetoma, syphilis, tuberculosis, brucellosis, etc. most commonly in long bones of infants and young
children.
Type of osteomyelitis are as follows: l Clinical features of haematogenous pyogenic osteomy-
1. Pyogenic osteomyelitis elitis generally include painful and tender limb, fever,
2. Tuberculous osteomyelitis malaise and leucocytosis.
l Pathological changes: The basic pathological changes in l Pathology gross appearance

any stage of osteomyelitis are suppuration, ischaemic l Giant cell tumour is eccentrically located in the
necrosis, healing by fibrosis and bony repair. epiphyseal end of long bones which is expanded. It
l The infection begins in the metaphysical end of the is well circumscribed, dark tan and covered by thin
marrow cavity which is largely occupied by the pus shell of subperiosteal bone.
and the infection spreads into the endosteum and in l Cut surface is characteristically haemorrhagic, ne-
Haversian and Volkman’s canal causing periostitis. crotic and honeycombed due to focal areas of cystic
The infection reaches the subperiosteal surface degeneration.
forming subperiosteal abscess. l Microscopic examination
l Suppuration and impaired blood supply result in ero- l Hallmark of osteoclastoma or giant cell tumour is
sion, thinning and infarct necrosis of cortex known presence of large number of multinucleate osteoclast-
as sequestrum. like giant cells which are regularly scattered through-
l This devitalized sequestrum in the course of time out the stromal mononuclear cells.
may be reabsorbed or is sometimes sloughed to form l Giant cells usually contain as many as 100 benign nu-
a free foreign body that on occasion dissects though clei and they have very high acid phosphatase activity.
the skin. l Stromal cells are mononuclear cells and are real
l Later there is formation of new bone around ne- tumour cells. They are uniform, plump, spindle-shaped
crosed bone known as involucrum. or round to oval with numerous mitotic figures.
l Complications: Osteomyelitis may result in following l Other features of stroma are—scanty collagen con-
complications: tent, rich vascularity, areas of haemorrhages and

1. Septicaemia presence of macrophages.
2. Acute bacterial and pathologic arthritis l Cell of origin: True tumour cells are round to spin-
3. Secondary amyloidosis in long standing cases dled mononuclear cells and are possibly of mesen-
4. Vertebral osteomyelitis may cause vertebral collapse chymal origin and perhaps derived from fusion of
monocytes.
l Giant cell tumours are best described as aggressive
TUBERCULOUS OSTEOMYELITIS lesions.
l It occurs by the infection of Mycobacterium tuberculo-
sis which reaches the bone marrow and synovium most Q. 3. Osteosarcoma
commonly by haematogenous dissemination from Ans.
infection elsewhere in the body usually lungs. Most
frequently involved are spine and bone of extremities. l Osteosarcoma or osteogenic sarcoma is the most com-
l Pathologic changes: Bone lesion in tuberculosis con- mon primary malignant tumour of the bone. It is thought
sists of central caseation necrosis surrounded by tuber- to arise from primitive osteoblasts forming mesenchyme.
culous granulation tissue. l Depending upon their location in bone, osteosarcomas
are classified into

Q. 2. Osteoclastoma l medullary or central and
l parosteal or juxtacortical.
Ans.
l It commonly occurs in following bones in descending
Osteoclastoma or giant cell tumour is a distinctive neo- frequency: Knee joint (lower end of femur and upper
plasm of bone with uncertain histogenesis. end of tibia) (60%) . upper end of humerus (10%) .
hip joint (pelvis and upper end of femur) (15%) and less
often in jawbones, vertebrae and skull.
Clinical Features l It is a highly malignant tumour. It arises centrally and ex-
l It commonly occurs in patients between 20 and 40 years tends longitudinally in medullary cavity for variable dis-
of age with no sex predilection. tance, it also expands laterally on either side breaking
l Location: Tumour arises in the epiphysis of long bones through the cortex and lifting the periosteum. If periosteum
close to the articular cartilage. Most common sites of is breached, the tumour grows into the surrounding tissue.
involvement are lower end of femur and upper end of l Pathology
tibia, lower end of radius and upper end of fibula. l Gross appearance of the tumour is greyish white and
l Pain, especially on weight bearing areas and noticeable as a bulky mass at the metaphyseal end of the long
swelling and pathological fracture. bones of the extremity.
l Radiological findings: Radiolographically, it appears l At initial stage, the articular ends are uninvolved.
as a large, lobulated and osteolytic lesion at the end of l Codman’s triangle formed at the angle between the
an expanded long bone with characteristic soap bubble elevated periosteum and underlying cortical bone
appearance. surface may be obvious.
Tumours with abundance of osteoid bone and

l polymorphism. They also show hyperchromatism
cartilage exhibit hard gritty and mucoid areas. and atypical mitosis.
l Microscopic examination: It reveals sarcoma cells and l Anaplastic sarcoma cells form osteoid matrix and
osteogenesis. bone directly which is found interspersed in the areas
l The sarcoma cells are undifferentiated mesenchymal of tumour cells.
stromal cells exhibiting marked pleomorphism and
SHORT NOTES
Q. 1. Sequestrum l Pyogenic or suppurative osteomyelitis is caused by
bacterial infections like Staphylococcus aureus, strepto-
Ans.
cocci, E. coli, Pseudomonas. It is the blood-borne infec-
l Sequestrum is seen in the pyogenic osteomyelitis. tion of the bone arising from various systemic diseases
l Sequestrum is erosion, thinning and infarction necrosis such as enteric fever, actinomycosis, mycetoma, syphi-
of a small or large fragment of cortex of bone due to lis, tuberculosis, brucellosis, etc.
suppuration and impaired blood supply to cortical bone. l The haematogenous pyogenic osteomyelitis occurs
l This devitalized sequestrum in the course of time may most commonly in long bones of infants and young
be reabsorbed or is sometimes sloughed to form a free children.
foreign body that on occasion dissects though the skin. l Clinical features of haematogenous pyogenic osteomy-
elitis generally include painful and tender limb, fever,

Q. 2. Microscopic picture of osteosarcoma malaise and leucocytosis.
l Pathological changes: The basic pathological changes in
Ans.
any stage of osteomyelitis are suppuration, ischaemic
Microscopic examination of osteosarcoma reveals sarcoma necrosis, healing by fibrosis and bony repair.
cells and osteogenesis. l Complications associated with pyogenic osteomyelitis
l The sarcoma cells are undifferentiated mesenchymal may be the followings:

stromal cells exhibiting marked pleomorphism and 1. Septicaemia
polymorphism. They also show hyperchromatism and 2. Acute bacterial and pathologic arthritis
atypical mitosis. 3. Secondary amyloidosis in long standing cases
l Anaplastic sarcoma cells form osteoid matrix and bone
directly which is found interspersed in the areas of Q. 5. Classify osteoporosis.

tumour cells. Ans.
l The sarcoma cells may also produce cartilage, fibrous
tissue or myxoid tissue. l Osteoporosis is a disease characterized by increased po-

rosity of the skeleton resulting from reduced bone mass.
Q. 3. Osteoclastoma l It may be localized or generalized and generalized
osteoporosis may be primary or secondary to a large
Ans.
variety of conditions.
l Osteoclastoma or giant cell tumour is a distinctive l Categories of generalized osteoporosis are as follows:
neoplasm of bone with uncertain histogenesis. 1. Primary

l It commonly occurs in patients between 20 and 40 years a. Postmenopausal
of age with no sex predilection. b. Senile
l Located mainly in the epiphysis of long bones close to 2. Secondary
the articular cartilage. a. Endocrine disorders, e.g. hypo- and hyperthyroid-
l Radiologically, it appears as a large, lobulated and ism, hyperparathyroidism, pituitary tumours
osteolytic lesion at the end of an expanded long bone b. Neoplasia, e.g. multiple myeloma, carcinomatosis
with characteristic soap bubble appearance. c. Gastrointestinal disorders, e.g. malnutrition, malab-
l On microscopic examination hallmark of osteoclastoma sorption, hepatic insufficiency, idiopathic
or giant cell tumour is presence of large number of l Disease drugs: Anticoagulants, anticonvulsants, cortico-
multinucleate osteoclast-like giant cells which are regu- steroids, alcohol

larly scattered throughout the stromal mononuclear cells. l Miscellaneous: Osteogenesis imperfecta, immobiliza-
l Giant cell tumours are best described as aggressive tion, homocystinuria, anaemia, etc.
lesions. l The most common forms of osteoporosis are senile and
postmenopausal. Senile osteoporosis affects all aging

Q. 4. Pyogenic osteomyelitis individuals while postmenopausal osteoporosis affects
only women after menopause.
Ans.
Topic 18
Skin
SHORT ESSAYS
Q. 1. Premalignant lesions the ear and the angle of the mouth. The common sites
are inner and outer canthus of the eye, eyelids, bridge of
Ans. A group of conditions which predispose to the subse-
the nose and around nasolabial fold.
quent development of cancer are known as premalignant
lesions.
Clinical Features
Some of the premalignant lesions of the skin are as
follows: l These tumours present as pearly papules, often contain-
1. Solar keratosis: Also called as actinic or senile kerato- ing prominent dilated subepidermal blood vessels.
sis, is induced by sun rays or ultraviolet rays. The condi- l The most common pattern is a nodulo-ulcerative in
tion is a forerunner of invasive squamous cell and/or which a slow-growing small nodule undergoes central
basal cell carcinoma. ulceration with pearly, rolled margins.
2. Bowen’s disease: It is also known as carcinoma in situ of l The tumour enlarges in size by burrowing and by
the entire epidermis often having solitary lesions on the destroying the tissues locally like a rodent and hence the
sun-exposed as well as sun-unexposed areas of the skin. name rodent ulcer.
3. Autosomal recessive disorders like xeroderma pigmen- l Some tumours contain melanin pigment and thus appear
tosum and albinism have increased predisposition to similar to melanocytic naevi or melanomas.
skin cancer.
4. Chronic scar: Burns, scars, scars of varicose ulcers, snake
bite scar, lupus vulgaris scar, etc. Squamous cell carcinoma
which develops in a scar tissue is called Marjolin’s ulcer. Two common patterns of microscopic appearance are seen.
5. Radiodermatitis: Increased incidence of skin cancer was
1. Multifocal growths originating from the epidermis. Pro-
found in persons who worked in radiology department.
liferation of basaloid cells is the most characteristic
6. Leukoplakia: About 10% of leukoplakia patients de-
feature. They may be seen arranged in solid masses,
velop oral cancer.
strands and nests of tumour cells.
Q. 2. Describe gross and microscopic picture of basal 2. Nodular lesions growing downwards into the dermis
cell carcinoma. as cords and islands of variable basophilic cells with hyper-
chromatic nuclei embedded in a fibrotic to mucinous matrix.
Ans. Basal cell carcinoma also known as rodent ulcer is
the most common malignant tumour worldwide.
Treatment
It is a locally invasive, slow-growing tumour of middle-
l These tumours are usually treated with complete local
aged individuals which rarely metastasizes.
excision.
l Basal cell carcinoma responds well to radiation. Radia-
Aetiology tion is indicated in elderly patients with extensive lesions;

dose: 4000–6000 cGy units.
l Prolonged exposure to strong sunlight
l Ultraviolet rays Q. 3. Squamous cell carcinoma (epithelioma)
l Arsenic used in skin ointments increases the risk of
basal cell carcinoma Ans.

l Dysregulation of the sonic hedgehog or PTCH pathway
Squamous cell carcinoma or epidermoid carcinoma com-
l Inherited defects in PTCH gene causing basal cell
prises 90% of all malignant oral cavity tumours and is second
carcinoma, Gorlin syndrome common malignant skin tumour after basal cell carcinoma.
l Mutations in p53 gene
Aetiology
Common Sites
l Exposure to sunlight especially UV light exposure
l Majority of lesions (90% cases) of basal cell carcinoma l Tobacco smoking and tobacco chewing, chronic alcohol
occurs on the face, usually above a line joining lobe of consumption
l Human papilloma virus infection particularly HPV 16, 2 . Cauliflower-like or proliferative growth
18 and 11 3. Nodular type: Firm, slow-growing submucosal nodule
l Exposure to radiation 4. Scirrhous type : Infiltration into deeper structures
l Chronic friction from ill-fitting dentures or jagged teeth
l Plummer-Vinson syndrome
l Immunosuppressed patients, particularly organ trans-

plant recipients 1. It ranges from well-differentiated keratinizing carci-
l p53 mutations noma to highly undifferentiated neoplasm.
2. Surrounding areas of lesion shows changes of epithelial
Clinical Features dysplasia.
3. The intraoral squamous cell carcinoma and carcinoma
l Squamous cell carcinoma has peak incidence in the age of lip are usually always well differentiated.
group of 40–45 years with definite male predilection.
l Invasive squamous cell carcinomas of the skin are dis-
covered while small and resectable and less than 5% of Mode of Spread
them exhibit metastases to regional nodes at diagnosis. 1. Local spread: Occurs by infiltration into surrounding
l Mucosal squamous cell carcinoma as oral, pharyngeal, tissues.
oesophageal, pulmonary, etc are generally much more 2. Lymphatic spread is the chief method of spread even
aggressive. though it occurs relatively late.
l The intraoral carcinomas are detected late and thus have 3. Blood spread is rare.
poor prognosis except papillary type. The carcinoma of
lip is easily visible and accessible and therefore have
good prognosis. Treatment
Treatment can be classified as follows:
Preferential Sites 1. Treatment of the primary: Treatment of the primary
squamous cell carcinoma is by surgery or radiotherapy,
l Sun-exposed sites of older individuals in advanced cases where both the above methods fail
l Lips (commonly lower lip) then chemotherapy is used.
l Tongue 2. Treatment of the secondaries: Treatment of the second-
l Anterior floor of mouth aries include following methods:
l Buccal mucosa in the region of alveolar lingual sulcus a. If mobile lymph nodes, then radical block dissection
l Palate should be performed.
b. In case of fixed lymph nodes, palliative radiotherapy
Pathological Types is given.
1. Ulcerative type: Most common type and is character-

ized by indurated ulcer and firm everted or rolled edges.
SHORT NOTES
Q. 1. Rodent ulcer l Common sites: Head and neck, lower extremity and
trunk. A few cases occur in upper extremities, genitalia,
Ans.
choroid of eye, etc.
l Basal cell carcinoma also known as rodent ulcer and is l Aetiopathogenesis
the most common malignant tumour worldwide. l Ultraviolet rays
l It is a locally invasive, slow-growing tumour of middle- l Genetic factors
aged individuals which rarely metastasizes. l Pre-existing moles
l As the tumour enlarges in size by burrowing and by l Xeroderma pigmentosa and albinism
destroying the tissues locally like a rodent, hence the l The clinical types of malignant melanoma are as follows:
name rodent ulcer. 1. Lentigo maligna melanoma: Occurs in old people

from Hutchinson’s melanotic freckle.
Q. 2. Malignant melanoma 2. Superficial spreading melanoma: Most common type
occurs on any part more in the trunk.
Ans.
3. Nodular melanoma: Most malignant invasive type
l Malignant melanoma is a tumour arising from pigment occurs more in the leg.
forming cells, i.e. melanoblasts which are derived from 4. Acral lentiginous melanoma: Located on palm, sole
the neural crest. and digits.
5. Amelanotic melanoma: It is rare and is difficult to The most common pattern is a nodulo-ulcerative
l
diagnose. in which a slow-growing small nodule undergoes

l Treatment: Surgery is the main modality of treatment central ulceration with pearly, rolled margins.
available for malignant melanoma. All other modalities l Microscopic examination
are only palliative and supportive.

Two common patterns of microscopic appearance are seen.
Q. 3. Basal cell carcinoma 1 . Multifocal growths
Ans. 2. Nodular lesions
l Treatment: These tumours are usually treated with
l Basal cell carcinoma also known as rodent ulcer is complete local excision. They also respond well to
the most common malignant tumour worldwide. It is a radiation.
locally invasive, slow-growing tumour of middle-aged
individuals which rarely metastasizes. Q. 4. Carcinoma in situ
l Aetiology: Prolonged exposure to strong sunlight, ultra-
Ans.
violet rays, arsenic and inherited defects in PTCH gene
causing basal cell carcinoma, Gorlin syndrome, etc. l Bowen’s disease is also a carcinoma in situ of the entire
l Common sites: Majority of lesions (90% cases) of basal epidermis often having solitary lesions on the sun-
cell carcinoma occurs on the face, usually above a line exposed as well as sun-unexposed area of the skin.
joining lobe of the ear and the angle of the mouth. l It may remain confined to the surface for many years.
l Clinical features l It occurs anywhere on the skin but is often found on the
l These tumours present as pearly papules, often trunks, buttocks and extremities.
containing prominent dilated subepidermal blood
vessels.
Topic 19
Nervous System
Q. 1. Immunization of rabies l The smaller doses were considered adequate as it is
believed to be more antigenic.
Ans. For immunization of rabies, antirabic vaccines used
are of two main categories as follows:
1. Neural vaccines Infant Brain Vaccines
2. Non-neural vaccines
l Were developed to reduce neurological complications,
as infant brain does not contain myelin (encephalito-
NEURAL VACCINES genic factor).
l Vaccines were prepared using infant mouse, rat or rabbit
Consist of suspension of nervous tissues of animals in-
brain. Neural vaccines are cheap but unsatisfactory
fected with fixed rabies virus.
for reasons like poor immunogenicity and are encephali-
togenic.
Semple Vaccine
l Most widely used vaccine developed by Semple at Cen- NON-NEURAL VACCINES
tral Research Institute, Kasauli.
l It is a 5% suspension of sheep brain infected with fixed
Egg Vaccines
virus and inactivated with phenol at 37°C, leaving no l Duck egg vaccine is a fixed virus grown in duck eggs
residual virus. and inactivated with BPL.
l Live attenuated chick embryo vaccines: Following two
Beta-propiolactone (BPL) Vaccine types were developed with the Flury strain:
1. Low egg passage (LEP) vaccine at 40–50 egg
l This is a modification of Semple vaccine, in which passage level, for immunization of dogs.
instead of phenol, the beta-propiolactone was used as 2. High egg passage (HEP) vaccine at 180 passage
inactivating agent. level for cattle and cats.
Tissue Culture Vaccines from serious side effects. High cost is the only disadvantage
of this vaccine.
The following cell culture vaccines are available in India
PCEC vaccine containing BPL inactivated Flury-LEP
and all of them are equally safe and effective:
strain is now widely used. PVC vaccine is under study.
1. Human diploid cell (HDC) vaccine
2. Purified chick embryo cell culture (PCEC) vaccine
3. Purified vero cell (PVC) vaccine Subunit Vaccine
HDC vaccine is a purified and concentrated preparation The glycoprotein subunit on virus surface, which is
of fixed rabies virus (Pitman-Moore strain) grown on the protective antigen, has been cloned and recombi-
human diploid cells (WI 38 or MRC 5) and inactivated with nant vaccines are produced. They are in experimental
BPL or tri-n-butyl phosphate. It is highly antigenic and free stages.
Topic 20
Miscellaneous
SHORT ESSAY
Q. 1. Mention the diseases transmitted through blood 4. Syphilis
transfusion and screening tests. 5. Malaria
6. Toxoplasmosis, etc.
Ans.
l The usual screening tests performed before blood trans-
l The common diseases transmitted through blood transfusion are as follows:
fusion are as follows: 1. ELISA for HIV (type 1 and 2) and hepatitis B
1. AIDS 2. VDRL for syphilis
2. Hepatitis B and C 3. PS for malarial parasites
3. CMV
SHORT NOTES
Q. 1. Anticoagulants used in blood bank Q. 2. Specific gravity of urine
Ans. Ans.
l Anticoagulants are substances which prevent or post- l The normal specific gravity of urine is 1.012–1.024.
pone coagulation of blood. l Specific gravity of urine is increased in the following:
l They are of following types: 1. All cases of oliguria like acute glomerulonephritis,
1. Natural anticoagulants shock, renal ischaemia, toxic nephropathy, bilateral
2. Anticoagulants used in blood banks hydronephrosis, urinary flow obstruction, etc.
3. Anticoagulants used in laboratory 2. Excessive sweating
4. Therapeutic anticoagulants 3. Glycosuria
l Common anticoagulants used in blood bank are as 4. Albuminuria
follows: l Decreased specific gravity is seen in the following:
1. Acid citrate dextrose (ACD) 1. Chronic glomerulonephritis

2. Citrate phosphate dextrose (CPD) 2. All cases of polyuria like diuretic therapy, Addison’s
disease, hyperparathyroidism except diabetes mel-
They are used to store blood in the blood banks. The litus
citrates combine with Ca21 in blood to form calcium 3. Benign nephrosclerosis, etc.
citrate complex and decreases ionic calcium levels, thus
preventing coagulation.

Cell injury, cell death and adaptations
Cell injury
l Cell injury can be of two types:
A. Reversible
B. Irreversible
A. Reversible cell injury
Changes seen in reversible cell injury are:
i. Decreased cellular ATP
ii. Reduced intracellular pH
iii. Damage to plasma membrane sodium pump
iv. Reduced protein synthesis
v. Functional disturbances
vi. Ultra structural changes like: Detachment of membrane-bound polyribosomes from the surface of rough
endoplasmic reticulum, segregation of granular and fibrillar components of nucleolus and reduced syn-
thesis of ribosomal RNA etc.
B. Irreversible cell injury
l It includes necrosis and apoptosis.
l Necrosis is cell death due to denaturation of proteins and enzymatic digestion of organelles and other
cytotoxic components released by the cell.
Necrosis is of following types:
Type Characters Occurs in

Coagulation l Most common type Commonly affected organs are:
l
necrosis l Denaturation of cytoplasmic protein with preservation of the frame- l Myocardium

work of the coagulated cell l Kidney
l Microscopic findings: conversion of normal cells into ‘tomb-stones’ l Liver & spleen
Liquefaction l Autolysis and heterolysis prevail over protein denaturation and is Abscess cavity
l
necrosis due to degradation of tissue by hydrolytic enzymes Infarct of brain

l
l The necrotic area is soft and filled with fluid

l Commonly due to ischaemic injury and bacterial and fungal infection
Caseous ne- l Combines features of both coagulative and liquefactive necrosis and Usually found in the centre of
l
crosis appears as soft, friable, cheesy material foci of tuberculous infections

l Combines features of both coagulative and liquefactive necrosis
Fat necrosis l Due to action of lipases that catalyze enzymatic release of fatty ac- Seen in acute pancreatic ne-
l
ids, which then complex with Ca21 to form Ca21 soaps crosis and traumatic fat necro-
l Special form of cell death occurring at two anatomically different sis commonly in breasts
locations but morphologically similar lesions
Apoptosis
l A programmed cell death through activation of an internal suicide programme to eliminate unwanted
cells selectively with minimal disturbance to surrounding cells
E.g. Cell death during embryogenesis, cell death in tumours, cell death in cytotoxic T cells;
phagocytosis by macrophages
Gangrene
l Gangrene is a form of necrosis of tissue with super added putrefaction. It is usually coagulative due to
ischaemia.
Types of gangrene are:

i. Dry gangrene
ii. Wet gangrene
iii. Gas gangrene
Feature Dry Gangrene Wet Gangrene Gas Gangrene

Most common Limbs (distal part), toes and feet Moist tissues such as mouth, Bacteria enter through contaminated
location bowel, lungs, cervix, vulva, wound in muscle or as a complication
vagina etc. of operation of colon
Mechanism l Atherosclerosis and arterial More commonly venous Wet gangrene caused by gas forming
occlusion in old persons obstruction, less often arterial clostridia
l TAO (Burger’s disease) occlusion
l Trauma
Clinically Organ looks dry, shrunken and Involved part moist, soft, swol- Swollen, oedematous, painful and
black. len, writhen and dark within due to accumulation of gas
bubbles in the tissues
Putrefaction Limited due to very little blood Marked due to stuffing of organ Marked
with blood
Line of demar- Present at the junction between No clear line of demarcation No clear line of demarcation
cation healthy and gangrenous part between gangrenous segment
and viable bowel
Presence of Bacteria fail to survive. Numerous bacteria are present. Large number of Gram-positive bacilli
bacteria may be found.
Microscopic l Necrosis with smudging of the l Coagulative necrosis with l Coagulative necrosis with
appearance tissue, line of separation con- stuffing of blood liquefaction
sists of inflammatory granula-
tion tissue
Prognosis Usually better due to little septi- Generally poor (due to profound Generally poor
caemia toxaemia)
Calcification
l Pathologic calcification is of two types:
i. Dystrophic calcification
ii. Metastatic calcification
Feature Dystrophic Calcification Metastatic Calcification

Type Deposits of calcium salts in dead and degen- Deposits of calcium salts in normal tissues
erated tissues
Calcium metabolism Normal Deranged
Serum calcium level Normal Hypercalcaemia
Causes Necrosis, infarcts, thrombi, haematomas, dead Hyperparathyroidism (due to adenoma, hyperplasia, CRF),
parasites, old scars, atheromas, Monckeberg’s bony destructive lesions (e.g., myeloma, metastatic carci-
sclerosis, certain tumours, cysts, calcinosis noma), prolonged immobilization, hypervitaminosis D,
cutis Milk-alkali syndrome, hypercalcaemia of infancy
Pathogenesis Akin to formation of normal hydroxyapatite Favoured by relatively high pH (alkaline) at certain sites,
involucrin phases of initiation and propaga- e.g. in lungs, stomach, blood vessels, and cornea
tion.
Cellular adaptations
Response of cells to physiologic stresses or pathologic stimuli to survive is altered environment.
Adaptation Pathogenesis Causes Examples

Hyperplasia, increase in the l Due to action of growth factors (hepatocytes growth l Hormonal hyperplasia
number of cells in an organ or factor, TGFa, EFG), cytokines, interleukins l Compensatory hyperplasia.
tissue l Pathologic: excessive hormonal stimulation
Hypertrophy: increase in the l Increased functional demand l Hypertrophy of striated
number of organelles and size l Hormonal stimulation E.g stretch, growth factors muscles in builders
of cells l Uterine hypertrophy
Atrophy: decrease in cell size l Diminution of blood supply l Senile atrophy
or number, resulting in shrink- l Reduced functional activity l Atrophy of skeletal muscle
age of affected tissues and l Interrupted nerve supply
organs l Loss of endocrine stimulation
l Pressure
Metaplasia: a reversible l Occurs from genetic reprogramming of stem cells, l Squamous metaplasia of
change in which one adult cell that are brought about by changes in signals gener- respiratory epithelium
type is replaced by another ated by mixtures of cytokines, growth factors, ECM
components in the cell environment
Inflammation
l Inflammation is defined as the local response of living mammalian tissues to injury due to any agent.
l Cardinal signs of inflammation are rubor (redness), tumour (swelling), colour (heat), dolor (pain) and
functio laesa (loss of function).

l Acute inflammation involves vascular events and cellular events.
l Sequence of events in acute inflammation are:
A. Vascular events:
a. Haemodynamic changes:
i. Transient vasoconstriction of arterioles due to reflex spasm
ii. Persistent progressive vasodilatation causing increased blood flow responsible for redness and
warmth
iii. Elevation of local hydrostatic pressure resulting in transudation of fluid into extracellular space
responsible for swelling
iv. Slowing or stasis of microcirculation
v. Leucocytic margination and emigration
b. Leucocytic margination: peripheral orientation of leucocytes in the blood vessels
c. Emigration: leucocytes migrate through the gaps between the endothelial cells into the extravascular
space.
B. Cellular event
l Exudation of leucocytes:
i. Changes in the formed elements of blood–margination and pavementing

ii. Adhesion or rolling–adherence of leucocytes to the vascular endothelium is brought about by
four types of distinct adhesion molecules: selectins, addressins, integrins, and Ig superfamily adhesion
molecule
iii. Emigration or transmigration–here emigration and diapedesis take place.
iv. Chemotaxis
l Diapedesis is a passive phenomenon in which RBCs are being forced out either by raised hydrostatic
pressure or RBCs may escape through the endothelial defects left after emigration of leucocytes.
Chemical mediators of acute inflammation
I. Cell-derived mediators
i. Vasoactive amines
a. Histamine
b. 5-Hydroxytryptamine
ii. Arachidonic acid metabolites
a. Metabolites via COX pathway (prostaglandins, thromboxane A2, and prostacyclin)
b. Metabolites via LOX pathway (5-HETE, leukotrienes)
iii. Lysosomal components
iv. Platelet activating factor
v. Cytokines: (IL- l, TNF-a, TNF-b, IF-g, Chemokines)
vi. Nitric oxide and oxygen metabolites
II. Plasma-derived mediators (Plasma proteases):
These are products of:
i. The kinin system
ii. The clotting system
iii. The fibrinolytic system
iv. The complement system
Granulomatous inflammation
l It is a distinctive chronic inflammatory reaction in which the predominant cell type is an active macro-
phage with a modified epithelium like appearance and is characterized by granuloma.
Sequence of events in granulomatous inflammation are:
Injury or weak acute inflammatory response or chronic inflammation

(e.g. malignant tumour ) or persistence of injurious agent results in
T-cell mediated response
T-cell mediated immune response
Activation of T-cells monocyte
Chemotactic factor growth factor
Recruitment and proliferation of macrophages
Transformation to epithelioid cells
Epithelioid cells condense to multinucleate giant cells resulting in
Granuloma
Some Granulomatous Conditions
Bacterial Condition Causative Organism

Tuberculosis Mycobacterium tuberculosis
Leprosy Mycobacterium leprae
Syphilis Treponema pallidum
Granuloma inguinale (Donovanosis) C. donovani
Brucellosis (Mediterranean fever) Brucella abortis
Cat scratch disease Coccobacillus
Tularaemia (Rabbit fever) Francisella (Pasteurella tularensis)
Glanders Actinobacillus mallei
Actinomycosis Actinomycosis israelii
The differences between transudate and exudate are as follows:
Transudate Exudate
Noninflammatory oedema Inflammatory oedema
Protein content less than 3 gm/l00 mL High protein content greater than 4 gm/100mL
No tendency to coagulate Shows tendency for coagulation
Specific gravity less than 1.015 Specific gravity more than 1.018
Mesothelial cells are found, e.g. oedema in nephrotic Inflammatory cells are found e.g. suppurative lesions.
syndrome and congestive cardiac failure.
Thrombosis and Embolism

l Virchow described three primary events which predispose to thrombus formation (Virchow’s triad):
i. Endothelial injury
ii. Alteration in blood flow
iii. Hypercoagulability of blood
l Distinguishing features of arterial and venous thrombi are as follows:
Characteristics Arterial Thrombi Venous Thrombi

Blood flow Formed in rapidly flowing blood of Formed in slow moving blood in veins
arteries and heart
Sites Common in coronary, cerebral, Common in superficial varicose veins, deep
iliac, and femoral arteries leg veins, popliteal, femoral and iliac veins
Thrombogenesis Formed following endothelial cell Formed following venous stasis, e.g. in
injury, e.g. atherosclerosis abdominal operations, child birth etc.
Development Usually mural, not occluding the Usually occlusive; take the cast of vessel
lumen completely; may propagate. in which formed; may propagate in both
directions.
Macroscopic features Grey-white, friable with lines of Red-blue with fibrin strands and lines of
Zahn on surface Zahn
Microscopic features Distinct lines of Zahn composed of Lines of Zahn with more abundant red cells
platelets, fibrin with entangled red
and white blood cells
Effects Ischaemia leading to infarcts, e.g. Thromboembolism, oedema, skin ulcers,

infarcts of heart, brain etc. poor wound healing
Types of haemorrhage
Primary Immediately after injury, fresh injury Due to rupture of blood vessel
Secondary Approximately one week after being injured Bleeding from wound due to infection
Reactionary 24 hours to 48 hours Due to dislodgement of sutures or clots
Benign and malignant tumours
Characteristics Benign Malignant

Macroscopic features
Boundaries Encapsulated or well circumscribed Poorly circumscribed and irregular
Surrounding tissue Often compressed Usually invaded
Size Usually small Often larger
Secondary changes Occur less often Occur more often
Microscopic features Resembles tissue of origin closely Poor resemblance to tissue of origin
Function Usually well maintained May be retained, lost or become abnormal.
Growth rate Usually slow Usually rapid
Local invasion Often compresses the surrounding tissues Usually infiltrates and invades adjacent tissue
without invading or infiltrating them
Metastasis Absent Frequently present
Terminology related to benign and malignant tumours
Neoplasia A mass of tissue formed as a result of abnormal excessive, uncoordinated and purposeless
proliferation of cells
Dysplasia Disorder in cellular structure and metabolism
Metaplasia Replacement of new cell type in place of old one
Anaplasia Lack of differentiation
Hamartoma Abnormal proliferation of tissues native to that area
Choristoma Ectopic rests of normal tissue
Teratoma Tumour of a tissue, which has representation from more than one germ layer
Sarcoma Malignant tumour of connective tissue
Carcinoma Malignant tumour of epithelial tissue

Some of the most commonly occurring tumours
Most common malignancy in females Breast cancer

Most common malignancy in females in India Carcinoma of cervix
Most common malignancy in males Lung cancer
Most common malignancy in males in India Oral cancer
Most commonly occurring skin cancer Basal cell carcinoma followed by squamous cell
and malignant melanoma
Most common oral cancer Squamous cell carcinoma
Most common benign tumour of bone Osteochondroma
Most common bone tumour Metastatic carcinoma
Most common malignant bone tumour in children Ewing’s sarcoma
Most common malignant salivary gland tumour Cylindroma
Most common malignant salivary gland tumour in children Mucoepidermoid carcinoma
Most common salivary gland tumour Pleomorphic adenoma (benign tumour)
Various skin lesions
l Macule Flat circumscribed discoloured area of any size

l Papule Elevated solid area of less than 5 mm
l Pustule Discrete pus filled raised area
l Vesicle Fluid filled raised area of less than 5 mm
l Bulla Fluid filled raised area of more than 5 mm
l Blister Any fluid filled lesion like bulla or vesicle
l Scales Dry horny plate-like excrescence
Section III
Microbiology
PART I: GENERAL MICROBIOLOGY

Topic 1 Historical Introduction 241
Topic 2 Morphology and Physiology of Bacteria 242
Topic 3 Sterilization and Disinfection 248
Topic 4 Culture Media 256
Topic 5 Culture Methods 260
Topic 6 Identification of Bacteria and Bacterial Taxonomy 264
Topic 7 Bacterial Genetics 264
Topic 8 Infection 267
Topic 9 Immunity 269
Topic 10 Antigens and Antibodies: Immunoglobulins,
Antigen–Antibody Reactions 273
Topic 11 Complement Systems 277
Topic 12 Structure and Function of Immune System,
Immune Response and Immunodeficiency Diseases 277
Topic 13 Hypersensitivity 280
Topic 14 Autoimmunity, Immunology of Transplantation
and Malignancy 285
PART II: SYSTEMIC BACTERIOLOGY

Topic 16 Staphylococcus, Streptococcus, Pneumococcus
and Neisseria 288
Topic 17 Corynebacterium 297
Topic 18 Mycobacterium (Tuberculosis, Atypical Mycobacteria
and Mycobacterium Leprae) 301
Topic 19 Clostridium 304
Topic 20 Nonsporing Anaerobes 308
Topic 21 Enterobacteriaceae (Coliforms: Proteus, Shigella and

Salmonella) 309
Topic 22 Vibrio 312
Topic 23 Pseudomonas, Yersinia, Pasteurella, Francisella,
Haemophilus, Bordetella and Brucella 314
Topic 24 Spirochetes: Treponema Pallidum, Borrelia Vincentii 315
Topic 25 Actinomycetes, Rickettsiaceae and Chlamydiae 319
PART III: MEDICAL VIROLOGY

Topic 27 General Properties of Viruses 321
Topic 28 Bacteriophage: Structure and Significance 324
Topic 29 Poxviruses 324
Topic 30 Herpes Viruses 324
Topic 31 Adenoviruses and Picornaviruses 326
Topic 32 Orthomyxo and Paramyxo Viruses 327
Topic 33 Arbo and Rhabdoviruses 328
Topic 34 Hepatitis Viruses 330
Topic 35 Oncogenic Viruses 332
Topic 36 Human Immunodeficiency Virus (HIV)/AIDS 333
PART IV: SYSTEMIC MYCOLOGY

Topic 37 Fungal Diseases 336
PART V: MEDICAL PARASITOLOGY

Topic 38 Protozoans 339
Topic 39 Helminthes 347
PART VI: DENTAL MICROBIOLOGY

Topic 40 Dental Microbiology 350
Section III
Microbiology
Part I
General Microbiology
Topic 1
Historical Introduction
SHORT NOTES
Q. 1. Louis Pasteur Q. 2. Robert Koch
Or, Or,
Louis Pasteur’s contributions to microbiology Koch’s postulates
Ans. Ans.
l Louis Pasteur (1822–1895) was a French chemist. He l Robert Koch (1843–1910) was a German practitioner
propounded microbial theory of fermentation. who is known as the father of medical microbiology.
l It was he who coined the term vaccine. l His contributions to the field of microbiology are as
l The various contributions by Pasteur in 30 years follows:

(1860–1890) of long, brilliant and active research are 1. He introduced staining techniques for bacteria.
as follows: 2. He described various methods of obtaining bacteria
1. Microbial theory of fermentation: Conclusive evidence in pure culture using solid media.
of role of microorganisms in disease production 3. He isolated first bacteria (Bacillus anthracis) in pure
2. Development of methods and technique for cultivation culture.
of microorganisms 4. He discovered the bacillus of tuberculosis and the
3. Studies on silkworm disease, anthrax, chicken cholera cholera vibrio.
and hydrophobia 5. He demonstrated Koch phenomenon, which is a hyper-
4. Control of diseases of silkworm sensitivity reaction seen in a guinea pig already infected
5. Principles and practice of sterilization: Introduction with the tuberculous bacilli when the tubercle bacillus
of sterilization technique and development of steam or its protein is injected into it.
sterilizer, hot air oven and autoclave 6. He proposed the Koch postulates, which are the criteria
6. Development of live attenuated vaccine against laid down by Koch.
a. chicken cholera, According to these a microorganism can be accepted as the
b. anthrax and causative agent of an infectious disease only if the following
c. rabies virus. conditions are satisfied:
These works of Pasteur were acclaimed throughout the a. The bacterium should be constantly associated with
world. In 1889, the Pasteur Institute, Paris was built by the lesions of the disease.
public contribution and Louis Pasteur served as its first b. It should be possible to isolate the bacterium in pure
director. culture from the lesions.
241
c. Inoculation of such pure culture into suitable laboratory l He won Nobel Prize for medicine in 1905 for investiga-
animals should reproduce the lesions of the disease. tion and discoveries related to tuberculosis.
d. It should be possible to reisolate the bacterium in
pure culture from the lesions produced in the
experimental animals.
Topic 2
Morphology and Physiology of Bacteria

Q. 1. Describe the morphology of bacterial cell with a 4. Chemically the cell wall is composed of mucopeptide
neat labelled diagram and explain briefly. (peptidoglycan or murein) scaffolding formed by
N-acetyl-glucosamine and N-acetyl-muramic acid mol-
Or
ecules alternating in chains, which are cross-linked by
Describe the various structures of a bacterial cell with a peptide chains.
neat diagram. 5. The interstices of this scaffolding contain other chemicals
varying in different species.
Ans. Bacteria are unicellular prokaryotic microorganisms.
6. The mucopeptide component of cell wall possesses target
The morphology of ideal bacterial cell is as follows (Fig. 2.1): sites for antibodies, lysozymes and bacteriophages.
1. The outer layer or cell envelope of bacteria consists of 7. The chemical structure of cell wall of Gram-positive and
two components: (a) a rigid cell wall and (b) cytoplas- Gram-negative bacteria differs considerably. In general
mic membrane or plasma membrane. the cell wall of Gram-positive bacteria has simpler
chemical nature than that of Gram-negative bacteria.
Capsule
Mesosomes
Ribosomes
Gram-Positive Bacterial Cell Wall
Cell wall
Flagellum
Cytoplasmic a. The peptidoglycan layer is much thicker (16–80 nm)
membrane
than the Gram-negative cell wall (2 nm).
b. The periplasmic space is absent and the peptidoglycan
Pili DNA Granular
inclusion
is closely associated with the cytoplasmic membrane.
c. Special components: Most Gram-positive cell walls
FIGURE 2.1 Structure of bacterial cell.
contain significant amounts of teichoic and teichuronic
2. The cell envelope encloses the protoplasm comprising of acids. The teichoic acids constitute major surface anti-
cytoplasm, cytoplasmic inclusions or organelles such as nu- gens of Gram-positive bacteria.
clear body, ribosomes, granules, vacuoles, mesosomes, etc.
3. In addition to these essential structural components,
some bacteria also possess some additional appendages
Cell Wall of a Gram-Negative Bacteria
like capsule or loose slime layer, flagella, fimbriae, etc. It is complex and contains three components outside the
peptidoglycan layer.
a. Lipoprotein layer: It connects the outer membrane to
CELL WALL
peptidoglycans.
1. Bacterial cell wall is about 10–25 nm in thickness and b. Outer membrane: It is a phospholipid bilayer and con-
accounts for the shape of the bacterial cell and confers tains various proteins known as outer membrane proteins.
on its rigidity and ductility. Among these are porins which form transmembrane
2. It is a tough and rigid structure surrounding the bacte- pores that serve as diffusion channels for small mole-
rium like a shell. The cell wall carries bacterial antigens cules. Hydrophilic molecules are transported through
that are important in virulence and immunity. these porins. They also serve as specific receptors for
3. It may be demonstrated by plasmolysis, microdissection, some bacteriophages.
reaction with specific antibody, mechanical rupture of c. Lipopolysaccharides (LPS): They are present on the
the cell, differential staining procedures or by electron cell walls of Gram-negative bacteria and account for
microscopy. their endotoxic activity and the O antigen specificity.
Section | III Microbiology 243
The LPS consists of three regions as follows: 3. Function: They are the principal sites of respiratory
1. Region I is the polysaccharide portion determining the enzymes and the site of synthesis of cross wall septa.
O antigen specificity.
2. Region II is the core polysaccharide. INTRACYTOPLASMIC INCLUSIONS
3. Region III is the glycolipid portion (lipid A), which is
responsible for the endotoxic activities. 1. These are of various types, the chief types of which are
volutin, polysaccharides, lipids and crystals.
2. Volutin granules or metachromatic or Babes-Ernst gran-
Periplasmic Space ules are highly refractive, strongly basophilic bodies
1. It is the space in between the inner and outer mem- containing of polymetaphosphate and are characteristi-
branes and contains a number of important proteins and cally present in diphtheria bacilli.
oligosaccharides. 3. Special staining techniques like Albert’s or Neisser’s
demonstrate the granules more clearly.
4. Polysaccharide granules are demonstrated by iodine and
CYTOPLASMIC MEMBRANE (PLASMA
lipid inclusions with fat soluble dyes like Sudan Black.
MEMBRANES) 5. Function: They act as the source of stored energy.
1. Cytoplasmic membrane is a thin (5–10 nm) layer lining
the inner surface of the cell wall and separating it from VACUOLES
the cytoplasm. It consists of three layers constituting a
1. These are fluid containing cavities separated from the
‘unit membrane’ structure.
cytoplasm by a membrane.
2. The central layer is of protein molecules and on its
either side there are lipid molecules. It also contains
small amounts of carbohydrates. NUCLEUS
1. They appear as oval or elongated bodies generally one
Functions of Cell Membrane per cell. The bacterial nucleus is a thin fibre of double-
a. It acts as a semipermeable membrane controlling the inflow stranded DNA helix tightly coiled in the form of a circle
and outflow of metabolites to and from the protoplasm. inside the cytoplasm.
b. This flow is not dependant on molecular size but 2. Bacterial nuclei have no nuclear membrane or nucleolus.
in many cases depends upon the presence of specific 3. Some bacteria may possess extranuclear genetic elements
enzymes known as permeases. consisting of DNA, which are called plasmids or episomes.
c. It also contains cytochrome oxides enzymes of TCA 4. They are not important for life of the bacteria but confer
cycles and polymerizing enzymes necessary for synthe- certain properties like toxigenicity and drug resistance
sis of cell wall. on the bacteria.
CYTOPLASM SLIME LAYER AND CAPSULE

1. It is a colloidal system of a variety of organic and inor- 1. Many bacteria secrete a viscid material around the cell sur-
ganic solutes in a viscous watery solution. face. When this secretion is organized into a sharply defined
2. It does not exhibit internal motility or protoplasmic stream- structure, it is called as capsule, e.g. Pneumococcus and
ing and lacks endoplasmic reticulum or mitochondria. when it is loose undemarcated secretion, it is called as slime
3. Function: It contains ribosomes, mesosomes, inclusions layer, e.g. Leuconostoc.
and vacuoles. 2. Capsules are usually 98% water and 2% solid.
3. Capsules too thin to be demonstrated under microscope
are called as microcapsules, e.g. Haemophilus influenzae.
RIBOSOMES 4. This amorphous viscid material is generally but not in-
1. Ribosomes are slightly smaller (70 S) and are seen inte- variably polysaccharide or polypeptide or hyaluronic
grated in the linear strands of mRNA to form polysomes. acid in nature.
2. Function: They are the centres for protein synthesis. 5. Some bacteria may have both the capsule and slime
layer, e.g. Streptococcus salivarius.
MESOSOMES (CHONDROIDS) 6. Demonstration (Gram stain): Slime and capsule have
little affinity for basic dyes and is not visible in gram-
1. These are vesicular, convoluted, multilaminated struc- stained smears. They can be demonstrated by special
tures formed as invaginations of the plasma membrane staining technique employing copper salts.
into the cytoplasm. 7. Capsule may be readily demonstrated by negative strain-
2. They are often seen in relation to the nuclear body and ing in wet films with India ink where they are seen as clear
are more prominent in Gram-positive bacteria. haloes around the bacteria against a black background.
8. Capsular material is antigenic and may be demonstrated i. filament,

by serological methods. When a suspension of a capsu- ii. hook and
lated bacterium is mixed with specific anticapsular se- iii. basal body.
rum and examined under microscope the capsule be- d. The filament is the external portion outside the cell
comes very prominent and appears swollen due to an wall attached to the hook at the cell surface. The
increase in its refractivity. This is known as capsule hook and basal body portion is embedded in the cell
swelling or Quellung reaction. envelope.
l Function 9. Functions: Flagella are the organs of the locomotion in
a. Capsule protects the bacteria from deleterious agents the bacteria.
such as lytic agents and bacteriophages. 1 0. They are best developed in freshly isolated strains
b. It contributes to the bacterial virulence by inhibiting and in liquid cultures and tend to disappear following
phagocytosis. subcultures on solid media.
c. Loss of capsule renders certain bacteria virulent.
d. Capsular antigen is hapten in nature and specific for
FIMBRIAE OR PILI
bacteria. Thus, it also helps in typing of bacteria.
1. These are very fine, thin, hair-like surface appendages
projecting from the cell surface of some Gram-negative
FLAGELLA bacilli as straight filaments.
1. Motile bacteria possess organs of locomotion known as 2. Fimbriae are antigenic.
flagella, which are filamentous, cytoplasmic append- 3. Sex pili are special type of fimbriae, which are longer,
ages protruding from the bacterial cell wall. fewer in number.
2. These are unbranched, long, sinuous thread-like struc- 4. They are found on male bacteria and help in the attach-
tures composed entirely of a protein flagellin. ment of those bacteria to female bacteria, forming hollow
3. They are 3–20 mm long and are of uniform diameter conjugation tubes through which it is assumed genetic
(0.01–0.013 mm) and terminate in a square tip. material is transferred.
4. The number of flagella varies from 10 to 20 per cell 5. Types: There are three main types of fimbriae: Common
depending on the species. pili, sex or F (fertility) pili and COL I (colicin) pili.
5. The wavelength and thickness of the flagella is charac- 6. Certain fimbriated bacteria (Escherichia, Klebsiella) ag-
teristic of a species of a bacteria but some may have glutinate erythrocytes of guinea pigs, fowls, horses, pigs
flagella of two different wavelengths. strongly, human and sheep cells weakly and ox cells
6. Flagella of different genera of bacteria have same chem- scarcely at all. This haemagglutination provides a sim-
ical composition but they are different antigenically. ple test for detecting the presence of fimbriae.
7. Flagella antigens induce production of specific antibod- 7. Functions
ies in high titre but they are not protective, they only a. Fimbriae function as organs of adhesion helping the
help in serodiagnosis. bacteria to adhere firmly on cells.
8. Parts of flagella b. Sex pili functions as channels for transfer of genetic
a. Each flagellum consists of three distinct parts as material.
SHORT ESSAYS
Q. 1. Growth curve and metabolic intermediates are built up in adequate quan-
tities for multiplication to proceed.
Ans.
l The duration of the lag phase varies with the species,
l A bacterial growth curve (Fig. 2.2) is obtained by plot- size of inoculum, nature of culture medium and environ-
ting the bacterial counts made at intervals after inocula- mental factors such as temperature.
tion and plotted in relation to time. l The bacteria have the maximum size towards the end of
l The growth curve shows following four main phases: this phase.
Lag Phase Log (Logarithmic) or Exponential Phase

l Immediately following the seeding of a culture medium, l The cells start dividing following the lag phase and their
there is no appreciable increase in the numbers though numbers increase exponentially or by geometric pro-
there may be an increase in the size of the cells. gression with time.
l This initial period is the time required for adaptation to the l If the logarithm of viable count is plotted against time it
new environment during which the necessary enzymes gives a straight line.
Total cell count Procedure

Log Viable cell count The Gram staining procedure involves four basic steps.
phase 1. The primary staining with a para rosaniline dye such as
Number of bacteria
Stationary crystal violet, methyl violet or gentian violet

Lag phase Phase of decline 2. Application of a dilute solution of iodine
phase 3. Decolourization with an organic solvent such as etha-
nol, acetone or aniline
4. Counterstaining with a dye of contrasting colour such as
carbol fuschin, safranine or neutral red
The exact mechanism of the gram reaction is not under-
Time
stood.
FIGURE 2.2 Bacterial growth curve. a. The bacteria are first stained with the basic dye crys-
l The cells formed are typical, smaller and stain uniformly. tal violet. Both Gram-positive and Gram-negative
bacteria become directly stained and appear purple
after this step.
Stationary Phase b. The bacteria are then treated with Gram’s iodine
l Cell division stops after a varying period of exponential solution. This allows the stain to be retained better by
growth due to depletion of nutrients and accumulation forming an insoluble crystal violet-iodine complex.
of toxic products. Both Gram-positive and Gram-negative bacteria
l The number of progeny cells formed is just enough to
remain purple after this step.
replace the number of cells that die. c. Gram’s decolourizer, a mixture of ethyl alcohol and
l The viable count remains stationary or constant as an
acetone, is then added. This is the differential step.
equilibrium exists between the dying cells and the Gram-positive bacteria retain the crystal violet io-
newly formed cells. dine complex while Gram-negative are decolourized.
l In this phase, cells are frequently gram variable and
Finally, the counterstain, i.e. safranin is applied.
show irregular staining due to the presence of intracel- d. Since the Gram-positive bacteria are already stained
lular storage granules. Sporulation occurs at this stage. purple, they are not affected by the counterstain.
Gram-negative bacteria, that are now colourless, be-
come directly stained by the safranin. Thus, Gram-
Phase of Decline positive appear purple and Gram-negative appear pink.
l This is the phase where the bacterial population de- The Gram staining is an essential procedure used in the
creases due to the death of cells. identification of bacteria and is frequently the only method
l Besides nutritional exhaustion and toxic accumulation,
required for studying their morphology.
cell death may also be caused by autolytic enzymes.
Q. 3. Bacterial spore
l When total count of bacteria is plotted, it parallels the
viable count up to the stationary phase but it continues Ans.

steadily without any phase of decline.
l Involution forms of bacteria are common in this phase.
l Spores are highly resistant resting stage of the bacteria
l The various stages of growth curve are associated with
formed in unfavourable environmental conditions.
l Each bacterium forms one spore which on germination
morphological and physiological alterations of the cells.
forms a single vegetative cell.
Q. 2. Gram stain
Example of Spore Forming Bacteria
Ans.
1 . Gram-positive bacilli: Genus Bacillus and Clostridia
l The Gram stain is the most widely used differential 2. Other bacteria: Sporosarcina, Coxiella burnetii.
staining procedure in bacteriology.
l It is called a differential stain since it differentiates be-
Structure of a Bacterial Spore (Fig. 2.3)
tween Gram-positive and Gram-negative bacteria.
l Bacteria that stain purple with the Gram staining proce- l The fully formed spore has the nuclear body as its core is
dure are termed Gram-positive; those that stain pink are surrounded by the spore wall, a delicate membrane from
said to be Gram-negative. which the cell wall of the future vegetative bacterium will
l Gram-positive and Gram-negative bacteria stain differ- develop.
ently because of fundamental differences in the struc- l Outside this is the thick spore cortex, which in turn is
ture of their cell walls. enclosed by a multilayered tough spore coat.

1. Cocci (kokkos meaning berry): Spherical or oval cells

Exosporium
example: The cocci may be arranged in pairs (diplo-
Spore coat cocci), chains (streptococci), groups of fours (tet-
rads) or eight (sarcina) or as grape-like clusters
(staphylococci).
Core 2. Bacilli (baculus meaning rod) are rod-shaped cells.
Spore membrane For example: Streptobacillus corynebacteria
a. Vibrios are comma shaped, curved rods and their
Spore cortex name is derived from their characteristic motility.
b. Spirilla are rigid spiral forms.
c. Spirochaetes (speira meaning coil and chaite meaning
hair) are flexuous spiral forms.
d. Actinomycetes are branching filamentous bacteria,
FIGURE 2.3 Structure of bacterial spore. they are named so due to their resemblance to the
radiating rays of sun.
l Some spores have an additional outer covering called
exosporium which may have distinctive ridges and Q. 5. Bacterial capsule
grooves. Ans.
l Shape and position of spore: Young spores are seen at-
tached to the parent cells. The shape and position of the 1. Many bacteria secrete a viscid material around the cell
spore and its size relative to the parent cell are species surface. When this secretion is organized into a sharply
characteristics. defined structure it is called as capsule, e.g. Pneumo-
l The spores may be coccus and when it is loose undemarcated secretion, it
1. central (equatorial), subterminal or terminal, is called as slime layer, e.g. Leuconostoc.
2. bulging or not bulging and 2. Capsules are usually 98% water and 2% solid.
3. round or oval. 3. Capsules too thin to be demonstrated under microscope
l Resistance are called as microcapsules, e.g. Haemophilus influenzae.
1. Spores are some of the most resistant forms of life, 4. This amorphous viscid material is generally but not in-
may even remain viable for centuries. variably polysaccharide or polypeptide or hyaluronic
2. They are extremely resistant to desiccation and acid in nature.
relatively to the chemicals and heat. 5. They are not visible on Gram-stained smears. They can
3. Spores of medical importance are destroyed by be demonstrated by special staining technique employ-
autoclaving at 120°C for 15 min. ing copper salts.
l Germination 6. Capsule may be readily demonstrated by negative
1. When transferred to conditions conductive to vegeta- straining in wet films with India ink where they are seen
tive growth spores germinate by loosing its refractil- as clear haloes around the bacteria against a black back-
ity and the spore wall is shed and germ cell appears ground.
by rupturing the spore coat. The germ cell elongates 7. Capsular material is antigenic and may be demonstrated
to form the vegetative bacterium. by serological methods. When a suspension of a capsu-
l Demonstration lated bacterium is mixed with specific anticapsular
1. On Gram stain, spores appear as an unstained retrac- serum and examined under microscope the capsule
tile body within the bacterial cell. becomes very prominent and appears swollen due to an
2. On modified ZN staining it appears acid fast. increase in its refractivity. This is known as capsule
l Laboratory use: Spores of certain bacteria are used as swelling or Quellung reaction.
sterilization control like Bacillus stearothermophilus
destroyed at 121°C in 10–20 min and Bacillus subtilis
Function
destroyed at 105°C in 5 min.
l Capsule protects the bacteria from deleterious agents
Q. 4. Different morphological forms of bacteria such as lytic agents and bacteriophages. It contributes to
Ans. the bacterial virulence by inhibiting phagocytosis.
l Loss of capsule renders certain bacteria virulent.
Bacteria are classified into several varieties depending on l Capsular antigen is hapten in nature and specific for
their shape as follows: bacteria. Thus, it also helps in typing of bacteria.

SHORT NOTES
Q. 1. Write short note on ZN staining. 2. They are best developed in freshly isolated strains
and in liquid cultures and tend to disappear follow-
Ans. The ZN stain, i.e. Ziehl-Neelsen stain is an acid fast
ing subcultures on solid media.
stain. Some organisms retain carbol fuchsin even when deco-
lourized with acid. Such organisms are called as acid fast Q. 3. Bacterial fimbriae
organisms.
Ans.
For example: Mycobacteria, bacterial spores, inclusions in
lungs from cases of lipid pneumonia, actinomyces, etc. l Bacterial fimbriae are very fine, thin, hair-like surface
appendages projecting from the cell surface of some
Procedure Gram-negative bacilli as straight filaments.
1. The smear is stained with concentrated solution of car- l Types
bol fuschin with gentle heat application. There are three main types of fimbriae as follows:
2. Then discolourize the smear with 3% solution of HCl in a. Common pili
95% ethyl alcohol or 20% aqueous sulphuric acid. b. Sex or F (fertility) pili
3. Wash the slide with water and counter stain it with c. COL I (colicin) pili
methylene blue or malachite green. Acid fast organisms l Certain fimbriated bacteria (Escherichia, Klebsiella) ag-
retain the fuschin (red) colour and appear red, while the glutinate erythrocytes of guinea pigs, fowls, horses, pigs
others take the counter stain. strongly, human and sheep cells weakly and ox cells
scarcely at all. This haemagglutination provides a sim-
Q. 2. Write short note on flagella.
ple test for detecting the presence of fimbriae.
Ans. l Functions
1. Fimbriae function as organs of adhesion helping the

l Motile bacteria possess organs of locomotion known as bacteria to adhere firmly on cells.
flagella, which are filamentous, cytoplasmic append- 2. Sex pili functions as channels for transfer of genetic
ages protruding from the bacterial cell wall. material.
l Parts of flagella
Each flagellum consists of three distinct parts as follows: Q. 4. Write briefly on spores of bacteria.
1. Filament Ans.
2. Hook
3. Basal body l Spores are highly resistant resting stage of the bacteria
l The filament is the external portion outside the cell wall formed in unfavourable environmental conditions.
attached to the hook at the cell surface. The hook and l Each bacterium forms one spore which on germination
basal body portion is embedded in the cell envelope. forms a single vegetative cell.
l Types of flagella l Example of spore forming bacteria:
1. Depending on position and arrangement of flagella 1. Gram-positive bacilli: Genus Bacillus and Clostridium
a. Polar: At one/both ends. They may be as follows: 2. Other bacteria: Sporosarcina, Coxiella burnetii
i. Monotrichous: Single flagella at one pole
(vibrio) Types
ii. Amphitrichous: At both poles, e.g. Listeria
monocytogenes Two types of bacterial spores are
iii. Lophotrichous: Tuft of flagella at one/both a. endospores or true spores and
poles, e.g. spirilla pseudomonas b. exospores or candida.
b. Peritrichous: Flagella are present all around the True spores are found in lower bacteria and exospores in
cell, e.g. typhoid bacilli higher bacteria.
2. Depending on configuration of filament
a. Monomorphic/conventional: All flagella are of Structure of a bacterial spore
same length. l The fully formed spore has the nuclear body as its core
b. Dimorphic: Two flagella having different wave- surrounded by the spore wall, a delicate membrane from
lengths which the cell wall of the future vegetative bacterium will
l Functions develop.
1. Flagella are the organs of the locomotion in the l Outside this is the thick spore cortex, which in turn is
bacteria. enclosed by a multilayered tough spore coat.

l Some spores have an additional outer covering called Spores of certain bacteria are used as sterilization con-
exosporium which may have distinctive ridges and grooves. trol like Bacillus stearothermophilus destroyed at 121°C
l The spores may be in 10–20 min and Bacillus subtilis destroyed at 105°C
a. central (equatorial), subterminal or terminal, in 5 min.
b. bulging or not bulging and
c. round or oval. Q. 5. Write note on acid fast bacilli with an example.
l Resistance
Ans. Acid fast bacteria are those which retain the concen-
Spores are some of the most resistant forms of life, may trated dye (carbol fuschin) and resist decolourization by a
even remain viable for centuries. strong acid like 20% sulphuric acid, thus being stained red.
l Germination
When transferred to conditions conductive to vegetative For example: Mycobacteria which has a lipid rich cell wall
growth spores germinate. The germ cell elongates to prevent staining by ordinary dyes but on staining with concen-
form the vegetative bacterium. trated dyes like carbol fuschin, they retain the dye and resist
l Laboratory use decolourization with strong acid. Such bacteria are acid fast.
Topic 3
Sterilization and Disinfection

LONG ESSAYS
Q. 1. Define and classify sterilization. Describe an d. Passing steam under pressure (autoclaving)
autoclave. 5 . Filtration by candles, asbestos pads, membranes
Or, 6. Ionizing radiations: X-rays, beta rays, gamma rays
7. Ultrasonic and sonic vibrations
Discuss in detail about sterilization by autoclaving.
Or, CHEMICAL METHODS
Define sterilization. Add a note on moist heat sterilization. 1 . Alcohols: Ethyl, isopropyl, trichlorobutanol
2. Aldehydes: Formaldehyde, glutaraldehyde
Or, 3. Dyes
Define sterilization. What are the various methods of 4. Halogens
moist heat sterilization? 5. Phenols
6. Surface active agents
Ans. Sterilization is defined as the process by which an 7. Metallic salts
article, surface or medium is freed of all living microorgan- 8. Gases: Ethylene oxide, formaldehyde, beta-propiolactone
isms either in the vegetative or spore state.
Various methods of sterilization are classified as follows: Sterilization by Moist Heat
1. Heat is the most reliable method of sterilization. The
PHYSICAL METHODS moist heat kills the bacteria by denaturation and coagu-
lation of the cytoplasmic proteins.
1 . Sunlight
2. There are various methods of sterilization by moist heat
2. Drying
using varying range of temperature, they are as follows:
3. Dry heat
a. Flaming
Temperatures Below 100°C
b. Incineration
c. Hot air 1. Vaccine bath
4. Moist heating a. Serum or body fluids containing coagulable proteins
a. Pasteurization can be sterilized in water bath at 56°C for 1 h and vac-
b. Boiling cines of nonsporing bacteria are sterilized at 60°C for
c. Passing steam under normal pressure 1 h in a special water bath known as the vaccine bath.
2. Pasteurization of milk AUTOCLAVE

a. Pasteurization of milk is carried out by the following
1. Autoclaving (Fig. 3.1) is the process of sterilization by
methods:
saturated steam under high pressure, above 100°C.
i. By heating it at a temperature of 63°C for 30 min
2. The simplest form of autoclave consists of a vertical or
(holder method)
horizontal cylinder made up of gunmetal or stainless
ii. By heating at 72°C for 20 s (flash method) fol-
steel in a supporting sheet iron case (double jacketed).
lowed by rapid cooling quickly to 13°C or lower.
3. The lid or the door is fastened by screw clamps and
b. By these processes all nonsporing pathogens such as
made airtight by a suitable washer.
mycobacteria, brucellae and salmonellae are de-
4. The structures present on the lid are
stroyed but a relatively heat-resistant bacteria Coxi-
a. a discharge tap for air and steam,
ella burnetii may survive the holder method.
b. a pressure gauge, and
3. Fractional sterilization
c. a safe valve.
a. Media containing serum or egg such as Lowenstein-
The safety valve can be set to blow off at any desired
Jensen media and Loeffler’s serum are sterilized at
pressure.
80–85°C for half an hour on 3 successive days in an
5. The heating is done by gas or electricity.
inspissator.
Temperature Air-steam outlet
gauge and safety valve
Temperature at 100°C Pressure
gauge
1. Boiling Water tank
a. Most of the vegetative bacteria are killed immediately
by boiling for 10–30 min at 90–100°C, but many spor-
ing bacteria require considerable period of boiling. Chamber
b. For boiling, hard water should be not used and addi-
tion of 2% sodium bicarbonate to water may pro- Gravity filled Temperature
mote sterilization. boiler with controller
This method is usually employed when better methods are immersion
heater
not available or absolute sterility is not essential like for Valve for water entry
glass syringes, tubes, rubber stoppers and small surgical and water plus
instruments. steam discharge
2. Steam at atmospheric pressure at 100°C for 90 min FIGURE 3.1 A simple autoclave.
a. To create an atmosphere of free steam, a gas or elec-
trically operated steamer like a Koch or Arnold Principle
steam sterilizer is used in order to sterilize culture 1. Water boils when its vapour pressure equals that of the
media such as sugar media which may decompose if surrounding atmosphere.
subjected to higher temperature. 2. Hence pressure inside a closed vessel increases, the
b. The article to be sterilized is kept on a perforated temperature at which water boils also increases to more
tray through which steam passes to escape from an than 100°C.
opening at the top. 3. This saturated steam has greater penetrative power. When
c. Most of the vegetative organisms are destroyed by steam comes into contact with a cooler surface it condenses
this process except thermolabiles. to water and gives up its latent heat to that surface (1600 mL
3. Steaming at 100°C for 3 successive days (tyndalization) of steam at 100°C at atmospheric pressure condenses to
a. The culture media to be sterilized is placed on a per- 1 mL of water at 100°C and liberates 518 cal of heat).
forated tray of a Koch’s or Arnold’s steam sterilizer. 4. Thus there is a large reduction in volume which sucks in
b. Then it is exposed to steam for 30 min each day for more steam to the area and this process continues till the
3 consecutive days. This is known as intermittent temperature of that surface is raised to that of the steam.
sterilization or tyndalization. 5. The condensed water ensures the moist conditions for
c. The underlying principle of this method that the killing of the microbes present.
vegetative cells are destroyed at first exposure, in the
intervals between the heating the remaining spores
Procedure
germinate in favourable nutrient media which are
killed on subsequent heating. 1. Sufficient water is poured in the cylinder, the material to
This method is used for sterilizing egg, serum or sugar be sterilized is placed on the tray and heating is started.
containing media and gelatin media which will be damaged 2. The lid is tightened with the discharge tap open and the
at higher temperatures. safety valve adjusted to the required pressure.
3. The steam air mixture is allowed to escape freely till all Q. 2. Define sterilization and disinfection. Add a note on
air has been displaced. chemical disinfectants.
4. The steam is allowed to escape into a pail of water
Ans.
through a rubber tubing and when no more air bubbles
come out the discharge tap is closed. l Sterilization is defined as the process by which an arti-
5. The steam pressure rises inside and once it reaches the cle, surface or medium is freed of all living microorgan-
desired set level the safety valve opens letting out ex- isms either in the vegetative or spore state.
cess steam. l Disinfection means the destruction of all pathogenic
6. From this point the holding period is calculated. When organisms or organisms capable of giving rise to infec-
the holding period is over, the heater is turned off and tion but not necessarily spores. All organisms may not
the autoclave is allowed to cool till the inside pressure be killed, but the number is reduced to a level that is no
reaches atmospheric pressure. longer harmful to health.
7. Then the discharge tap is opened slowly and air is al-
lowed to enter the autoclave.
Disinfectants
Precautions Ideal requirements of a disinfectant are as follows:
1. Disinfectants are chemical substances used to destroy
1. If the tap is opened when the pressure inside is high viruses and microbes (germs), such as bacteria and
liquid media will tend to boil violently and spill fungi.
from their containers and sometimes even causing 2. Complete sterilization would be offered by an ideal
explosion. disinfectant, without harming other forms of life, be
2. If not opened till the pressure inside falls below the at- inexpensive and noncorrosive.
mospheric pressure, an excessive amount of water will 3. By the very nature all disinfectants, potentially are
be evaporated from the media. harmful or toxic to humans and animals.
3. The contents should be arranged loosely to ensure free 4. They are used more frequently in hospitals, dental clin-
circulation of steam. ics, kitchens and bathrooms to kill infectious organisms.
5. Unfortunately ideal disinfectants do not exist.
Sterilization Time 6. The choice of the disinfectant to be used depends on the
particular situation.
1. Usual sterilization time for an autoclave is as follows:
a. 121°C at 15 lb/in2 for 15–20 min Various chemical disinfectants are classified as follows:
b. 126°C at 20 lb/in2 for 10 min 1. Chemical disinfectants that interfere with membrane
c. 134°C at 30 lb/in2 for 3 min functions
a. Surface acting agents: Quaternary ammonium com-
Sterilization Control pounds, Tween 80 Soaps and fatty acids
b. Phenols: Phenol, cresol, hexylresorinol
Sterilization control which is used to determine effective- c. Organic solvent: Chloroform, alcohol
ness of sterilization are as follows: 2. Chemical disinfectants that cause denaturation of proteins
1. Bacterial spores: Bacillus stearothermophilus is an or- a. Acids and alkalies: Organic acids, hydrochloric acid,
ganism of choice whose spores require an exposure of sulphuric acid
10–12 min at 121°C to be killed. 3. Chemical disinfectants that destroy functional groups of
2. Chemical indicators: At 120°C chemical indicators proteins
such as pellets of sulphur gets melted with change in a. Heavy metals: Copper, silver, mercury
shape or red solution of Browne’s sterilizer control b. Oxidizing agents: Iodine, chlorine, hydrogen peroxide
tubes turns green. c. Dyes: Acridine orange, acriflavine
3. Autoclave tapes d. Alkylating agents: Formaldehyde, ethylene oxide
4. Thermocouples
Commonly used disinfectants are as follows:
Uses
Chlorine
Common articles sterilized in autoclave are as follows:
1. Culture media 1 . It is used in 5% dilutions and is most useful disinfectant.
2. Rubber articles like tubes, gloves, etc. 2. Used to disinfect swimming pools, and is added in
3. Syringes and surgical instruments small quantities to drinking water to reduce waterborne
4. OT gowns, dressing materials diseases.
5. Endodontic instruments 3. Chlorine dioxide is used as an advanced disinfectant for
6. Hand instruments drinking water to reduce waterborne diseases.
Sodium Chlorite, Sodium Chlorate 2. Phenol is probably the oldest disinfectant (used by Lister)
and Potassium Chlorate and was called carbolic acid in the early days of antiseptics.
3. The active ingredient in most bottles of household
1. They have very minute disinfection effect but are used disinfectant.
as precursors for generating chlorine dioxide. They all 4. It is also found in some mouthwashes and in disinfec-
act by liberating chlorine. tant soap and handwashes.
5. Phenol and other phenolic disinfectants derived from
Hypochlorites coaltar are widely used as disinfectants for various pur-
1. Sodium hypochlorite, often in the form of common poses in hospitals.
household bleach, is used in the home to disinfect drains
and toilets. Potassium Permanganate
2. Other hypochlorites like calcium hypochlorite are also 1. Is an oxidizing agent used in the treatment of urethritis.
used, especially as a swimming pool additive.
3. Hypochlorites liberate free chlorine and it is the chlo-
rine that is the true disinfectant.
Quaternary Ammonium Salts (Quats)
1. These are a large group of related compounds used as
Hydrogen Peroxide low level disinfectants.
2. They are effective against bacteria, but not against
1. Hydrogen peroxide in a 3% solution is a harmless but
spores or viruses.
very weak disinfectant and is also used as an antiseptic.
3. Quats are biocides which also kill algae and are used as
2. Used in hospitals to disinfect surfaces.
additives in large-scale industrial water systems to
3. It is often preferred because it causes far fewer allergic
minimize undesired biological growth.
reactions than alternative disinfectants.
4. Hydrogen peroxide is broken down into water and oxy-
gen when it comes into contact with the catalase enzyme Parvo-Virucide
in cells and it is that oxygen which kills bacteria. 1. It is a total biocidal agent that inactivates viruses, bacte-
ria, spores, fungi etc.
Iodine 2. It is used mainly in animal contact areas such as ken-
nels, catteries, veterinary surgeries, etc.
1. It is used usually dissolved in an organic solvent or as
3. It can be used in clean as well as dirty areas contami-
Lugol’s iodine solution.
nated with high levels of organic matter such as urine
2. Iodine is rapidly neutralized by the presence of organic
and faeces without loss of biocidal activity.
material, so surfaces must be cleaned thoroughly prior
to disinfection.
3. Tincture of iodine has also been used as an antiseptic Virkon
for skin cuts and scrapes with consistently magnificent 1 . A wide-spectrum disinfectant used in labs.
results. 2. It kills bacteria, viruses and fungi.
4. It is bactericidal and is effective against sporulating organ- 3. It is used as a 1% solution in water and kept for 1 week
isms also. once it is made up.
5. Mixtures of various surface acting agents with iodine The applications and in-use dilutions of various chemi-
are known as iodophores. cal disinfectants are listed in Table 3.1.
Ozone TABLE 3.1 Applications and Use of Chemical Disinfectants

1. A gas that can be added to water for sanitation. Dilution
to Be
Alcohol Agents Used (%) Common Use
1. Alcohols are more effective combined with water, 70% 1. Chlorine compounds 5 . Water treatment
1
2. Disinfect inanimate objects
alcohol is more active than 95% alcohol.
2. Usually ethanol or isopropanol are used, they are applied 2. Iodine 2 . Disinfect inanimate objects
1
on skin and allowed to evaporate for quick disinfection. 2. Skin antiseptic
3. Alcohol is not effective against bacterial spores. 3. Alcohols 70 . Surface disinfectant
1
2. Skin antiseptic
Phenol and Other Phenolics 4. Phenolic compounds 0.5–5 1. Antiseptic skin washes
1. Phenol (carbolic acid) is a powerful microbicidal sub- 5. Quaternary ammo- ,1 . Skin antiseptic
1
stance. nium compounds 2. Disinfect inanimate objects
Q. 3. Define sterilization and classify sterilization c. Heat

methods. Write briefly about chemical methods of
Based on nature of heat sterilization is of two types as follows:
sterilization.
1. Dry heat
Or, 2. Moist heat
Define sterilization. Classify sterilization methods and i. Dry Heat
write about physical methods of sterilization.
Killing effect of dry heat is due to protein denaturation or oxi-
Or, dative damage or toxic effect of elevated levels of electrolytes.
Define sterilization and in brief different methods of 1. Flaming
sterilization. It is used to sterilize metallic objects by holding them in
Ans. Sterilization is a process by which articles are flame till they are red hot, e.g. inoculating loop or wires, the
freed of all microorganisms both in vegetative and spore tip of forceps and searing spatulas are held over flame till
state. they become red hot.
Sterilization methods are classified as follows: 2. Incineration

1. Physical methods This is an excellent method for safely destroying materials, e.g.
a. Sunlight soiled dressing, animal carcasses and pathological materials.
b. Drying
c. Dry heat 3. Hot Air Oven
i. Flaming Sterilization by hot air oven requires temperature of 160°C
ii. Incineration for 1 h. We can sterilize all glass syringes, Petri dishes, test
iii. Hot air tubes, pipettes, cotton swabs, scalpels, scissors, etc.
d. Moist heating
i. Pasteurization ii. Moist Heat
ii. Boiling The lethal effect of moist heat is by denaturation and coagu-
iii. Passing steam under normal pressure lation of proteins.
iv. Passing steam under pressure (autoclaving)
e. Filtration by candles, asbestos pads, membranes a. Temperature Below 100°C
f. Ionizing radiations: X-rays, beta rays, gamma rays i. Pasteurization of milk: Temperature employed is either
g. Ultrasonic and sonic vibrations 63°C for 30 min. (Holder method) or 72°C for 15–20 s
2. Chemical methods (Flash method). Organisms like mycobacterium, salmonella
a. Alcohols: Ethyl, isopropyl, trichlorobutanol and brucellae are killed.
b. Aldehydes: Formaldehyde, glutaraldehyde ii. Vaccine bath: It is used for killing nonsporing bacteria
c. Dyes which may be present in vaccine.
d. Halogens iii. Inspissation: The slow solidification of serum or egg is
e. Phenols carried out at 80°C in an inspissator.
f. Surface active agents
g. Metallic salts b. Temperature at 100°C
h. Gases: Ethylene oxide, formaldehyde, beta propio- i. Tyndallization: This is the process by which medium
lactone is placed at 100°C in flowing steam for 30 min each
on 3 successive days. The mechanism underlying this
Physical Methods method is that vegetative cells get destroyed at 100°C.
ii. Boiling: Most of vegetative form of bacteria, fungi and
a. Sunlight viruses are killed at 50–70°C in short time. For needles
1. It possesses appreciable bactericidal activities due to and instruments boiling in water for 10–30 min is suf-
its content of UV rays. ficient to sterilize them.
2. Direct sunlight as in the tropical countries has an ac- iii. Steam at atmospheric pressure: Here free steam is used
tive germicidal effect due to the combined effect of to sterilize culture media which may decompose if sub-
ultraviolet and heat rays. jected to higher temperature.
c. Temperature Above 100°C

b. Drying i. Autoclave: In this apparatus material for sterilization is
1. Drying in air has deleterious effect on many bacteria. exposed to 121°C for 15–20 min at 15 lb/in2. Autoclave
Spores are unaffected. is used for culture media, rubber goods, syringes, gowns
2. This is an unreliable method. and dressings.
d. Filtration 1. They are best bactericidal agents. Halogen kills vegeta-

tive bacteria, fungi, viruses but not spores.
1. This method of sterilization helps to remove bacteria from
2. Chlorine is mainly used to disinfect swimming pools,
heatlabile liquids, e.g. antibiotic solution, sera, carbohy-
and is added in small quantities to drinking water to
drate solutions, hydrated fluid, serum and blood products.
reduce waterborne diseases.
2. Various types of filters available are as follows:
3. Mixtures of various surface acting agents with iodine
a. Candle filters
are known as iodophores. They are bactericidal and are
b. Asbestos filters
effective against sporulating organisms also.
c. Sintered glass filters
d. Membrane filters
b. Formaldehyde
e. Radiation 1. In aqueous solutions it is markedly bactericidal and
sporicidal and also has lethal effect on viruses.
1. Two types of radiation are used for sterilization:
2. 5–10% solution in water kills many bacteria and is used
a. Nonionizing radiation
in sterilization of bacterial vaccines.
b. Ionizing radiation
i. Nonionizing Radiation c. Soap and Detergents

1. Here electromagnetic rays with wavelengths longer than 1. They are bacteriocidal and bacteriostatic for Gram-
visible light are used. For example: Infrared radiation, positive and some acid fast organisms. They act by concen-
UV radiation. trating at the cell membrane and this disrupts its normal
2. Infrared radiation is used for rapid mass sterilization. functions.
3. Ultraviolet radiation is used for disinfecting enclosed ar-
eas such as entryways, operation theatres and laboratories.
d. Alcohol
ii. Ionizing Radiation
1. Ethanol with 70% concentration is used for sterilization.
1. X-rays, gamma radiation and other ionizing radiations It does not kill spores.
like cosmic rays are used.
2. Commercial plants use gamma radiation for sterilizing e. Aerosol and Gaseous Disinfectants
items like plastics, syringes, swabs, catheters, oils,
greases, fabrics and metal foils. 1. Sulphur dioxide, chlorine and formalin vapours have
been used as gaseous disinfectants.
Methods of Chemical Sterilization
f. Oxidizing Agents
a. Use of Halogens
1. They are weak antiseptics. For example: Hydrogen per-
Examples: Halogens like chlorine, bromine and iodine, etc. oxide, potassium permanganate
SHORT ESSAYS
Q. 1. Moist heat Pasteurization of Milk
Ans. l Pasteurization of milk is carried out by the following:
1. By heating it at a temperature of 63°C for 30 min
l Heat is the most reliable method of sterilization. The (holder method)
moist heat kills the bacteria by denaturation and coagu- 2. By heating at 72°C for 20 s (flash method) followed
lation of the cytoplasmic proteins. by rapid cooling quickly to 13°C or lower.
l There are various methods of sterilization by moist heat
l By these processes all nonsporing pathogens such as
using varying range of temperature. They are as follows: mycobacteria, brucellae and salmonellae are destroyed
but a relatively heat resistant bacteria Coxiella burnetii
Temperatures Below 100°C
may survive the holder method.
Vaccine Bath
Fractional Sterilization
l Serum or body fluids containing coagulable proteins
can be sterilized in water bath at 56°C for 1 h and vac- l Media containing serum or egg such as Lowenstein-
cines of nonsporing bacteria are sterilized at 60°C for Jensen media and Loeffler’s serum are sterilized at 80–85°C
1 h in a special water bath known as the vaccine bath. for half an hour on 3 successive days in an inspissator.
Temperature at 100°C of steam at 100°C at atmospheric pressure condenses to

1 mL of water at 100°C and liberates 518 cal of heat).
Boiling l Thus there is a large reduction in volume which sucks in
l Most of the vegetative bacteria are killed immediately more steam to the area and this process continues till the
by boiling for 10–30 min at 90–100°C, but many sporing temperature of that surface is raised to that of the steam.
bacteria require considerable period of boiling. l The condensed water ensures the moist conditions for
killing of the microbes present.

Steam at Atmospheric Pressure at 100°C Q. 3. Uses of hot air oven
for 90 Min
Ans.
l To create an atmosphere of free steam, a gas or electri-
cally operated steamer like a Koch’s or Arnold’s steam l Hot air oven is one of the most widely used methods of
sterilizer is used in order to sterilize culture media such sterilization by dry heat.
l Usually recommended sterilization time is 160°C for
as sugar media which may decompose if subjected to
higher temperature. 1 h. Articles sterilized in hot air oven are glassware,
surgical instruments, some pharmaceutical products like
liquid paraffin, dusting powder, fat, grease, etc.
Steaming at 100°C for 3 Successive Days l Cutting instruments as those used in ophthalmic surgery
(Tyndalization) should ideally be sterilized for 2 h at 150°C.
1. The culture media to be sterilized is placed on a perfo- Q. 4. Chemical disinfectants
rated tray of a Koch’s or Arnold’s steam sterilizer.
2. Then it is exposed to steam for 30 min each day for 3 Ans. Disinfection means the destruction of all pathogenic
consecutive days. This is known as intermittent steril- organisms or organisms capable of giving rise to infection.
ization or tyndalization. Ideal requirements of a disinfectant are as follows:
1. Disinfectants are chemical substances used to destroy
Temperature Above 100°C viruses and microbes (germs), such as bacteria and fungi.
2. Complete sterilization would be offered by an ideal
Autoclaving is the process of sterilization by saturated disinfectant, without harming other forms of life, be
steam under high pressure, above 100°C. inexpensive and noncorrosive.
3. By the very nature all disinfectants, potentially are
Q. 2. Principle of autoclave
harmful or toxic to humans and animals.
Ans. The simplest form of autoclave consists of a vertical 4. They are used more frequently in hospitals, dental clin-
or horizontal cylinder made up of gunmetal or stainless ics, kitchens and bathrooms to kill infectious organisms.
steel in a supporting sheet iron case (double jacketed). 5. Unfortunately ideal disinfectants do not exist.
6. The choice of the disinfectant to be used depends on the
l The lid or the door is fastened by screw clamps and particular situation.
made airtight by a suitable washer.
l The structures present on the lid are
Various chemical disinfectants are classified as follows:
a. a discharge tap for air and steam, 1. Chemical disinfectants that interfere with membrane
b. a pressure gauge and functions
c. a safe valve. a. Surface acting agents: Quaternary ammonium com-
l The safety valve can be set to blow off at any desired
pounds, Tween 80 soaps and fatty acids.
pressure. b. Phenols: Phenol, cresol, hexylresorcinol
l The heating is done by gas or electricity.
c. Organic solvent: Chloroform, alcohol
2. Chemical disinfectants that cause denaturation of proteins
a. Acids and alkalies: Organic acids, hydrochloric acid,
Principle of Autoclave sulphuric acid
l Water boils when its vapour pressure equals that of the 3. Chemical disinfectants that destroy functional groups of
surrounding atmosphere. proteins
l Hence pressure inside a closed vessel increases, the
a. Heavy metals: Copper, silver and mercury
temperature at which water boils also increases to more b. Oxidizing agents: Iodine, chlorine, hydrogen peroxide
than 100°C. c. Dyes: Acridine orange, acriflavine
l This saturated steam has greater penetrative power. When
d. Alkylating agents: Formaldehyde, ethylene oxide
steam comes into contact with a cooler surface it condenses The applications and in-use dilutions of various chemical
to water and gives up its latent heat to that surface (1600 mL disinfectants are listed in Table 3.2.
TABLE 3.2 Applications and Use of Chemical Disinfectants carbohydrate solutions, hydrated fluid, serum and blood
Dilution
products.
l Various types of filters available are as follows:
to Be
Agent Used (%) Common Use
1. Candle filters
2. Asbestos filters
1. Chlorine 5 . Water treatment
1
3. Sintered glass filters
compounds 2. Disinfect inanimate objects
4. Membrane filters
2. Iodine 2 . Disinfect inanimate objects
1 l Candle filters are of two types as follows:
2. Skin antiseptic
1. Unglazed ceramic filters
3. Alcohols 70 . Surface disinfectant
1 2. Diatomaceous earth filters
2. Skin antiseptic
They are mainly used for purification of water for indus-
4. Phenolic 0.5–5 1. Antiseptic skin washes
compounds
trial and drinking purposes.
5. Quaternary ammo- ,1 . Skin antiseptic
1 l Asbestos filters: Seitz filters, Sterimat filters
nium compounds 2. Disinfect inanimate objects They are disposable single use discs with high absorbing
capacity and tend to alkalinize filtered liquids.
Q. 5. Filtration l Membrane filters are made of cellulose esters or other poly-

mers and they have largely replaced other types of filters.
Ans.
They are routinely used in water purification and analysis,
l This method of sterilization helps to remove bacteria sterilization and sterility testing and for preparation of solu-
from heat-labile liquids, e.g. antibiotic solution, sera, tions for parenteral use.
SHORT NOTES
Q. 1. Seitz filters 1. The spores of nontoxigenic strain of Clostridium tetani
2. Browne’s tube (green spot)
Ans.
3. Thermo couples
l Seitz filters are a type of asbestos filters.
l They are disposable single use discs with high absorb- Q. 3. Autoclave
ing capacity and tend to alkalinize filtered liquids. Or,
l The carcinogenic potential of these filters have discour-
aged their use. Moist heat sterilization

Ans.
Q. 2. Hot air oven
Ans. l Autoclaving is the process of sterilization by saturated
steam under high pressure, above 100°C.
l This is most widely used method of sterilization by dry l Autoclave is the apparatus which works on pressure
heat. cooker principle for the sterilization by using moist heat,

l Sterilization by hot air oven requires a holding period of which ensures moist conditions for killing bacteria.
1 h at 160°C.
l All glass syringes, Petri dishes, test tubes, flask, pipette,
Sterilization Time
scalpel, cotton swab, scissor, dusting powder, liquid
paraffin, etc. can be sterilized by this method. Usual sterilization time for an autoclave is as follows:
l Precautions in use of hot air oven: 1. 121°C at 15 lb/in2 for 15–20 min
1. It must be fitted with fans to ensure distribution of 2. 126°C at 20 lb/in2 for 10 min
hot air. 3. 134°C at 30 lb/in2 for 3 min
2. It should not be overloaded.
3. Oven must be allowed to cool for about 2 h before
Uses of Autoclave
opening the doors, otherwise glasswares are likely to
get cracked. Common articles sterilized in autoclave are as follows:
4. Long-term effect on instruments: It affects temper 1. Culture media
and brittleness of sharp edges. 2. Rubber articles like tubes, gloves, etc
l Sterilization control of hot air oven can be accom- 3. Syringes and surgical instruments
plished by using the following: 4. OT gowns, dressing materials
5 . Endodontic instruments c. dry heat,

6. Hand instruments d. moist heat,
e. filtration,
Q. 4. Define sterilization. Enumerate various methods f. radiation and
of sterilization. g. ultrasonic vibration.
Ans. 2. Chemical methods include:
a. acids and alkalis,
Sterilization is a process by which articles are freed of all b. salts,
microorganisms both in vegetative and spore state. c. halogens,
There are two broad methods of sterilization: d. oxidizing agents,
1. physical methods and e. reducing agents,
2. chemical methods. f. formaldehyde,
1. Physical methods include g. phenol,
a. sunlight, h. soap,
b. drying, i. dyes, etc.
Topic 4
Culture Media
LONG ESSAY
Q. 1. Define and classify culture media with examples. iv. Differential media, e.g. MacConkey’s medium
Write briefly on selective and anaerobic media. v. Indicator media, e.g. incorporation of sulphite in
Ans. The culture media are the bacteriological media Wilson and Blair’s medium
used for isolation and characterization of various bacte- vi. Transport media, e.g. Stuart’s medium
rial pathogens and are classified in several ways as vii. Sugar or carbohydrate media, e.g. 1% of sugar
follows: in peptone water
4 . Based on uses
1. Based on physical nature a. Media for isolation and growth
a. Liquid media b. Media for biochemical tests
b. Solid media c. Media for transport
c. Semisolid media
2. Based on O2 tension SELECTIVE MEDIA
a. Aerobic media
1. They are solid media which contain a substance incor-
b. Anaerobic media, e.g. Robertson’s cooked meat
porated into it which has selective stimulating effect on
medium
the bacteria to be grown and an inhibitory effect on the
3. Based on functions
growth of the unwanted commensal and nonpathogenic
a. Simple or basal media, e.g. nutrient broth
bacteria.
b. Complex media
2. They enable a greater number of the required bacte-
c. Synthetic or defined media, e.g. simple peptone
ria to form colonies than the other bacteria. For
water medium
example: Desoxycholate citrate medium for dysen-
d. Semidefined media
tery bacilli, blood tellurite agar for Corynebacterium
e. Special media: Special media are further classified
diphtheriae.
into the following:
3. They are similar to the enrichment media, the only dif-
i. Enriched media, e.g. blood agar, chocolate agar
ference is that selective media are solid and enrichment
and egg media
media are liquid.
ii. Enrichment media, e.g. tetrathionate broth
iii. Selective media, e.g. desoxycholate citrate me- Various examples of selective media with their compo-
dium for dysentery bacilli sition and purpose are listed in Table 4.1.
TABLE 4.1 Examples of Selective Media with Their Examples

Composition and Purpose
a. Robertson’s Cooked Meat Broth
Name of Used for Composition: Meat infusion or nutrient broth, minced,
Medium Composition Isolation of cooked beef heart tissue and covered on top with liquid
1. Wilson and Bismuth sulphite 1 phos- Typhoid and paraffin to prevent the entry of air.
Blair’s bismuth phate 1 glucose 1 iron paratyphoid Chopped meat contains unsaturated fatty acids which
sulphite agar citrate in nutrient agar bacilli
act as reducing agents and absorb oxygen.
2. Monsur’s GTTA Gelatin 1 taurocholate Vibrio cholerae
agar 1 tellurite b. Thioglycollate Medium
3. Ludlam’s Lithium chloride 1 Staphylococcus Composition: Sodium thioglycollate, glucose, vitamin C,
medium tellurite aureus cysteine and agar at a concentration of 0.05% with methy-
4. Thayer-Martin Vancomycin 1 Neisseria gono- lene blue as indicator.
medium colistin 1 nystatin cocci and Neisse- Thioglycollate acts as a reducing agent and creates anaero-
ria meningococci bic environment. Glucose and vitamin C maintain the anaero-
5. McLeod’s Heated rabbit’s blood 1 Corynebacterium bic condition. Agar prevents diffusion of air into the medium.
medium potassium tellurite diphtheriae
c. Nutrient Broth with Red Hot Iron Pieces
Simple nutrient broth containing red hot iron pieces and
ANAEROBIC MEDIA
layered with liquid paraffin.
1 . These media are used to grow anaerobic organisms.
2. They contain a reducing agent that absorbs all the oxy- d. Smith-Noguchi Medium
gen and create an anaerobic condition favouring growth Nutrient broth containing fresh animal tissue such as rabbit
of anaerobes. kidney, spleen, testes or heart etc.
SHORT ESSAY
Q. 1. Media for cultivation of bacteria iii. Selective media
iv. Differential media
Ans.
v. Indicator media
l Bacteria have to be grown or cultured on media to be vi. Transport media
identified, as only rarely they can be identified by their vii. Sugar or carbohydrate media
morphology. 4. Based on uses
l Study of bacteriology involves study of bacterial popu- a. Media for isolation and growth
lation rather than single bacterium. b. Media for biochemical tests
l For studying, bacteria need to be grown separately and c. Media for transport
isolated in the pure cultures because they occur in
mixed population in a natural setting. Q. 2. Enrichment media
l Various media have been devised for cultivation of
Ans.
bacteria and they are classified as follows:
1. Based on physical nature l Enrichment media are essentially liquid media contain-
a. Liquid media ing specific nutrients required to enhance the growth of
b. Solid media a particular bacterial pathogen, which may be inhibitory
c. Semisolid media to nonpathogenic commensals.
2. Based on O2 tension l The media that favours multiplication of a particular
a. Aerobic media species of bacteria by incorporating special substances,

b. Anaerobic media which favours its growth or inhibits its competitors is
3. Based on functions known as enrichment media.
a. Simple or basal media l Examples of enrichment media for specimens other
b. Complex media than blood are as follows:

c. Synthetic or defined media a. Selenite F broth: Consists of Na selenites and pep-
d. Special media: Special media are further classi- tone water. It is used for Salmonella and Shigella.
fied into the following: b. Tetrathionate broth: Consists of nutrient broth, sodium
i. Enriched media thiosulphate, CaCO3 and iodine. It is used for Salmo-
ii. Enrichment media nella typhi and paratyphi.
c. Alkaline peptone water: Consists of peptone water Q. 3. Write about artificial culture media.
1 20 g NaOH at a pH of 8.6 used for Vibrio
Ans. Artificial culture medium is an artificial environment
cholerae.
with essential nutrients at optimum quantity and optimum
l Examples of enrichment media for blood specimens are
pH which is suitable for bacterial growth in vitro.
as follows:
a. Bile broth: Nutrient broth 1 0.5% bile, used for Examples
Salmonella.
The artificial media are as follows:
b. Brain heart infusion broth: Peptone water 1 brain
1. Basic/basal media: Natural agar is used. It consists of
infusion, used for bacteria and fungi.
essential amino acids, meat/yeast extracts and NaCl.
Q. 3. Enriched media 2. Synthetic/defined media: They are added to produce
definite chemical product, e.g. simple peptone water,
Ans. casein hydroxylate, Tween 80 etc.
3. Selective media: It is a solid media which suppresses
l Enriched media are special basal media prepared by add-
or inhibits the growth of all except particular species or
ing highly nutritious substances such as blood, serum,
strain of bacteria, e.g. Lowenstein-Jensen media for
egg, milk, glucose, etc.
Mycobacterium tuberculosis.
l They allow growth of fastidious organisms because of
4. Enriched media: Blood agar, chocolate agar, serum
the presence of specific nutritive additives like haemin,
agar and egg media.
cystine etc.
5. Enrichment media: Tetrathionate broth inhibits growth
l They are used for cultivation of bacteria possessing ex-
of E. coli and help S. typhi to grow freely.
act growth requirements.
6. Indicator media: This media is prepared by incorpora-
tion of some indicator substance that is changed visi-
Examples
bly, indicated by some visible changes in the media, as
1. Blood agar a result of some particular and distinctive metabolic
l Composition is agar and sterile sheep blood 5–10%. activities of particular organism. It is used to detect
l Used for cultivation of fastidious organisms like colonies of particular bacterial species.
streptococci, pneumococci, Haemophilus and to 7. Differential media: It is a medium which has substances
demonstrate haemolysis. incorporated in it enabling to bring out different charac-
2. Chocolate agar teristics of bacteria and helping to distinguishing them.
l Used for cultivation of Haemophilus, meningococci, 8. Transport media: It is a medium to protect and pre-
gonococci. serve pathogens during delay in transport of delicate
l It is prepared by heating 10% sterile blood in sterile organisms, which may not survive the time taken for
nutrient agar. transporting specimen to laboratory.
3. Loeffler’s serum slope is used for cultivation of Diph- 9. Sugar media: Sugar denotes any fermentable sub-
theria bacilli. stance. Sugar media consists of 1% sugar in peptone
4. Milk agar is used for cultivation of staphylococci water and appropriate indicator, e.g. Hiss serum sugar
(enhance pigment production). used for pneumococci.
5. Dorset’s egg medium is used for cultivation of diphthe- 10. Anaerobic media: This is used to grow anaerobes, e.g.
ria and tubercle bacilli. Robertson’s cooked meat medium.
SHORT NOTES
Q. 1. Blood agar Q. 2. Blood culture
Ans. Ans.
l Blood agar is an enriched media, in which blood is an l Blood culture is one of the most important investiga-
additive nutrient to the basal medium. tions in clinical microbiology.
l Though the blood agar is an enriched medium, the l It is indicated
bacteria lysing red cells show a clearing around 1. where the possibility of septicaemia or bacteraemia
their colonies, thus acting as indicator medium is suggested by the clinical picture.
as well. 2. for diagnosis of pyrexia of unknown origin.
l As blood agar acts as enriched medium, it is helpful for
the growth of bacteria which have importance in nutri- Q. 3. Enriched media

tional value. Ans.
l Enriched media are prepared by the addition of l Indicator media are the special media which contain an
special nutrients like blood, serum, egg to a basal indicator which changes colour when a bacterium grows
medium. in them.
l They are used to grow bacteria which are more exacting l They indicate the presence of a specific bacteria and
in their nutritional needs. For example: Blood agar, property of the bacterium.
chocolate agar, serum agar and egg media
Examples
Q. 4. Transport media
a. MacConkey agar contains neutral red indicator which in-
Ans. dicates lactose fermenting property of bacteria, i.e. lactose
fermenting bacteria produce pink colonies whereas non-
l Special media devised for transporting the specimens to lactose fermenting bacteria produce colourless colonies.
the laboratory are known as transport media. b. Incorporation of sulphite in Wilson and Blair’s medium
l These media are used in case of delicate organisms, e.g.
Salmonella typhi reduces sulphite to sulphide in the
gonococci which may not survive the time taken for presence of glucose and the colonies of S. typhi have a
transporting the specimen to the laboratory or may be black metallic sheen.
overgrown by nonpathogens, e.g. dysentery or cholera c. Potassium tellurite in McLeod’s medium is reduced to
organisms in faeces. metallic tellurium by diphtheria bacillus to produce
l Examples of various transport media used are: Stuart’s
black colonies.
medium for gonococci and buffered glycerol saline for
enteric bacilli. Q. 9. Anaerobic culture media
Q. 5. Enrichment media Or,
Ans. Enrichment media is a liquid media that favours Write short note on Robertson’s cooked meat media.
multiplication of particular species either by providing Ans.
enrichment to selectively favour its growth or inhibitors
to suppress its competitors. For example: Tetrathionate 1. Anaerobic culture media are used to grow anaerobic organ-
broth inhibits growth of E. coli and helps S. typhi to grow isms. For example: The Robertson’s cooked meat medium.
freely. 2. Uses
1. It is used for anaerobic culture.
Q. 6. Preparation of blood agar medium 2. For preservation of stock culture of aerobic organisms.
3. Valuable medium for preserving cultures of delicate
Ans.
organisms.
l Blood agar is prepared by adding 10 mL of defibrinated 4. May be used as recovery medium for spores.
sheep blood to 100 mL of nutrient agar.
Q. 10. Mention four selective media.
l The sterile nutrient agar is melted by steaming and then
temperature is brought down to 45°C. The required Ans.

quantity of sheep blood is added aseptically with con-
stant gentle shaking without froth formation. Various examples of selective media with their composition
l The medium is immediately poured into the plates and
and purpose are listed in Table 4.2.
allowed to set. TABLE 4.2 Examples of Selective Media with Their
Composition and Purpose
Q. 7. Selective media
Name of Used for
Ans. Medium Composition Isolation of
l Selective media contain additives that enhance the 1. Wilson and Bismuth sulphite 1 Typhoid and
Blair’s bismuth phosphate 1 glucose 1 paratyphoid
growth of the desired organisms by inhibiting other or-
sulphite agar iron citrate in nutrient agar bacilli
ganisms.
l They enable a greater number of the required bacteria 2. Ludlam’s Lithium chloride 1 Staphylococcus
medium tellurite aureus
to form colonies than the other bacteria. For example:
Desoxycholate citrate medium for dysentery bacilli, 3. Thayer-Martin Vancomycin 1 Neisseria gono-
blood tellurite agar for Corynebacterium diphtheriae. medium colistin 1 nystatin cocci and Neisse-
ria meningococci
Q. 8. Indicator media 4. McLeod’s Heated rabbit’s blood 1 Corynebacte-
medium potassium tellurite rium diphtheriae
Ans.
Topic 5
Culture Methods
LONG ESSAY
Q. 1. Describe anaerobic culture methods. Detailed description of various anaerobic culture methods
are as follows:
Ans.
1. Anaerobes are the microorganisms which differ in their 1. Cultivation in Vacuum

requirement of and sensitivity to oxygen for their growth. a. Vacuum Desiccators
2. Obligate anaerobes grow only in absence of oxygen and
are killed in presence of oxygen due to accumulation of Cultivation in vacuum is done in vacuum desiccators but
toxic H2O2, these bacilli require special methods for the method has some disadvantages like
their cultivation. 1 . some O2 may be left behind,
3. The anaerobiosis can be achieved based on following 2. fluid culture may boil over in vacuum and
principles: 3. media may get detached from the culture plates in vacuum.
a. Exclusion of oxygen
b. Production of vacuum This method is not in use now.
c. Displacement of oxygen with other gases
d. Use of chemical or biological means to absorb b. Anaerobic Chambers or Cabinets or Glove
oxygen Boxes
e. Reduction of oxygen 1. Anaerobic chamber is a self-contained anaerobic system
Various anaerobic culture methods available are as follows: with an airtight, glass-fronted cabinet filled with inert
1. Cultivation in vacuum gas, with an entry lock for the introduction and removal
a. Anaerobic chambers or cabinets or glove boxes of materials, and gloves or sleeves that form airtight
b. Anaerobic bags or pouches seals round the arms to handle items inside the chamber.
2. Displacement of oxygen with gases like hydrogen, ni- 2. A gas mixture of 5% CO2, 10% H, 85% N and a palla-
trogen, helium or CO2 dium catalyst maintains the anaerobic environment inside
a. Candle jar method the chamber.
3. Absorption of oxygen 3. Some cabinets use methylene blue as an indicator to
a. Chemical methods monitor anaerobiosis.
i. Alkaline pyrogallol method 4. They are used for processing of specimens, incubation of
– Spray anaerobic dish cultures, periodic examination of culture plates, subcul-
– Ordinary Petri dish tures and to make prereduction of the media for anaerobic
ii. Buchner’s tube organism in an oxygen-free atmosphere.
iii. Rosenthal method
c. Anaerobic Pouches or Bags
iv. Phosphorus stick method
b. Biological method: Absorption of oxygen from jar by 1. They are useful for laboratories processing small num-
incubating cultures with germinating seeds, chopped ber of specimens.
vegetables (potatoes) and aerobic organisms like 2. They can be used to transport specimens and also to
Pseudomonas aeruginosa. incubate one or two agar plates.
4. McIntosh Filde’s anaerobic jar
5. GasPak system 2. Displacement of Oxygen with Gases like
6. Reduction of oxygen Hydrogen, Nitrogen, Helium or CO2
a. Anaerobic media
a. Candle Jar Method
Examples: 1. Candle jar method is the most popular but ineffective
a. Robertson’s cooked meat broth method.
b. Thioglycollate medium 2. Inoculated culture plates are placed inside a large air
c. Nutrient broth with red hot iron pieces light container and a lighted candle is kept in it before
d. Smith-Noguchi medium the lid is sealed.
3. The burning candle is expected to use up all the oxygen aeruginosa or Serratia marcescens. However, this method
inside the jar before it is extinguished and create anaero- is slow and ineffective.
bic environment.
4. However, it is ineffective as some O2 is always left behind.
It also provides a CO2 concentration which stimulates the
4. McIntosh Filde’s Anaerobic Jar (Fig. 5.1)
growth of most bacteria. 1. This is the most reliable and widely used anaerobic
method.
3. Absorption of Oxygen 2. It consists of a glass or metal jar with a metal lid that
can be clamped down on a gasket to make it air tight
a. Chemical Methods
with a screw clamp.
i. Alkaline Pyrogallol Method 3. The lid has two tubes with taps, one is gas inlet and the
1. Alkaline pyrogallol absorbs oxygen and is used in other is outlet. The lid also has two terminals, which can
various modifications. be connected to an electric supply.
2. This method was first introduced by Buchner (1888). 4. One or more capsules containing palladiumized alu-
mina pellets are suspended under the lid with wires and
ii. Spray Anaerobic Dish connected to electric terminals on the lid for heating.
1. It consists of a small glass dish with its bottom par- 5. Alternatively room temperature catalyst called deoxopel-
titioned in to two halves to keep the pyrogallic acid lets, which is palladium coated on alumina can be used.
and NaOH separately in them. 6. Inoculated culture plates are placed in the jar with the
2. The top half accommodates a Petri dish carrying the medium in the bottom half of the plates and lid clamped
medium. tight.
3. The inoculated culture plate is inverted on the top of
the dish and is sealed with paraffin completely.
4. The jar is slightly rocked to mix the chemicals and the
pyrogallol absorbs the oxygen producing anaerobiosis. Valve
5. This method is not in use now.
iii. Ordinary Petri Dish

1. Here a disc of filter paper is sprayed with dry pow- Inlet
dered form of pyrogallol and sodium carbonate. Outlet
2. The inoculated Petri dish is inverted over the filter
paper and sealed with the molten wax. Catalyst
Electric
3. The anaerobiosis is achieved in 2 h by activation of terminals
the dry pyrogallol and NaCO3 by the moisture pres-
ent in the closed system.
iv. Buchner’s Tube

Pyrogallic acid added to a solution of NaOH in a large test
tube placed inside an airtight jar provides anaerobiosis. The
method has been applied to single tube and plate cultures. FIGURE 5.1 McIntosh Filde’s anaerobic jar.
v. Rosenthal Method
The production of anaerobic conditions in the jar can be
Here the mixture of chromium and sulphuric acid produces brought about by the following:
anaerobiosis by reducing oxygen to water.
vi. Phosphorus Stick Method i. Displacement of Oxygen

Yellow phosphorus sticks are burnt in the jar to absorb O2 1. The outlet tube is connected to a vacuum pump and
and it continues to burn till all the O2 gets exhausted and the air inside it.
only inert gases and partial vacuum remains. 2. The outlet tap is then closed and the inlet tube is con-
nected to a hydrogen supply.
b. Biological Method 3. After the jar is filled with hydrogen the inlet valve is
Absorption of oxygen from jar can also be achieved by in- closed and the electrical terminals are connected to a cur-
cubating cultures with germinating seeds, chopped vegeta- rent supply and the jar is incubated at 37°C. When room
bles (potatoes) and aerobic organisms like Pseudomonas temperature catalyst is used, heating is not required.
ii. Displacement and Combustion of Oxygen i ii. Nutrient broth with red hot iron pieces
iv. Smith-Noguchi medium
1. Palladiumized asbestos is heated by supplying the
electric current through it. i. Robertson’s Cooked Meat Medium
2. It acts as a catalyst for combination of hydrogen with
the residual oxygen available in the jar. 1. It is the most widely used fluid medium for the culture
3. This method ensures complete anaerobiosis but has of anaerobes.
a slight risk of explosion. 2. Composition
a. Meat infusion or nutrient broth, minced, cooked beef
iii. GasPak System heart tissue and covered on top with a layer of sterile
vaseline or liquid paraffin to prevent the entry of air.
1. This current method of choice for preparing anaerobic b. Chopped meat contains unsaturated fatty acids which
jars was devised by Brewer and Allegeir. act as reducing agents and absorb oxygen thus creat-
2. GasPak is commercially available as disposable enve- ing anaerobiosis.
lopes containing chemicals which generate hydrogen c. Haematin catalyses this reducing action and sulfhy-
and carbon dioxide on addition of water. dryl group creates a low redox potential.
3. This gaspak envelope is kept in the jar, with water added
along with inoculated plates and the lid is tightened. All these factors favour the growth of anaerobic bacteria.
4. The chemicals in gaspak generate hydrogen and CO2 and
the presence of a cold catalyst enables the combination ii. Thioglycollate Medium
of this hydrogen with the available oxygen to produce 1. It contains sodium thioglycollate, glucose, vitamin C,
anaerobic environment. cysteine and agar at a concentration of 0.05% with
5. Reduced methylene blue or resazurin indicators are methylene blue as indicator.
used to verify anaerobiosis, however production of heat 2. Thioglycollate acts as a reducing agent and creates
and development of moisture on the walls of the jar are anaerobic environment. While glucose and vitamin C
enough indications of anaerobiosis. maintains the anaerobic condition.
6. The gaspak is simple and effective. 3. Small quantity of agar enhances the anaerobic capacity
of the medium by slowing the diffusion of air into the
5. Reduction of Oxygen medium.
a. Anaerobic Media iii. Nutrient Broth with Red Hot Iron Pieces
These are media containing a reducing agent that absorbs Broth is an easily prepared anaerobic medium into which pieces
all the oxygen and creates on anaerobic condition favouring of red hot metallic iron are introduced. It is then layered with
growth of anaerobes. sterile vaseline and can be used as a simple anaerobic medium.
Examples iv. Smith-Noguchi Medium

i. Robertson’s cooked meat broth Nutrient broth containing fresh animal tissue such as rabbit
ii. Thioglycollate medium kidney, spleen, testes or heart is used as anaerobic media.
SHORT ESSAYS
Q. 1. McIntosh Filde’s anaerobic jar 4. Alternatively room temperature catalyst called deoxopel-
lets, which is palladium coated on alumina can be used.
Ans. This is the most reliable and widely used anaerobic
5. Inoculated culture plates are placed in the jar with the me-
method.
dium in the bottom half of the plates, and lid clamped tight.
1. It consists of a glass or metal jar with a metal lid that The production of anaerobic conditions in the jar can be
can be clamped down on a gasket to make it airtight brought about by the following:
with a screw clamp.
2. The lid has two tubes with taps, one is gas inlet and the 1. Displacement of Oxygen
other is outlet. The lid also has two terminals, which can l The outlet tube is connected to a vacuum pump and the
be connected to an electric supply. air inside it is avacuated.
3. One or more capsules containing palladiumized alu- l The outlet tap is then closed and the inlet tube is connected
mina pellets are suspended under the lid with wires and to a hydrogen supply. After the jar is filled with hydrogen
connected to electric terminals on the lid for heating. the inlet valve is closed and the electrical terminals are
connected to a current supply and the jar is incubated at 3. Absorption of oxygen

37°C. When room temperature catalyst is used, heating is a. Chemical methods
not required. i. Alkaline pyrogallol method
– Spray anaerobic dish
2. Displacement and Combustion of Oxygen – Ordinary Petri dish
l Palladiumized asbestos is heated by supplying the elec- ii. Buchner’s tube
tric current through electric terminals. iii. Rosenthal method
l It acts as a catalyst for combination of hydrogen with iv. Phosphorus stick method
the residual oxygen available in the jar. b. Biological method: Absorption of oxygen from jar
l This method ensures complete anaerobiosis but has a by incubating cultures with germinating seeds,
slight risk of explosion. chopped vegetables (potatoes) and aerobic organ-
isms like Pseudomonas aeruginosa.
Q. 2. Anaerobic culture methods 4. McIntosh Filde’s anaerobic jar
Ans. Various anaerobic culture methods available are as 5. GasPak system
follows: 6. Reduction of oxygen
a. Anaerobic media
1. Cultivation in vacuum
a. Anaerobic chambers or cabinets or Glove boxes Examples
b. Anaerobic bags or pouches 1. Robertson’s cooked meat broth
2. Displacement of oxygen with gases like hydrogen, 2. Thioglycollate medium
nitrogen, helium or CO2 3. Nutrient broth with red hot iron pieces
a. Candle jar method 4. Smith-Noguchi medium
SHORT NOTES
Q. 1. Indications for culture of bacteria a. Gram-positive: Peptostreptococci, anaerobic strepto-
cocci
Ans. The indications of bacterial culture are to
b. Gram-negative: Veillonella
1 . isolate them in pure form, 2 . Bacilli
2. demonstrate their properties, a. Sporulating: Clostridia
3. prepare antigens, b. Nonsporulating
4. determine sensitivity to antibiotics and i. Gram-positive: Actinomyces, Lactobacillus, Eu-
5. maintain stock cultures. bacterium and Propionibacterium
ii. Gram-negative: Bacteroids, fusobacteria and
Q. 2. Name few anaerobic organisms. leptotrichia
iii. Spirochaetes: Treponema, Borrelia
Ans.
Q. 3. Write short note on anaerobiosis.
l Anaerobic organisms are those organisms which do not
require oxygen for growth. Ans. Anaerobiosis means attaining oxygen-free environment.
l Anaerobic bacteria differ in their requirement and sen-
sitivity of oxygen. The following methods can be used to obtain complete

l Some bacteria like Clostridium, histolytica are aerotolerant
anaerobiosis:
while Clostridium tetani are strict anaerobe and form sur- 1. Exclusion of oxygen or production of vacuum
face growth only if oxygen tension is less than 2 mm of Hg. 2. Displacement of oxygen with other gases
3. Absorption of oxygen by chemical or biological
They are classified as follows: means
1. Cocci 4. Reduction of oxygen
Topic 6
Identification of Bacteria and Bacterial Taxonomy

SHORT NOTES
Q. 1. Indole test 48 h is taken to which 1 volume (0.2 mL) of 40% KOH
Ans. and 3 volumes (0.6 mL) of 5% solution of a-naphthol in
ethanol are added.
l This test is one of the biochemical tests used for identi- l In a positive reaction, a pink colour appears in
fication and classification of bacteria. 2–5 min which deepens to magenta or crimson in
l This test demonstrates production of indole from tryp- half an hour.
tophan. This is tested in peptone water culture after l In a negative reaction no colour change is observed for
48 or 96 h incubation at 37°C. half an hour, it remains colourless.
l Add 0.5 mL of Kovac’s reagent and shake gently. Red
colour indicates a positive reaction. Q. 3. Urease test

Ans.
Q. 2. Voges-Proskauer test
Ans. l Urease test is done in Christensen’s urease medium.
l After inoculating the slope heavily incubate it at
l This test depends on the production of acetyl methylcar- 37°C and examine after 4 h and after overnight incu-
binol from pyruvic acid as an intermediate stage in its bation.
conversion to 2:3 butylene glycol. l Urease positive cultures produce purple pink colour.
l 1 mL of glucose phosphate medium culture of the Urease producing bacteria reduce urea to ammonia
organisms incubated at 30°C for 5 days or 37°C for which is responsible for the colour.
Topic 7
Bacterial Genetics
LONG ESSAY
Q. 1. Describe the methods of genetic transfer. DNA
fragments
Ans. Transmission of genetic material or gene transfer in
bacteria occurs by following methods:
Uptake
1 . Transformation
2. Transduction
3. Lysogenic conversion
4. Conjugation Natural New
cell lysis bacterium
FIGURE 7.1 Transformation.
TRANSFORMATION
1. Transformation is the transfer of genetic information
through the agency of free DNA (Fig. 7.1). Following factors influence the successful transformation:
2. Transformation is otherwise uptake of naked DNA. a. The physical state of donor DNA
It was discovered to be the first example of genetic b. The competency of recipient cell
exchange in bacteria. c. The fate of DNA upon entering the cell
The bacterium must be competent to take up the DNA from 5. The transducing particle in restricted transduction transfers
the environment and incorporate it into its DNA. donor DNA along with phage DNA to the recipient cell. The
3. Griffith in 1928 found that mice died when injected with transduced donor DNA integrated with the recipient’s chro-
a mixture of live noncapsulated (R) pneumococci and mosome expresses new characters. Restricted transduction
heat killed capsulated (S) pneumococci, neither of has been studied extensively in the lambda phage of E. coli.
which separately proved fatal. 6. Extrachromosomal localization of the DNA of the de-
In an experiment Griffith injected living type II (R) bac- fective transducing agent is of autonomous replication
teria mixed with large number of killed type III (S) into and is therefore segregated to one daughter cell at each
mice. Many of the mice died and from heart blood he division. This state is called abortive transduction.
obtained pure live type III (S) bacteria. Something must 7. Transduction is not confined to transfer of chromosomal
have passed from dead type III bacteria and change type DNA but can transfer episomes and plasmids also.
II (R) strain into virulent type III (S) which killed mice. For example: The plasmids determining penicillin resis-
This process is called transformation. tance in staphylococci are transduced from cell to cell.
4. Transformation occurs naturally in Bacillus subtilis,
Streptococcus pneumoniae, Haemophilus influenzae, Significance
Neisseria, Moraxella, Pasteurella novicida.
5. It can also be induced in the laboratory by artificial a. Transduction is the most widespread mechanism of
application of forces such as treatment with high salt gene transfer among prokaryotes.
and temperature shock in E. coli, Pseudomonas putida, b. It acts as an excellent tool for genetic mapping of bacteria.
Salmonella typhimurium, Staphylococcus aureus. c. Any bacteria susceptible to bacteriophage can be
6. There are three mechanisms of transformation as follows: subjected to transduction.
a. In Pneumococcus and some Gram-positive bacteria, the d. It can also be used in genetic engineering in treatment
invading DNA fragment is cut to 7–10 kb by endonucle- of some inborn errors of metabolism.
ase of the membrane and only one strand enters the cell.
b. In Gram-negative bacteria like Haemophilus, a mem-
LYSOGENIC CONVERSION
brane protein binds a sequence of about 10 nucleotides 1. It is a unique method of genetic transfer where instead of
and the DNA enters as double strand inside the cells. transferring a genetic material from one bacteria to an-
c. In case of enteric group of bacteria, transformation takes other, a new genetic material is incorporated into the
place after modification of cell envelope by conversion bacterial chromosome which is known as prophage, cour-
to spheroplasts or otherwise. The modified cell surface tesy bacteriophages in their temperate or nonlytic cycle.
permits taking up double stranded DNA fragments. 2. This additional genetic material or the prophage DNA
confers genetic information to a bacterium which may
TRANSDUCTION code for new characteristics.
1. The transfer of a portion of DNA from one bacterium to 3. The bacteria possessing this prophage DNA is called
other by bacteriophages is known as transduction (Fig. 7.2). lysogenic bacterium. For example: Diphtheritic bacilli
2. A bacteriophage is a virus that parasitizes bacteria and acquire toxigenicity by lysosomic conversion with
consists of a nucleic acid core and a protein coat. phage beta and elimination of the phage from a toxi-
genic strain renders it nontoxigenic.
DNA
Empty phage
fragments
Phage coat CONJUGATION
DNA
1. Conjugation is the process where by a male or donor
bacterium mates or make physical contact with a female
Phage Daughter or recipient bacterium and transfers genetic elements
Cell lysis
phage
New into it (Fig. 7.3).
bacterium
FIGURE 7.2 Transduction. Pilus
Chromosome
3. A phage particle may carry a segment of host DNA
besides its own nucleic acid. When this infects another
bacterium DNA transfer is affected and the recipient cell
acquires new characteristics coded by the donor DNA.
4. Transduction is generalized when it involves any segment F+ F- F+ F- F+ (x2)
of donor DNA and it may be restricted when a specific Plasmid
bacteriophage transduces only a particular genetic trait. FIGURE 7.3 Conjugation.
2. It is considered as the bacterial equivalent of sexual donor status and can in turn conjugate with other female
mating in higher organisms. cells.
3. Conjugation takes place between a male cell and a 5. The maleness in bacteria is therefore a transmissible or
female cell. The maleness or donor status of a bacterium infectious characteristic.
is determined by the presence of F plasmid which codes 6. Along with plasmid DNA portions of the host DNA are
for specialized fimbria (sex pilus) which projects from also sometimes transferred to the recipient.
the surface of the cell. 7. The donor DNA combines with the recipient DNA re-
4. The plasmid DNA replicates and a copy of it passes sulting in genetic recombination.
from the donor to the recipient cell along the sex pilus 8. The role of plasmids in conjugation was first recognized
or conjugation tube. As a result the recipient attains in E. coli K-12.
SHORT NOTES
Q. 1. Methods of genetic transfer 4. DNA probes for the detection of many pathogens
(bacteria, viruses and protozoa) are now commer-
Ans. Transmission of genetic material or gene transfer in
cially available.
bacteria occurs by following methods:
1 . Transformation Q. 4. Polymerase chain reaction

2. Transduction Ans.
3. Lysogenic conversion
4. Conjugation 1. Polymerase chain reaction (PCR) is an in vitro method
for producing large amounts of specific DNA fragment
Q. 2. Transduction of defined length and sequences from small amount of
complex template.
Ans.
2. It was invented by Kary B Mullis in 1983, for which he
l The transfer of a portion of DNA from one bacterium to won a noble prize in 1993.
other by bacteriophages is known as transduction. 3. PCR consists of several cycles of sequential DNA repli-
l A phage particle may carry a segment of host DNA be- cation where the products of first cycle become the
sides its own nucleic acid. When this infects another template for the next cycle.
bacterium DNA transfer is affected and the recipient cell 4. PCR is a versatile tool useful in
acquires new characteristics coded by the donor DNA. a. diagnosis of infectious, genetic or neoplastic diseases,
l Transduction is generalized when it involves any segment b. forensic investigations and
of donor DNA and it may be restricted when a specific c. archeobiologic studies of ancient specimens as in ex-
bacteriophage transduces only a particular genetic trait. amination of phylogenetic relationships in evolution.
5. PCR is carried out in following four steps:
Q. 3. DNA probes a. Denaturation
b. Primer annealing
Ans.
c. DNA synthesis
l DNA probes are radioactive, biotinylated or labelled d. Detection of amplified product
copies of cloned single stranded DNA fragments, usu-
ally 20–25 nucleotides long which will hybridize with Q. 5. Plasmids
and thereby detect and locate complementary sequences Ans.
among DNA fragment on a southern blot.
l Southern blot is a technique of transferring DNA frag- l Plasmids are double stranded circular DNA molecules
ments which have been separated by electrophoresis present in the cytoplasm of bacteria, capable of autono-
on an agar gel to a nitrocellulose filter where they can mous replication.
hybridize with probe. l Plasmids have become important vectors in genetic en-
l The advantages of DNA probes for diagnosis are as gineering by their ability to transfer genes from one cell
follows: to another.
1. High degree of specificity l Two members of same group of plasmids cannot coexist
2. Ability to detect minute quantities of complementary in same cells.

DNA even in the presence of other microbes. l Plasmids are not essential for the life and function of the
3. Capacity to recognize microbes that are either diffi- bacterium. They confer properties like toxigenicity and
cult or impossible to culture. drug resistance.
Topic 8
Infection
SHORT ESSAYS
Q. 1. Enumerate the differences between endotoxins b. Indirect contact may be through the agency of fomi-
and exotoxins. tes which are inanimate objects like clothing, pencils
Ans. The various differences between exotoxins and endo- or toys, e.g. diphtheria and trachoma.
toxins are listed in Table 8.1. 2. Inhalation: The respiratory infections usually spread
through inhalation of pathogens.
The microbes are shed by the patient into environment
TABLE 8.1 Differences between Exotoxins and Endotoxins
in secretions from the nose or throat during sneezing,
Exotoxins Endotoxins speaking or coughing which remain suspended in the
Exotoxins are heat-labile Endotoxins are heat stable air for long periods acting as sources of infection, e.g.
proteins lipopolysaccharides influenza, tuberculosis, smallpox, etc.
3. Inoculation: In some instances pathogens may be
They are actively secreted by They form an integral
cells and diffuse readily into part of the Gram-negative directly inoculated into the tissues of the host, e.g.
surrounding medium bacterial cell wall tetanus spores in deep wounds, rabies virus deposited
They can be readily separated from They are obtained only by
subcutaneously by dog bite, etc.
cultures by means of filtration cell lysis Infection by inoculation may be iatrogenic when unster-
ilized syringes and equipments are used, e.g. tetanus,
Highly potent in minute amount Active only in large doses
hepatitis B, HIV, etc.
They exhibit specific tissue They do not exhibit 4. Insects: They act as mechanical or biological vectors of
affinities specific tissue affinities
infectious diseases, e.g. dysentery and typhoid by
Pharmacological effects are Pharmacological effects are housefly, malaria by mosquito, etc.
specific for each exotoxins nonspecific, action is com- 5. Congenital: Some pathogens are able to cross the pla-
mon to all endotoxins
cental barrier and infect the fetus in utero. This is known
Highly antigenic and their Poor antigens and their as vertical transmission which may result in abortion or
action is specifically toxicity is not completely miscarriage.
neutralized by antibodies neutralized by the homolo-
gous antibodies
The infections may spread congenitally and infants may
be born with manifestation of disease, e.g. congenital
Its action is enzymatic They have no enzymatic action syphilis, rubella, etc.
They cannot cause pyrexia in a They can cause pyrexia in a Intrauterine infections with rubella may interfere
host host with organogenesis and lead to congenital malforma-
tions, such infections are known as teratogenic in-
fections.
Q. 2. Write briefly on methods of transmission of infec- 6. Iatrogenic and laboratory infections: Sometimes infec-
tion. tions may be transmitted during administration of injec-
Ans. Infection is the lodgment and multiplication of organ- tions, lumbar puncture, catheterization, etc. if proper
ism in or on the tissues of a host. care is lacking.
Modern methods of treatment like exchange transfu-
Various methods of transmission of infection are as follows: sion, dialysis and organ transplant surgery have in-
1. Contact: Various infections are acquired by the contact, creased the possibilities for atrogenic infections.
which may be direct or indirect. Laboratory personnel handling infectious material are at
a. The diseases spread by direct contact are sexually risk and special care should be taken to prevent labora-
transmitted diseases like syphilis and gonorrhoea. tory infection.
SHORT NOTES
Q. 1. Sources of infection marked by fever, leucopenia, thrombocytopenia, significant
fall in BP, circulatory collapse and bloody diarrhoea lead-
Ans.
ing to death.
The various sources of infection are as follows:
1. Humans: Humans themselves are the commonest source Q. 3. Write short note on bacterial virulence.
of infection. Ans. Virulence is referred to the ability of microbial strains
2. Animals to produce disease. For example: Polio virus contains strain
a. Bacterial—plague from rats of varying degree of virulence.
b. Viral—rabies from dogs
c. Protozoal—toxoplasmosis from cats Virulence is the sum total of following determinants:
d. Helmenthic—hydatid disease from dogs 1. Adhesion: The attachment of the bacteria to body sur-
e. Fungal—zoophilic dermatophytes from cats and dogs faces through adhesive structures are called adhesins.
3. Insects 2. Invasiveness: It is the ability of a pathogen to spread in
a. Domestic fly—transmits dysentery or typhoid bacilli a host tissue after establishing infection.
b. Aedes aegypti mosquito—in yellow fever 3. Toxigenicity: Some bacterial products like exotoxins
c. Anopheles mosquito—in malaria and endotoxins which cause fever, muscle proteolysis
4. Soil: Spores of tetanus bacilli remain viable in soil for and shock.
decades serving as source of infection. 4. Communicability: The ability of a parasite to spread
5. Water from one host to another is known as communicability.
a. Cholera vibrio It mainly determines the survival and distribution of
b. Infective hepatitis virus parasite in a community.
c. Cyclops in guinea worm infection 5. Other bacterial products: The other bacterial products
6. Food: Food poisoning by Staphylococcus like coagulase, fibrinolysin, hyaluronidase, haemolysin,
etc. though devoid of intrinsic toxicity may contribute to
Q. 2. Exotoxins and endotoxins virulence by inhibiting the mechanisms of host resis-
tance.
Ans.
6. Bacterial appendages: Certain bacteria will stand
Exotoxins phagocytosis, For example: Pneumococcus, influenza,
etc.
l Exotoxins are heat-labile proteins that are secreted by 7. Infecting dose: The minimum infection or minimum
certain species of bacteria and diffuse readily into the lethal dose (MLD) is minimum number of organisms
surrounding medium. required to produce death of susceptible animal.
l They are highly potent in minute quantities and consti- 8. Route of infection: Various microbes produce infec-
tute some of the most poisonous substances. tion through various routes. For example: Strepto-
l They are generally produced by the Gram-positive bac- cocci can initiate infection what ever may be the mode
teria but may also be produced by some Gram-negative of entry whereas Vibrio cholerae is effective only
bacteria. orally.
Endotoxins Q. 4. What are opportunistic infections?
l Endotoxins are heat-stable lipopolysaccharides which Ans. Opportunistic infections are those occurring in pa-
form an integral part of the Gram-negative bacterial tients with AIDS or other debilitating diseases like cancer,
cell wall. diabetes, etc. or in patients where the physiological status
l Their toxicity depends upon the lipid component (lipid A). has been upset by immunosuppressive drugs, steroids,
l They are active only in large doses. X-ray or broad-spectrum antibiotics caused by fungi. This
is normally avirulent.
Intravenous injections of large doses of endotoxin and
massive Gram-negative septicaemia cause endotoxic shock For example: Aspergillus, Mucor, Penicillium, Candida
Topic 9
Immunity
LONG ESSAY
Q. 1. Define and classify immunity. Discuss acquired 5. Once developed the active immunity is long lasting.
immunity. Following antigenic exposure it develops slowly over a
period of days or weeks but persists for a long time,
Ans.
usually for years.
The resistance exhibited by the host towards injury caused by 6. Active immunity is associated with immunological
microorganisms and their products is known as immunity. memory besides the development of humoral and cel-
Immunity may be classified into different types as follows: lular immunity.
7. It is more effective and confers better protection than
Innate or Native Immunity passive immunization.
8. Active immunity is of two types as follows:
a. Natural
Nonspecific Specific b. Artificial
9. Natural active immunity
a. It is acquired after the natural infection by the or-
Species Racial Individual Species Racial Individual ganisms or recovery from disease or subclinical
infection.
Acquired or Adaptive Immunity b. In large majority of cases, it occurs by subclinical
infections after repeated exposure to small doses of
the infecting organism which pass unnoticed.
Active Passive c. Subclinical attacks by pathogenic microorganisms
play important roles in preventing epidemics, e.g.
poliomyelitis, tuberculosis.
Natural Artificial Natural Artificial d. Natural active immunity may follow overt infec-
tions, e.g. smallpox.
e. Such immunity is usually long lasting.
ACQUIRED OR ADAPTIVE IMMUNITY 10. Artificial active immunity
1. The resistance that an individual acquires during life is a. It is the resistance produced by vaccination.
known as acquired immunity. b. Vaccines are the preparations of live attenuated
2. It is of two types as follows: or killed microorganisms or active materials de-
a. Active rived from the microorganisms (toxoids) used for
b. Passive immunization.
c. Examples of various vaccines are as follows:
i. Bacterial vaccines
I. Active Immunity
– Live: BCG, anthrax, plague, brucella vac-
1. It is the resistance developed by an individual as a re- cines
sult of an antigenic stimulus. – Killed: Cholera vaccine
2. It is also known as adaptive immunity as it represents – Subunit: Typhoid VI antigen
an adaptive response of the host to a specific pathogen – Bacterial products: Tetanus toxoid
or other antigen. ii. Viral vaccines:
3. It usually follows either natural infection or vaccina- – Live: Oral polio vaccine (sabin), smallpox,
tion. It involves active functioning of the person’s im- measles, influenza and mumps
mune apparatus leading to the synthesis of antibodies – Killed: Injectable polio vaccine (salk)
and production of immunologically active cells. – Subunit : Hepatitis B vaccine
4. It develops only after a latent period. iii. Toxoids: Tetanus, diphtheria
They are prepared by inactivating the bacterial exotox- The agents used for this purpose are as follows:
ins by formalin or alum so that immunogenicity is retained 1. Hyperimmune sera of animal or human origin
but not toxigenicity. 2. Convalescent sera
3. Pooled human gamma globulin
II. Passive Immunity These are used for prophylaxis and therapy.
1. Passive immunity is the resistance induced in the 1. Hyperimmune sera of animal or human origin: Animal
recipient by transfer of antibodies preformed against antitoxin serum is produced by injection of toxoid into
infective agent or toxin in another host. horses in increasing doses till the blood is rich in circu-
2. The immune system plays no active role and the protec- lating antibodies.
tive mechanism comes into force immediately after Equine hyperimmune sera like antitetanus serum and
transfer of antibodies or immune serum. ATS prepared from hyperimmunized horses used to be
3. Passive immunization lasts for a short period and is in- employed extensively.
dicated for immediate and temporary protection in a They gave temporary protection but carried the risk of
nonimmune host faced with the threat of infection. hypersensitivity and immune elimination.
4. It is useful when instant immunity is required. Nowadays antisera of animal origin are recommended
5. Passive immunity is of two types as follows: only where human preparations are not available, for
a. Natural example: Antibotulism and polyvalent antigas gangrene
b. Artificial sera, antivenoms, equine antisera against diphtheria.
2. Convalescent sera: Sera of the patients recovering from
infectious diseases containing high levels of specific
a. Natural Passive Immunity antibody.
It is the resistance transferred from the mother to fetus or 3. Pooled human immunoglobulin (gamma globulins from
infant. pooled sera of healthy adults): It is prepared from plasma
Example: Transfer of maternal IgG to fetus transplacentally pools of healthy adults containing high levels of antibod-
or transfer of maternal IgA to infant through colostrums ies against all common pathogens prevalent in the region.
(first milk of mother after delivery) which gives protection Convalescent sera and pooled human gamma globulins
to neonates. were used for passive immunization against some viral
infections like viral hepatitis A.
The half-life of human immunoglobulin is 26 days and the
b. Artificial Passive Immunity
effect of passive immunization may last for 3–4 months.
It is the resistance passively transferred to a recipient by the Human gammaglobulins are used in treatment of pa-
administration of antibodies. tients with some immunodeficiencies.
SHORT ESSAYS
Q. 1. Classify immunity and describe active immunity period of days or weeks but persists for a long time,
with example. usually for years.
l Active immunity is associated with immunological
Ans.
memory besides the development of humoral and cel-
l Active immunity is a type of acquired immunity and is lular immunity.
the resistance developed by an individual as a result of l Active immunity develops either in form of humoral or
an antigenic stimulus. cell mediated or both.

l It is also known as adaptive immunity as it represents an
adaptive response of the host to a specific pathogen or

Humoral or Antibody-mediated Immunity
other antigen. l It depends upon the active production of the antibodies
l It usually follows either natural infection or vaccination. against the antigens by the plasma cells.
It involves active functioning of the person’s immune l The specific circulating antibodies in the host combine
apparatus leading to the synthesis of antibodies and specifically with the corresponding antigens and modify
production of immunologically active cells. their activity.
l It develops only after a latent period. l Thus antigen molecules or particles may be clumped or
l Once developed the active immunity is long lasting. lysed, their toxins may be neutralized and readily re-
Following antigenic exposure it develops slowly over a moved after phagocytosis by neutrophils or macrophages.
l Tissue invasion by virus particles may be prevented by Acquired or Adaptive Immunity

neutralizing activity of antiviral antibody.
Cell-mediated Immunity Active Passive
l It mainly depends on the specifically developed T cells by

certain antigens. The sensitized T lymphocytes are impor- Natural Artificial Natural Artificial
tant in resistance to chronic bacterial infections character-
ized by intracellular parasitism like TB, brucellosis, leprosy
and also in some viral diseases like herpes simplex. Active Immunity
l Active immunity is of two types as follows:
1. It is the resistance developed by an individual as a result
a. Natural of an antigenic stimulus.
b. Artificial 2. It is also known as adaptive immunity as it represents an
l Natural active immunity
adaptive response of the host to a specific pathogen or
1. It is acquired after the natural infection by the organ- other antigen.
isms or recovery from disease or subclinical infection. 3. It usually follows either natural infection or vaccination.
2. In large majority of cases, it occurs by subclinical It involves active functioning of the person’s immune
infections after repeated exposure to small doses of apparatus leading to the synthesis of antibodies and
the infecting organism which pass unnoticed. production of immunologically active cells.
3. Subclinical attacks by pathogenic microorganisms 4. It is more effective and confers better protection than
play important roles in preventing epidemics. For passive immunization.
example: Poliomyelitis, tuberculosis. 5. Active immunity is of two types as follows:
4. Natural active immunity may follow overt infec- a. Natural
tions. Example: Smallpox b. Artificial
5. Such immunity is usually long lasting. 6. Natural active immunity
l Artificial active immunity
a. It is acquired after the natural infection by the organ-
a. It is the resistance produced by vaccination. isms or recovery from disease or subclinical infec-
b. Vaccines are the preparations of live attenuated or tion. Examples: Poliomyelitis, tuberculosis.
killed microorganisms or active materials derived 7. Artificial active immunity
from the microorganisms (toxoids) used for immuni- a. It is the resistance produced by vaccination.
zation. Examples of various vaccines are as follows: b. Vaccines are the preparations of live attenuated or
i. Bacterial vaccines killed microorganisms or active materials derived from
– Live: BCG, anthrax, plague, brucella vaccines the microorganisms (toxoids) used for immunization.
– Killed: Cholera vaccine c. Examples of various vaccines are as follows:
– Subunit: Typhoid VI antigen i. Bacterial vaccines:
– Bacterial products: Tetanus toxoid – Live: BCG, anthrax, plague, brucella vaccines
ii. Viral vaccines – Killed: Cholera vaccine
– Live: Oral polio vaccine (sabin), smallpox, – Subunit: Typhoid VI antigen
measles, influenza and mumps – Bacterial products: Tetanus toxoid
– Killed: Injectable polio vaccine (salk) ii. Viral vaccines
– Subunit: Hepatitis B vaccine – Live: Oral polio vaccine (sabin), smallpox,
iii. Toxoids: Tetanus, diphtheria measles, influenza and mumps
They are prepared by inactivating the bacterial exotoxins by – Killed: Injectable polio vaccine (salk)
formalin or alum so that immunogenicity is retained but not – Subunit : Hepatitis B vaccine
toxigenicity. iii. Toxoids: Tetanus, diphtheria
Active immunity is more effective and confers better
protection than passive immunization.
Passive Immunity
Q. 2. Describe briefly about acquired immunity. l Passive immunity is the resistance induced in the recipi-
Ans. ent by transfer of antibodies preformed against infective
agent or toxin in another host.
l The resistance that an individual acquires during life is l The immune system plays no active role and the protec-
known as acquired immunity. tive mechanism comes into force immediately after
l It is of two types: active and passive. transfer of antibodies or immune serum.
l Passive immunity is of two types as follows: Booster effect on subsequent Subsequent dose is less
a. Natural dose effective
b. Artificial It is not applicable in immu- It is applicable in immunode-
nodeficient individuals ficient individuals
Natural Passive Immunity It is used in prophylaxis to It is used for treatment of
It is the resistance transferred from the mother to fetus or increase the resistance of acute infection
the body
infant. For example: Transfer of maternal IgG to fetus
transplacentally or transfer of maternal IgA to infant In it both cell-mediated and In it humoral immunity is
through colostrums (first milk of mother after delivery) humoral immunity take part involved
which gives protection to neonates. No inheritance of immunity May be acquired from the
mother
Artificial Passive Immunity
l It is the resistance passively transferred to a recipient by
the administration of antibodies. Q. 4. Mechanism of innate immunity in an individual
l The agents used for this purpose are as follows: Ans.
1. Hyperimmune sera of animal or human origin
2. Convalescent sera l The resistance to infections which an individual pos-
3. Pooled human gamma globulin sesses by virtue of his or her genetic and constitutional
make-up is known as innate or native immunity.
These are used for prophylaxis and therapy. For example: l The mechanism of innate or native immunity is related
Antibotulism and polyvalent antigas gangrene sera, antive- to the following:
noms, equine antisera against diphtheria 1. Epithelial surfaces: Intact skin and mucous mem-
l Convalescent sera and pooled human gamma globulins
brane covering the body protect it against invasion
were used for passive immunization against some viral by microorganisms.
infections like viral hepatitis A. 2. Antibacterial substances in blood and tissues: The
l Human gamma globulins are used in treatment of pa-
complement system possesses bactericidal activity
tients with some immunodeficiencies. that plays an important role in the destruction of
Q. 3. Enumerate the differences between active and pathogenic bacteria that invade the blood and tissues.
passive immunity. For example: Beta-lysine, basic polypeptides like
leukins and plakins, acidic substances like lactic
Ans. The differences between active and passive immunity acid, lactoperoxidase in milk, etc.
are given in Table 9.1. 3. Microbial antagonisms: By resident bacterial flora of
skin and mucous surfaces.
TABLE 9.1 Differences between Active and Passive 4. Cellular factors in innate immunity is by phagocytic
Immunity cells like polymorphonuclear leucocytes and macro-
Active Immunity Passive Immunity
phages (histiocytes).
5. Inflammation is an important nonspecific defense
It is produced actively by It is received passively by
host’s immune system the host. No active
mechanism.
participation of host’s 6. Fever is a natural defense mechanism. It destroys the
immune system infecting pathogens; e.g. Treponema pallidum.
It is induced by infection or It is conferred by introduc- It stimulates the production of interferons and aids recovery
by immunogens tion of vaccines, i.e. ready- from viral infections.
made antibodies
Immunity effective only after Immunity is effective
7. Acute phase proteins: C-reactive protein (CRP) and
a period of lag immediately other acute phase proteins like mannose binding
protein, serum amyloid P component activate the
Durable effective protection It is transient and less effective
alternate pathway of complement system and en-
It exhibits immunological No immunological memory hance the host resistance, prevent tissue injury and
memory present
promote repair of inflammatory lesions.
SHORT NOTES
Q. 1. Write short note on acquired active immunity. l Natural passive immunity is a type of passive immunity
where the resistance is transferred from the mother to
Ans.
fetus or babies in the form of antibodies preformed
l Active immunity is a type of acquired immunity which
against infective agent or toxins.
is acquired during the lifetime of the individual.
l The immune system plays no active role and the protec-
l Active immunity is the resistance developed by an im-
tive mechanism comes into force immediately after
munity as the result of antigenic stimulus.
transfer of antibodies or immune serum.
l Active immunity is of two types as follows:
l Passive immunity is short living only for days or weeks.
a. Natural
l It is useful when instant immunity is required.
b. Artificial
l Natural active immunity: This is acquired after one infec- Examples:
tion or recovery from disease or subclinical infection after
1. Transfer of maternal IgG to fetus transplacentally
repeated exposure to small doses of infecting organism.
2. Transfer of material IgA to infant through colostrum
Examples:
Q. 3. Innate immunity
1. A person who has recovered from an attack of measles
develops natural active immunity. Ans.
2. Large majority of adults in developing countries posses
l The resistance to infections which an individual pos-
natural active immunity to poliomyelitis.
sesses by virtue of his or her genetic and constitutional
l Artificial active immunity: It may be acquired artificially
make-up is known as innate or native immunity.
by inoculation of bacteria, viruses or other products.
l It is not affected by prior contact with microorganisms
Examples: or immunization.
l It may be specific or nonspecific. It is specific where
1. Killed organisms without changing antigenic structure
resistance to a particular pathogen is concerned and
of bacteria, e.g. typhoid vaccine, cholera vaccine.
nonspecific when it indicates a degree of resistance to
2. Living organism after proper attenuation, e.g. smallpox
infections in general.
and BCG.
l Innate or native immunity is of three types as follows:
Q. 2. Natural passive immunity 1. Species immunity

2. Racial immunity
Ans. 3. Individual immunity
Topic 10
Antigens and Antibodies: Immunoglobulins,

Antigen–Antibody Reactions
SHORT ESSAYS
Q. 1. Immunoglobulin A l It is the major immunoglobulin present in colostrum,
Ans. bile, saliva and tears.
l Immunoglobulins or antibodies are specialized serum 1. Serum IgA
proteins that are formed in response to an antigen and 2. Secretory IgA
react specifically with that antigen. Immunoglobulin A
is the fast moving a-globulin. Serum IgA
l The second most abundant class of immunoglobulins is l Serum IgA is a monomer, i.e. only a single molecule of
IgA constituting 10–13% of serum immunoglobulins. the basic four polypeptide chains (H2L2).
l Its normal serum level is 0.6–4.2 mg/mL with half-life l Its molecular weight is 160,000 and the sedimentation
of 6–8 days. coefficient is 7 s.
Secretory IgA tissues. The process of suppressing homologous anti-

l Secretory imunoglobulin (SIgA) is much larger body synthesis by a feedback process is utilized in iso-
molecule than serum IgA with a molecular weight of immunization of women by the administration of anti-
400,000 and the sedimentation coefficient of 11 s. Rh (D) IgG during delivery.
Properties of SlgA IgA

l SIgA is a dimer formed by two monomer units joined l It is the fast moving a-globulin and the second most
together at their carboxyterminals by a glycopeptide abundant class of immunoglobulins, constituting 10–13%
termed as J chain. of serum immunoglobulins.
l Its normal serum level is 0.6–4.2 mg/mL with half-life
l SIgA contains a secretory component or secretory piece
which is a glycine-rich polypeptide produced by muco- of 6–8 days.

l It occurs in two forms, which are
sal or glandular epithelial cell and protects IgA from
denaturation by bacterial proteases in sites such as 1. serum IgA and
intestinal mucosa rich and varied in bacterial flora. 2. secretory IgA.
l It is found in high concentration in colostrums, tear,
l SIgA is selectively concentrated in secretions and on
mucosal surfaces forming an antibody paste. bile, saliva, intestinal and nasal secretions. It promotes
phagocytosis and intracellular killing of organisms.
Functions of SlgA
IgM
l Plays an important role in local immunity against respi-
l It is also known as macroglobulin. It appears to be spher-
ratory and intestinal pathogens.
ical shape. IgM is mostly intravascular in distribution
l Inhibition of adherence of microorganisms to the muco-
about 80%.
sal cell surface and thereby preventing their entry into
l It is not transported across the placenta and hence its detec-
body tissues.
tion in fetus or newborn indicates intrauterine infections
l It promotes phagocytosis and intracellular killing of
like syphilis, rubella, HIV infection and toxoplasmosis.
microorganism.
Q. 2. Write in brief about immunoglobulins. IgD

Ans. l It resembles IgG structurally and is mostly intravascular.
l IgD may function as mutually interacting antigen receptor
l Immunoglobulin is defined as a protein of animal origin
for the control of leucocyte activation and suppression.
also by lymphocytes. IgE

globulins may not be antibodies. and intestinal tracts.
Types of hypersensitive reaction and is mostly extravascular in
Various classes of immunoglobulins are as follows: distribution.
IgG cells and mediates the Prausnitz-Kustner reaction.

l Trace amounts of IgE, i.e. few nanograms per mL are
l It is the major serum immunoglobulin comprising 80% of present in normal serum but in atopic or type I allergic
the total immunoglobulins and distributed almost equally conditions like asthma, hay fever and eczema the levels
between intravascular and extravascular compartments. of IgE are greatly elevated.
l It is the only maternal immunoglobulin that passes l Physiological role of IgE
across the placenta and provides passive immunity to 1. Protection against pathogens by release of inflamma-
the newborn. tory mediators through mast cell degranulation.
l It is considered as general purpose antibody protective 2. Has special role in defence against helminthic infec-
against infectious agents that are active in blood and tions.
Functions 3. Prevention of microbial attachment to the host

cells
Functions of immunoglobulins are as follows: 4. Neutralization of toxins
1. Complement activation 5. Restriction of motility of microorganisms.
2. Opsonization resulting in phagocytosis
SHORT NOTES
Q. 1. Functions of antibodies tissues. The process of suppressing homologous antibody
synthesis by a feedback process is utilized in isoimmu-
Ans. The functions of antibodies are as follows:
nization of women by the administration of anti-Rh (D)
l IgA takes part in localized defence mechanisms in external IgG during delivery.
secretions like tears, saliva, colostrum, bile, etc.
l IgG is responsible for complement fixation and it is Q. 4. Write briefly about IgM.
the only maternal immunoglobulin that passes across Ans.
the placenta and provides passive immunity to the
newborn. l It is also known as macroglobulin. It appears to be
l IgD involves in recognition of antigen by B lympho- spherical in shape. IgM is mostly (80%) intravascular in
cyte. distribution constituting 5–8% of serum immunoglobu-
l IgE takes part in allergic reactions. lins.
l IgM is also responsible for complement fixation. It is l IgM is an immunoglobulin polymer made up of five
more effective than IgG in opsonization, bactericidal or four peptide subunits each bearing an extra CH
action and bacterial agglutination. domain.
l It is not transported across the placenta and hence its
Q. 2. Immunoglobulin A (IgA) detection in fetus or newborn indicates intrauterine in-
fections like syphilis, rubella, HIV infection and toxo-
Ans.
plasmosis.
l It is the fast moving alpha globulin and the second most l Functions
abundant class of immunoglobulins constituting 10–13% 1. IgM is the earliest antibody to be produced in any
of serum immunoglobulins. infection.
l Its normal serum level is 0.6–4.2 mg/mL with half-life 2. It is particularly suited to provide protection against
of 6–8 days. microorganisms and other large antigens having re-
l It occurs in two forms as follows: peating antigenic determinants on their structure.
1. serum IgA and 3. Monomeric IgM is the major antibody receptor on
2. secretory IgA. the surface of B lymphocytes for antigen recognition.
l It is found in high concentration in colostrums, tear,
bile, saliva, intestinal and nasal secretions. It promotes Q. 5. Precipitation reaction
phagocytosis and intracellular killing of organisms. Ans.
Q. 3. Write briefly about IgG. l In the presence of electrolytes (NaCl), at a suitable tem-
Ans. perature and pH when a soluble antigen combines with
antibody an antigen–antibody complex forms an insolu-
l It is the major serum immunoglobulin comprising ble precipitate.
80% of the total immunoglobulins and distributed al- l Precipitation test is very sensitive in detection of anti-
most equally between intravascular and extravascular gens while less sensitive in detecting antibodies.
compartments. l Precipitation test finds forensic application in
l It is the only maternal immunoglobulin that passes 1. medicolegal tests for identification of blood and
across the placenta and provides passive immunity to seminal stains,
the newborn. 2. testing food adulterants and
l It is considered as general purpose antibody protective 3. identification of bacteria and their antigenic compo-
against infectious agents that are active in blood and nents.
Q. 6. Name antigen–antibody reactions giving example l ELISA means enzyme-linked immunosorbent assay. It
of each. is a major type of heterogeneous enzyme immunoassay.
l ELISA is named so because it involves use of an im-
Ans. Antigen antibody reactions in vitro are known as
munosorbent which is an absorbing material specific for
serological reactions. They are useful in laboratory diag-
either antigen or antibody.
nosis of various diseases and in identification of infectious
l It is especially useful for the detection of rotavirus and
agent.
hepatitis A virus.
l Several variations of the ELISA technique have been
Various antigen antibody reactions are as follows:
1. Precipitation: VDRL test for syphilis (slide test), the developed to provide simple diagnostic tests suitable for
Kahn’s test for syphilis (tube flocculation test) clinical laboratory and bedside applications, e.g. card and
2. Agglutination: WIDAL test for typhoid, hemoaggluti- dipstick methods.
l Cylinder or cassette ELISA is a simple modification
nation test for blood grouping and typing, Coombs’ test
for detection of incomplete antibodies of ELISA used for detection of HIV type 1 and 2
3. Complement fixation: Test for kala-azar, amoebiasis, antibodies.
viral disease.
Q. 10. Agglutination
Q. 7. Immunoglobulin Ans.
Ans. l In the presence of electrolytes (NaCl) at a suitable
temperature and pH when a particulate antigen is
l Immunoglobulin is defined as a protein of animal origin
mixed with antibody then the particles are clumped or
agglutinated.
l For the detection of antibodies this is more sensitive
also by lymphocytes.
than precipitation reaction.
l Uses of agglutination are as follows:
globulins may not be.
a. Bacterial identification, e.g. serotyping of Salmo-
l Various classes of immunoglobulins are IgG, IgA, IgM,
nella and Shigella
IgD and IgE.
b. Haemoagglutination test, e.g. Paul-Bunnell and
Q. 8. Write briefly about IgE. RoseWaaler test
c. Serological diagnosis of infection, e.g. Widal test for
Ans. typhoid
d. For detection of incomplete antibodies, e.g. Coombs’
test
and intestinal tracts.
Q. 11. Coombs’ test
of hypersensitive reaction and is mostly extravascular in
distribution. Ans.
l This test was devised by Coombs, Mourant and Race for
cells and mediates the Prausnitz-Kustner reaction.
the detection of anti-Rh antibodies that do not aggluti-
l Trace amounts of IgE, i.e. few nanograms per millilitre
nate Rh-positive erythrocytes in saline.
are present in normal serum but in atopic or type I al-
l Coombs’ test may be direct or indirect.
lergic conditions like asthma, hay fever and eczema the
1. In the direct Coombs’ test the sensitization of eryth-
levels of IgE are greatly elevated.
rocytes with incomplete antibodies takes place in
l Physiological role of IgE
vivo, e.g. haemolytic disease of newborn where
1. Protection against pathogens by release of inflamma-
the direct Coombs’ test is negative due to ABO in-
tory mediators through mast cell degranulation.
compatibility.
2. Has special role in defence against helminthic
2. In the indirect Coombs’ test sensitization of erythro-
infections.
cytes with antibody globulin is performed in vitro,
e.g. detection of anti-Rh antibodies.
Q. 9. ELISA
3. Coombs’ test is useful in demonstrating any type of in-
Ans. complete or nonagglutinating antibody, e.g. brucellosis.
Topic 11
Complement Systems
SHORT NOTES
Q. 1. Complement system l The C cascade can be triggered off by two parallel but
independent mechanisms or pathways named as
Ans.
1. the classical C pathway and
l The complement ‘C’ refers to series of factors which oc- 2. the alternative or properdin pathway.
cur in normal serum and are activated by characteristic
antigen antibody interaction and subsequently mediate a Q. 2. Functions of complement
number of biologically significant consequences. Ans. The functions of complement are as follows:
l The complement system consists of
1. complement components, which are nothing but l It mediates immunological membrane damage like
chemically and immunologically distinct serum pro- cytolysis and bacteriolysis.
teins at least 20 in number, l It participates in the pathogenesis of certain hypersensitiv-
2. the properidin system, and ity reactions by amplifying the inflammatory response.
3. control proteins. l It exhibits antiviral activity and promotes phagocytosis
l When the activity of complement is induced by anti- and immune adherence.

gen–antibody interaction or any other stimuli, C compo- l It interacts with coagulation, fibrinolytic and kinino-
nents react in a specific sequence as a cascade. genic systems of blood.
Topic 12
Structure and Function of Immune System,

Immune Response and Immunodeficiency Diseases
SHORT ESSAYS
Q. 1. Interferon Beta-Interferon (IFN-b)
Ans. l Also known as fibroblast interferon.
l It is a glycoprotein produced by fibroblasts and epithe-
l Interferon was originally identified as antiviral agent but
lial cells following stimulation by viruses or polynucle-
now it is classified as a more general regulatory peptide
otides.
belonging to the class of cytokines.
l Interferons have been classified into three types as Gamma-Interferon (IFN-g)
follows:
l Also known as immune interferon
1. Alpha-interferon (IFN-a)
l It is a glycoprotein produced by T lymphocytes on
2. Beta-interferon (IFN-b)
stimulation by antigens or mitogens.
3. Gamma-interferon (IFN-g)
l It is more involved in immunomodulatory and antipro-
Alpha-Interferon (IFN-a) liferative functions than antiviral defence.
l Also known as leucocyte interferon. The main biological effects of interferons are as follows:
l It is a nonglycosylated protein produced by leucocytes 1. Antiviral effects—by induction of resistance to infec-
following induction by suitable viruses. tions
2. Antimicrobial effects—by inducing resistance to intra- a. IFN-a

cellular parasitic infections like malaria, toxoplasmosis b. IFN-b
and chlamydia c. IFN-g
3. Cellular effects 6 . Others
a. Inhibition of cell growth and proliferation as well as a. Transforming growth factor-b (TGF-b)
DNA and protein synthesis b. Leukaemia inhibitory factor (LIF)
b. Increased expression of MHC antigens on cell surfaces
4. Immunoregulatory effects Q. 3. Major histocompatibility complex (MHC)
a. Enhanced cytotoxic activity of NK, K and T cells Ans.
b. Activation of macrophage cytocidal activity
c. Modulation of antibody formation l The cell surface antigens that induce an immune re-
d. Activation of suppressor T cells sponse leading to rejection of allografts are known as
e. Suppression of DTH histocompatibility antigens.
H-2 antigen system was found to be major histocompat-
Q. 2. Cytokines ibility antigen for mice and to be coded for by a closely
Ans. linked multiallelic cluster of genes which were called
the major histocompatibility complex.
l Cytokines are peptide mediators or intercellular mes- l Major histocompatibility complex is a closely linked
sengers which regulate immunological, inflammatory multiallelic cluster of genes which codes for those cell
and reparative host responses. surface antigens or histocompatibility antigens that
l They are produced by widely distributed cells like lym- induce a strong effect on the incompatibility of tis-
phocytes, macrophages, platelets and fibroblasts. sues between genetically nonidentical individuals
l They are highly potent hormone-like substances active (allografts).
even at femtomolar (10215 m) concentration. l These genes are located on a segment of one chromo-
l In general they are pleiotropic with multiple effects on some pair and codes for three different classes of
growth and differentiation of various cells. There is consid- proteins.
erable overlap in the effect produced by different cytokines. 1. Class I proteins that determine histocompatibility
l They exhibit paracrine or autocrine effects. Paracrine fate of allograft.
effect means they act locally near the producing cells; au- 2. Class II proteins that regulate the immune response.
tocrine effect means directly on the cells producing them. 3. Class III proteins that include some components of
l Production of cytokines is regulated by exogenous stimuli complement system and few others.
like antigens and mitogens, as well as by endogenous fac- 4. In human beings the major antigens determining
tors such as neuroendocrine hormonal peptides like corti- histocompatibility are characteristically found on the
costeroids, endorphins and eicosanoids as well as prod- surface of leucocytes; hence are called human leuco-
ucts of lipoxygenase and cyclooxygenase pathways. They cyte antigen (HLA) complex.
regulate each other by positive and negative feedbacks. l Role of HLA antigens in immunity
l Cytokines and their agonists and antagonists may be a. The importance of HLA antigens in immunity is in-
used in the management of inflammatory, infectious, dicated by the fact that T cells respond to processed
autoimmune and neoplastic conditions. antigens on the macrophages and other antigen pre-
senting cells only when they are presented along
Examples with the self-HLA antigen.
Some of the important cytokines are as follows: b. Protein antigens processed by macrophages or den-
1. Interleukins 1–13 dritic cells to form small peptides are presented to
2. Colony stimulating factors (CSF) CD8 or CD4 T cells.
a. Granulocyte-macrophage colony stimulating factor c. The CD8 T cells will recognize antigen only when
(GM-CSF) presented as a complex with the HLA class I antigen
b. Granulocyte-colony stimulating factor (G-CSF) and CD4 T cells when presented as a complex with
c. Mononuclear and colony stimulating factor (M-CSF) HLA class II antigen.
3. Tumour necrosis factors (TNF) d. Class I HLA antigens are responsible for graft rejec-
a. TNF-a tion and destruction of virus infected cells while class
b. TNF-b II HLA antigens are responsible for the graft versus
4. Interferons (IFN) host reaction and the mixed leucocyte reaction.
SHORT NOTES
Q. 1. Cytokines c. Lymphokines affecting granulocytes
i. Colony stimulating factor (CSF)
Ans.
ii. Chemotactic factor
l Cytokines are peptide mediators or intercellular mes- d. Lymphokines affecting cultured cells
sengers which regulate immunological, inflammatory i. Lymphotoxin (LT)
and reparative host responses. ii. Interferons (IFN)
l They are produced by widely distributed cells like lym-
Q. 3. B lymphocytes
phocytes, macrophages, platelets and fibroblasts.
l They are highly potent hormone-like substances active Ans.
even at femtomolar (10215 m) concentration.
l In general they are pleiotropic with multiple effects on
l B-lymphocyte precursors, pro-B cells during embryonic
growth and differentiation of various cells. life develop in fetal liver and afterwards continuously
l Examples
throughout life in the bone marrow.
l When viewed under scanning microscope B cells have an
Some of the important cytokines are as follows: extensively filamentous surface, with numerous microvilli.
1. Interleukins 1–6 l B cells have immunoglobulins on their surface. Each B
2. Colony stimulating factors (CSF) cell approximately carries about 105 identical Ig mole-
3. Tumour necrosis factors (TNF) cules on its surface. The surface Ig on a B cell will have
4. Interferons (IFN) only single antigen specificity. Therefore, it serves as
the antigen recognition unit.
Q. 2. Lymphokines l B cells undergo blast transformation with bacterial en-
Ans. dotoxins Staphylococcus aureus or Epstein-Barr virus.
l Biologically active substances released by activated Q. 4. Role of T and B cells in immune response
T lymphocytes responsible for manifestation of cell- Ans.
mediated immunity (CMI) are called lymphokines.
l Macrophages under the effect of lymphokines cause l T and B cells play an important role in immune
destruction of microorganisms involved in CMI. response.
l They participate in many functions of T cells and trans- l T cells
mit various growth, differentiation and behavioural sig- 1. Activated T cells on antigenic stimulation produce
nals between the cells of immune system. an array of cytokines which are important for pro-
l Examples duction and regulation of immune response.
a. Lymphokines affecting lymphocytes are 2. Some T cells are also involved in killing of viruses
i. Blastogenic factor (BF) by recognition of viral antigens.
ii. T cells growth factor (TGF) 3. T cells are also involved with allograft rejection.
iii. B cells growth factor (BGF) l B cells
b. Lymphokines affecting macrophages a. B cells produce antibody-mediated immune response

i. Migration inhibiting factor (MIF) by specific differentiation and proliferation of plasma
ii. Macrophage chemotactic factor (MCF) cells which produce antigen specific antibodies.
Topic 13
Hypersensitivity
LONG ESSAY
Q. 1. Define and classify hypersensitivity. Describe ana- Factors influencing anaphylaxis are as follows:
phylaxis.
i. Sensitization
Ans.
a. Sensitization may occur by any route such as injec-
Definition tion, ingestion, inhalation or contact. But it is most
effective when the antigen is introduced parenterally.
Hypersensitivity or allergy refers to a condition is which b. Minute dose (0.l mg) of antigen can sensitize suscep-
immune response results in excessive or exaggerated tible host. Once sensitized, the individual remains so
reactions leading to tissue damage, disease or even death for long period.
following contact with specific antigens.
ii. Waiting Period
Classification of Hypersensitivity a. There should be an interval of at least 2–3 weeks
between the sensitizing dose and the shocking dose.
1. Based on the time required for a sensitized host to de- b. During this interval cytotrophic antibody IgE is pro-
velop clinical reactions on re-exposure to the antigen duced against the antigen attached to mast cell and
hypersensitivity is classified into following types: basophils.
a. Immediate hypersensitivity
b. Delayed hypersensitivity iii. Shocking or Eliciting Dose
a. When injected intravenously the shocking dose is
They are subdivided into several distinct clinical types as
most effective and is less effective intraperitoneally
follows:
or subcutaneously and least effective intradermally.
a. Immediate hypersensitivity (B cell or antibody-
b. Antigens as well as haptens can induce anaphylaxis.
mediated)
c. The shocking antigens must be identical or immuno-
i. Anaphylaxis
logically closely related to the sensitizing antigen.
ii. Atopy
iii. Antibody-mediated cell damage
Mechanism of Anaphylaxis
iv. Arthus phenomenon
v. Serum sickness 1. Cytotropic IgE antibody is the major antibody respon-
b. Delayed hypersensitivity (T cell-mediated) sible for anaphylaxis. Free IgE antibody in circulation is
i. Infection (tuberculin) type not relevant in anaphylaxis.
ii. Contact dermatitis type 2. On introduction of the shocking dose of the antigen, cer-
2. Coombs and Gell (1963) classified hypersensitivity retain subsets of T helper cells produce particular profiles
actions into following four types based on the different of lymphokines which are responsible for production of
mechanisms of pathogenesis: IgE by B cells.
a. Type I (anaphylactic, IgE or regain dependant type) 3. IgE molecules are bound to the surface receptors on the
b. Type II (cytotoxic or cell stimulating) mast cells and basophils. These cells carry large number
c. Type III (immune complex or toxic complex disease) of surface receptors called FcER receptors analogous to
d. Type IV (delayed or cell-mediated hypersensitivity) TCR receptors on T cell surface. IgE molecules attach
This classification is now widely used. to these receptors by their Fc end.
4. Following exposure to the shocking dose, the antigen
molecules combine with the cell-bound IgE, bridging
Anaphylaxis the gap between adjacent antibody molecules.
1. It is the typical classical immediate hypersensitivity reac- 5. This crosslinking increases the permeability of the cell
tion. The term anaphylaxis was coined by Richet (1902). to the calcium ions and leads to degranulation which
2. It is a type of IgE-mediated hypersensitivity reaction, releases biologically active substances contained in the
which develops quickly after introduction of a large granules. It is these biologically active substances or
shocking dose of antigen following one or more small chemical mediators which are responsible for the mani-
sensitizing doses. festations of the anaphylaxis.
6. Two kinds of pharmacological mediators responsible a. Prostaglandins and Leukotrienes

for the manifestations of the anaphylaxis are They are derived from arachidonic acid by cyclooxygenase
a. primary mediators and and lipooxygenase pathways respectively.
b. secondary mediators. 1. Prostaglandin F2 a and thromboxane A2 are powerful,
but transient bronchoconstrictors.
A. Primary Mediators 2. Slow reacting substance of anaphylaxis (SRS-A) is
identified as a family of leukotrienes (LTB4, LIC4,
1. These are preformed contents of mast cells and baso-
LTD4, LTE4) and are produced by leucocytes.
phile granules. They are
3. They increase the vascular permeability and smooth
a. histamine,
muscle contraction.
b. serotonin,
c. eosinophil chemotactic factor of anaphylaxis, b. Platelet-Activating Factor
d. neutrophil chemotactic factor, 1. It is a low molecular weight lipid released from baso-
e. heparin and phils and causes aggregation of platelets and releases
f. various proteolytic enzymes. their vasoactive amines.
a. Histamine Other Mediators of Anaphylaxis
1. It is the most important vasoactive amine in human ana- 1. Several other biologically active substances have been
phylaxis. It is formed by the decarboxylation of histidine implicated in anaphylaxis, which include the anaphylatox-
found in the granules of mast cells, basophils and platelets. ins released by complement activation and bradykinin and
2. Histamine stimulates sensory nerves producing burning other kinins formed from plasma kininogens.
and itching sensations once released in to the skin.
3. It causes vasodilatation and hyperemia by an axon re- Manifestations of Anaphylaxis
flex (flare effect) and oedema by increasing capillary
1. Clinical effects of anaphylaxis are due to smooth mus-
permeability (wheal effect).
cle contraction and increased vascular permeability.
4. Histamine induces smooth muscle contraction in diverse
2. Slight cellular damage occurs. The organs affected vary
tissues and organs, including vasculature, intestines, GI
with the species. Organs predominately involved are
tract, uterus and especially bronchioles.
called target tissues or shock organs.
5. It also stimulates secretions (secretagogue effect).
3. In human beings fatal anaphylaxis is rare.
b. Serotonin (5-Hydroxy Tryptamine) a. The manifestations of the anaphylaxis depend upon
the species of animal, amount of shocking dose, site
1. It is derived from decarboxylation of tryptophan and is
of injection and portal of entry of antigen.
found in the intestinal mucosa, brain tissue and platelets.
b. Reaction occurs immediately within a few seconds
2. It causes smooth muscle contraction, increased vascular
to few minutes following administration of shocking
permeability and vasoconstriction.
dose of antigen and is of short duration.
c. Chemotactic Factors c. IgE antibodies have affinity mainly for skin cells.
1. The eosinophil chemotactic factors of anaphylaxis Various forms of anaphylaxis in humans are as follows:
(ECF-A) are acidic tetrapeptides released from mast cell
granules, which are strongly chemotactic for eosinophils. a. Systemic Anaphylaxis
These may contribute to eosinophilia accompanying 1. Is produced due to parenteral administration of a large
many hypersensitivity states. shocking dose of antigen. The signs and symptoms be-
2. A high molecular weight chemotactic factor which at- gin with itching of the scalp and tongue, flushing of skin
tracts neutrophils (NCF) responsible for chemotaxis of over the whole body and difficulty in breathing due to
the neutrophils has been identified. bronchospasm and laryngeal oedema.
2. There is also nausea, vomiting, abdominal pain and di-
d. Enzymes arrhoea with blood in stool, occasionally acute hypoten-
Proteolytic enzymes such as proteases and hydrolyses are sion, loss of consciousness and death follows.
also released from the mast cell granules and they damage 3. The lung is the principal shock organ.
the neighbouring cells. 4. Administration of 0.5 mL of 1:1000 solution of adrena-
line subcutaneously or intramuscularly is life saving.
B. Secondary Mediators b. Cutaneous Anaphylaxis
These are newly formed substances on stimulation of the mast 1. It is produced on administration of small shocking dose
cells, basophils and other leucocytes. They are as follows: of an antigen intradermally to a sensitized host. It is
manifested by appearance of local wheal and flare re- c. Mucosal Anaphylaxis

sponse, urticaria or angioneurotic oedema. 1. Application of small dose of antigen on mucosal surface
2 . It is useful in testing hypersensitivity to any particular such as conjunctiva, nasal mucosa, respiratory tract leads to
drug or allergen. conjunctivitis, rhinorrhoea and bronchospasm respectively.
SHORT ESSAYS
Q. 1. Define hypersensitivity. Describe in detail the prin- leading to tissue damage, disease or even death following
ciple and mechanism of hypersensitive reaction. contact with specific antigens.
Ans.
Classification of Hypersensitivity
Definition
1. Based on the time required for a sensitized host to de-
Hypersensitivity or allergy refers to a condition in which velop clinical reactions on re-exposure to the antigen
immune response results in excessive or exaggerated reac- hypersensitivity is classified into following types:
tions leading to tissue damage, disease or even death fol- a. Immediate hypersensitivity
lowing contact with specific antigens. b. Delayed hypersensitivity
The principle and mechanism of hypersensitive reaction is
They are subdivided into several distinct clinical types as
as follows:
follows:
1. Cytotropic IgE antibody is the major antibody respon-
a. Immediate hypersensitivity (B cell- or antibody-
sible for anaphylaxis, it is induced by allergen and
mediated)
binds to mast cells and basophils. When exposed to
i. Anaphylaxis
the allergen again, the bound IgE is crosslinked which
ii. Atopy
induces degranulation and releases mediators like
iii. Antibody-mediated cell damage
histamine.
2. Antigens on a cell surface combine with antibody; this
v. Serum sickness
leads to complement-mediated lysis, e.g. transfusion or
b. Delayed hypersensitivity (T cell-mediated)
Rh reactions, or autoimmune haemolytic anaemia.
i. Infection (tuberculin) type
3. Antigen–antibody immune complexes are deposited in
ii. Contact dermatitis type
tissues, complement is activated and polymorphonu-
2. Coombs and Gell (1963) classified hypersensitivity re-
clear cells are attracted to the site. They release lyso-
actions into following four types based on the different
somal enzymes, causing tissue damage.
mechanisms of pathogenesis:
4. Helper T lymphocytes sensitized by antigen release
a. Type I (anaphylactic, IgE or regain dependant type)
lymphokines upon second contact with same antigen.
b. Type II (cytotoxic or cell stimulating)
The lymphokines induce inflammation and activate
c. Type III (immune complex or toxic complex disease)
macrophages, which in turn, release various mediators.
d. Type IV (delayed or cell-mediated hypersensitivity)
5. This increases the permeability of the cell to the calcium
ions and leads to degranulation which releases biologi- This classification is now widely used.
cally active substances contained in the granules. It is
these biologically active substances or chemical media- Serum Sickness
tors which are responsible for the manifestations of the
anaphylaxis. l It is a systemic form of type III hypersensitivity, which
6. Two kinds of pharmacological mediators, i.e. primary appears 7–12 days following a single injection of a high
mediators and secondary mediators are responsible for concentration of foreign serum such as diphtheria anti-
the manifestations of the anaphylaxis. toxin.
l The clinical syndrome consists of fever, lymphadenopa-
Q. 2. Classify hypersensitivity and write about serum thy, splenomegaly, arthritis, glomerulonephritis, endocar-
sickness. ditis, vasculitis, urticarial rashes, abdominal pain, nausea
and vomiting.
Ans. l Pathogenesis: Consists of the formation of immune
complexes between the foreign serum and antibody to

Definition it, which gets deposited on the endothelial lining of the
Hypersensitivity or allergy refers to a condition in which im- blood vessels in the various parts of the body resulting
mune response results in excessive or exaggerated reactions in inflammatory infiltration.
l Due to massive complement activation and fixation by haemolytic anaemia, agranulocytosis and thrombo-
antigen–antibody complexes the plasma concentration cytopenic purpura.
of the complement falls and the disease is self-limited. l In some type II reactions, the antibody on combining
l The immune complexes become larger and susceptible with the cell surface receptors disrupts the normal func-
to phagocytosis and immune elimination with continued tion of the cell either by uncontrolled activation, e.g.
rise in antibody production. Graves’ disease or blocking of the receptors, e.g. myas-
l When all the foreign antigen is eliminated and free anti- thenia gravis.
body appears, the symptoms clear without any sequelae. l Type II hypersensitivity reactions are intermediate
l With subsequent injections, the disease appears early as between hypersensitivity and autoimmunity.
the antibodies are already present in the body.
l Serum sickness differs from the other types of sensitiv- Q. 5. Write briefly on type III hypersensitivity.
ity reactions that here a single injection serves as both
the sensitizing and shocking dose. Ans.
l Type III hypersensitivity is also called as immune com-

Q. 3. Delayed hypersensitivity
plex or toxic complex disease. It is a type of humoral
Ans. antibody mediated hypersensitivity reaction.
l Here the tissue damage is caused by Ag–Ab complexes.
l Delayed hypersensitivity or type IV hypersensitivity They precipitate in and around small blood vessels,
constitutes one aspect of cell-mediated immune re- causing damage to cells secondarily or on membranes,
sponse. interfering with their function.
l These are typically provoked by intracellular infections
l Pathogenesis
or haptens-like simple chemicals applied on skin, evolve 1. When an antigen combines with its corresponding
slowly and consist of a mixed cellular reaction involv- antibody, Ag–Ab complex is formed.
ing lymphocytes and especially macrophages. 2. Normally these immune complexes are removed by the
l The reaction is induced by sensitized T cells which on
reticuloendothelial system whereas RE cells are ineffi-
contact with specific antigen, release cytokines that cient to remove smaller complexes formed in antigen
cause biological effects on leucocytes, macrophages excess which occasionally persists and are deposited in
and tissue cells. body tissues, which activate the complement system.
l Delayed hypersensivity can be transferred by lympho-
3. The resulting complement fragments attract poly-
cytes or the transfer factor. morphonuclear leucocytes and platelets causing in-
l There are two types of delayed hypersensivity as
flammation and tissue injury.
follows: l Types
1. The tuberculin (infection) type
2. The contact dermatitis type Two types of typical type III reactions are
a. Arthus reaction (localized) and
Examples of delayed hypersensitivity response:
b. Serum sickness (generalized).
1. Tuberculosis—tuberculin testing
2. Typhoid fever
3. Allergic contact dermatitis Arthus Reaction
4. Graft rejection It is a localized form of type III hypersensitivity. When an
antigen is injected subcutaneously or intradermally in an
Q. 4. Type II hypersensitivity
animal in whom there were repeated administration of the
Ans. same antigen previously, there occurs intense local oedema
and haemorrhage which reaches peak in 3–6 h, this is called
l Type II hypersensitivity reactions are also called as cyto- as Arthus reaction.
toxic or cell stimulating reactions because they involve a
combination of IgG antibodies with the antigenic deter-
Serum Sickness
minants on the surface of cell leading to cytolytic or
cytotoxic effects. For example: Autoimmune anaemia It is a systemic form of type III hypersensitivity, which ap-
and haemolytic disease of the newborn. pears 7–12 days following a single injection of a high con-
l Following antigen and antibody reaction cell dam- centration of foreign serum such as diphtheria antitoxin.
age may occur even if a free antigen or hapten is The clinical syndrome consists of fever, lymphadenopathy,
absorbed on the cell surface. Numerous drugs may splenomegaly, arthritis, glomerulonephritis, endocarditis,
act in this manner leading to complement-mediated vasculitis, urticarial rashes, abdominal pain, nausea and
lysis of red cells, leucocytes and platelets causing vomiting.
SHORT NOTES
Q. 1. Classify hypersensitive reactions. concentration of foreign serum such as diphtheria anti-
toxin.
Ans.
l The clinical syndrome consists of fever, lymphadenopa-
Classification of Hypersensitivity thy, splenomegaly, arthritis, glomerulonephritis, endo-

carditis, vasculitis, urticarial rashes, abdominal pain,
1. Based on the time required for a sensitized host to de- nausea and vomiting.
velop clinical reactions on re-exposure to the antigen l Pathogenesis: Consists of the formation of immune
hypersensitivity is classified into following types: complexes between the foreign serum and antibody to
a. Immediate hypersensitivity it, which gets deposited on the endothelial lining of the
b. Delayed hypersensitivity blood vessels in the various parts of the body resulting
They are subdivided into several distinct clinical types as in inflammatory infiltration.
l Due to massive complement activation and fixation by
follows:
a. Immediate hypersensitivity (B cell- or antibody- antigen–antibody complexes the plasma concentration
mediated) of the complement falls and the disease is self-limited.
i. Anaphylaxis Q. 4. Arthus reaction
ii. Atopy
iii. Antibody-mediated cell damage Ans.
l Arthus reaction is a localized form of type III hypersen-
v. Serum sickness
sitivity.
b. Delayed hypersensitivity (T cell-mediated)
l When an antigen is injected subcutaneously or intra-
i. Infection (tuberculin) type
dermally in an animal in whom there were repeated
ii. Contact dermatitis type
administration of the same antigen previously, there
2. Coombs and Gell (1963) classified hypersensitivity re-
occurs intense local oedema and haemorrhage which
actions into following four types based on the different
reaches peak in 3–6 h, this is called as Arthus
mechanisms of pathogenesis:
reaction.
a. Type I (anaphylactic, IgE or regain dependant type)
l It occurs at a local site in and around the walls of small blood
b. Type II (cytotoxic or cell stimulating)
vessels when an appreciable level of precipitating IgG
c. Type III (immune complex or toxic complex disease)
antibody is produced following repeated immunization.
d. Type IV (delayed or cell-mediated hypersensitivity)
l Neutrophils ingest the complexes and release lysosomal
This classification is now widely used. enzymes which damage neighbouring cells and cause
necrosis and inflammatory reaction.
Q. 2. Tuberculin reaction l Platelet aggregation also causes vascular occlusion
leading to ischaemic necrosis of blood vessels.

Ans.
l Tuberculin reaction is the archetype of delayed hypersen- Q. 5. Type I hypersensitive reaction
sitivity. When a small dose of tuberculin is injected intra- Ans.
dermally in an individual sensitized to tuberculoprotein by
prior infection or immunization, an indurated inflammatory l Type I hypersensitivity is a B cell-mediated immediate
reaction develops at the site within 48–72 h. The tuberculin type of hypersensitivity. The antibody involved is IgE.
injection provokes no response in unsensitized individuals. l Antibodies are fixed on the surface of tissue cells, i.e.
l The tuberculin test provides useful indication of the mast cells and basophils in a sensitized individual.
state of delayed hypersensitivity to the bacilli. l The antigen combines with the cell-fixed antibody, lead-
l Tuberculin type of hypersensitivity develops in many infec- ing to release of pharmacologically active substances, i.e.
tions with bacteria, fungi, viruses and parasites especially vasoactive amines which produce the clinical reaction.
when infection is subacute or chronic and the pathogen l It occurs in two forms as follows:
is intracellular. Similar type of hypersensitivity develops 1. The acute, potentially fatal systemic form called
in allograft reaction and many autoimmune diseases. anaphylaxis.
2. The chronic or recurrent, nonfatal typically localized
Q. 3. Serum sickness form called atopy.
Ans. Q. 6. Clinical types of immediate type of hypersensitive

reaction
l It is a systemic form of type III hypersensitivity, which
appears 7–12 days following a single injection of a high Ans.
l Based on the time required for a sensitized host to de- the thrombi leading to necrosis of vessel walls and
velop clinical reactions on re-exposure to the antigen haemorrhage.
hypersensitivity is classified into immediate hypersensi- l Because of the absence of specificity and the short interval
tivity and delayed hypersensitivity. between the two doses there is no immunological basis for
l They are subdivided into several distinct clinical types. the reaction. Because of superficial resemblance it is usu-
l The clinical types of immediate hypersensitivity (B cell ally described along with hypersensitivity reactions.
or antibody mediated) are as follows:
1. Anaphylaxis Q. 8. Atopy
2. Atopy Ans.
3. Antibody-mediated cell damage
4. Arthus phenomenon l Atopy is a form of type I hypersensitivity naturally oc-
5. Serum sickness curring in human beings with familial distribution, e.g.
hay fever and asthma.
Q. 7. Shwartzman reaction l Features of atopy
Ans. 1. Atopy shows marked familial distribution and the

inheritance is probably linked to MHC genotype.
l Shwartzman in 1928 observed that if a culture of Salmo- 2. The antigens commonly involved are characteristi-
nella typhi is injected intradermally in a rabbit, followed cally inhalants or ingestants. Some are contact allergens.
24 h later by the same filtrate intravenously, a haemor- 3. The artificial induction of atopy is difficult. Atopic
rhagic necrotic lesion develops at the site of intradermal sensitization is developed spontaneously following
injection. natural contact with atopens.
l The initial or preparatory dose is characteristically an 4. Atopy is IgE-mediated hypersensitivity reaction.
endotoxin, the intravenous injection can be a variety of 5. The antigen–antibody complex stimulates the re-
substances like bacterial endotoxins, Ag–Ab complexes, lease of mediators that are responsible for the mani-
serum, starch, etc. festations of the atopy.
l The preparatory injection causes an accumulation of l Manifestations of atopy are usually determined by the por-
leucocytes which condition the site by release of lyso- tal of entry, i.e. conjunctivitis, rhinitis, bronchospasm, GI
somal enzymes damaging capillary walls. Following symptoms and dermatitis following exposure through eyes,
provocative dose there occurs intravascular clotting, nose, respiratory tract, intestines and skin respectively.
Topic 14
Autoimmunity, Immunology of Transplantation

and Malignancy
SHORT ESSAYS
Q. 1. Write a short note on autoimmunity. 1. Immunological Factors
1. Immunological damage resulting from immune re-
Ans.
sponses induced by crossreacting antigens.
l Autoimmunity is a condition in which structural or 2. Polyclonal B cell activation: Generation of self-reacting
functional damage is produced by the action of immu- B cell clone due to certain stimuli-like chemicals
nologically competent cells or antibodies against nor- (2-mercaptoethanol), bacterial products (PPD, lipopoly-
mal components of the body. saccharide), enzymes (trypsin), antibiotics (nystatin) and
l Autoimmunity is a state in which the body immune infections with some bacteria (mycoplasma), viruses
system fails to distinguish between self and nonself and (Epstein-Barr virus) and parasites (malaria).
reacts by formation of autoantibodies against one’s own 3. Enhanced helper T cell and decreased suppressor T cell
tissue antigens. functions
l Pathogenesis of Autoimmunity 4. Defects in the thymus, in stem cell development and
macrophage function
The mechanisms by which the immune tolerance of body is 5. Sequestered antigens released from tissues, e.g. lens
broken causing autoimmunity are as follows: antigen of the eye
6. Defects in the idiotype—anti-idiotype network 2. Localized or Organ-Specific Diseases

In these, the autoantibodies formed react specially against
2. Genetic Factors
an organ or target tissue component. For example:
1. Defective IR or immunoglobulin genes a. Autoimmune diseases of thyroid gland
2. Increased familial incidence of some of the autoimmune i. Hashimoto’s disease (lymphadenoid goitre)
disorders ii. Thyrotoxicosis (Graves’ disease)
b. Addison’s disease
3. Microbial Factors
c. Myasthenia gravis
1. Infections with microorganisms especially viruses, e.g. EBV d. Insulin-dependent diabetes mellitus
infection, less commonly by bacteria and mycoplasma. e. Pernicious anaemia
Q. 2. Autoimmune diseases 3. Systemic or Nonorgan-Specific Diseases Causes
Systemic Lesions. For Example:
Ans. Depending upon the site of involvement and nature of
lesions, autoimmune diseases are classified as follows: a. Systemic lupus erythematosus
b. Rheumatoid arthritis
1 . Haemocytolytic c. Scleroderma
2. Localized (organ-specific) d. Polyarteritis nodosa
3. Systemic or (nonorgan-specific) e. Sjogren’s syndrome
4. Transitory diseases
4. Transitory Diseases
1. Haemocytolytic Autoimmune Diseases The disease is transient and undergoes spontaneous
a. Autoimmune haemolytic anaemias cure once the infection is controlled or the drug is
b. Autoimmune thrombocytopenia withdrawn. For example: Anaemia, thrombocytopenia,
c. Autoimmune leucopenia nephritis, etc.
SHORT NOTE
Q. 1. Allograft reaction known as the first set response or first set rejection or
reaction.
Ans. When an allograft is performed, i.e. graft from
an animal is applied on a genetically unrelated animal If in an animal which has rejected the graft by the first set
of the same species the graft appears to be accepted response another graft from the same donor is applied, it
initially but later around 10 days the graft assumes will be rejected in an accelerated fashion. Necrosis sets in
a scab-like appearance and sloughs off. This sequence early and the graft sloughs off by the sixth day. The acceler-
of events resulting in rejection of the allograft is ated allograft rejection is known as the second set response.
Topic 15
Miscellaneous
SHORT ESSAY
Q. 1. Hospital acquired infection at the time of hospitalization are known as hospital
Or, acquired infections or nosocomial infections.
l They may manifest during their stay in the hospital or
Nosocomial infection sometimes after the patient is discharged.
l They may spread through droplet infections, dust,
Ans.
skin scales, inanimate sources; spread directly
l The infections developing in patients after admission to through contact and indirectly through equipments
hospital which were neither present nor in incubation and materials.
Factors Favouring Infection 2. Lower respiratory Haemophilus influenzae,

tract infections Streptococcus pneumoniae,
1. Age: Due to their inefficient immunity neonates and elderly (15–20%) Staphylococcus aureus,
people have a greater risk towards nosocomial infections. Enterobacteriaceae, etc.
2. Infected patients: These people are the source of spread
3. GI infections Salmonella, Shigella sonnei,
of infection to their close contacts. viruses
3. Drug resistance: It increases the virulence or transmis-
4. Sepsis S. aureus, E. coli, Proteus,
sibility of the microorganisms as well as limits the
Enterococcus, Anaerobes, etc.
choice of therapy.
4. Susceptible patients: Patients with pre-existing diseases
like diabetes, immunosuppression, etc are at high risk.
5. Surgical procedures: Natural defence mechanisms of
the body surface may be bypassed by injury or by a Prevention (Control)
diagnostic or therapeutic intervention.
They can be controlled by the following:
l Common nosocomial infections and causative organ-
1. Administration of antibiotics and antiseptic therapy to
isms are listed in Table 15.1.
the carrier staff or source patient
2. Isolation of an infectious patient
TABLE 15.1 Nosocomial Infections and Causative Organisms 3 . Proper sterilization and disinfection of the inani-
mate objects; disinfection of excreta and infected
Disease Organisms
materials
1. Urinary tract E. coli, Klebsiella, Serratia, Pro- 4. Control of route of transmission by regular washings of
infections (40%) teus, Pseudomonas aeruginosa,
hand, disinfection of equipments
Enterococcus, Candida albicans
5. Vaccination to susceptible hosts
SHORT NOTES
Q. 1. Hospital infections 3. It enables to compare patterns across regions and
with other regions.
Ans. Hospital acquired infections or nosocomial infections
are the infections developing in patients after admission to
Q. 3. Castaneda’s method of culture
hospital which were neither present nor in incubation at the
time of hospitalization. Ans.
Such infections may manifest during their stay in the hos- l Castaneda’s method of culture is a type of blood culture.
pital or sometimes after the patient is discharged. It is a laboratory method used in the diagnosis of Salmo-
For example: UTI, lower respiratory tract infections. nella, Brucella and Chlamydiae.
l Method of culturing
Q. 2. Antibiogram
1. Here both liquid and solid media are available in the
Ans. same bottle.
2. The blood is inoculated into the broth and the bottle
l The overall profile of antimicrobial susceptibility is is incubated in upright position.
known as antibiogram. 3. For subculture it is enough if the bottle is tilted so
l It is a chart produced by clinical laboratories which
that the broth flows over the surface of the agar slant.
documents the percentage of microbial isolates that are It is again incubated in upright position.
sensitive to particular antibiotics. 4. The colonies appear on the slant.
l Every 6–12 months the hospitals typically generate
l Advantages
antibiograms. 1. It minimizes materials and manipulation.
l Uses
2. Reduces chances of contamination and risk of infec-
1. It guides the doctors in empiric antibiotic selection. tion to laboratory workers.
2. It helps to track and monitor resistance patterns
throughout a region.
Part II
Systemic Bacteriology
Topic 16
Staphylococcus, Streptococcus, Pneumococcus

and Neisseria
LONG ESSAYS
Q. 1. Describe the morphology, staining characters and 5. MacConkey’s medium: Due to fermentation of lactose
pathogenicity of Staphylococcus. Add a note on labora- the colonies on the MacConkey’s medium are pink in
tory diagnosis of staphylococcal infections. colour and are very small about pinhead size.
6. Liquid medium: In liquid medium uniform turbidity is
Ans.
produced.
MORPHOLOGY OF STAPHYLOCOCCUS 7. Selective media: Several selective media are used for
isolating S. aureus from specimens such as faeces. These
AUREUS include following media:
1. They are spherical cocci, approximately 1 mm in diam- a. Salt milk agar or salt broth (media containing NaCl)
eter, arranged characteristically in grape-like clusters b. Ludlam’s medium (media containing lithium chlo-
due to cell division occurring in three planes, with ride and tellurite)
daughter cells tending to remain in close proximity. c. Media containing polymyxin
2. They may be found singly, in pairs and in short chains
of three or four cells. Long chains never occur.
PATHOGENICITY
3. They are Gram-positive, nonsporing, nonmotile, non-
capsulated, aerobic and normally facultative anaerobic. 1. Staphylococcus produces two types of diseases as follows:
a. Infections
b. Intoxications
CULTURAL CHARACTERISTICS 2. In the infections cocci gain access to damaged skin,
1. They grow readily on ordinary media within a tempera- mucosal or tissue sites colonized by adhering to cells or
ture range of 10–42°C, the optimum temperature being extracellular matrix, evade host defence mechanisms
37°C and pH 7.4–7.6. multiply and cause tissue damage.
2. On nutrient agar after incubation for 24 h, S. aureus pro- 3. In intoxications the disease is caused by the bacterial toxins
duces large around 2–4 mm diameter, circular, convex, produced either in the infected host or preformed in vitro.
smooth, raised, shiny, opaque and easily emulsifiable
colonies.
STAPHYLOCOCCAL DISEASES
a. Though some of them may be white, orange or yel-
low, most strains produce golden yellow pigment. S. aureus is an important pyogenic organism and its lesions
b. The pigment production occurs optimally at 22°C are characteristically localized in nature.
and only in aerobic cultures and it can be enhanced Common staphylococcal infections are as follows:
by incorporation of 1% glycerol monoacetate or
milk in the medium.
A. Skin and Soft Tissue Infections
3. Nutrient agar slope: The growth on nutrient agar slope is
confluent presenting a characteristic oil paint appearance. 1. These may be of varying severity and are important
4. Blood agar: Colonies of S. aureus on blood agar are cause of hospital acquired infection.
similar to those on the nutrient agar. Most strains are 2. They include folliculitis, furuncles (boil), styes, boils, ab-
haemolytic especially when incubated under 20–25% scesses, carbuncles, impetigo and pemphigus neonatorum.
CO2 and they produce marked haemolysis on rabbit or 3. Sepsis in wounds and burns is also usually caused by
sheep blood and weak on horse blood agar. the S. aureus.
B. Deep Infections 2. The underlying pathogenic mechanism is the stripping

of the superficial layers of the skin from the underlying
i. Musculoskeletal infections
tissues by the exfoliative or epidermolytic toxin.
a. Acute osteomyelitis is the commonest deep infection,
3. The severe form of SSSS is known as Ritter’s disease in the
the bacteria being implicated as the cause in 90% cases.
newborn and toxic epidermal necrolysis in older patients.
b. Tropical pyomyositis is formation of multiple ab-
4. Milder forms are bullous impetigo and pemphigus neo-
scesses in the voluntary muscles observed usually in
natorum.
young adults.
c. Arthritis and bursitis
ii. Respiratory infections: In the respiratory tract, it causes E. Toxic Shock Syndrome
tonsillitis, pharyngitis, sinusitis, otitis, bronchopneumo- Toxic shock syndrome is a potentially fatal multisystem
nia, lung abscess, empyema and rarely pneumonia. disease produced by S. aureus strains usually presenting
iii. Central nervous system: Abscess, meningitis, intracra- with fever, hypotension, myalgia, vomiting, diarrhoea, mu-
nial thrombophlebitis. cosal hyperaemia and an erythematous rash which desqua-
iv. Endovascular infections: Bacteraemia, septicaemia, py- mates subsequently. This is associated with infection of
aemia, and endocarditis. Staphylococcal septicaemia is mucosal or sequestrated sites by the toxic shock syndrome
rare but a serious condition. toxin (TSST) producing S. aureus.
v. Urinary infections: Staphylococci are uncommon in 1. Staphylococcal enterotoxins and toxic shock syndrome
routine urinary tract infections, though they do cause toxin-1 (TSST-1) are superantigens and potent activa-
infections in association with local instrumentation, tors of T lymphocytes.
implants or diabetes. Renal abscess may be produced 2. They stimulate very large number of T cells without rela-
due to haematogenous spread. tion to their epitope specificity. This leads to an excessive
and dysregulated immune response with release of cyto-
C. Staphylococcal Food Poisoning kines IL-1 and IL-2, tumour necrosis factor, and interferon-
gamma. This is responsible for multisystem involvement.
1. Staphylococcal food poisoning results on consumption 3. It was first observed in 1978 in children and adolescents
of food contaminated with enterotoxin producing staph- but showed wide outbreaks in 1980 in menstruating
ylococci. women using highly absorbent vaginal tampons.
2. The bacteria produce this toxin when grown in carbohy- 4. Convalescents show TSST–1 antibody is protective and
drate and protein foods. Common food items usually absence of it is a factor in the pathogenesis of the condition.
involved are meat, fish, milk and milk products.
3. Sufficient time should elapse between the contamina-
LABORATORY DIAGNOSIS
tion of the food and ingestion of the contaminated food
so that the organism can produce enough enterotoxin. Specimen to be collected depends on type of lesion as
The diarrhoea and vomiting sets in within 6 h of ingest- follows:
ing the contaminated food. 1. Pus from suppurative lesions
a. Enterotoxin is a heat-stable toxin and is also resistant 2. Sputum for respiratory infections
to action of GIT enzymes. 3. CSF for meningitis
b. Eight antigenic types of enterotoxins are currently 4. Blood for septicaemia
known, named A, B, C1–3, D, E and H of which type A 5. Suspected food, vomit or feces for food poisoning
is responsible for most of the cases.
Diagnosis is made by the following:
c. The toxin is believed to act directly on autonomic
nervous system to cause the illness, rather than on GI
a. Direct microscopy
mucosa.
d. Ingestion of enterotoxin as little as microgram amounts 1. Examination of a Gram-stained smear of pus or other
can cause illness like vomiting and diarrhoea in humans. specimen may show Gram-positive cocci in clusters
The emetic effect is brought about by the stimulation of with some single and paired cocci.
the CNS through the neural receptors in the GIT. 2. This is useful for pus and not for other specimen such
e. The toxin also exhibits pyrogenic, mitogenic, hypo- as sputum or feces where mixed bacterial flora is nor-
tensive, thrombocytopenic, and cytotoxic effects. mally present.
b. Culture
D. Exfoliative Diseases
Diagnosis is readily made by culture.
1. Exfoliative toxin is also known as ET or exfoliatin and
is responsible for the staphylococcal scalded skin syn- 1. The specimen is plated on the nutrient agar or blood
drome (SSSS). agar and incubated overnight. S. aureus colonies are
identified as large, circular, convex, smooth, raised, 2. It is exacting in nutritive requirements and growth oc-
shiny and opaque colonies on both the media. curs only in media enriched with blood or serum or
2 . Specimens such as feces for food poisoning, swabs media containing fermentable carbohydrates.
from carriers where the bacteria are scanty, are inocu- 3. On blood agar, after incubation the colonies are small,
lated on selective media like Ludlam’s or salt-milk agar circular, semitransparent, convex discs with beta hae-
or Robertson’s cooked meat medium containing 10% molysis.
NaCl. 4. Growth and haemolysis are promoted by 10% CO2.
3. The smears from the culture media are examined under Virulent strains on fresh isolation from lesions produce
the microscope and biochemical tests done to confirm a matt or finely granular colonies while avirulent strains
the S. aureus. form glossy colonies. Strains with well-marked cap-
sules form mucoid colonies.
c. Coagulase test
PATHOGENESIS
1. Coagulase test is done by two methods as follows:
a. Tube coagulase test 1. Streptococcus pyogenes adheres to the pharyngeal epi-
b. Slide coagulase test thelium by means of lipoteichoic acid covering the sur-
2. Tube coagulase test detects free coagulase. The slide face epithelial cells.
coagulase test detects bound coagulase and usually 2. The infection may spread to the surrounding tissues
gives results parallel with tube test. leading to suppurative complications like otitis media,
3. When there is a divergence, the tube test will be decid- mastoiditis, quinsy, Ludwig’s angina and suppurative
ing factor. adenitis. Meningitis may occur rarely.
3. Scarlet fever occurs when the infecting strain of S. pyo-
genes produces erythrogenic toxin in a patient usually a
d. Antibiotic sensitivity tests child with no antitoxic immunity leading to a combina-
1. Should be done simultaneously as a guide to treatment. tion of sore throat and a generalized erythematous rash.
This is important as staphylococci readily develop resis-
tance to drugs.
Specimens collected are pus, throat swab, sputum, genital
e. Serological tests swabs, blood and CSF. Specimens can be transported in
1. These may sometimes help to diagnose hidden deep Pike’s medium.
infections. 1. Microscopy: The presence of Gram-positive cocci in chains
2. ASO titre more than 2 units/mL with rising titre is of under Gram’s staining is indicative of Streptococcus
value in diagnosing deep seated infections such as bone infections. But smears from throat and genitalia are of no
abscess. value, where Streptococcus forms part of normal flora.
2. Culture: The specimen is plated on blood agar and in-
Q. 2. Write in detail about the morphology, pathogene- cubated at 37°C anaerobically or under 5–10% CO2.
sis, laboratory diagnosis and the treatment of Strepto- The growth is identified by beta haemolysis, Gram’s
coccus pyogenes. staining and antibiotic sensitivity. S. pyogenes is more
Ans. sensitive to bacitracin, hence, a filter paper disc dipped
in a solution of bacitracin (1 unit/mL) is applied on the
MORPHOLOGY OF STREPTOCOCCUS surface of an inoculated blood agar. After incubation,
1. They are Gram-positive cocci arranged in chains or wide zone of inhibition is seen with S. pyogenes, but not
pairs. Individual cocci are spherical or oval in shape, with other streptococci.
measuring 0.5–1.0 mm in diameter. 3. Serology
2. Chain formation is due to cocci dividing in one plane a. Haemolytic streptococci are grouped by Lancefield’s
only and daughter cells failing to separate completely. method. The fluorescent antibody technique has
3. They are nonmotile and nonsporing. Some strains of S. pyo- been employed for rapid identification of group A
genes and some group C strains possess capsules made of streptococci.
hyaluronic acid while polysaccharide capsules are found in b. In poststreptococcal lesions ASO test is used. ASO
groups B and D. Capsules are best seen in young cultures. test is used for retrospective diagnosis of rheumatic
fever and glomerulonephritis.
c. Streptolysin O is antigenic and antistreptolysin ap-
Cultural Characteristics pears in sera following streptococcal infections. Es-
1. It is an aerobe and facultative anaerobe growing best at timation of this antibody known as antistreptolysin,
the temperature of 37°C and an optimum pH of 7.2–7.4. is used as a standard serological procedure for
retrospective diagnosis of poststreptococcal compli- a convenient, specific, sensitive screening test. It becomes
cations. positive after all types of streptococcal infections.
d. ASO titres higher than 200 are indicative of poststrep-
tococcal infection. High levels are found in acute
TREATMENT
rheumatic fever, but in glomerulonephritis, titres are
low. 1. All beta haemolytic group A streptococci are sensitive
e. DNAase B test is also used. Titres of higher than 300 to penicillin G and most are sensitive to erythromycin.
are taken as significant. 2. In patients allergic to pencillin, erythromycin or cepha-
4. Streptozyme test lexin may be used.
A passive slide haemagglutination test using RBC sen- 3. Antimicrobial drugs have no effect on established glo-
sitized with crude extracellular antigens of Streptococcus is merulonephritis and rheumatic fever.
SHORT ESSAYS
Q. 1. Lesions caused by Staphylococcus aureus Exfoliative Diseases
Ans. Common staphylococcal infections are as follows: l Exfoliative toxin is also known as ET or exfoliatin and
is responsible for the staphylococcal scalded skin syn-
Skin and Soft Tissue Infections drome (SSSS).
l The severe form of SSSS is known as Ritter’s disease in
l They include folliculitis, furuncles (boil), styes, boils,
abscesses, carbuncles, impetigo and pemphigus neona- the newborn and toxic epidermal necrolysis in older
torum. patients.
l Milder forms are bullous impetigo and pemphigus neo-
l Sepsis in wounds and burns.
natorum.
Deep Infections
Toxic Shock Syndrome
1. Musculoskeletal infections
a. Acute osteomyelitis Toxic shock syndrome is a potentially fatal multisystem
b. Tropical pyomyositis disease produced by S. aureus strains usually presenting
c. Arthritis and bursitis with fever, hypotension, myalgia, vomiting, diarrhoea, mu-
2. Respiratory infections: In the respiratory tract, it causes cosal hyperaemia and an erythematous rash which desqua-
tonsillitis, pharyngitis, sinusitis, otitis, bronchopneumo- mates subsequently. This is associated with infection of
nia, lung abscess, empyema and rarely pneumonia. mucosal or sequestrated sites by the toxic shock syndrome
3. Central nervous system: Abscess, meningitis, and intra- toxin (TSST) producing S. aureus.
cranial thrombophlebitis
Q. 2. Describe Staphylococcus aureus.
4. Endovascular infections: Bacteraemia, septicaemia, pyae-
mia, and endocarditis Ans.
5. Urinary infections: Staphylococci do cause urinary tract
infections in association with local instrumentation, MORPHOLOGY OF STAPHYLOCOCCUS
implants or diabetes. AUREUS
l They are spherical cocci, approximately 1 mm in diam-
Staphylococcal Food Poisoning eter, arranged characteristically in grape-like clusters.
l They may be found singly, in pairs and in short chains
l Staphylococcal food poisoning results on consumption of three or four cells. Long chains never occur.
of food contaminated with enterotoxin producing staph- l They are Gram-positive, nonsporing, nonmotile, non-
ylococci. capsulated, aerobic and normally facultative anaerobic.
l Sufficient time about 6 h should elapse between the
contamination of the food and ingestion of the contami-

nated food so that the organisms can produce enough
CULTURAL CHARACTERISTICS
enterotoxin. Ingestion of enterotoxin as little as micro- l On ordinary media, they grow readily at an optimum
gram amounts can cause illness like vomiting and diar- temperature of 37°C and pH 7.4–7.6.
rhoea in humans. l On nutrient agar, S. aureus produces large around 2–4 mm
l The emetic effect is brought about by the stimulation of diameter, circular, convex, smooth, raised, shiny, opaque
the CNS through the neural receptors in the GIT. and easily emulsifiable colonies. Though some of them
l The toxin also exhibits pyrogenic, mitogenic, hypoten- may be white, orange or yellow, most strains produce
sive, thrombocytopenic and cytotoxic effects. golden yellow pigment.
l On nutrient agar slope, the growth presents a character- Haemolytic toxins: At least four types of haemolysins are
istic oil paint appearance. produced known as alpha, beta, gamma and delta.
l Blood agar: Colonies of S. aureus on blood agar are 1. Alpha haemolysin: It is leucocidal, cytotoxic, dermone-
similar to those on the nutrient agar. They produce crotoxic and lethal.
marked haemolysis on rabbit or sheep blood and weak 2. Beta haemolysin: It is a sphingomyelinase, it exhibits
on horse blood agar. hot-cold phenomenon, i.e. haemolysis is initiated at
l On MacConkey’s medium, S. aureus produces very 37°C but becomes evident only after chilling.
small about pinhead size pink colour colonies. 3. Gamma haemolysin: It is necessary for haemolytic activity.
l Liquid medium: In liquid medium uniform turbidity is 4. Delta haemolysin: It has a detergent-like effect on cell
produced. membranes of erythrocytes, leucocytes, macrophages
l Selective media: Several selective media are used for and platelets.
isolating S. aureus, these include following media:
Leucocidin: It is a bicomponent membrane active toxin and
1. Salt-milk agar or salt broth (media containing NaCl)
has leucocidal activity.
2. Ludlam’s medium (media containing lithium chlo-
ride and tellurite)
3. Media containing polymyxin Enterotoxins
l Staphylococcal food poisoning results on consumption
PATHOGENICITY of food contaminated with enterotoxin producing staph-
ylococci.
Staphylococcus produces two types of diseases as follows:
l Enterotoxin is a heat-stable toxin and is also resistant to
1. Infections
action of GIT enzymes.
2. Intoxications
l Eight antigenic types of enterotoxin are currently
known, named A, B, C1–3, D, E and H of which type A

LABORATORY DIAGNOSIS OF is responsible for most of the cases.
STAPHYLOCOCCUS l The toxin also exhibits pyrogenic, mitogenic, hypoten-
Collection of specimens: Pus, wound exudates, throat sive, thrombocytopenic and cytotoxic effects.
swabs, blood for culture, and mild stream urine.
Exfoliative Toxins
Direct evidences l Exfoliative toxin is also known as ET or exfoliatin and
1. Smear from clinical material and Gram staining shows is responsible for the staphylococcal scalded skin syn-
Gram-positive cocci. drome (SSSS).
2. Culture: Inoculation into nutrient agar, golden yellow l Toxic shock syndrome toxin (TSST type-1 toxin)
pigmented/white colonies.
Other Toxins: Nucleases, lipases, etc.
Indirect evidences
1. Coagulase test: Slide and tube coagulase test ENZYMES
2. Biochemical test Extracellular enzymes produced by S. aureus are as follows:
a. Mannitol fermentation with acid production 1. Coagulase: It is an enzyme which brings about clotting
b. S. aureus is catalase and phosphate positive. of human or rabbit plasma. It acts along with a coagu-
3. Serotyping: ASO test and DNAase B test are used. lase reacting factor (CRF) present in plasma, binding to
4. Phage typing prothrombin and converting fibrinogen to fibrin.
S. aureus strains usually form both coagulase and
Q. 3. Name the toxins and enzymes produced by clumping factor. Coagulase test is standard criterion for
Staphylococcus aureus. identification of S. aureus isolates.
Ans. 2. Lipases: They help them in infecting the skin and sub-
cutaneous tissues.
TOXINS 3. Hyaluronidase: Breaks down the connective tissue and
helps in spread of infections.
The toxins produced by Staphylococcus aureus are as follows:
4. Nuclease: A heat-stable nuclease is a characteristic fea-
1. Cytolytic toxins
ture of S. aureus.
2. Enterotoxins
5. Protein receptors: These facilitate staphylococcal adhe-
3. Exfoliative toxins
sion to host cells and tissues.
Cytolytic Toxins Q. 4. Classification of streptococci

They are membrane active substances consisting of four Ans. On the basis of their haemolytic properties strepto-
haemolysins and a leucocidin. cocci are classified into a, b and g haemolytic.
1. a-haemolytic: It produces a greenish discolouration Q. 6. Name four diseases caused by Streptococcus pyogenes.
with partial haemolysis around the colonies. For exam-
Ans.
ple: Streptococcus viridans group (S. salivarius), SABE
by alpha-haemolytic streptococcus (S. viridans). 1. Streptococcus pyogenes produces generalized or spread-
2. b-haemolytic: It produces a sharply defined, clear, co- ing pyogenic infections.
lourless zone of haemolysis, e.g. S. pyogenes. 2. The organism is normally present in the upper respira-
Lancefield classified b -haemolytic streptococci based tory tract of patients and carriers and spreads by droplet
on C polysaccharides on cell wall. infection.
The b -haemolytic streptococci are classified by Lance-
field into 19 Lancefield groups based on the nature of a
carbohydrate (c) antigen on the cell wall. PYOGENIC INFECTIONS
The great majority of haemolytic streptococci that pro- Respiratory Infections
duce human infections belong to group A. Haemolytic
streptococci of group A are known as S. pyogenes. 1. Sore throat: Throat is the primary site of invasion caus-
ABE esp. by b -haemolytic streptococci ing sore throat. It may be localized in tonsils (tonsillitis)
3. g-haemolytic (nonhaemolytic streptococci): It produces or may involve pharynx (pharyngitis).
no change in the medium. For example: S. faecalis 2. From throat streptococci may spread to surrounding tis-
sues, producing pyogenic complications such as otitis
Q. 5. Enumerate toxins and enzymes of streptococci. media, mastoiditis and suppurative adenitis.
3. Streptococci pneumonia may occur as a complication of
Ans.
influenza or other viral respiratory diseases.
Various toxins of streptococci are as follows:
1. Haemolysins: These are of two types: (a) streptolysin O Skin and Soft Tissue Infections
and (b) streptolysin S.
Streptolysin is oxygen stable and is responsible for the 1. It may cause suppurative infection of skin, e.g. wound,
haemolysis around streptococcal colonies on surface of burns, lymphangitis and cellulitis.
blood agar plates. 2. The two typical streptococcal infections of skin are ery-
a. Alpha-haemolysin is pathogenic in man. sipelas and impetigo. Infection of abrasion may lead
b. An ASO titre higher than 160 is indicative of previ- to fatal septicaemia which may cause erysipelas and
ous streptococcal infection. impetigo.
2. Erythrogenic (dick, scarlantinal, pyrogenic) toxins: a. Erysipelas is a diffuse infection involving superfi-
Used to identify the children susceptible to scarlet fever, cial lymphatics, the involved skin becomes red and
which is a type of acute pharyngitis with extensive ery- swollen.
thematous rash. b. Impetigo may lead to glomerulonephritis in children.
3. Streptodornase (deoxyribonucleases) c. Genital Infections: Both aerobic and anaerobic
a. causes depolymerization of DNA. streptococci are normal inhabitants of the female
b. helps to liquefy the pyogenic exudates. genitalia. S. pyogenes is an important cause of
4. Streptokinase: Promotes the lysis of fibrin clot puerperal sepsis, with the infection usually being
5. Hyaluronidase: This enzyme breaks down the hyal- exogenous.
uronic acid of the tissues, which is a ground substance, d. Other Suppurative Infections: S. pyogenes may
and helps in spread of infection. cause septicaemia, pyaemia and abscess of internal
organs like brain, lungs, liver and kidney.
Various enzymes produced by streptococci are as shown in
Table 16.1.
NONSUPPURATIVE COMPLICATIONS
TABLE 16.1 Enzymes Produced by Streptococci S. pyogenes infections lead to two important nonsuppura-
Enzymes Functions
tive sequelae as follows:
1. Acute rheumatic fever
Streptokinase (fibrinolysin) Dissolves fibrin clot
2. Acute glomerulonephritis
Streptodornase Produces exudative inflammation
Hyaluronidase Dissolves ground substance Acute Rheumatic Fever
and spreads the infection
Erythrogenic toxin Causes scarlet fever l It is a nonsuppurative systemic inflammatory condition
characterized by fever, pancarditis, migratory polyar-
Streptolysin ASO titres increased in
thritis, sometimes chorea and subcutaneous nodules
rheumatic fever
(Aschoff nodules).
l This disease is preceded by an attack of streptococ- Q. 6. Morphology and cultural characteristics of pneu-
cal sore throat, septic tonsillitis or respiratory tract mococcus
infection.
l Lesion of rheumatic fever may be the result of hyper-
Ans.
sensitivity to some streptococcal component produced
by repeated attack.
MORPHOLOGY OF PNEUMOCOCCUS
1. Pneumococci are Gram-positive, lanceolate or flame-
Acute Glomerulonephritis shaped diplococci.
2. Cocci are small, slightly elongated, with one end broad
1. The nephritis is a self-limiting episode that resolves or rounded and the other pointed, presenting a flame
without any permanent damage. Skin infections like shape or lanceolate appearance.
pyoderma or impetigo are more important in this respect 3. They occur in pairs (diplococci) with the broad ends in
than throat infections. opposition.
2. Pathogenesis may be due to antigenic cross reaction, 4. They are capsulated, the capsule enclosing each pair.
between glomerular antigens and some component of Capsules can be demonstrated by negative staining,
nephritogenic streptococci, more often it may be im- Quellung reaction and Hiss stain.
mune complex disease.
Q. 5. Antistreptolysin O test CULTURAL CHARACTERISTICS

Ans. The pneumococci have complex growth requirements and
grow only in enriched media.
1. Antistreptolysin O test (ASO test) is a toxin neutraliza-
tion test used to detect presence of antistreptolysin O in On Blood Agar
the patient’s sera. 1. After incubation for 18 h the colonies are small, dome
2. Antistreptolysin O is an antitoxin secreted by the shaped and glistening with area of green discolouration,
body against the exotoxin streptolysin O of strepto- i.e. a-haemolysis around them.
cocci. 2. On further incubation the colonies become flat with
3. It blocks the haemolysis caused by the streptolysin O. raised edges and central umbonation giving draughts-
An ASO titre higher than 160 or 200 is indicative of man or carom coin appearance.
prior streptococcal infection. High levels are usually 3. Some strains that develop abundant capsular material
found in acute rheumatic fever but in self-limiting form large mucoid colonies.
episode are often low. 4. Under anaerobic conditions colonies on blood agar are
4. The ASO test is used as an aid in the diagnosis of surrounded by a zone of b-haemolysis.
rheumatic fever and acute haemorrhagic glomerulone- 5. In liquid medium like glucose broth: Growth occurs as
phritis. uniform turbidity.
SHORT NOTES
Q. 1. C-reactive protein l The CRP is tested by passive agglutination using latex
particles coated with anti-CRP antibody as a routine
Ans. diagnostic procedure.
l C-reactive protein (CRP) is an abnormal protein (beta
globulin) that precipitates with the somatic C antigen of Q. 2. Media used for gonococcus
pneumococci. Ans.
l It appears in acute sera of cases of pneumonia but disap-
pears during convalescence. It also occurs in some other l Gonococci grow well on chocolate agar and Muller-
pathological conditions. Hinton agar.
l It is not an antibody produced as a result of pneumococ- l Popular selective medium is Thayer-Martin medium
cal infection but it is an acute phase substance produced (containing vancomycin, colistin and nystatin).
in hepatocytes.
l Its production is stimulated by bacterial infections, Q. 3. Coagulase test
inflammation, malignancies and tissue destruction. It Ans.
disappears when inflammatory reactions subside.
l The CRP is an index of response to treatment in rheu- l Coagulase test is done by two methods which are
matic fever and certain other conditions. 1. tube and
2. slide coagulase tests. 4. Micrococcus: They are Gram-positive cocci which oc-
l Tube coagulase test detects free coagulase. The slide cur mostly in pairs, tetrads or irregular clusters. They
coagulase test detects bound coagulase and usually are parasitic on mammalian skin.
gives results parallel with tube test. 5. Sarcinococcus: It is similar to micrococcus except that
l When there is a divergence, the tube test will be deciding it forms pocket of eight. It is mostly nonpathogenic.
factor.
Q. 7. Add a note on coagulase delivered by staphylococcus.
Q. 4. Name four diseases caused by Staphylococcus au-
Ans.
reus.
Ans. Staphylococcal diseases may be grouped as follows: 1. Coagulase is an enzyme which brings about clotting of
human or rabbit plasma.
1. Cutaneous infections: Furuncles, styes, boils, abscesses, 2. Eight types of coagulase have been identified. Most hu-
caubuncles, impetigo and pemphigus neonatorum and man strains form coagulase type A.
sepsis in wounds and burns, breast abscess in lactating 3. It acts along with a coagulase reacting factor (CRF)
mothers. present in plasma, binding to prothrombin and convert-
2. Respiratory infections: Tonsillitis, pharyngitis, sinusitis ing fibrinogen to fibrin.
and pneumonia, which is secondary to other infections. 4. Staphylococcus aureus strains usually form both coagu-
3. Deep infections: Acute osteomyelitis, endocarditis, lase and clumping factor.
meningitis. 5. Coagulase test is standard criterion for identification of
4. Staphylococcal food poisoning or toxic type of food S. aureus isolates.
poisoning: Results when food contaminated with en-
terotoxin producing staphylococci is consumed. Q. 8. Poststreptococcal complications
Or,
Q. 5. Classify staphylococci.
Nonsuppurative lesions caused by Streptococcus pyogenes
Ans.
Ans. S. pyogenes infections lead to two important post-
Classification of Staphylococci streptococcal complications as follows:
Based on pigment production and virulence, staphylococci 1 . Acute rheumatic fever
is divided into three important species as follows: 2. Acute glomerulonephritis
1. S. aureus: Forms golden yellow pigment
2. S. albus or epidermidis: Forms white pigment Acute Rheumatic Fever
3. S. citreus: Forms lemon yellow pigment l It is a nonsuppurative systemic inflammatory condition
Based on coagulase production it is divided into characterized by fever, pancarditis, migratory polyar-
thritis, sometimes chorea and subcutaneous nodules
1 . coagulase positive, and (Aschoff nodules).
2. coagulase negative. l It may be the result of hypersensitivity to some strepto-
Based on susceptibility to bacteriophages, they can be coccal component produced by repeated attack.
typed into many phage types. Acute Glomerulonephritis
Q. 6. Write briefly on Gram-positive cocci. l The nephritis is a self-limiting episode that resolves
without any permanent damage.
Ans. Gram-positive cocci are those that resist deco-
l Pathogenesis may be due to antigenic cross-reaction
lourization and retain primary stain appearing violet, e.g.
between glomerular antigens and some component of
streptococci, staphylococci, pneumococci, micrococcus
nephritogenic streptococci, more often it may be im-
and sarcinococcus.
mune complex disease.
1. Streptococci: They are Gram-positive and are ar-
ranged in chains. Streptococci are aerobic and faculta- Q. 9. Viridans streptococci
tive anaerobes. Ans.
2. Staphylococci: They are important human pathogens
which produce pyogenic infections. Spherical cocci l Viridans group of streptococci are the commensals pres-
arranged characteristically in grapes like cluster. ent in human mouth and throat.
3. Pneumococci: They are also responsible for the nonsup- l They produce alpha type of haemolysis on blood agar.
purative lesions, acute rheumatic fever and glomerulo- Based on biochemical reactions, they have been classi-
nephritis. fied into five species as follows:
1. S. salivarius 3. Streptococcus pharyngitis: Sore throat is the most com-

2. S. mutans mon form of streptococcal infection localized as tonsillitis
3. S. sanguis in older children and adults or spread diffusely as pharyn-
4. S. mitior gitis in younger children. Causative agent is Streptococcus
5. S. milleri pyogens.
l They are normally nonpathogenic, but in persons with
predisposing factors such as valvular disease of the Q. 12. Toxins and enzymes produced by Streptococcus
heart; they produce subacute bacterial endocarditis. Ans. Various toxins of streptococci are as follows:
Therefore, any dental procedure in such people should
be done under antibiotic cover. 1 . Haemolysins
l Following tooth extraction or other dental procedures 2. Erythrogenic (dick, scarlantinal, pyrogenic) toxins
they cause transient bacteraemia. 3. Streptodornase (deoxyribonucleases)
4. Streptokinase
Q. 10. Streptococcal infections 5. Hyaluronidase
Ans. Various enzymes produced by streptococci are as follows:
1. Streptokinase (fibrinolysin)
Pyogenic Streptococcal Infections 2. Streptodornase
1. Respiratory infections: Sore throat, tonsillitis and phar- 3. Hyaluronidase
yngitis 4. Erythrogenic toxin
2. Skin and soft tissue infections: Wounds, burns, lym- 5. Streptolysin
phangitis, cellulitis, erysipelas and impetigo
3. Genital infections: Puerperal sepsis Q. 13. Discuss laboratory investigations of meningitis.
4. Other infections like septicaemia, pyaemia and abscess Ans. Laboratory investigations of meningitis include the
of internal organs like brain, lungs, liver and kidney. following:
Nonsuppurative Complications 1 . Examination of CSF

2. Blood culture: In meningococcaemia and in early cases
Two important nonsuppurative sequelae are of meningitis, blood cultures are positive.
1 . acute rheumatic fever and 3. Nasopharyngeal swab: Useful for detection of carriers
2. acute glomerulonephritis. 4. Meningococci may sometimes be demonstrated from
petechial lesions.
Q. 11. Sore throat 5. At autopsy, specimens may be collected from meninges,
lateral ventricles or the surface of brain and spinal cord
Ans.
for smear and culture.
1. Sore throat is acute tonsillitis or pharyngitis character- 6. Retrospective evidence of meningococcal infection may
ized by redness and oedema of mucosa, exudation of be obtained by demonstrating antibodies by complement
tonsils, pseudomembrane formation, oedema of uvula fixation test (CFT), passive heamagglutination and radio-
and enlargement of cervical lymph nodes. immunoassay (RIA).
2. Causative agents are as follows:
a. Bacteria Q. 14. Name the laboratory diagnosis of pneumococcal
i. Streptococcus pyogens (most common cause) infections.
ii. Streptococcus group C and G Ans. The aetiological diagnosis of pneumococcal infec-
iii. Corynebacterium diphtheriae tions is made by following laboratory tests as they are of
iv. Haemophilus influenzae great importance in treatment.
v. Bordetella pertussis
vi. Treponema vincentii The various laboratory tests for diagnosis of pneumococcal
vii. Leptotrichia buccalis infections are as follows:
b. Fungus 1. Gram stain: To demonstrate pneumococci in sputum of
i. Candida albicans acute phase of lobar pneumonia.
c. Viruses 2. Direct serotyping of pneumococci in wet films of spu-
i. Epstein-Barr virus tum by the quellung test (routine bedside test).
ii. Adenoviruses 3. Innoculation of sputum on blood agar plates at 37°C
iii. Coxsackievirus A and 5–10% CO2.
4. Isolation from respiratory secretions is facilitated by iii. Indirect haemagglutination: Indirect FA test and
using blood agar containing 5 mg/mL of gentamicin. radioimmunoassay have been employed.
5. Intraperitoneal inoculation in mice: For the specimens
where pneumococci are expected to be scanty. Q. 15. Bacteria causing meningitis
6. In acute stage of pneumonia: The organisms may be Ans. Causative agents of meningitis are as follows:
obtained from blood culture in glucose broth. Isolation
from blood indicates a bad prognosis. 1. Pneumococci
a. Pneumococci may be demonstrated in fluid aspirated 2. Meningococci
from middle ear in acute otitis media. 3. Haemophilus influenzae
b. Gram-stained films of CSF are used in diagnosis of 4. E. coli and Klebsiellae
meningitis. 5. Pseudomonas
c. Other laboratory diagnostic aids for demonstration 6. Clostridium welchii
of pneumococci are as follows: 7. Bacteroides
i. Counterimmunoelectrophoresis 8. Listeria and Nocardia asteroides
ii. Antibodies are detected by agglutination, precipi- 9. Mycoplasma
tation mouse protection tests and bactericidal tests. 10. Group B streptococci
Topic 17
Corynebacterium
LONG ESSAY
Q. 1. Briefly describe the morphology, pathogenesis, 1. C. diphtheriae bacillus is a slender rod measuring
laboratory diagnosis and prophylaxis of Corynebacte- 3–6 3 0.6–0.8 mm with tendency to clubbing at one or
rium diphtheriae. both ends.
Or, 2. The bacilli are pleomorphic. They are Gram-positive,
nonsporing, noncapsulated and nonmotile.
Describe the morphology, cultural characters, and diag- 3. The cells show granules composed of polymetaphos-
nosis of Corynebacterium diphtheriae. Add a note on phate and are called metachromatic or volutin or Babes-
immunization. Ernst granules usually situated at the poles of bacilli and
Ans. are hence known as polar bodies.
4. The bacilli are arranged in pairs or small groups at vari-
MORPHOLOGY ous angles to each other, resembling letter ‘V’ or ‘L’.
This is called Chinese letter or cuneiform arrangement
Morphological features of Corynebacterium diphtheriae and is due to incomplete separation of daughter cell
are as follows (Fig. 17.1): after binary fission.
1. C. diphtheriae is an aerobe and a facultative anaerobe
and grows at 37°C and pH of 7.3.
2. On nutrient agar, the growth is scanty and requires en-
richment like blood, serum or egg for good growth.
On Loeffler’s serum slope, the bacilli grow very rapidly
and colonies at first are small, circular white opaque
disc but enlarge on continued incubation and acquire a
distinct yellow tint.
Tellurite blood agar and its modifications like McLeod’s
and Hoyle’s media are used as a selective media and colo-
FIGURE 17.1 Morphology of C. diphtheriae. nies produced are grey or black in colour and depending
upon the colonial morphology three types of diphtheria a. In Vivo Tests

are seen.
a. Gravis i. Subcutaneous Test
b. Intermedius Growth from an overnight culture on Loeffler’s slope is
c. Mitis emulsified in 2–4 mL broth and 0.8 mL of the emulsion is
injected subcutaneously into two guinea pigs of which one
PATHOGENESIS is protected with prior administration of 500 units of diph-
theria antitoxin. If the strain is virulent, then the unpro-
1. Incubation period in diphtheria is commonly 3–4 days tected animal dies in 4 days.
or on occasion may be as short as 1 day.
2. The site of infection may be faucal, laryngeal, nasal, ii. Intracutaneous Test
otitic, conjunctival genital and cutaneous.
3. The bacilli are present in throat and nose of the carri- Broth emulsion is injected intracutaneously about 0.l mL
ers. It is typically a disease of schools and institutions into two guinea pigs where one is protected with 500 units
where children of susceptible age are present in great of diphtheria antitoxin given the previous day and acts as a
numbers. control. However, other is given 50 units of antitoxin intra-
4. Diphtheria is a toxaemia. Bacilli remain at the site of peritoneally 4 h after the skin test, in order to prevent death.
entry and multiply to produce toxin. The toxin causes Toxigenicity is indicated by inflammatory reaction at
local necrosis, resulting in fibrinous exudates together the site of injection progressing to necrosis in 48–72 h in
with disintegrating epithelial cells, leucocytes, RBC and the test animal and no change in the control animal.
bacteria constitute pseudomembrane, which is charac-
teristic of diphtheria infection. b. In Vitro Tests
5. The mechanical complications are due to pseudomem-
i. Eleck’s Gel Precipitation Test
brane, while systemic effects are due to toxins.
1. Eleck’s test is an in vitro immunodiffusion test de-
scribed by Eleck for demonstrating the toxigenicity of
LABORATORY DIAGNOSIS C. diphtheriae.
Laboratory diagnosis of diphtheria consists of isolation of 2. Procedure: A rectangular strip of filter paper impreg-
the bacteria and demonstration of its toxicity. nated with diphtheria antitoxin (1000 units/mL) is
Two swabs from the site of lesion, i.e. throat, nose or lar- placed on the surface of a 20% normal hoarse serum
ynx, one for smear. agar in a Petri dish while the medium is still fluid. Then
the surface is dried.
1. Bacteriological studies or isolation of the bacteria
3. Once the agar is set narrow streaks of the test strains are
a. Direct smear examination: Smears are stained by
made at right angle to the filter paper strip. A positive
Albert’s stain show beaded slender rods in typical
and negative control is set. The plate is incubated at
Chinese letter pattern.
37°C for 24–48 h where the toxins produced diffuse in
b. Culture
the agar.
i. Swabs are inoculated on Loeffler’s serum slope,
4. Interpretation: Toxigenic strains of C. diphtheriae pro-
tellurite agar and a plate of ordinary blood agar.
duce arrow head lines of precipitation where the bacterial
ii. On Loeffler’s serum slope the growth appears in
toxin meets with the antitoxin in optimum concentration.
4–8 h but if negative reincubate for 24 h whereas
5. No precipitate is formed in the case of nontoxigenic
colonies on blood tellurite medium and blood
strains.
agar appear in 36–48 h they should be incubated
iii. Any growth on culture should be stained with
ii. Tissue Culture Test
methylene blue or Neisser’s or Albert’s stain 1. Toxigenicity of diphtheria bacilli is demonstrated by
which shows metachromatic granules and typi- incorporating the strains in the agar overlay of cell cul-
cal Chinese letter pattern. ture monolayers.
2. Demonstration of its toxicity by virulence tests 2. The toxins produced diffuse into the cells below and kill
a. In vivo tests them.
i. Subcutaneous test
ii. Intracutaneous test
b. In vitro tests
PROPHYLAXIS OF DIPHTHERIA
i. Eleck’s gel precipitation test Immunoprophylaxis of diphtheria is done by active immuni-
ii. Tissue culture test zation, passive immunization and combined immunization.
a. Active Immunization b. Passive Immunization

It is done by a primary course of DPT vaccine injected It is done by 500–1000 units of antitoxin or antidiphtheritic
subcutaneously consisting of three doses with an interval of serum (ADS) administered subcutaneously as an emer-
4–8 weeks between the first and second and 8–12 weeks gency measure.
between the second and third doses, i.e.
First dose 6 weeks c. Combined Immunization

Second dose 10 weeks It consists of administration of first dose of adsorbed toxoid
Third dose 14 weeks (purified toxoid adsorbed to aluminium phosphate or to alu-
minium hydroxide) on one arm while ADS is given on the other
Booster dose 18 months
arm to be continued by the full course of active immunization.
SHORT ESSAYS
Q. 1. Immunization against diphtheriae l C. diphtheriae bacillus is a slender rod measuring
3–6 3 0.6–0.8 mm with tendency to clubbing at one or
Ans.
both ends.
Immunoprophylaxis of diphtheria is done by active immuni- l The bacilli are pleomorphic. They are Gram-positive,
zation, passive immunization and combined immunization. nonsporing, noncapsulated and nonmotile.
l The cells show granules composed of polymetaphos-
Active immunization phate and are called metachromatic or volutin or Babes-

Ernst granules usually situated at the poles of bacilli and
The schedule of primary course of vaccine injected subcu- are hence known as polar bodies.
taneously in infants and children consists of three doses of l The bacilli are arranged in pairs or small groups at vari-
DPT given at intervals of at least 4 weeks and preferably ous angles to each other, resembling letter ‘V’ or ‘L’.
6 weeks or more, followed by a fourth dose about 1 year This is called Chinese letter or cuneiform arrangement
afterwards. A further booster is given at school entry. and is due to incomplete separation of daughter cell af-
ter binary fission.
First dose 6 weeks
Second dose 10 weeks
Third dose 14 weeks
1. C. diphtheriae is an aerobe and a facultative anaerobe
Booster dose 18 months
and grows at 37°C and pH of 7.3.
2. On nutrient agar, the growth is scanty and requires en-
Passive Immunization richment like blood, serum or egg for good growth.
It consists of subcutaneous administration of 500–1000 On Loeffler’s serum slope, the bacilli grow very rapidly and
units of antitoxin or antidiphtheric serum (ADS) as an colonies at first are small, circular white opaque disc but
emergency measure in susceptibles exposed to infection. enlarge on continued incubation and acquire a distinct yel-
low tint.
Combined Immunization Tellurite blood agar and its modifications like McLeod’s
It consists of administering first dose of toxoid (purified tox- and Hoyle’s media are used as a selective media and colo-
oid adsorbed to aluminium phosphate or to aluminium hy- nies produced are grey or black in colour.
droxide) on one arm while antitoxin is given on the other arm
to be continued by the full course of active immunization. Q. 3. Describe laboratory diagnosis of diphtheria.
Ans.
Q. 2. Describe the morphology and cultural characteris-
tics of Corynebacterium diphtheriae. LABORATORY DIAGNOSIS
Ans. Laboratory diagnosis of diphtheria consists of isolation of
the bacteria and demonstration of its toxicity.
Morphology
Two swabs from the site of lesion, i.e. throat, nose or lar-
The morphological features of Corynebacterium diphthe- ynx, one for smear are as follows:
riae are as follows: 1. Bacteriological studies or isolation of the bacteria:
a. Direct smear examination: Smears are stained by of diphtheria antitoxin given the previous day and acts as a
Albert’s stain show beaded slender rods in typical control. However, other is given 50 units of antitoxin intra-
Chinese letter pattern. peritoneally 4 h after the skin test, in order to prevent death.
b. Culture Toxigenicity is indicated by inflammatory reaction at
i. Swabs are inoculated on Loeffler’s serum slope, the site of injection progressing to necrosis in 48–72 h in
tellurite agar and a plate of ordinary blood agar. the test animal and no change in the control animal.
ii. On Loeffler’s serum slope the growth appears in
4–8 h but if negative reincubate for 24 h whereas
colonies on blood tellurite medium and blood In Vitro Tests
agar appear in 36–48 h they should be incubated Eleck’s Gel Precipitation Test
iii. Any growth on culture should be stained with l Eleck’s test is an in vitro immunodiffusion test de-
methylene blue or Neisser or Albert stain which scribed by Eleck for demonstrating the toxigenicity of
shows metachromatic granules and typical Chinese the C. diphtheriae.
l Procedure: A rectangular strip of filter paper impreg-
letter pattern.
2 . Demonstration of its toxicity by virulence tests nated with diphtheria antitoxin (1000 units/mL) is
a. In vivo tests placed on the surface of a 20% normal hoarse serum
i. Subcutaneous test agar in a Petri dish while the medium is still fluid. Then
ii. Intracutaneous test the surface is dried.
l Once the agar is set narrow streaks of the test strains are
b. In vitro tests
i. Eleck’s gel precipitation test made at right angle to the filter paper strip. A positive
ii. Tissue culture test and negative control is set. The plate is incubated at
37°C for 24–48 h where the toxin produced diffuses in
the agar.
In Vivo Tests l Interpretation: Toxigenic strains of C. diphtheriae
Subcutaneous Test produce arrowhead lines of precipitation where the

bacterial toxin meets with the antitoxin in optimum
Growth from an overnight culture on Loeffler’s slope is concentration.
emulsified in 2–4 mL broth and 0.8 mL of the emulsion is l No precipitate is formed in the case of nontoxigenic
injected subcutaneously into two guinea pigs of which one strains.
is protected with prior administration of 500 units of diph-
theria antitoxin. If the strain is virulent, then the unpro-
tected animal dies in 4 days. Tissue Culture Test
l Toxigenicity of diphtheria bacilli is demonstrated by
Intracutaneous Test incorporating the strains in the agar overlay of cell cul-
ture monolayers.
Broth emulsion is injected intracutaneously about 0.l mL l The toxins produced diffuse into the cells below and kill
into two guinea pigs where one is protected with 500 units them.
SHORT NOTES
Q. 1. Name different species of genus Corynebacterium. 6. C. parvum
Ans. The Corynebacterium diphtheriae bacilli are pleomor- Q. 2. DPT vaccine
phic. They are Gram-positive, nonsporing, noncapsulated
and nonmotile. Or,
Various species of genus Corynebacterium are as follows: Triple vaccine

1. C. diphtheriae Ans.
2. C. ulcerans
3. C. minutissimum l DPT vaccine or triple vaccine is a combined vaccine
4. C. tenuis containing the toxoids of diphtheria and tetanus and a
5. C. pseudodiphtheriticum (C. hofmannii) killed suspension of pertussis bacilli.
l Route of administration: Given as subcutaneous injections. a. In vivo tests

l Immunization schedule: Immunoprophylaxis of diphthe- i. Subcutaneous test
ria is done by active immunization, passive immunization ii. Intracutaneous test
and combined immunization. b. In vitro tests
l Adverse reactions: Though rare, consists of transient i. Eleck’s gel precipitation test
local inflammation, fever and occasional convulsions. ii. Tissue culture test
l Advantages
1. Minimizes the number of injections. Q. 4. Name two media used for cultivation of Corynebac-
2. Improves the immune response as the pertussis com- terium diphtheriae.
ponent, acts as an adjuvant for the toxoids for the
Ans.
diphtheria and tetanus.
Media used for cultivation of C. diphtheriae are as follows:
Q. 3. Lab diagnosis of Corynebacterium diphtheriae 1. Loeffler’s serum slope
Ans. 2. Tellurite blood agar
l Laboratory diagnosis of diphtheria consists of isolation Q. 5. Staining reactions of Corynebacterium diphtheriae.

of the bacteria and demonstration of its toxicity.
Ans.
l Bacteriological studies or isolation of the bacteria
1. Direct smear examination: Smears are stained by l The C. diphtheria contains metachromatic granules, on
Albert’s stain show beaded slender rods in typical staining with Loffler’s methylene blue, the granules take
Chinese letter pattern. up bluish purple colour.
2. Culture: Swabs are inoculated on Loeffler’s serum l Special stains such as Albert’s, Neisser’s and Ponder’s
slope, tellurite agar and a plate of ordinary blood agar. have been devised for demonstrating the granules
3. Demonstration of its toxicity by virulence tests clearly.
Topic 18
Mycobacterium (Tuberculosis, Atypical Mycobacteria

and Mycobacterium Leprae)
LONG ESSAYS
Q. 1. Describe the morphology, cultural characters and 3. Any growth is smeared and tested by ZN staining. For
pathogenicity of Mycobacterium tuberculosis. routine purpose, a slow growing, nonpigmented, niacin-
Ans. positive, acid-fast bacilli is taken as Mycobacterium
tuberculosis.
MORPHOLOGY 4. Confirmation is done by following biochemical tests:
a. Niacin test: Human tubercle bacilli form niacin when
1. They are straight or slightly curved rod-shaped Gram- grown on an egg medium. When 10% cyanogen
positive acid fast bacilli. bromide and 4% aniline in 96% ethanol are added
2. It is nonsporing, noncapsulated, nonmotile, with granu- to a suspension of the culture, a canary yellow
lar or beaded staining occurring singly, in pairs or as colour indicates a positive reaction. The test is posi-
small clumps. tive with human type and negative with bovine type
of bacilli.
CULTURAL CHARACTERS b. Aryl sulphatase test: Negative
c. Neutral red test: Virulent strains bind neutral red in
1. Culture is a very sensitive diagnostic technique for tu- alkaline buffer solution.
bercle bacilli, detecting as few as 10–100 bacilli per mL. d. Catalase peroxidase test: Tubercle bacilli are weakly
2. Several media both solid and liquid have been described catalase positive.
for cultivation of tubercle bacilli. e. Amidase test: Positive
f. Nitrate reduction test: Positive with M. tuberculosis because of primary progression or endogeneous re-
and negative with M. bovis infection or by the exogenous reinfection.
b. The lesion of the adult type of tuberculosis may be
PATHOGENESIS healed by resorption, fibrosis and occasionally cal-
cification or progress to chronic fibrocaseous tuber-
1. M. tuberculosis is a typical tubercle bacilli causing hu-
culosis with formation of tubercles, caseation, cavi-
man lesions such as tuberculosis.
tation and shedding of the bacilli in sputum.
2. Inhalation is the most common route of infection
c. Rarely an acute fatal infection may occur.
along with congenital affection, ingestion and skin
inoculation. Q. 2. Describe morphology and laboratory diagnosis of
3. The essential pathology of tuberculosis consists of the Mycobacterium leprae.
production of a characteristic lesion, the tubercle in in-
fected tissues. A tubercle is an avascular granuloma com- Ans. The morphology and laboratory diagnosis of Myco-
posed of a central zone containing giant cells with or bacterium leprae are as follows:
without caseation necrosis, surrounded by epithelioid
cells and a peripheral zone of lymphocytes and fibro-
blasts. MORPHOLOGY
4. Fate of bacilli: The majority of inhaled bacilli are ar-
1. M. leprae or leprae bacillus was first discovered by
rested by the natural defences of the upper respiratory
Hansen, hence, also known as Hansen’s bacillus. It is a
tract. The bacilli reaching the lungs are phagocytosed
straight or slightly curved rod, seen singly and in
by the alveolar macrophages.
groups, intracellularly or lying outside the cells.
5. Tuberculous lesions are primarily of two types as
2. They appear as agglomerates, the bacilli being bound
follows:
together by a lipid like substance, the glia. These masses
a. Exudative
are known as globi.
b. Productive
3. The bacilli, within globi, are arranged in parallel rows
6. Exudative type is an acute inflammatory reaction with
and present a cigar bundle appearance. In tissue sec-
accumulation of oedema fluids, polymorphonuclear
tions, the clumps of bacilli resemble cigarette ends.
leucocytes and later monocytes around the bacilli.
The lesions may heal by resolution, lead to necrosis of Diseases caused are as follows:
the tissues or develop into productive type. a. Tuberculoid form of leprosy
7. Productive type: The productive type of lesion is pre- b. Lepromatous form of leprosy
dominantly cellular, composed of a number of tuber- c. Intermediate form of leprosy
cles which may enlarge, coalesce, liquefy and undergo
caesation.
8. Depending on the time of infection and the type of
response, tuberculosis may be classified as 1. Bacteriological diagnosis or microscopy is sensitive for
a. primary and the lepromatous form but not the tuberculoid form.
b. postprimary. 2. Skin testing required confirming tuberculoid leprosy.
9. Primary Infection Culture cannot be used.
a. Primary infection in young children leads to the
primary complex. It consists of a subpleural focus Treatment
of tuberculous pneumonia in the parenchyma of the
lungs usually in the lower lobe or lower part of the 1. Multiple drug therapy (MDT) is now recommended for
upper lobe (Gohn’s focus). leprosy.
b. The hilar lymph nodes are involved. The Gohn’s 2. The current recommendations for patients with pauci-
focus together with enlarged hilar lymph nodes bacillary lesions is the concurrent administration of
constitute the primary complex, which is usually rifampacin 600 mg once a month and dapsone 100 mg
asymptomatic and undergoes spontaneous healing. daily for 6 months.
c. The primary infection may rarely lead to miliary 3. For multibacillary lesions the recommendation is rifam-
tuberculosis, meningitis and lesions of other organs pacin 600 mg once a month and dapsone 100 mg daily
like spleen, liver and kidneys due to haematoge- and clofazimine 50 mg daily for 2 years or until skin
neous spread. smears are negative.
10. Postprimary Infection 4. A minimum follow-up of 4 years for paucibacillary and
a. The post primary or the adult type of the tuberculosis 8 years for multibacillary cases is found to be necessary
is generally due to reactivation of primary infection to detect any relapse.
SHORT ESSAYS
Q. 1. BCG 2. Babies born to mothers with AFB-positive sputum can
be given BCG vaccination after a course of preventive
Ans. BCG is a live attenuated and freeze-dried vaccine. It
chemotherapy.
was named bacille Calmette-Guerin (BCG).
All the BCG strains used today all over the world are Role of BCG
derived from the original BCG strain maintained at Pasteur
Institute in Paris. 1. Vaccination does not give absolute protection against
tuberculosis. However, it makes the disease milder and
noninfectious in immunized children.
Dose and Administration 2. Vaccine prevents serious forms of primary tuberculosis
l BCG vaccine is available either as fresh liquid vaccine such as meningitis, skeletal tuberculosis and military
or in the form of freeze-dried (lyophilized) vaccine spread of the disease.
which is commonly used.
l The dose of the vaccine is a single intradermal injection
Q. 2. Classification of mycobacteria
of 0.1 mL containing 0.05–0.1 mg of the constituent Ans.
vaccine containing about 1–2 million viable organisms.
l It should be administered soon after birth failing which Classification of mycobacteria is as follows:
it should be given anytime during the first year of life 1. Cultivable
but not after age of 2 years. a. Tubercle bacilli
i. Human: M. tuberculosis
ii. Bovine: M. bovis
Immune Response iii. Murine: M. microti
Injection of the BCG vaccine induces a self-limited infec- iv. Avian: M. avium
tion with multiplication and dissemination of the bacillus in v. Cold blooded: M. marinum
different organs and production of small tubercles. This b. Mycobacteria causing skin ulcers
gives rise to delayed hypersensitivity and immunity. The i. M. ulcerans
immunity may last for 10–15 years and is similar to the ii. M. balnei
immunity following natural infection. c. Atypical mycobacteria
i. Photochromogens
ii. Scotochromogens
Complications iii. Nonphotochromogens
The recognized complications of the BCG vaccination are iv. Rapid growers
as follows: d. Johne’s bacillus
1. Local abscess, indolent ulcer, keloid, tuberculides, con- i. M. paratuberculosis
fluent lesion, lupoid lesions, lupus vulgaris e. Saprophytic mycobacteria
2. Regional enlargement and suppuration of draining i. M. smegmatis
lymph nodes ii. M. butyrium
3. Systemic fever, mediastinal adenitis, erythema nodo- iii. M. phlei
sum, very rarely nonfatal meningitis iv. M. stercori
2. Noncultivable
a. Lepra bacilli
Contraindications i. Human: M. leprae
1. Infants and children with active HIV disease ii. Murine: M. leprae murinum
SHORT NOTES
Q. 1. Give an account of morphology of tubercular l It is nonsporing, noncapsulated, nonmotile.
bacilli l Slightly curved rod with granular or beaded staining.
l It occurs singly, in pairs, in bundles or clumps.
Ans.
Morphology of tubercular bacilli is as follows: Q. 2. Tuberculin test

l It is slender, Gram-positive, acid fast-bacilli. Or,
Mantoux test Q. 3. Lab diagnosis of Mycobacterium leprae

Ans. Ans.
l The routinely used method for tuberculin testing is the Laboratory diagnosis of Mycobacterium leprae consists of
technique of Mantoux. the following:
l In the Mantoux test 0.1 mL of PPD (purified protein 1. Bacteriological diagnosis or microscopy is sensitive for
derivative) containing 5 TU is injected intradermally on the lepromatous form but not the tuberculoid form.
the flexor aspect of forearm with a tuberculin syringe 2. Skin testing required confirming tuberculoid leprosy.
raising a wheal. It is essential that the injection is given Culture cannot be used.
between the layers of the skin and not subcutaneously.
l The site is examined 48–72 h later and induration is Q. 4. Laboratory diagnosis of pulmonary tuberculosis
measured at its widest point transversely to the long axis Ans.
of the forearm and the induration of diameter.
a. 10 mm or more is considered—positive Laboratory diagnosis of pulmonary tuberculosis is estab-
b. 5 mm or less—negative lished by the following:
c. 6–9 mm—equivocal 1. Demonstrating the bacillus in the lesion by micro
l A positive tuberculin test indicates hypersensitivity to scopy
tuberculoprotein denoting infection with tubercle bacil- 2. Isolating it in culture
lus or BCG immunization, recent or past with or without 3. Transmitting the infection to experimental animals
clinical disease. 4. Demonstrating hypersensitivity to tuberculoprotein.
Topic 19
Clostridium
LONG ESSAY
Q. 1. What is the aetiology of gas gangrene? Add a b. Less pathogenic
note on pathogenesis, laboratory diagnosis of gas gan- i. C. histolyticum
grene. ii. C. fallax
Ans. c. Doubtful pathogens
i. C. sporogenes
1. Gas gangrene was defined by Oakley in 1954 as ii. C. bifermentans
a rapidly spreading oedematous myonecrosis, occur- 4. Pathogenesis
ring characteristically in association with severe a. Clostridia usually enter the wound along with im-
wounds of extensive muscle masses that have been planted foreign particles like soil, road dust, bits of
contaminated with pathogenic clostridia, especially clothing or shrapnel or from their natural habitat like
C. perfringens. perineal or thigh skin.
2. The bacteriology of gas gangrene is varied. Generally b. The spores of clostridia germinate under favourable
several species of clostridia are found in association conditions like deceased O2 tension, reduced Eh and
with anaerobic streptococci and facultative anaerobes pH, breakdown of carbohydrates, liberation of amino
like E. coli, proteus and staphylococci. acids from protein. Provide an ideal conditions for
3. Aetiologic Agents clostridia to multiply and liberate exotoxins which
The gas gangrene group of pathogens are as follows: further cause tissue damage.
a. Established pathogens c. The lecithinases damage cell membranes and in-
i. C. perfringens (60%) creases capillary permeability leading to extravasa-
ii. C. septicum tion and increased tension in affected muscle thus
iii. C. novyi (20–40%) further causing anoxic damage.
d. The collagenases destroy collagen barriers in from the exudate in the deeper parts of the
the tissues and hyaluronidases breaks down inter- wounds.
cellular substance furthering invasive spread of ii. Exudate from the parts where infection appears
clostridia. to be most active and from the depth of the
e. The abundant production of gas reduces the blood wound to bed collected with a capillary pipette
supply still further by pressure effect extending the or swab.
area of anoxic damage thus making the lesion a pro- iii. Necrotic tissue and muscle fragments.
gressive one. Accumulation of gas makes the tissues c. Aerobic and anaerobic cultures are made on fresh and
crepitant. heated blood agar, preferably on 5–6% agar to prevent
f. In untreated cases the disease process extends rap- swarming.
idly and inexorably profound toxemia and prostra- d. A plate of serum or egg yolk agar with C. perfringens
tion develop and death occurs due to circulatory antitoxin spread on one half is used for Nagler reaction.
failure. Four tubes of Robertson’s cooked meat broth are inocu-
lated and heated at100°C for 5, 10, 15 and 20 min and
then incubated at 45°C for 4–6 h. Subcultured on the
Laboratory Diagnosis blood agar plates to yield predominant growth of pure
a. Only helps to confirm the clinical diagnosis and identify C. welchii.
and enumerate the infective organism. e. Good growth also occurs in Robertson’s cooked meat
b. The specimens to be collected are as follows: medium, turning the meat pink but not digesting it.
i. Films from the muscles at the edge of the f. The isolates are identified based on their morphological,
affected area, from the tissue in necrotic area and cultural, biochemical and toxigenic character.
SHORT ESSAYS
Q. 1. Classify clostridium. Based on the Diseases
Ans. a. Gas gangrene group: C. welchii, C. oedemati, C.
septicum, C. histolyticum, C. fallax, C. bifermentans,
Many methods have been adopted for classifying bacteria C. sporogenes
as below: b. Tetanus group: C. tetani
c. Food poisoning: Gastroenteritis (C. welchii type A),
Based on Shape and Position of Spores Botulism (C. botulinum)
d. Acute colitis: C. difficile
1. Central or subterminal: C. perfringens, C. bifermentans,
C. botulinum, C. novyi
Q. 2. Prophylaxis of tetanus
2. Oval and terminal: C. tertium, C. cochlearum
3. Spherical and terminal Example: C. tetani, C. tetano- Ans. The nature of prophylaxis for tetanus depends largely
morphum, C. sphenoides on the type of the wound and the immune status of the patient.
The methods of prophylaxis available for tetanus are as

Based on Biochemical Properties follows:
1. Both proteolytic and saccharolytic 1. Surgical attention
a. Proteolytic-predominating: C. bifermentans, C. his- 2. Antibiotics
tolyticum, C. botulinum A, B and F, C. sporogenes, 3. Immunization
C. sordelli a. Active
b. Saccharolytic predominating: C. perfringens, C. welchii, b. Passive
C. septicum, C. novyi, C. difficile c. Combined
2. Slightly proteolytic but not saccharolytic Example:
C. tetani Surgical Prophylaxis
3. Saccharolytic but not proteolytic: C. botulinum C, D
and E, C. tenanomorphum, C. fallax, C. tertium, It aims at removal of foreign bodies, necrotic tissues and
C. sphenoids blood clots to prevent anaerobic environment favourable for
4. Neither proteolytic nor saccharolytic: C. cochlearum tetanus bacillus.
Depending on type of wound the extent of surgical treat- Combined Immunization

ment varies from simple cleansing to radical excision.
l It consists of administering to a nonimmune person ex-
posed to the risk of tetanus TIG (human antitetanus im-
Antibiotic Prophylaxis munoglobulin) injection at one site, along with the first
dose toxoid at contralateral site, followed by the second
It aims at destroying or inhibiting tetanus bacilli and pyo-
and third doses of toxoid at appropriate monthly intervals.
genic bacteria in wounds so that the production of toxin is
l It is important to use adsorbed toxoid as the immune
prevented. Long acting penicillin injection is the drug of
response to plain toxoid may be inhibited by TIG.
choice. Antibiotics are to be started before wound toilet.
l Ideally, combined immunization should be employed
Bacitracin or neomycin may be applied locally also. Anti-
whenever passive immunization is called for.
biotics have no action on the toxin. Hence they do not re-
place immunization, but serves as useful adjunct. Q. 3. Enumerate the various pathogenic clostridia. De-
scribe the morphology and laboratory diagnosis of Co-
Immunization rynebacterium tetani.
Active Immunization Ans.
l It is achieved by spaced injections of formal toxoid, The various pathogenic clostridia are as follows:
which is available as a plain toxoid or adsorbed on alu- 1. C. welchii
minium hydroxide or phosphate. The adsorbed toxoid is 2. C. tetani
a better antigen. 3. C. botulinum
l Tetanus toxoid is given either alone or along diphtheria 4. C. septicum
toxoid and pertussis vaccine as a triple vaccine in which 5. C. histolyticum
pertussis vaccine acts as an adjuvant also. 6. C. bifermentans
l A course of immunization consists of three doses of 7. C. difficile
tetanus toxoid given intramuscularly with an interval of
4–6 weeks between the first two injections and the third
MORPHOLOGY
dose 6 months later as per National Immunization Pro-
gramme. A full course of immunization confers immu- l They are Gram-positive, slender bacillus, about 4–8 mm
nity for a period of at least 10 years. A booster dose of in length.
toxoid is recommended after 10 years. l It has a straight axis, parallel sides and rounded ends.
l It occurs singly and occasionally in chains.
l Spores are spherical, terminal, bulging giving the bacil-

Passive Immunization
lus a characteristic drumstick appearance.
l It is achieved by injection of tetanus antitoxin. Antiteta- l It is noncapsulated and motile by peritrichate flagella.
nus serum (ATS) or tetanus antitoxin from hyperim-
mune horses.
l The recommended dose is 1500 IU administered subcu-
taneously or intramuscular in nonimmune persons soon It is made by demonstration of C. tetani by
after receiving any tetanus prone injury. ATS was useful a. microscopy,
not only in reducing the incidence of tetanus but also b. culture or
lengthens the incubation period and diminishes the mor- c. animal inoculation.
tality when it did not prevent the disease.
l ATS carries two disadvantages as follows:
1. Immune elimination
Microscopy
2. Hypersensitivity 1. It is unreliable and the mere demonstration of typical drum-
l The half-life of ATS in human beings is normally about stick bacilli in wounds is not diagnostic of tetanus as they
7 days, but in persons who had prior injections of horse may be present in the wounds without tetanus developing.
serum, it is eliminated much quickly by combination 2. It may not be possible to differentiate C. tetani from
with pre-existing antibodies, this is known as immune morphologically similar bacilli such as C. tetanomor-
elimination. Prior sensitization also leads to hypersensi- phum and C. sphenoids.
tivity reactions, which may range from mild local reac-
tions to serum sickness, and even fatal anaphylaxis.
l Passive immunization is emergency procedure to be
Culture
used only once. l Diagnosis by culture is more dependable.
l Isolation is more likely from excised bits of tissue from 2 days. Toxigenic C. tetani strains show haemolysis
necrotic depths of wounds than from wound swabs. around the colonies only on the half without the anti-
l The material is inoculated on one-half of blood agar toxin. Haemolysis is inhibited by the antitoxin on the
plate. C. tetani produces swarming growth, which may be other half.
detected on the opposite half of the plate after 1–2 days l This may help in the identification of the culture
incubation anaerobically. as C. tetani, but is unreliable for toxigenicity test,
l The material is also inoculated into three tubes of since it indicates the production only of tetanolysin
cooked meat broth, one of which is heated to 80°C for and not of tetanospasmin which is the pathogenic
15 min, the second for 5 min and the third left unheated. toxin.
The purpose of heating for different periods is to kill
vegetative bacteria, while leaving tetanus spores un-
damaged, which vary widely in heat resistance.
Animal Inoculation
l The cooked meat tubes are incubated at 37°C and l A 2–4 day-old cooked meat culture (0.2 mL) is inocu-
subcultured on one-half of blood agar plates daily up lated into the root of the tail of a mouse. A second
to 4 days. C. tetani may be isolated in pure culture by mouse that has received tetanus antitoxin (1000 units)
subculturing from the swarming edge of the growth. one hour earlier serves as the control.
l For identification and toxigenicity testing, blood agar l Symptoms develop in the test animal in 12–24 h begin-
plates with 4% agar to inhibit swarming, having tetanus ning with stiffness of the tail. Rigidity proceeds to the leg
antitoxin (1500 units/mL) spread over one-half of the on the inoculated side, the opposite leg, trunk and fore-
plate are used. limbs in that order. The animal dies within 2 days, but
l The suspected C. tetani strains are stab-inoculated on each may be killed earlier as the appearance of ascending teta-
half of the plate, which is then incubated anaerobically for nus is diagnostic.
SHORT NOTES
Q. 1. Triple antigen l Surgical prophylaxis aims at removal of foreign bodies,
necrotic tissues and blood clots to prevent anaerobic
Ans.
environment favourable for tetanus bacillus.
l Tetanus toxoid is given either alone or along diphtheria l Antibiotic prophylaxis aims at destroying or inhibiting
toxoid and pertussis vaccine as a triple vaccine in which tetanus bacilli and pyogenic bacteria in wounds so that
pertussis vaccine acts as an adjuvant also. the production of toxin is prevented.
l A course of immunization consists of 3 doses of tetanus l Immunization may be
toxoid given intramuscularly with an interval of 4–6 weeks 1. active,

between the first two injections and the third dose 6 months 2. passive or
later as per National Immunization Programme. A full 3. combined.
course of immunization confers immunity for a period of
at least 10 years. A booster dose of toxoid is recommended Active immunization achieved by spaced injections of for-
after 10 years. mal toxoid, which is available as a plain toxoid or adsorbed
on aluminium hydroxide or phosphate.
Q. 2. Prophylaxis of tetanus Passive immunization is achieved by injection of tetanus
antitoxin. Antitetanus serum (ATS) or tetanus antitoxin
Or,
from hyper immune horses.
Immunization against tetanus Combined immunization, ideally, should be employed when
ever passive immunization is called for.
Ans.
l The nature of prophylaxis for tetanus depends largely Q. 3. Name four clostridia causing gas gangrene.
on the type of the wound and the immune status of the
Ans. Various clostridia causing gas gangrene are as follows:
patient.
l The methods of prophylaxis available for tetanus are as 1 . C. welchii (perfringens)
follows: 2. C. septicum
1. Surgical attention 3. C. novyi
2. Antibiotics 4. C. histolyticum
3. Immunization 5. C. bifermentans
Q. 4. Mention the toxins of Clostridium tetani. of the interneurons of inhibitory pathways and motor neu-
rons to produce blockade of spinal inhibition.
Ans.
l Clinical features
l C. tetani produces at least two pharmacologically and 1. Incubation period: 6–10 days.
antigenically distinct toxins as follows: 2. Generalized tetanus is characterized by lockjaw or
1. Haemolysin or tetanolysin trismus due to spasm of masseter, which is initial
2. Neurotoxin or tetanospasmin symptom. Dysphagia, stiffness or pain in the neck,
l Tetanolysin is heat labile and oxygen labile and is re- shoulder or back muscles appear concurrently.
sponsible for haemolysis on blood agar. Laryngeal spasm may lead to asphyxia.
l Tetanospasmin (neurotoxin) is responsible for tetanus. 3. Sustained contraction of facial muscles results in
It is neurotoxic and is oxygen stable and relatively heat grimace or sneer called as risus sardonicus. The
labile, being inactivated by heating at 65°C in 5 min. contraction of muscles of the back produces an
l A third toxin, a nonspasmogenic peripherally active arched back called opisthotonus.
neurotoxin, has been identified. Its role in the pathogen- 4. Treatment:
esis of tetanus is not known. a. General measures: Cardiopulmonary monitoring
should be maintained continuously. Sedation, air-
Q. 5. Tetanus way and nutrition should be maintained.
Or, b. Antibiotics should be given to eradicate vegeta-
tive organisms or source of toxins.
Lock jaw c. Antitoxin is injected to neutralize circulating
Ans. toxin and unbound toxin with wound. Human
tetanus immunoglobin (TIG) 3000–6000 units
l Tetanus also known as lock jaw, is an acute infection of IM individual doses.
nervous system characterized by intense activity of mo- d. Prophylaxis: Wound debridement and booster
tor neurons and resulting in severe muscle spasms. doses of TT should be given.
l Aetiology: It is caused by the exotoxin of the anaerobic e. Unimmunized individuals: ATS 1500 units or
Gram-positive bacillus C. tetani, which acts at the synapse TIG 250 units should be given.
Topic 20
Nonsporing Anaerobes
SHORT ESSAY
Q. 1. Bacteroides l They are the normal inhabitants of intestine, upper re-
Ans. spiratory tract and female genital tract.
l The most common species are B. fragilis from large
l Bacteriodes are the nonsporing, nonmotile, obligate intestine and B. melaninogenicus from oropharynx, gut
anaerobes, Gram-negative bacilli with round ends. and vagina.
l They possess capsular polysaccharides which are their l They grow in media such as brain-heart infusion agar
virulence factors and their antibodies can be detected in under 10% CO2.
patient’s serum. l They cause abdominal and brain abscesses and empy-
l They are pleomorphic, commonly isolated from clinical ema. They cause suppuration in surgical infection such
specimens appearing as slender rods, branching forms as peritonitis following bowel injury and pelvic inflam-
or coccobacilli seen singly, in pairs or in short chains. matory disease.
SHORT NOTE
Q. 1. Lactobacillus l Some species are most common in intestine. e.g. L. aci-
dophilus which are beneficial in synthesizing vitamins
Ans.
such as biotin, B12 and vitamin K, which may be ab-
l Lactobacilli are nonsporing anaerobic Gram-positive ba- sorbed by the host.
cilli and are acidophilic and grow best at pH of 5 or less. l They constitute the normal flora of vagina and ferment
l They are normally present in the mouth, intestines and the glycogen deposited in the vaginal epithelial cells,
typically in the adult vagina. forming lactic acid, which accounts for the highly acidic
l Normally those present in mouth cause dental caries. pH of vagina.
They form lactic acid by fermentation of sugars which l Several species of lactobacilli occur in vagina and are
destroys enamel and dentine. collectively known as Doderlein’s bacillus.
Topic 21
Enterobacteriaceae (Coliforms: Proteus, Shigella

and Salmonella)
LONG ESSAY
Q. 1. Describe the morphology, cultural characteristics 4. LABORATORY DIAGNOSIS
of causative agent of enteric fever and laboratory diag-
nosis of enteric fever. The bacteriological diagnosis of enteric fever consists of
a. isolation of the bacteria from the patient,
Ans. b. demonstration of antibodies in the serum,
1. Enteric fever includes typhoid fever caused by Salmo- c. demonstration of circulating typhoid bacillus antigen in
nella typhi and paratyphoid fever caused by Salmonella blood or urine, and
paratyphi A, B and C. d. general blood picture.
A. Isolation of Bacteria from the Patient

2. MORPHOLOGY
1. For isolation of bacteria specimen may be obtained
a. Salmonella are Gram-negative rods measuring 1–3 from blood, faeces, urine, aspirated duodenal fluid bile,
3 0.5 mm in size. bone marrow or rose spots.
b. They are motile with peritrichate flagella.
c. They do not form capsules or spores but may possess i. Blood Culture
fimbriae.
1. The blood cultures yield as much as 90% positive re-
sults in first week as bacteriaemia occurs early in the
3. CULTURAL CHARACTERISTICS course of the disease.
a. Salmonella are aerobic and facultatively anaerobic, 2. Blood cultures rapidly become negative on treatment
readily growing on simple media over a range of pH with antibiotics.
6–8 and temperature 15–41°C.
b. Usually on nutrient agar, colonies are large, 2–3 mm in ii. Faeces Culture
diameter, circular, low convex, smooth and translucent. 1. Salmonellae are shed in faeces throughout the course
c. On MacConkey and deoxycholate citrate media, of disease and even in convalescence; hence faecal
colonies are colourless due to absence of lactose cultures are almost as valuable as blood cultures in
fermentation. diagnosis.
d. On Wilson and Blair’s bismuth sulphite medium, jet 2. It becomes positive even in carriers.
black colonies with a metallic sheen are formed due to 3. Faecal samples are directly plated on MacConkey, DCA
production of H2S whereas S. paratyphi A and other and Wilson-Blair’s media, which are enrichment and selec-
species that do not form H2S produce green colonies. tive media.
4. Salmonella produce pale colonies on MacConkey and Result

DCA media. 1. The highest dilution of patient’s serum in respect to
5. On Wilson and Blair’s bismuth sulphite medium salmo- each salmonella antigen is read as the Titre.
nella produce jet black colonies with metallic sheen due
to production of H2S. But S. paratyphi A produces green Interpretation
colonies due to absence of H2S production. The result of the Widal test should be interpreted taking
6. For enrichment, specimens are inoculated into one tube into account the following:
each of selenite and tetrathionate broth for 12–18 h be- a. The agglutinin titre depends on the stage of the disease.
fore subculturing onto media plates. Agglutinins usually start appearing by the end of the
first week with sharp rise in second and third week and
iii. Urine Culture the titre remains steady till the fourth week after which
it declines gradually.
1. Salmonellae are shed in the urine irregularly and infre-
b. Demonstration of rising titre of four folds or greater of
quently, hence, they are less useful.
both H and O agglutinins at an interval of 4–7 days is
2. It becomes positive only in second or third week in only
most important diagnostic criterion. A rising titre of H
about 25% of cases.
or O antibodies between test done in the first week and
third week is highly significant.
iv. Duodenal Juice or Bile Culture
In a single test titre of 1:160 or above for O and 1:200 or more
1. These are cultured to detect chronic carriers on selective for H signifies active infection but this has to be interpreted
media. with caution taking into consideration the following factors:
a. Local titre: In endemic areas, due to presence of sub-
B. Demonstration of Antibodies in Serum clinical infection normal individuals show low titre of
(Serological Tests) agglutinins. This is known as local titre and may cause
i. Widal Test positive reaction. It varies from place to place.
b. Immunization: Individuals with H/O immunization with
1. It is an agglutination test which detects presence of se- the TAB vaccine may show high titres of antibody to
rum agglutinins H and O in the patients’ serum suffering each of the salmonellae. H agglutinins tend to persist in
from enteric fever. titres of 1:50–1:800 for many months and even years but
2. In enteric fever antibodies to salmonella start appearing O agglutinins do not reach high levels (1:100) and dis-
in serum at the end of the first week and rises sharply appears within 6 months. Thus marked rise of O agglu-
during the third week. tinins and rise of H agglutinins of a specific salmonella
3. It is preferable to test two specimens of sera at an inter- species is diagnostically significant.
val of 7–10 days to demonstrate a rising antibody titre. c. H agglutination: H agglutination is more reliable than O
agglutination as different salmonellae have same O an-
Procedure tigen in common and many enterobacteria also show
1. Two types of test tubes are used in Widal test as follows: similar antigen. Moreover, H agglutination is specific
a. A narrow tube with a conical bottom (Dreyer’s tube) for species. Its rise in a nonvaccinated individual indi-
for H agglutination. cates enteric fever or a latent infection.
b. A short round bottomed tube (Felix tube) for O agglu- d. Anamnestic reaction: Person with H/O enteric fever or
tination. immunization with TAB vaccine show transient rise in
2. Equal volume (0.4 mL) serial dilutions of serum from H antibody during unrelated fevers such as malaria, in-
1:10 to 1:640 and H and O antigens are mixed in Dreyer fluenza. This is known as anamnestic reaction.
and Felix tubes respectively. e. Nonspecific antigens: Test suspension containing non-
3. Five test tubes are set up. Four for the test and the fifth specific antigens like febrial antigens may cause false
for a nonserum control for checking autoagglutination. positive reaction.
4. The test tubes are thoroughly mixed by shaking the rack and f. Effect of antibiotic treatment: Cases treated with chloram-
then they are incubated in a water bath at 37°C overnight. phenicol may show poor response or rise subsequently.
g. Carriers: Carriers also give positive results for Widal test.
Observation
1. H agglutination leads to formation of loose cotton
woolly clumps and O agglutination produces disc-like
ii. ELISA Test
granular deposit at the bottom of the tube in both the 1. ELISA is a sensitive method of measuring antibody
supernatant fluid rendered clear. against the lipopolysaccharide of the salmonellae or
2. The antigens used in Widal test are the O and H antigens detecting protein, the outer membrane proteins of
of S. typhi and the H antigens of S. paratyphi A and B. S. typhi.
C. Demonstration of Circulating Antigen D. General Blood Picture

1. Antigens of the typhoid bacilli are consistently present 1. General blood picture in enteric fever may show leuko-
in the blood and the urine of the patient in the early penia (leucocyte count: 2000–2500 cells/cu mm) with
stage of the disease. relative lymphocytosis.
2. These antigens can be demonstrated by the sensitized
staphylococcal coagglutination test. Cowen I strain of
E. Other Laboratory Tests
S. aureus which contains protein A, is stabilized with
formaldehyde and coated with S. typhi antibody. 1. Where bacteriological facilities are not available, an-
One percent suspension of these cells is mixed with other valuable test is diazo test of urine.
patient’s serum on a slide during the first week of the 2. Equal volume of the patient’s urine and the diazo re-
enteric fever. The lymphoid antigen present in the agent are mixed in a test tube and a few drops of 30%
serum of these patients combines with the antibody ammonium hydroxide are added.
attached to the staphylococcal cells producing visible 3. If the test is positive, a red or pink coloured froth devel-
agglutination within 2 min. ops on shaking the mixture.
3. The test is rapid, sensitive and specific but is not posi- 4. The diazo reagent is made up to 40 part of solution A
tive after first week of the disease. (0.5 g sulphalinic acid 1 5 mL of conc H2SO4 1 100
4. Other modes of detecting antigen are counterimmuno- mL of distilled water) and 1 part of solution B (0.5 g
electrophoresis and ELISA. sodium nitrite 1 100 mL distilled water).
SHORT ESSAY
Q. 1. Lab diagnosis of enteric fever deposit at the bottom of the tube in both the supernatant
fluid rendered clear.
Ans.
Interpretation
The laboratory diagnosis or the bacteriological diagnosis of
enteric fever consists of the following: The result of the Widal test should be interpreted taking
1. Isolation of the bacteria from the patient into account the following:
2. Demonstration of antibodies in the serum 1. The agglutinin titre depends on the stage of the disease.
3. Demonstration of circulating typhoid bacillus antigen in Agglutinins usually start appearing by the end of the
blood or urine first week with sharp rise in second and third weeks and
4. General blood picture the titre remains steady till the fourth week after which
it declines gradually.
2. Demonstration of rising titre of four folds or greater of
Isolation of Bacteria from the Patient both H and O agglutinins at an interval of 4–7 days is
For isolation of bacteria specimen may be obtained from most important diagnostic criterion. A rising titre of H
blood, faeces, urine, aspirated duodenal fluid bile, bone or O antibodies between test done in the first week and
marrow or rose spots. third week is highly significant.
Demonstration of Antibodies in Serum ELISA Test

(Serological Tests) l ELISA is a sensitive method of measuring antibody
against the lipopolysaccharide of the salmonellae or de-
Widal Test
tecting protein, the outer membrane proteins of S. typhi.
l It is an agglutination test which detects presence of se-
rum agglutinins H and O in the patients’ serum suffering
from enteric fever.
Demonstration of Circulating Antigen
l In enteric fever antibodies to salmonella start appearing 1. Antigens of the typhoid bacilli are consistently present
in serum at the end of the first week and rises sharply in the blood and the urine of the patient in the early
during the third week. stage of the disease.
l It is preferable to test two specimens of sera at an inter- 2. These antigens can be demonstrated by the sensitized
val of 7–10 days to demonstrate a rising antibody titre. staphylococcal coagglutination test. The test is rapid,
sensitive and specific but is not positive after first week
Observation of the disease.
H agglutination leads to formation of loose cotton woolly 3. Other modes of detecting antigen are counterimmuno-
clumps and O agglutination produces disc-like granular electrophoresis and ELISA.
General Blood Picture Other Laboratory Tests

General blood picture in enteric fever may show leukopenia Where bacteriological facilities are not available, another
(leucocyte count: 2000–2500 cells/cu mm) with relative valuable test is diazo test of urine.
lymphocytosis.
SHORT NOTE
Q. 1. Widal test l It is preferable to test two specimens of sera at an inter-
val of 7–10 days to demonstrate a rising antibody titre.
Or
l The result of the Widal test should be interpreted taking into
Widal reaction account the agglutinin titre and the demonstration of rising
titre of four folds or greater of both H and O agglutinins.
Ans.
l In a single test titre of 1:160 or above for O and 1:200
l Widal test is an agglutination test which detects pres- or more for H signifies active infection but this has to be
ence of serum agglutinins H and O in the patient’s se- interpreted with caution taking into consideration the
rum suffering from enteric fever. various factors like local titre, immunization, H aggluti-
l In enteric fever antibodies to salmonella start appearing nation, anamnestic reaction, nonspecific antigens, effect
in serum at the end of the first week and rises sharply of antibiotic treatment.
during the third week. l The carriers also give positive results for Widal test.
Topic 22
Vibrio
SHORT ESSAYS
Q. 1. Describe the morphology, cultural characteristics, CULTURE CHARACTERISTICS
toxins and laboratory diagnosis of vibrio cholera.
Discuss briefly about cholera. l Vibrio cholerae is strongly aerobic, exhibiting scanty
and slow growth anaerobically.
Ans. l It grows within a temperature range of 16–40°C with
optimum temperature being 37°C.

1 MORPHOLOGY l It grows best in alkaline media at an optimum pH of 8.2.
l Vibrio cholerae is a Gram-negative, curved or comma- l Growth on ordinary media
shaped rod measuring 1.5 mm 3 0.2 mm. l It grows well on ordinary media. On nutrient agar the
l It is nonsporing, noncapsulated and motile with a single colonies are moist, translucent, round discs, around
polar flagellum exhibiting darting motility (Fig. 22.1). 1–2 mm in diameter with a bluish tinge in transmitted
light.
l On MacConkeys agar, the colonies are colourless at
first but become reddish on prolonged incubation due

to late fermentation of lactose.
l On blood agar, colonies are initially surrounded by a
zone of greening, which later becomes clear due to

hemodigestion.
l In gelatin stab culture, infundibuliform (funnel
shaped) or napiform (turnip-shaped) liquefaction

occurs in 3 days at 22°C.
l A number of special media have been employed for the
cultivation of cholera vibrios which have been classified

as follows:
1. Holding or transport media
FIGURE 22.1 Vibrio cholerae. a. Venkatraman–Ramakrishnan (VR ) medium
b. Cary–Blair medium l The media usually employed are bile salt agar,
c. Autoclaved sea water MacConkey’s agar for nonselective and TCBS agar for
2. Enrichment media selective plates.
a. Alkaline peptone water at pH of 8.6
b. Monsur’s taurocholate tellurite peptone water at
Technique
pH of 9.2
Both of them are good transport as well as enrichment media. The plates should not be older than 3–5 days and should be
3. Plating media well dried before streaking. Generally the plates are exam-
a. Alkaline bile salt agar (BSA) at pH of 8.2. This ined after overnight incubation at 37°C.
simple medium is widely used and colonies are
similar to those on nutrient agar. Colony Characteristics
b. Monsur’s gelatin taurocholate trypticase tellurite
agar (GTTA) medium: The cholera vibrios produce l The Vibrio cholerae produces moist, translucent, round
colonies that are translucent with a greyish black discs about 1–2 mm in diameter with a bluish tinge in
centre and a turbid halo around them due to hydro- transmitted light and has distinctive odour on bile salt
lysis of gelatin. agar and nutrient agar.
c. Thiosulphate citrate bile sucrose (TCBS) agar at l On MacConkey’s agar the colonies are colourless first
the pH of 8.6. It is available commercially and is but on prolonged incubation they become reddish.
very widely used at present. The colonies are large, l On Monsur’s GTTA medium the colonies are small
convex and yellow which turns green on continued translucent of 3–4 mm in size with a greyish black cen-
incubation. tre and a turbid halo.
l On TCBS medium the colonies are large yellow convex
which become green on continued incubation.

l Specimen collected: Faeces or rectal swabs can be taken. Agglutination Test
Stool collected in the acute stage of the disease, before
antibiotic administration is the most useful specimen for l Colonies from selective media are picked up with a
laboratory diagnosis. Specimen is best collected by rub- straight wire and tested by slide agglutination with chol-
ber catheter no. 26 or 28. Rectal swab made with good era O subgroup I serum.
l If positive, the agglutination test is repeated using
quality cotton wool absorbing 0.1–0.2 mL of fluid can be
used in carriers or contacts. monospecific Ogawa and Inaba sera for serotyping.
l If agglutination test is negative with one colony, the test
l Specimens should be transported in transport media or
preserved in enrichment media. is repeated with at least five colonies.

l If slide agglutination is positive, the isolate is tested for
l As far as possible, specimens should be plated at the
bedside and inoculated plates sent to laboratory. chick red cell agglutination.
This is employed for presumptive differentiation between
Direct Microscopic Examination EI Tor and classical vibrios.
l Diagnosis by direct microscopic examination of cholera

stool is not recommended, as the results are not reliable. Serological Tests
l For rapid diagnosis, the characteristic motility of the l These tests are of little use in diagnosis of cholera.
vibrios and its inhibition by specific antiserum can be l The tests available are agglutination using live or killed
demonstrated under the dark field or phase contrast vibrio suspensions, indirect haemagglutination, vibrio-
microscope using cholera stool from acute cases. cidal test and antitoxin assay. Of these, the complement
dependent vibriocidal antibody test is most useful.
Culture
Biochemical Tests
l The specimen received on holding or transport medium
are first inoculated into enrichment media such as alkaline l Glucose, mannitol, maltose, mannose and sucrose are
peptone water or Monsur’s liquid medium and incubated fermented producing acid but no gas.
for 6–8 h before plating on a selective medium. l Inositol, arabinose, lactose are not fermented.
l When the specimen is collected in enrichment medium l Indole is formed.
such as Monsur’s liquid media it should be incubated l Nitrates are reduced.
for 6–8 h including the transit time before subculturing l Catalase test, oxidase test and urease test are positive.
on solid medium. l Voges–Proskauer (VP) test is negative.

Q. 2. Cholera l In severe cases, as much as 1 L of fluid may be lost each

hour. The patient usually feels bloated and may have
Ans.
abdominal pain before the onset of diarrhoea.
l Vibrio cholerae is the aetiologic agent of human chol- l Death is caused by electrolyte abnormalities and mas-
era, a diarrhoea like syndrome that can be fatal owing to sive fluid loss.
severe loss of water and electrolytes.
l Cholera is spread by the ingestion of fecally contami- Laboratory Diagnosis
nated food and water.
l V. cholerae may be viewed directly in stool samples,
l The nutritional status of infected people may play an im-
particularly in dark-field microscopy.
portant role in the disease. Those with an alkaline pH in the
l Selective media for culture are based on the ability of
stomach and intestines appear to be more easily infected.
vibrios to grow at an alkaline pH and identification can
l Bacterial levels increase in contaminated water during
be made by biochemical tests.
the warm months.
Treatment, Prevention and Control

Pathogenicity
l Intravenous administration of fluids and electrolytes is
l V. cholerae colonizes the intestinal tract in very high num-
critical for recovery.
bers. The cells attach to but do not invade intestinal mucosa.
l Oral administration of a solution containing glucose
l A potent enterotoxin is released and binds to ganglio-
and electrolytes has been successful, but the patient
side receptors on the mucosal cells.
must be capable of consuming the liquid by mouth.
l Increased intracellular cAMP results in the excretion of
Severely ill patients generally are too weak to ingest
electrolytes such as chloride and bicarbonate ions along
fluids.
with massive quantities of water.
l Antibiotic therapy does not affect the disease once, the
enterotoxin attaches to the intestinal cells, but can pre-

Symptomatology vent later attacks by reducing the number of toxin pro-
l Diarrhoea is the major symptom of cholera. The faeces ducing V. cholerae in the intestines.
contain epithelial cells, mucus and large numbers of V. l Doxycycline (adults) trimethoprim–sulphamethethoxazole
cholerae. Disease is characterized by profuse watery (children) or furazolidone (pregnant women) is administered.
diarrhoea (rice water stools). l Improved hygiene is critical for control.
Topic 23
Pseudomonas, Yersinia, Pasteurella, Francisella,

Haemophilus, Bordetella and Brucella
SHORT ESSAY
Q. 1. Whooping cough Respiratory complications are self-limited but the neurologi-
Ans. cal complications may result in permanent sequelae such
as epilepsy, paralysis, retardation, blindness or deafness.
l The disease whooping cough is caused by the bacillus l Laboratory diagnosis is by microscopy or more reliably
known as Bordetella pertussis. by culture.
l It is predominantly a paediatric disease, with incidence
and mortality being highest in first year of life. Prophylaxis

l It usually lasts for 6–8 weeks and complications may be
due to 1. Specific immunization with killed Bordetella pertussis

1. pressure effects during violent bouts of coughing— vaccine is very effective. Pertussis vaccine is usually
subconjunctival haemorrhage, subcutaneous em- administered in combination with diphtheria and teta-
physema, nus toxoid (triple vaccine).
2. respiratory—bronchopneumonia, lung collapse or 2. Three injections at intervals of 4–6 weeks are to be
3. neurological—convulsions, coma. given before the age of 6 months followed by a booster
at the end of first year of life.
Topic 24
Spirochetes: Treponema Pallidum, Borrelia Vincentii

SHORT ESSAYS
Q. 1. Describe the morphology, pathogenicity, cultural l Nonpathogenic treponemes related to T. pallidum, e.g.
characteristics and laboratory diagnosis of Treponema Reiter’s strain are cultivable. Virulent T. pallidum can be
pallidum. maintained by serial passage in rabbit testis. One such
Or, strain (Nichol’s strain) has been maintained for several
decades by serial testicular passage since its first isola-
Classify spirochetes. Discuss morphology, pathogenesis tion in 1912 from the brain of a fatal case of general
of Treponema pallidum. paralysis.
Ans.
The laboratory diagnosis of T. pallidum includes the fol-
CLASSIFICATION OF SPIROCHETES
lowing:
l Spirochaetes belong to the order spirochetales, divided 1. Microscopy
into two families as follows: 2. Culture
1. Family spirochetaceae—containing the genera 3. Serological tests
Spirocheta, Cristispira, Treponema, Borrelia
2. Family leptospiraceae—containing the genus Lepto-
spira
Microscopy
It is useful in primary and secondary stages and congenital
syphilis with superficial lesions.
MORPHOLOGY
Another sensitive microscopic method is direct fluores-
l It is the causative agent of syphilis. Trepo means to turn, cent antibody test for T. pallidum (DFA-TP) where the ac-
nema means thread, pallidum refers to its pale staining. etone fixed smear is subjected to fluorescent tagged anti-T.
l It is a thin delicate spirochete with tapering ends. It has pallidum antiserum.
about 10 regular spirals, which are sharp and angular, at
regular intervals of about 1 mm.
l It is actively motile, exhibiting rotation round the long
Serological Tests
axis, backward and forward movements and flexion Serological tests form the mainstay in laboratory diagnosis
of the whole body. During motion, secondary curves of syphilis. These tests are classified as follows:
appear and disappear in succession, but the primary a. Tests for antibodies reacting with cardiolipin antigen
spirals are unchanged. regain tests, standard tests for syphilis (STS).
l It can be seen by dark ground microscope or negative b. Tests for antibodies reacting with group specific trepo-
staining. For staining, Fontana’s method is used. Leva- nemal antigen
diti’s method is used for staining tissues. It can be c. Tests for specific antibodies to pathogenic treponema
stained by silver impregnation methods. It stains light (T. pallidum)
rose red with Giemsa stain. a. Standard tests for syphilis (lipoidal or cardiolipin anti-
gen is used)
PATHOGENCITY i. Wassermann test
ii. Kahn test
Natural infection with Treponema pallidum occurs only in iii. VDRL test
human beings. b. Group specific treponemal tests
i. Reiter protein complement fixation (RPCF) test.
CULTURAL CHARACTERISTICS c. Specific Treponema pallidum tests
i. Treponema pallidum immobilization (TPI) test
l Pathogenic treponemas do not grow in artificial media, ii. Fluorescent treponemal antibody absorption (FTA-
chick embryos or tissue culture. ABS)
l It is possible to maintain T. pallidum in motile and iii. Microhaemagglutination test for Treponema pallidum
virulent form 10–12 days in a complex medium under (MHA-TP)
anaerobic conditions. iv. Enzyme immunoassay (EIA).
Q. 2. Laboratory diagnosis of syphilis b. Treponema pallidum immune adherence (TPIA) test

c. Fluorescent treponemal antibody (FTA) test
Ans. Syphilis is a venereal disease caused by spirochete
4 . Tests using T. pallidum extract
Treponoma pallidum.
a. Treponema pallidum haemagglutination (TPHA) test
LABORATORY DIAGNOSIS OF SYPHILIS Standard Tests

Microscopy The standard tests that are usually employed for syphilis are
1. Wassermann,
l It is useful in primary and secondary stages and con- 2. Kahn, and
genital syphilis with superficial lesions. 3. The Venereal Disease Research Laboratory (VDRL) tests.
l The lesions are cleaned with warm saline and margins
are abraded. With gentle pressure to the base of lesion,

the serum that exudes is collected and wet films are Wassermann Reaction
prepared from it to be examined under microscope. This is a complement fixation test.
l T. pallidum can be identified by its slender spiral structure
and slow movement. Another sensitive microscopic Procedure

method is direct fluorescent antibody test for Treponema l The patient’s serum is inactivated by heating at 56°C for
pallidum (DFA-TP) where the acetone fixed smear is sub- 30 min to destroy the complement. It is then incubated
jected to fluorescent tagged anti-T. pallidum antiserum. with cardiolipin antigen and guinea pig antigen. The
mixture is incubated at 37°C for 1 h in water bath.
l If the serum contains antibody to cardiolipin, the
Serological Tests
added complement is used up in antigen–antibody re-
Serological tests form the mainstay in diagnosis of syphilis. actions. If the antibodies are absent, the complement is
These tests are as follows: left behind.
1. Standard tests for syphilis (STS) or nonspecific tests for l The presence or absence of complement in the system is
syphilis—cardiolipin antigen is used. done by adding an indicator, haemolytic system consist-
2. Treponemal tests—treponemes are used as antigens. ing of sheep erythrocytes and antisheep erythrocyte an-
These are of two kinds as follows: tiserum (amboceptor) prepared by immunization of
1. Those using cultivable treponemes like Reiter’s strain rabbits. This amboceptor causes lysis of the erythro-
2. Those in which pathogenic T. pallidum, Nichol’s strain cytes if the complement is available. The mixture is
is used as antigen again incubated for 1 h at 37°C in a water bath.
They may be classified according to whether the antigen Interpretation

employed is If haemolysis does not occur, it indicates that the complement
l live T. pallidum antigen—TPI test, has been utilized in the first primary reaction and hence, there
l killed T. pallidum—TPA test, TPIA test and FTA test and is no haemolysis. This is positive Wassermann test.
l extract of T. pallidum—TPHA test, TP-EIA test. If haemolysis takes place, it indicates that complement
has not been utilized in the primary reaction but utilized by
Standard tests for syphilis (lipoidal the indicator system resulting in lysis of red cells.
or cardiolipin antigen is used)
1 . Wassermann test Kahn Test
2. Kahn test This is a tube flocculation test.
3. VDRL test
Procedure
Treponemal Tests (Treponemas Used as In this test, 0.15 mL of inactivated serum is taken in three
test tubes containing 0.05, 0.025 and 0.0125 mL of freshly
Antigen)
prepared antigen dilution. The tubes are then shaken on
1. Tests using Reiter’s treponeme Kahn’s shaker and examined.
a. Reiter protein complement fixation test (tests using
Reiter treponeme) Interpretation
2. Tests using live T. pallidum l Uniform opalescence is seen in negative test.
a. Treponema pallidum immobilization (TPI) test l Floccules are seen in positive test and the result is
3. Tests using killed T. pallidum graded depending upon the appearance of floccules in
a. Treponema pallidum agglutination (TPA) test the three tubes.
VDRL Test Treponema Pallidum Agglutination (TPA) Test

This test employs a suspension of Nichol’s strain inacti-
It is the most widely used serological test for diagnosis of
vated by formalin. When the test serum and antigen are
syphilis. It is a simple and rapid test which requires only
incubated and examined under dark ground illumination,
a small quantity of serum and is as sensitive and no less
the treponemes are found agglutinated in the presence of
specific than the other tests.
antibodies.
Procedure
Treponema Pallidum Immune Adherence (TPIA) Test
l The inactivated serum is mixed with cardiolipin antigen
If a suspension of treponemes is mixed with the test serum,
on a special slide and rotated for 4 min.
complement and fresh heparinized blood from a normal
l Uniform distribution of crystals in the drop indicates the
person, and incubated, the treponemes will be found to ad-
serum is nonreactive while formation of clumps indi-
here to the erythrocytes in the presence of antibodies. They
cates it is reactive.
will then be phagocytosed and will disappear. In the ab-
l By testing serial dilutions, the antibody titre can be de-
sence of antibodies, immune adherence will not occur.
termined.
Major disadvantages of the standard tests is that the Fluorescent Treponemal Antibody (FTA) Test
antigen is nonspecific and accounts for the biological false It is an indirect immunofluorescence test, here treponeme
positive (BFP) reaction. fixed smear is treated with appropriately diluted serum of
patient and then treated with labelled antihuman immuno-
globulin fluorescent conjugate. The excess conjugate is
Treponomal Tests for Syphilis washed off and smear is examined under immunofluores-
Tests Using Reiter’s Treponemes cent microscope. In positive test treponemes fluoresce.
l Fluorescent treponemal antibody absorption (FTA-
In Reiter’s protein complement fixation (RPCF) test, lipo- ABS) test is the modification of FTA test, test serum is
polysaccharide protein complex antigen derived from the preabsorbed with a sonicate of the Reiter treponemes
cultivable Reiter’s strain is used. Though it is less sensitive (sorbent) to eliminate group specific reactions. It can
than standard tests and tests using T. pallidum but is more detect IgG as well as IgM and is the earliest serological
specific and sensitive in late and latent syphilis. test to become positive in syphilis.
Tests Using Live T. Pallidum (Nichol’s Strain) Tests Using T. Pallidum Extract
Treponema Pallidum Immobilization (TPI) Test Treponema pallidum haemagglutination (TPHA) test
Here diluted test serum is mixed with complement and ac- T. pallidum antigen is coated onto the surface of red cells.
tively motile Nichol’s strain of T. pallidum and incubated Tanned sheep RBCs are sensitized with an extract of T. palli-
anaerobically. If the antibodies are present, the treponemes dum. When sensitized red cells are mixed with patient’s serum
are immobilized, i.e. rendered nonmotile when examined containing antitreponemal antibodies, the cells clump together.
under dark ground illumination. Nowadays it has become a standard confirmatory test.
Tests Using Killed T. Pallidum Enzyme Immunoassays (EIA)

They have been developed using T. pallidum antigens and
1 . Treponema pallidum agglutination (TPA) test are available commercially (Bio-Enza Bead test, Captia
2. Treponema pallidum immune adherence (TPIA) test Syphilis-G test). It is claimed to be as specific as TPHA and
3. Fluorescent treponemal antibody (FTA) test more sensitive.
SHORT NOTES
1. Describe the serological diagnosis of syphilis. Serological Tests
Or, Serological tests form the mainstay in laboratory diagnosis
of syphilis. These tests are classified as follows:
Discuss laboratory diagnosis of syphilis.
1. Tests for antibodies reacting with cardiolipin antigen
Ans. regain tests, standard tests for syphilis (STS)
2. Tests for antibodies reacting with group specific trepo-
The laboratory diagnosis of syphilis of includes the following: nemal antigen
1. Microscopy 3. Tests for specific antibodies to pathogenic treponema
2. Culture (T. pallidum)
3. Serological tests
Laboratory Diagnosis l It is insidious in onset, with less fever and less discom-
1. Standard tests for syphilis (lipoidal or cardiolipin anti- fort in throat.
l Membrane which usually forms over the tonsil, can be
gen is used)
a. Wassermann test easily removed revealing an irregular ulcer on the
b. Kahn test tonsil.
c. VDRL test
Q. 4. Borrelia vincentii
2. Group specific treponemal tests
a. Reiter protein complement fixation (RPCF) test Ans.
3. Specific Treponema pallidum tests
a. Treponema pallidum immobilization (TPI) test l Borrelia vincentii is a motile spirochete which is normal
b. Fluorescent treponemal antibody absorption (FTA- mouth commensal, but under predisposing conditions
ABS) like malnutrition or viral infections gives rise to ulcer-
c. Microhemagglutination test for Treponema pallidum ative gingivostomatitis or oropharyngitis, i.e. Vincent’s
(MHA-TP) angina.
l B. vincentii in association with Fusobacterium fusi-
d. Enzyme immunoassay (EIA)
forme causes an infection known as fusospirochetosis.
l Diagnosis is made by demonstrating spirochetes and
Q. 2. VDRL test
fusiform bacilli in stained smears of exudates from the
Ans. lesions.
l Penicillin and metronidazole are effective in treatment.
l Venereal Disease Research Laboratory (VDRL) test is
the most widely used serological test for diagnosis of Q. 5. Congenital syphilis
syphilis.
l It is a simple and more rapid test which gives more quan- Ans.
titative results. It requires only a small quantity of serum
l In congenital syphilis the infection is transmitted from
and is as sensitive and no less specific than the other tests.
mother to fetus transplacentally. It may lead to abortion
l Procedure
or stillbirth followed by live birth of infants with lesions
l The inactivated serum is mixed with cardiolipin anti-
of syphilis and finally of healthy infants.
gen on a special slide and rotated for 4 min.
l In congenital syphilis with superficial lesions, the diag-
l Uniform distribution of crystals in the drop indicates
nosis may be done by demonstrating spirochetes in le-
the serum is nonreactive while formation of clumps
sions under dark ground microscope.
indicates it is reactive.
l IgM FTA-ABS test, the modification of indirect immu-
l By testing serial dilutions, the antibody titre can be
nofluorescence test, is useful for diagnosis of congenital
determined.
syphilis and distinguishing from seropositivity due to
l Major disadvantages of the standard tests are that the
passively transferred maternal antibodies.
antigen is nonspecific and accounts for the biological
l Congenital syphilis exhibits the following clinical
false positive reactions (BFP).
features:
1. Hutchinson’s teeth (centrally notched, widely-
Q. 3. Vincent’s angina
spaced peg-shaped upper central incisors)
Ans. 2. Mulberry molars
3. Frontal bossing
l Vincent’s angina is a painful condition of the throat 4. Saddle nose
characterized by local ulceration of the tonsils, mouth 5. Poorly developed maxillae
and pharynx. 6. Enlarged liver and spleen
l Vincent’s bacillus (fusiform bacilli) is the causative
7. Anaemia
organism. 8. Lymph node enlargement
l It may occur as an acute illness with diffuse involve-
9. Jaundice
ment of tissue or as chronic illness consisting of ulcer- 10. Pseudoparalysis
ation of tonsil. 11. Snuffles (rhinitis)
Topic 25
Actinomycetes, Rickettsiaceae and Chlamydiae

SHORT ESSAY
Q. 1. Write notes on morphology, laboratory diagnosis Under microscope the granules are seemed to be bacterial
and lesions produced by actinomycosis. colonies consisting of Gram-positive filaments surrounded
Ans. by peripheral zone of swollen club-shaped structure giving
sunray appearance.
MORPHOLOGY
LESIONS PRODUCED
They are Gram-positive, nonmotile, nonsporing, noncap-
sulated filaments that break up in bacillary and coccoid l Actinomycosis—a chronic granulomatous infection,
form. where there is indurated swelling of connective tissue
with suppuration and discharge of sulphur granules
through multiple sinuses.
LABORATORY DIAGNOSIS l It is found in three forms as follows:
l Is by demonstration of actinomyces in lesion. 1. Cervicofacial

l Sulphur granules may be demonstrated in pus which are 2. Thoracic
white, yellow and varying in size. 3. Abdominal
Actinomycosis may be present as mycetoma.
SHORT NOTES
Q. 1. Sulphur granules Ans.
Ans. l Actinomycosis is a chronic slowly progressive suppurative
infection of the subcutaneous tissue caused by actinomycetes.
l Sulphur granules are white or yellowish in colour.
l Orofacial actinomycosis is a chronic granulomatous
l Sulphur granules are bacterial colonies, consisting
disease characterized by multiple abscess, tissue de-
of a dense network of thin Gram-positive filaments,
struction, fibrosis and formation of multiple sinuses.
surrounded by a peripheral zone of swollen radiating
l Laboratory diagnosis: Specimen is the pus from the
club-shaped structures, presenting a sun ray appearance.
lesion, sputum, tissue biopsy.
l Granules or pus may be inoculated into thioglycollate broth
Microscopic examination: Under the microscope, the sul-
or streaked on brain-heart infusion agar and incubated an-
phur granules are found to consist of a dense network of
aerobically at 37°C. The isolate is identified by microscopy,
thin Gram-positive filaments, surrounded by a peripheral
biochemical reactions and fluorescent antibody methods.
zone of swollen radiating club-shaped structures, present-
Q. 2. Cervicofacial actinomycosis ing a sun ray appearance.
Topic 26
Miscellaneous
SHORT ESSAYS
Q. 1. Malignant pustule l It follows the entry of the infection through the skin
Ans. usually on the face, neck, hands, arms and back.
l The lesion starts as a papule, 1–3 days after infection
l Malignant pustule is the cutaneous infection caused by and becomes vesicular. It contains either clear or blood-
anthrax.
stained fluid. The surrounding area is congested and l During transfer, the donor plasmid containing a transpo-
oedematous. son cointegrates with the acceptor plasmid and during
l Several satellite lesions filled with serum or yellow fluid this process, transposon can replicate. For example:
are arranged around a central necrotic lesion. Some strains of staphylococci and enterococci acquire
l The central necrotic lesion is called malignant pustule resistance transferred by transposon.
which is covered by a black eschar from which anthrax
derives its name (anthrax means coal). Mutation
l It usually resolves spontaneously but 10–20% land up in
fatal septicaemia or meningitis. Mutation refers to a stable and heritable genetic change in
l Cutaneous anthrax is also known as hide porters’ dis- the DNA structure of a gene occurring spontaneously and
ease as it was common in dock workers carrying loads randomly.
of skins and hides on their bare backs. 1. Single step mutation: A single gene mutation emerges
rapidly and may confer high degree of resistance, e.g.
Q. 2. Drug resistance in bacteria enterococci to streptomycin.
2. Multistep mutation: A number of gene modifications are
Ans.
involved, gradually decreasing sensitivity in stepwise
l Drug resistance refers to unresponsiveness of microor- manner, resistance to chloramphenicol and tetracy-
ganism to an antibiotic after its repeated use. clines.
l Types of drug resistance are as follows:
a. Intrinsic (natural) Biochemical Methods of Antibiotic Resistance

b. Acquired
1. Production of Antibiotic Inactivating Enzyme
Examples:
Intrinsic Drug Resistance l b-lactam antibiotics are inactivated by b-lactamase en-
l It is the natural resistance of bacteria to certain zyme produced by Staphylococcus aureus, Neisseria
antibiotics due to their characteristic morphology or gonorrhoeae, Haemophilus influenzae and some enteric
properties. Gram-negative rods.
l Such type of resistance do not pose significant clinical l Chloramphenicol is inactivated by chloramphenicol
problem and requires only selection of appropriate acetyltransferase produced by resistant strains.
antibiotics. l Aminoglycosides are inactivated by acetyltransferases,
For example: Mycobacterium tuberculosis is resistant to phosphotransferases and adenylyl transferases present
numerous commonly used antibiotics as these antibiotics in both Gram-negative and Gram-positive bacteria.
cannot cross its outer membrane or bind to target sites.
2. Prevention of Drug Accumulation in the Bacteria
The bacterial envelope may undergo biochemical altera-
Acquired Drug Resistance tion, either not allowing influx or promoting efflux of
l It is the resistance of bacteria to antibiotics to which it the drug.
was previously susceptible and it develops due to wide- Example: Some Gram-negative bacteria inhibit the plasmid-
spread and irrational use of antibiotics. mediated synthesis of poring channels which obstructs influx
l This type of resistance poses a significant clinical prob- of hydrophilic penicillins to confer resistance.
lem in treatment.
3. Modification or Protection of Target Site
Examples:
Mechanism of Antibiotic Resistance l Ribosomal point mutation for tetracyclines, macrolides
l The antibiotic resistance develops either by and clindamycin

1. gene transfer, l Altered DNA gyrase and topoisomerase for fluoroqui-
2. mutation or nolones
3. modification in biochemical mechanism. l Modified penicillin binding proteins in Streptococcus
pneumoniae.
Gene Transfer (by Transposons) 4. Use of Alternative Pathways for Metabolism or

Growth Requirement
l Transposons are DNA segments that cannot self-
replicate but can self-transfer between plasmids or from Example: Sulphonamides develop resistance from overpro-
plasmid to chromosomes. duction of PABA
SHORT NOTE
Q. 1. Define bacteraemia, septicaemia and pyaemia. 2. Septicaemia is the condition where bacteria circulate
and multiply in the blood and form toxic products caus-
Ans.
ing high swing type of fever.
1. The circulation of bacteria in the blood is known as 3. Pyaemia is a condition where pyogenic bacteria pro-
bacteraemia. The bacteraemia of greater severity and duce septicaemia with multiple abscesses in the internal
longer duration is seen during generalized infections organs such as the spleen, liver and kidney.
like typhoid fever.
Part III
Medical Virology
Topic 27
General Properties of Viruses

SHORT ESSAYS
Q. 1. Classification of viruses
Ans. The classification of major virus groups based on the
type of nucleic acid they possess and the genera included
under each group are as follows:
1. DNA Viruses 2. RNA Viruses

a. Pox viridae family a. Picorna viridae family: Three genera
i. Several genera i. Entero virus—polio, coxsackie, echo, etc.
b. Herpes viridae family: Only one genus ii. Rhinovirus—of human, bovine and equine.
i. Herpesvirus iii. Hepato virus—hepatitis A virus
c. Adeno viridae family has two genera b. Orthomyxo viridae family
i. Mastadenovirus (mammalian adenoviruses) i. only one genus Influenzavirus
ii. Aviadenovirus (adenoviruses of birds) c. Paramyxo viridae family: Three genera
d. Papova viridae family: Two genera i. paramyxovirus—Newcastle disease virus, mumps virus
i. Papilloma virus and parainfluenza viruses of humans, other mammals
ii. Polyoma virus and birds
e. Parvo viridae family: Three genera ii. Morbilli virus—measles, canine distemper, rinderpest
i. Parvo virus and related viruses.
ii. Adenosatello virus iii. Pneumovirus—respiratory syncytial virus of humans
iii. Denso virus and related viruses
f. Hepadna viridae family d. Toga viridae family: Three genera (Alpha, Rubi and Pesti
i. Human hepatitis type B virus and related virus)
viruses of animals and birds e. Flavi viridae family
f. Bunya viridae family
g. Arena viridae family: Only one genus Arena virus
h. Rhabdo viridae family: Two genera
i. Vesiculo virus
ii. Lyssa virus—rabies and related viruses
i. Rheo viridae family
j. Retro viridae family
k. Corona viridae family
l. Calici viridae family
m. Filo viridae family
Q. 2. Cultivation of virus Organ culture

Ans. Viruses are obligate intracellular parasites. They can- l Small bits of organs can be maintained in vitro for days
not be grown on any inanimate culture medium. and weeks preserving their original architecture and
function.
They can be cultivated by l It is indicated mainly for highly specialized parasites of
a. inoculation into animals, certain organs.
b. embryonated eggs or Example: The tracheal ring organ culture for isolation of
c. tissue cultures. corona virus a respiratory pathogen.
ANIMAL INOCULATION
Explant culture
l Animal inoculation is used for primary isolation of cer-
l Fragments of minced tissue can be grown as explants
tain viruses and for studies of the pathogenesis, epide-
embedded in plasma clots.
miology, immune response and oncogenesis.
l They may also be cultivated in suspensions. This was
l Disadvantages of animal inoculation are that immunity
originally known as tissue culture.
may interfere with the viral growth and that animal
l This method is now rarely used.
often harbours latent viruses.
Example: Adenoid tissue explant cultures were used for
isolation of adenoviruses.
INOCULATION INTO EMBRYONATED
EGGS
Cell culture
Goodpasture (1931) was first to use the embryonated hen’s
l This is the culture routinely employed nowadays for
egg for cultivation of viruses.
growing viruses.
The embryonated eggs offer several sites for cultivation
l Tissues are dissociated into the component cells by the
of viruses as follows:
action of proteolytic enzymes such as trypsin and me-
Inoculation on the Chorioallantoic Membrane chanical shaking.
(CAM) of Chick Embryo l The cells are washed, counted and suspended in a
growth medium.
Produces visible lesions (pocks). Pocks produced by differ-
l The essential constituents of growth medium for tissue
ent viruses have different morphology. A single virion can
culture are basically physiological amounts of essential
produce one pock. Thus number of pocks indicates number
amino acids and vitamins, salts, glucose, and a buffering
of viruses present in the inoculum.
system generally consisting of bicarbonate in equilib-
Pock counting can be used for the assay of pock form-
rium with atmosphere containing 5% CO2.
ing viruses such as variola or vaccinia.
This is supplemented with up to 5% calf or fetal calf serum.
Inoculation into Allantoic Cavity Antibiotics are added to prevent the growth of bacterial
Inoculation into the allantoic cavity provides rich yield of contaminants and phenol red as indicator. Such media will
influenza virus. enable most of the cell types to multiply with a division
The allantoic inoculation is mainly used for growing influ- time of 24–48 h.
enza virus for vaccine production. The yellow fever and rabies
l This cell suspension is dispensed in bottles, tubes or
vaccines are other chick embryo vaccines in routine use.
Petri dishes. The cells adhere to the glass surface and on
Inoculation into the Amniotic Sac incubation, divide to form a confluent monolayer sheet
of cells covering the surface within 1 week.
It is mainly employed for primary isolation of influenza virus.
l Cell culture tubes are incubated in a sloped horizontal
Yolk Sac Inoculation position either as stationary culture or rolled in special

roller drums to produce better aeration. Some fastidious
It is inoculated for cultivation of some viruses and some
viruses grow only in such roller cultures.
bacteria like chlamydiae and rickettsiae.
l Based on their origin, chromosomal characters and the
number of generation through which they can be main-

TISSUE CULTURES tained.
There are three types of tissue culture as follows: The cell cultures are classified into three types as follows:
1. Organ culture 1. Primary cells cultures
2. Explant culture 2. Diploid cell strains
3. Cell culture 3. Continuous cell lines
1. Primary cells cultures are normal cells obtained from They are usually developed from human fibroblasts and
fresh organs of animals or humans and are capable of are useful for isolation of some fastidious pathogens and
only limited growth in culture and cannot be maintained production of viral vaccines.
in serial culture. They are commonly employed for pri- Example: Human embryonic lung strain, rhesus embryo
mary isolation of viruses and their cultivation for vac- cell strain
cine production. 3 . Continuous cell lines are the cells of the single type,
Example: Monkey kidney, human embryonic kidney, usually derived from cancer cells often of epithelial ori-
human amnion and chick embryo cell cultures gin that are capable of continuous serial cultivation in-
2. Semicontinuous cells strains (diploid cell strains) are definitely. They are used for isolation of viruses but not
cells of a single type that retain the original diploid for vaccine production.
chromosome number and karyotype during serial sub- Example: Standard cell lines derived from human can-
cultivation for limited number of times say about 50. cers are HeLa, Hep-2 and KB cell lines.
SHORT NOTES
Q. 1. Write briefly about the general characteristics of Q. 3. Name the diseases caused by DNA viruses.
virus.
Ans.
Ans. Viruses occupy a twilight zone that separates living
from ‘nonliving’ substances. As the smallest living units the The various DNA viruses and the diseases caused by them
viruses offer the best models for understanding the chemis- are as follows:
try of life. 1. Pox viridae family
a. Smallpox
General properties of viruses are as follows: b. Molluscum contagiosum
1. They are ultramicroscopic particles containing either 2. Herpes viridae family
RNA or DNA. a. Herpes simplex
2. They do not possess cellular organization. b. Varicella/herpes zoster
3. Contains only one type of nucleic acid, either RNA c. Cytomegalic inclusion disease
or DNA but never both. d. Epstein–Barr virus—infectious mononucleosis
4. They lack enzymes necessary for protein and nucleic 3. Adeno viridae family
acid synthesis and hence depend upon synthetic a. Pharyngoconjunctival fever
machinery of host cells. b. Epidemic keratoconjunctivitis
5. They multiply by a complex process and not by 4. Papova viridae family
binary fission. a. Human warts or papillomas
6. They are not affected by antibacterial antibiotics. b. Tumourigenic viruses in animals
5. Parvo viridae family
Q. 2. Name three RNA viruses and the diseases caused 6. Hepadna viridae family
by them. a. Human hepatitis B virus and related viruses of ani-
Ans. The various RNA viruses and the diseases caused by mals and birds
them are as follows:
Q. 4. Name three methods of isolation of viruses.
1. Orthomyxo virus Ans.
a. Influenza
2. Paramyxo virus 1. Viruses are obligate intracellular parasites, they cannot
a. Measles (rubella) be grown on any inanimate culture medium.
b. Mumps 2. Three methods popular for cultivation of viruses are
3. Rhabdovirus a. by inoculation into animals,
a. Rabies b. embryonated eggs or
b. Haemorrhagic fever c. tissue cultures.
4. Picornavirus 3. The tissue cultures are further divided into three types
a. Poliomyelitis as follows:
b. Coxsackie diseases a. Organ culture
c. Common cold b. Explant culture
d. Foot and mouth disease c. Cell culture
Topic 28
Bacteriophage: Structure and Significance

SHORT NOTE
Q. 1. Bacteriophage l Bacteriophages are tadpole shaped and are made up of
a hexagonal head, a cylindrical tail and base plate.
Ans.
l Head consists of a tightly packed core of nucleic acid
l The viruses that infect bacteria are known as bacterio- (double-stranded DNA ) surrounded by a protein coat
phages or commonly as phages. or capsid. The size varies from 28 nm to 100 nm.
l Certain bacteriophages that infect E. coli, called T even l The tail is composed of a hollow core, a contractile
phages (T2, T4, T6) traditionally serve as the proto- sheath surrounding the core and a terminal base plate
types in describing the properties of bacteriophages. which has attached to its prongs, tail fibres or both.
Topic 29
Poxviruses
SHORT NOTE
Q. 1. Smallpox l Smallpox used to occur in two distinct clinical varieties
as follows:
Ans.
1. The florid, highly fatal disease typically seen in Asia
l The variola virus is the causative agent of smallpox. 2. The mild nonfatal disease (alastrim) typically seen in
l On 8 May 1980, the WHO formally announced the Latin America
global eradication of smallpox. l The virus causing classical smallpox was called variola
l In 1796 Jenner introduced vaccination for smallpox, major and that causing alastrim is known as variola minor.
which was a live preparation of vaccinia virus propa- l The source of infection was a patient in early phase of
gated on the skin of calves. disease and infection usually occurred in close contacts.
l Smallpox was exclusively human infection with no Incubation period was 12 days.
animal reservoir. As the virus was completely elimi- l In laboratory the smallpox could be diagnosed by isola-
nated from the patient on recovery there were no tion of the virus from the blood in early phase in severe
carriers. cases or from eruptive lesion in all the cases.
Topic 30
Herpes Viruses
SHORT ESSAY
Q. 1. Herpes simplex viral infections l Herpes simplex virus is a DNA virus.
l There two types of herpes viruses as follows:
Ans.
1. Herpes virus type 1–more often associated with oral 4. Ophthalmic lesions: Acute keratoconjunctivitis
and ocular lesions. and follicular conjunctivitis with vesicle formation
2. Herpes virus type 2–frequently causes genital infections. on the lids, chorioretinitis and acute necrotizing
l Lesions caused by herpes simplex depending on the site retinitis
of infection, age and immune status of the individual are 5. Visceral lesions: HSV meningitis, sacral autonomic
as follows: dysfunction, transverse myelitis or Guillain-Barre
1. Cutaneous infections: Fever blisters or herpes febri- syndrome
lis on the cheeks, chin, around the mouth or on the 6. Nervous system: HSV oesophagitis, tracheobronchi-
forehead, napkin rash on the buttocks of children, tis and pneumonitis, erythema multiforme
herpetic whitlow in medical professionals 7. Genital lesions: Urethritis (males) infections of cervix,
2. Eczema herpeticum: Generalized herpetic eruption vagina, vulva and perineum (females)
seen in children suffering from eczema 8. Congenital lesions: Subclinical or localized infection
3. Mucosal lesions: Gingivostomatitis, pharyngitis and of skin, mouth or eyes
recurrent herpes labialis
SHORT NOTE
Q. 1. Varicella zoster or V-Z virus l Congenital infection: Intrauterine infection leads to cy-
tomegalic inclusion disease of new born which is often
Ans.
fatal and is characterized by hepatosplenomegaly, jaun-
1. The V-Z virus or varicella-zoster virus causes both vari- dice, thrombocytopenic purpura and haemolytic anae-
cella (chicken pox) and herpes zoster. mia. It also causes microcephaly and survivors may
2. Chicken pox or varicella follows primary infection in a show mental retardation.
nonimmune individual, while herpes zoster is a reacti- l Postnatal infection is usually inapparent, sometimes
vation of the latent virus when immunity has fallen to leads to insidious hepatitis or pneumonitis.
ineffective levels.
3. While chicken pox is typically a disease of childhood, Q. 3. Antiviral agents
herpes zoster is one of old age usually common after the Ans. Antiviral agents are the agents that selectively attack
age of 55 years. one of the stages of viral replication without harming the
4. In chicken pox the skin lesions appear prior to oral host cells.
lesions. The rash is centripetal in distribution affecting
mainly the trunk and sparing distal parts of the limbs, Examples:
and is very superficial without involving the deeper lay- 1. Acyclovir—for herpes group viruses (herpes simplex
ers of skin. Oral manifestations are painless blister like type 1 and 2, V-Z virus)
lesions on buccal mucosa, tongue, gingiva and palate. 2. Amantadine and ribavirin—for influenza A like viruses
5. In herpes zoster the rash is typically unilateral and con- 3. Vidarabine (adenine arabinoside)—for herpes infection
fined to the area supplied by a single sensory ganglion. of brain
Oral manifestations are unilateral lesions on the palate, 4. Idoxuridine and trifluorothymidine—herpes simplex
lips, buccal mucosa and pharynx. type 1
6. The diagnosis is usually clinical, the laboratory diagno- 5. Zidovudine—for retroviruses (HIV)
sis and treatment are same for both the diseases. 6. Interferons—nonselective
Q. 2. Cytomegalovirus Q. 4. Herpetic lesions in the oral cavity

Ans. Ans.
l Cytomegaloviruses were formerly known as salivary l Herpes simplex virus type I causes lesions in oral cavity.
gland viruses. l Oral lesions occur as primary infections and are often
l Cytomegalovirus infections are extremely common and asymptomatic.
asymptomatic while disease is rare. l The source of infection is saliva, skin lesions and oro-
l Infections are of two types as follows: pharyngeal lesions of patients and carriers.
1. Congenital l Children may show acute gingivostomatitis, while the
2. Postnatal most common infection is recurrent herpes labialis.

l Vesicles formed on buccal mucosa may ulcerate and Ans.

become secondarily infected.
l The Epstein-Barr virus is named after its discoverers
Epstein, Barr and Achong (1964). EB virus is a new type
Diagnosis of herpes virus. It is ubiquitous in all human populations.
l Infection with EB virus leads to latency, periodic reacti-
l Diagnosis is established by Tzanck smears prepared from
the base of vesicles, giant cells with faceted nuclei and ho- vation and lifelong persistence and it infects B lympho-
mogenously stained ground glass chromatin (Tzanck cell). cytes specifically.
l The Epstein-Barr virus infection may lead to the follow-
l Giemsa stained smears show intranuclear type A inclu-
sion bodies and virus particles may be demonstrated ing clinical conditions:
under electron microscope. 1. Infectious mononucleosis
l Rise in antibody titre can be demonstrated by ELISA,
2. EBV-associated malignancies
neutralization or complement fixation tests are useful in a. Burkitt’s lymophoma
diagnosis of primary infection. b. Lymphomas in immunodeficient persons like
AIDS patients and transplant recipients
Q. 5. Epstein-Barr virus or EB virus c. Nasopharyngeal carcinoma
Topic 31
Adenoviruses and Picornaviruses

SHORT ESSAY
Q. 1. Vaccine for polio l Viral pools of adequate titre are filtered to remove the
cell debris and clumps and inactivated with formalin
Or,
(1:4000) at 37°C for 12–15 days.
Poliomyelitis—prophylaxis l Stringent tests are carried out to ensure complete inacti-
vation and freedom from extraneous agents. The three

Or,
types are then pooled and issued for use after further
Immunization against polimyelitis tests for safety and potency.
1. Killed polio vaccine is given by injection and therefore
Ans.
called inactivated or injectable polio vaccine (IPV).
l In prophylaxis against poliovirus passive immunization 2. Three doses of IPV given 4–6 weeks apart constitute
by the administration of human gammaglobulin is of the primary vaccination to be followed by a booster
little value. 6 months later.
l Attempts at active immunization with vaccines date
The first dose should be given to babies at the age of
from 1910, but the early vaccines were crude. 6 months to ensure that immune response is not impaired
l By 1953 Salk has developed a killed vaccine, simultane-
by residual maternal antibodies. Immunity can be sustained
ously Koprowsky, Cox and Sabin independently devel- by booster doses every 3–5 years thereafter.
oped live attenuated vaccines.
l The two types of polio vaccines are as follows:
1. Salk’s polio vaccine (killed polio vaccine)

Sabin’s vaccine
2. Sabin’s vaccine (live polio vaccine) l Sabin’s vaccine is a live polio vaccine prepared by
growing the attenuated strains in monkey kidney tissue
cultures or human diploid cell cultures.
Salk’s polio vaccine
l Live polio vaccine is administered orally, hence it is
l Salk’s killed polio vaccine is a formalin inactivated known as oral polio vaccine (OPV).
preparation of the three types of poliovirus grown in l After the vaccine is tested for neurovirulence, genetic
monkey kidney tissue culture. stability and potency, it is issued either in monovalent or
l The three types of polioviruses are grown separately in trivalent form in a pleasantly flavoured syrup. The vac-
monkey kidney tissue cells. cine is usually given in the trivalent form.
l Under tropical conditions the vaccine is stabilized 4–8 week intervals, to ensure that all three types of
against the heat inactivation by use of molar MgCl2 or vaccine virus multiply in the intestine, overcoming
sucrose. interference among themselves and with other enteric
l It can be given to young infants, as the maternal anti- viruses.
body has little effect on intestinal infection. Theoreti- l OPV used in India is stated to contain type 1 virus
cally a single dose is sufficient to establish infection 10 lakh, type 2 virus 2 lakh and type 3 virus 3 lakh TC
and immunity but in practice three doses are given in ID50 per dose (0.5 mL).
SHORT NOTES
Q. 1. Killed polio vaccine l Live polio vaccine is administered orally, hence it is
known as oral polio vaccine (OPV).
Ans.
l The vaccine is issued either in monovalent or trivalent
l Salk’s killed polio vaccine is a formalin inactivated form in a pleasantly flavoured syrup.
preparation of the three types of poliovirus grown in l The vaccine is usually given in the trivalent form.
monkey kidney tissue culture. Theoretically a single dose is sufficient to establish

l Viral pools of adequate titre are filtered to remove the infection and immunity but in practice three doses are
cell debris and clumps and inactivated with formalin given in 4–8 week intervals, to ensure that all three
(1:4000) at 37°C for 12–15 days. types of vaccine virus multiply in the intestine, over-
l Stringent tests are carried out to ensure complete inacti- coming interference among themselves and with other
vation and freedom from extraneous agents. The three enteric viruses.
types are then pooled and issued for use after further
tests for safety and potency. Q. 3. Name four vaccines.
1. Killed polio vaccine is given by injection and therefore
called inactivated or injectable polio vaccine (IPV). Ans. The term vaccine was given by Pasteur.
2. Three doses of IPV given 4–6 weeks apart constitute The live viral vaccines are as follows:
the primary vaccination, to be followed by a booster 1. Sabin’s OPV for poliomyelitis
6 months later. Immunity can be sustained by booster 2. 17D vaccine for yellow fever
doses every 3–5 years thereafter. 3. MMR for measles, mumps and rubella
Q. 2. Sabin’s vaccine Killed viral vaccines are as follows:
Ans. 1. Salk’s vaccine for poliomyelitis
2. Rabies vaccine
l Sabin’s vaccine is a live polio vaccine prepared by 3. Japanese B encephalitis vaccine
growing the attenuated strains in monkey kidney tissue
cultures or human diploid cell cultures.
Topic 32
Orthomyxo and Paramyxo Viruses

SHORT ESSAY
Q. 1. Mumps viral infection l The virus replicates in the upper respiratory tract and
Ans. cervical lymph nodes and disseminated through blood
stream to various organs.
l Mumps is an acute infectious disease usually affecting l The incubation period is 12–25 days.
children and characterized by nonsuppurative enlarge- l Swelling of parotid is the first sign of illness though it
ment of parotid glands. may be preceded by prodromal malaise. Parotid swell-
l Infection is acquired by inhalation or direct contact or ing is unilateral to start with but may become bilateral
fomites or through the conjunctiva. and is accompanied by fever, local pain and tenderness.
l Involvement of extraparotid sites may be more serious l Other less common complications are arthritis, oophori-
as follows: tis, nephritis, pancreatitis, thyroiditis and myocarditis.
1. Epididymo-orchitis is a serious complication seen Laboratory diagnosis
in postpubertal male patients. Orchitis is usually The diagnosis may be established by virus isolation and
unilateral but when it is bilateral and followed by serological tests.
testicular atrophy sterility or low sperm counts 1. Isolation of virus from CSF, saliva or urine
may result. 2. Serological tests—paired serum samples are tested for
2. The CNS involvement may result in mumps menin- rise in titre of antibodies by CFT, HI, neutralization
gitis and meningoencephalitis. tests, ELISA, RIA
SHORT NOTES
Q. 1. Mumps vaccine Q. 2. Koplik’s spots
Ans. Ans.
l An effective live attenuated vaccine (Jeryl Lynn strain l Koplik’s spots are pathognomonic of measles or rubella
of mumps virus) grown in chick embryo fibroblast cul- infection. They are named after Henry Koplik, an
ture is against mumps. American pediatrician who first described them in 1896.
l The vaccine is given as single subcutaneous injection, l Koplik’s spots are bluish-white ulcerations seen on the
either alone or in combination with measles, mumps buccal mucosa opposite the lower molars.
and rubella (MMR) vaccines. l A day or two before the rash begins the Koplik’s spots
l Contraindications are pregnancy, immunodeficiency, usually appear on the buccal mucosa and occasionally
and hypersensitivity to neomycin or egg protein. on the conjunctiva and intestinal mucosa and can be a
l The MMR vaccine provides effective protection for at useful sign to look for in children known to be exposed
least 10 years. to the measles virus.
Topic 33
Arbo and Rhabdoviruses

SHORT ESSAYS
Q. 1. Kyasanur forest disease (KFD) bite of ticks. The principal vector being Haemaphysalis
spinigera.
Ans.
l KFD has a sudden onset with fever, headache, conjuncti-
l It is a tick-borne haemorrhagic fever that occurs in vitis, myalgia and severe prostration. Some cases develop
Sagar and Sorab, Shikarpur taluks of Shimoga district in haemorrhages into the skin, mucosa and viscera.
Karnataka state. l The virus appears to be more widely distributed, as
l It is caused by a virus, similar to Russian Spring Sum- antibodies to virus have been demonstrated in humans
mer Encephalitis (RSSE) complex, named as Kyasanur and animals in Kutch, Saurashtra and other parts of
forest virus (KFD virus) after the name of the place India also.
from where the fist isolation was made. l Though KFD is related antigenically to RSSE, the
l This outbreak is locally known as monkey fever as it RSSE vaccine does not confer protection against KFD.
infects monkeys also. Infection in monkeys is fatal. The KFD vaccine is under experimental trials.
l Forest birds, small mammals are believed to be the res-
ervoir hosts. The infection is transmitted through the Q. 2. Japanese B encephalitis

Ans. l After 1–6 days signs of encephalitis set in with nuchal

rigidity, convulsions, altered sensorium and coma.
l One of the mosquito-borne group of flavi viruses,
l Culex tritaeniorhynchus, a rural mosquito, is the princi-
i.e. Japanese encephalitis virus causes Japanese B
pal vector. Herons act as reservoir hosts and pigs as
encephalitis.
amplifier hosts.
l Since 1871 the disease has been recognized in Japan
l In India it has become a major public health problem of
and the virus was first isolated in Japan during an epi-
national importance.
demic in 1935.
l A formalin inactivated mouse brain vaccine produced
l Japanese B encephalitis to distinguish it from encepha-
by using Nakayama strain has been successfully used
litis A
for human immunization in Japan and even in India
l The disease typically has an abrupt onset with fever,
also.
headache and vomiting. The fever is high and continu-
Two doses at 2 weeks interval followed by a booster
ous. There is neutrophil leukocytosis in the peripheral
6–12 months later constitute a full course. Subsequent
blood and pleocytosis with normal or raised sugar and a
boosters are recommended every 3–4 years as the
slightly raised protein in the CSF. Majority of infections
immunity produced by the vaccine is short lived.
are asymptomatic.
SHORT NOTES
Q. 1. Arboviruses Neural Vaccines
Ans. Consist of suspension of nervous tissues of animals in-
fected with fixed rabies virus.
l Arboviruses are arthropod-borne viruses and are trans-
mitted by bloodsucking insects. Mosquitoes, ticks and Semple Vaccine
sandflies are the principal vectors. l Most widely used vaccine developed by Semple at Cen-
l Arboviruses have been named according to the disease
tral Research Institute, Kasauli.
caused (yellow fever), place of isolation of virus (Kyas- l It is a 5% suspension of sheep brain infected with fixed
anur forest disease) or the local name of the disease virus and inactivated with phenol at 37°C, leaving no
(chickengunya). residual virus.
l They are classified according to their physical and
chemical features into taxonomic families as listed Beta-Propiolactone (BPL) Vaccine

below: l This is a modification of Semple vaccine, in which
1. Togaviridae instead of phenol, the beta-propiolactone was used as
2. Flaviviridae inactivating agent.
3. Bunyaviridae l The smaller doses were considered adequate as it is
4. Rheoviridae believed to be more antigenic.
5. Rhabdoviridae
l Arboviruses cause two main types of disease which are Infant Brain Vaccines
a. encephalitis and l Were developed to reduce neurological complications,
b. fever, often with haemorrhage. as infant brain does not contain myelin (encephalito-
l The diagnosis of arbovirus infection can be established genic factor).
by virus isolation or serology. l Vaccines were prepared using infant mouse, rat or rabbit
brain. Neural vaccines are cheap but unsatisfactory for rea-

Q. 2. Vaccines for immunization of rabies sons like poor immunogenicity and are encephalitogenic.
Or
Nonneural Vaccines
Rabies vaccines
Egg Vaccines
Ans.
l Duck egg vaccine is a fixed virus grown in duck eggs
Antirabic vaccines are of two main categories as follows: and inactivated with BPL.
1. Neural l Live attenuated chick embryo vaccines of two types
2. Nonneural were developed with the Flury strain.

1. Low egg passage (LEP) vaccine at 40–50° egg pas- grown on human diploid cells (WI 38 or MRC 5)
sage level, for immunization of dogs and inactivated with BPL or tri-n-butyl phosphate.
2. High egg passage (HEP) vaccine at 180° passage It is highly antigenic and free from serious side
level for cattle and cats effects. High cost is the only disadvantage of this
vaccine.
Tissue Culture Vaccines b. Purified chick embryo cell culture (PCEC) vaccine
The following cell culture vaccines are available in India, containing BPL inactivated flury LEP strain is now
and all of them are equally safe and effective: widely used. Vero cell vaccine is under study.
1. Human diploid cell (HDC) vaccine
2. Purified chick embryo cell (PCEC) vaccine Subunit Vaccine
3. Purified vero cell (PVC) vaccine The glycoprotein subunit on virus surface, which is the
a. HDC vaccine is a purified and concentrated prepara- protective antigen, has been cloned and recombinant vac-
tion of fixed rabies virus (Pitman-Moore strain) cines are produced. They are in experimental stages.
Topic 34
Hepatitis Viruses
SHORT ESSAYS
Q. 1. Describe morphology, pathogenesis, prevention Pathogenesis
and lab diagnosis of hepatitis B virus.
l Pathogenesis of hepatitis appears to be immune medi-
Ans. ated. HBV causes serum hepatitis.
l Infection spreads by blood transfusion, serum inocu-
Morphology lation, sharing of syringes and needles, sharing of
l Hepatitis B virus (HBV) is a DNA virus belonging to razors, tattooing, acupuncture, sexual intercourse or
hepadnaviridae family. even kissing.
l HBV is 42 nm DNA virus with an outer envelope l The disease is more common in drug addicts, prosti-
and inner core, 27 nm in diameter, enclosing the viral tutes, homosexuals.

genome and a DNA polymerase. l Virus is highly infectious and even minute quantity of
l The core has icosahedral symmetry. Viral DNA and carrier sera can transmit the infection.
HBcAg are found in the nucleus and HBsAg in the
cytoplasm and at the cell membrane.
Clinical Features
l Under the electron microscope sera from type B hepati-
tis patients shows three types of particles as follows: l Incubation period is long, about 2–6 months.
1. Most abundant form is a spherical particle of 22 nm l The disease is more severe and protracted. Onset is in-
in diameter. sidious and fever is not prominent.
2. Second type of particle is tubular or filamentous with l Extrahepatic complications like urticaria, arthralgia,
a diameter of 22 nm and of varying length. polyarteritis nodosa and glomerulonephritis may occur
3. Third type is a double-walled spherical structure 42 due to antigen–antibody reaction and circulating im-
nm in diameter. mune complexes containing viral surface antigen.
l About 90% of adults with acute hepatitis B infection
It is the complete HBV and was first described by Dane in
recover within 1–2 months of onset and within about
1970, hence it is known as Dane particle.
6 months they eliminate the virus from the body.
Both the first and second type of particles are antigeni-
l Some patients progress to chronic active hepatitis and
cally identical and are surface components of HBV repre-
cirrhosis. Late consequence is primary hepatocellular
sent Australian antigen which is now named as hepatitis B
carcinoma.
surface antigen (HBsAg).
Lab Diagnosis Diagnosis

Markers of Hepatitis B Virus and their l Dark urine and yellow colouration of sclera due to jaundice.
Detection l Blood shows lymphocytosis.
l Prolonged prothrombin time due to damaged liver.
1. HBsAg (surface antigen or envelope protein)
l It is a specific marker for hepatitis B infection. It
Hepatitis B Vaccine
is the first marker to appear in blood. It becomes
detectable in circulation about 1 month after expo- l For passive immunity immune serum globulin may be
sure to infection and several weeks before appear- given.
ance of jaundice and elevation of transaminase l For active immunity following vaccine preparation may
levels. be useful:
l It reaches its peak in the preicteric phase. It disap- 1. HBsAg from human carriers
pears with recovery from clinical disease. 2. HBsAg produced in cell line from human hepatocel-
2. Anti-HBsAg antibody lular carcinoma
l It appears in the blood after disappearance of HbsAg 3. HBsAg inserted genome in plasmid by genetic engi-
and persists for very long periods. Anti-HBs is the neering
protective antibody. 4. Vaccine from polypeptide of HBsAg
3. HBcAg (core antigen)
l Although it is not detectable in patient’s serum, it Treatment
can be detected in the liver cells by immunofluo-
l By alpha interferon
rescence.
4. Anti-HBc antibody Q. 2. Mention differences between hepatitis A and
l It is often detected in the preicteric phase, usually
hepatitis B
1 or 2 weeks after appearance of HBsAg in blood. It is
therefore the earliest antibody marker to be seen in the Ans. The differences between the hepatitis A and hepatitis
blood. B are listed in Table 34.1.
l As anti-HBc remains lifelong it serves as useful indi-
cator of prior infection with HBV, even after all other TABLE 34.1 Differences between Hepatitis A and Hepatitis B
viral markers become undetectable.
Features Hepatitis A Hepatitis B
5. HBeAg (hidden antigenic component of virus core)
l It appears at the same time as HBsAg or soon after-
Structure Is a RNA virus Is a DNA virus
wards. In most cases, it disappears in few weeks. Common age of occurrence Children Adults
l Anti-HBe antibody appears in the blood after disap- Incubation period 2–6 weeks 2–6 months
pearance of HBeAg and lasts for several months. Crosses placental barrier No Yes
6. Viral DNA polymerase Serum IgM Raised Not raised
l It can be detected in the serum during preicteric
Extrahepatic lesions Absent Present
phase of the disease.
SHORT NOTES
Q. 1. Danes particles Ans.
Ans. l Hepatitis B virus is a DNA virus belonging to hepadna-
viridae family.
l HBV is 42 nm DNA virus with an outer envelope and
tis patients shows three types of particles.
inner core, 27 nm in diameter, enclosing the viral ge-
l The third type of particle is a double-walled spherical
nome and a DNA polymerase.
structure 42 nm in diameter.
l The core has icosahedral symmetry. Viral DNA and
l It is the complete hepatitis B virus and was first de-
HBcAg are found in the nucleus and HBsAg in the cy-
scribed by Dane in 1970, hence it is known as Dane
toplasm and at the cell membrane.
particle.
tis patients shows following three types of particles:

Q. 2. Hepatitis B virus 1. A spherical particle of 22 nm in diameter
2. A tubular or filamentous particle with a diameter of Ans. The serological tests such as molecular methods like
22 nm and of varying length DNA hybridization and PCR at present used for HBV DNA
3. Third type is a double-walled spherical structure testing are highly sensitive and quantitative tests for HBV.
42 nm in diameter.
It is the complete hepatitis B virus and was first described by Q. 4. Hepatitis B virus lab diagnosis
Dane in 1970, hence it is known as Dane particle.
Both the first and second type of particles are antigeni- Diagnosis
cally identical and are surface components of HBV repre-
l Dark urine and yellow colouration of sclera due to
sent Australian antigen which is now named as hepatitis B
jaundice
surface antigen (HBsAg).
l Blood shows lymphocytosis
l Prolonged prothrombin time due to damaged liver

Q. 3. Quantitative rapid test for hepatitis B antigen l Detection of markers of hepatitis B virus
Topic 35
Oncogenic Viruses
SHORT NOTES
Q. 1. Name oncogenic viruses. Q. 2. Oncogenic RNA viruses
Ans. Ans.
The various oncogenic viruses are as follows: l Oncogenic RNA viruses belong to retroviruses, which
1. RNA viruses are enveloped, spherical viruses that are developed by
a. Retroviruses budding through the host cell membrane.
i. Avian leukosis viruses l The presence of an unusual enzyme RNA-dependant
ii. Murine leukosis viruses DNA polymerase or reverse transcriptase within the
iii. Murine mammary tumour virus virion is the characteristic feature of retroviruses.
iv. Leukosis-sarcoma virus of various animals l The family retroviridae is classified into three subfami-
v. Human T cell leukaemia viruses lies as follows:

2. DNA Viruses 1. Oncovirinae: Comprises of all oncogenic RNA viruses
a. Papova virus 2. Spuma virinae: Containing the nononcogenic foamy
i. Papilloma viruses of human beings, rabbits and viruses
other animals 3. Lenti virinae: The viruses causing slow infections in
ii. Polyoma virus animals as well as the human and related animal im-
iii. Simian virus 40 munodeficiency viruses
iv. BK and JC viruses l Commonly retroviruses induce tumours by two mecha-
b. Pox virus nisms as follows:

i. Molluscum contagiosum a. By introducing into the cellular genome a new trans-
ii. Yaba virus forming gene, i.e. oncogene
iii. Shope fibroma b. By inducing or altering the expression of a pre-existing
c. Adenovirus cellular gene
i. Many human and nonhuman types Q. 3. Human papilloma virus
d. Herpes viruses
i. Marek’s disease virus Ans.
ii. Lucke’s frog tumour virus l Human papilloma virus (HPV) belongs to papova vi-
iii. Herpes virus pan, papio and saimiri ruses which are small, nonenveloped, icosahedral onco-
iv. Epstein-Barr virus genic DNA viruses.
v. Herpes simplex types 1 and 2 l Papilloma viruses cause benign tumours in their natural
vi. Cytomegalovirus hosts but some of them like condyloma acuminatum in
e. Hepatitis B and C viruses humans and rabbit papilloma may turn malignant.
l An association has been established between HPV infec- Q. 4. Oncogenic herpes viruses
tion (HPV types 16 and 18) and cancer of cervix uteri.
Ans. Oncogenic herpes viruses causing various malignant
l The continuous cell line (HeLa) derived from a cervical
diseases are as follows:
carcinoma and widely used in various laboratories con-
tains HPV-18 DNA. 1 . Epstein bar virus: African Burkitt’s lymphoma
l In general, infectious virus particles cannot be demon- 2. Cytomegalo virus: Kaposis sarcoma and carcinoma of
strated in tumours induced by DNA viruses but papil- prostrate
loma in the wild cotton tail rabbit is an exception. 3. HSV type II: Carcinoma of the uterine cervix
Topic 36
Human Immunodeficiency Virus (HIV)/AIDS

SHORT ESSAYS
Q. 1. Diagram of AIDS virus l The virus core is surrounded by a nucleocapsid shell
Ans. The aetiological agent of AIDS is human immunode- composed of protein.
l The HIV acquires a lipoprotein envelope when the na-
ficiency virus (HIV) which belongs to the lentivirus sub-
group of the retroviridae family. ked virus buds out through the host cell surface mem-
brane.
Structure of human immunodeficiency virus (HIV) is as l The lipid part of this lipoprotein envelope is derived
follows (Fig. 36.1): from the host cell membrane and the glycoproteins are
coded by the virus.
Envelope glycoprotein l The major virus coded envelope proteins are the pro-
Envelope
spike (gp120)
lipid bilayer jecting spikes on the surface and the anchoring trans-
membrane pedicles. The spikes constitute the major
Transmembrane Reverse
pedicle glycoprotein transcriptase
surface component of the virus.
Outer icosahedral shell
of nucleocapsid Q. 2. Laboratory diagnosis of HIV infection
Cone-shaped core
of nucleocapsid
Ans. Laboratory diagnosis of HIV infection includes tests
for immunodeficiency as well as specific tests for HIV,
Inner core
Viral RNA which are as listed in Table 36.1.
Viral proteins TABLE 36.1 Laboratory Diagnosis of HIV Infection

associated with RNA
Immunological Tests Specific Tests
FIGURE 36.1 Structure of HIV.
1. Total leucocyte and 1. Antigen detection
lymphocyte count
l HIV is an enveloped virus 90–120 nm in diameter, and 2. T cell subset assays 2. Virus isolation
has a nucleoprotein core containing single-stranded 3. Platelet count 3. Polymerase chain
RNA and proteins. reaction (PCR)
l Presence of the reverse transcriptase enzyme is the char-
4. Raised IgG and IgA 4. Antibody detection
acteristic feature of retroviruses. In the host cell, this levels
enzyme synthesizes single-stranded DNA from single- 5. Diminished cell-mediated
stranded RNA. immunity cell-mediated
l Later this single-stranded DNA is converted into double- immunity (CMI)
stranded DNA. This double-stranded DNA is incorporated
6. Lymph node biopsy
into the host cell chromosome.
Immunological Test l There are two types of serological tests for anti-HIV
antibodies which are,
1. Total leucocyte and lymphocyte count: Demonstrates 1. screening tests and
leukopenia and lymphocyte count usually below 2. confirmatory tests.
2000/mm3. l Screening tests are as follows:
2. T cell subset assays: Absolute CD41 T cell count will be 1. ELISA
usually less than 200/mm3 and T4:T8 ratio is reversed. 2. Fujirebio agglutination test
3. Platelet count: Shows thrombocytopenia. 3. Karpas test
a. Raised IgG and IgA levels 4. Indirect immunofluorescence
b. Diminished CMI: indicated by skin tests 5. RIA
c. Lymph node biopsy: Showing profound abnormalities The screening tests for HIV are highly sensitive for a
broad-spectrum of antibodies and easy to perform.
Specific Tests for HIV Infection These tests are not highly specific and sometimes may
give false positive results.
Antigen Detection l Confirmatory tests
l The major core antigen p24 is the earliest virus marker 1. Western blot test
to appear in blood and is the one tested for.
Q. 3. ELISA
l Shortly after HIV infection in about 2 weeks and before
detectable antibody response, free p24 antigen may be Ans.

detectable in the serum.
l The serum levels of p24 antigen is a useful guide to
l The most widely used screening test for HIV infection
monitor the degree of virus suppression during AZT is ELISA.
l Direct solid phase antiglobulin ELISA is the method
therapy.
l Patients with persistent p24 antigen in blood progress
most commonly used for which commercial test kits are
more rapidly to AIDS than those without it. available.
l The antigen is obtained from HIV grown in continuous
T lymphocyte cell line or by recombinant technique.

Virus Isolation This antigen is coated on the microtiter wells or other
l After infection, the virus is present in circulation and suitable solid surface. The test serum is added and if
body fluids, within lymphocytes or cell free. antibodies are present it binds to the antigen. After
l The virus is present in many parts of the body, it is most washing away the unbound serum, antihuman immuno-
readily isolated form peripheral lymphocytes (espe- globulin linked to suitable enzyme is added followed by
cially CD4 lymphocytes), bone marrow and serum. colour forming substrate.
l The technique of isolation is by cocultivation of l If the test serum contains anti-HIV antibodies a visible
patient’s lymphocytes with uninfected lymphocytes in or photometrical detectable colour is formed which is
the presence of interleukin-2. read visually or by ELISA reader.
l Virus replication is detected by demonstration of reverse l ELISA has sensitivity over 99.5% and is an extremely
transcriptase activity as well as antigens in the system. good screening test. Commercial ELISA test kits con-
l The virus titres are high early in the infection about tain both HIV1 and HIV2 antigens.
1 week before antibodies start appearing. The titre re-
duces during the asymptomatic phase to rise again when Q. 4. Western blot test
clinical AIDS sets in. Ans.
l It is not suitable as routine diagnostic test.
l The most widely used confirmatory test for HIV is the
Western blot test.
Polymerase Chain Reaction (PCR) l In this test, HIV proteins are separated according to
l As the most sensitive and specific test the PCR has be- their electrophoretic mobility and molecular weight by
come the gold standard for diagnosis in all stages of polyacrylamide gel electrophoresis.
HIV infection. l These separated proteins are bloated on the strips
of nitrocellulose paper. These strips are reacted with

test sera and then with enzyme conjugated antihuman
Antibody Detection globulin.
l Demonstration of antibodies is the simplest and most l Antibodies to HIV protein present in test serum com-
widely employed technique for diagnosis of HIV infection. bine with all or any fragment of HIV. The strips are
washed and treated with enzyme conjugated antihuman l The test may be considered positive even if it shows
gammaglobulin. Then a suitable substrate is added that bands against only one or two sites as with p24 or
produces colour bands. gp120. This may happen in early infection.
l The position of the band on the strip indicates the anti- l Western blot is a very useful confirmatory test but the
gen with which the antibody has reacted. In a positive interpretation remains subjective and demands consid-
serum, bands will be seen with multiple proteins typi- erable experience.
cally with p24 (gag gene, core proteins), p31 (pol gene, A positive result in any of the screening test may not be
reverse transcriptase) and gp41, gp120 or gp160 (env accepted without conformation with Western blot test
gene, surface antigen). which was considered as the ‘gold standard’.
SHORT NOTES
Q. 1. Mention modes of transmission of infection of HIV. Ans. Opportunistic infections and malignancies associated
with HIV infection are as follows:
Ans. The modes of transmission of HIV infection are as
follows: 1. Parasitic
a. Pneumocystis carinii pneumonia
1 . Sexual intercourse: Anal, vaginal and oral
b. Toxoplasmosis
2. Blood and blood products: Factor VII, blood transfusion
c. Cryptosporidiosis
3. Tissue and organ donation: Semen, cornea, bone marrow,
d. Isosporiasis
kidney, etc
e. Generalized strongyloidiasis
4. Injections and injuries: Shared needles by drug addicts,
2. Mycotic
injections with unsterile syringes and needles, needle
a. Candidiasis
stick and other injuries in health staff
b. Cryptococcosis
5. Mother to baby: Can take place transplacentally or at
c. Aspergillosis
birth and after birth through feeding the breast milk.
d. Histoplasmosis
3. Bacterial
Q. 2. Human immunodeficiency virus (HIV) infection a. Mycobacterial infections
Ans. b. Salmonellosis
c. Campylobacter infections
1. Human immunodeficiency virus (HIV) is the aetiologi- d. Nocardia and actinomycetes
cal agent of AIDS, which belongs to the lentivirus sub- e. Legionellosis
group of the retroviridae family. 4. Viral
2. The clinical course of HIV infection has been classified a. Cytomegalovirus (CMV)
under various groups by the Centers for Disease Control b. Herpes simplex
(USA) as follows: c. Varicella-zoster virus
a. Group I—acute HIV infection d. Adenoviruses
b. Group II—asymptomatic or latent infection 5. Malignancies
c. Group III—persistent generalized lymphadenopathy, a. Kaposi’s sarcoma
persistent low grade fever, malaise b. Lymphomas—Hodgkin and non-Hodgkin types
d. Group IV—other diseases such as AIDS related
complex; inverted T4:T8 ratio, anergy (skin fails to Q. 4. Window period
respond to antigen); malignancies—Burkitt’s lym-
Ans.
phoma, Kaposi’s sarcoma (cancer of the small blood
vessels of the skin). l After infection, for antibodies to appear it may take 2–8
e. Group V—Frank AIDS weeks to months. IgM antibodies appear first usually in
i. Neuropathies—encephalopathy, dementia, acute about 3–4 weeks after infection and disappear in 8–10
aseptic meningitis, vascular degenerative my- weeks. IgG antibodies appear later about 5–6 weeks
elopathy after infection and persists throughout.
ii. Lymphocytic interstitial pneumonia l During part of this period, the individual may be highly
iii. Wasting infectious. This seronegative infective stage is known as
the window period.
Q. 3. Mention opportunistic infections and malignancies l Infection can be detected during the window period by
associated with HIV infection. p24 assay.

Q. 5. Rapid tests for HIV infection 2 . Immunochromatographic tests

3. Coated particle agglutination
Ans. A number of rapid tests have been introduced for
4. Immunoperoxidase
the purpose of testing single samples quickly. They are as
5. Dip stick tests
follows:
Tests using finger prick blood, saliva and urine have also
1. Cylinder or cassette ELISA been developed.
Part IV
Systemic Mycology
Topic 37
Fungal Diseases
LONG ESSAY
Q. 1. Give an account of infections caused by Candida ii. Lesions of Skin
albicans. Describe laboratory diagnosis of candida.
1. Lesions of the skin usually develop in sites that may
Ans. become abnormally moist and warm, e.g. axilla, groin,
perineum, submammary folds and toe clefts.
1. Two forms of Candida albicans exist and both are 2. Cutaneous candidiasis presents as an erythematous,
Gram-positive. scaling or moist lesions with sharply demarcated bor-
a. Spherical or ovoid budding cells of 2–3 3 5–6 mm ders where papular lesions are most prominent.
size. These are yeast or Y forms.
b. Elongated filamentous cells joined end-to-end re-
sembling hyphae and producing spores. iii. Lesions of Nails
2. Various infections caused by C. albicans are as follows: 1. Commonly occur in people who frequently immerse
a. Superficial lesions affecting mucous membranes, their hands in water.
skin, nails, etc. 2. Infection of finger webs, nail folds and nails occur as
b. Systemic candidiasis reddened swelling resembling pyogenic paronychia.
a. Superficial Lesions iv. Chronic Mucocutaneous Candidiasis

Superficial lesions are as follows: It is a rare form of intractable disfiguring condition of face
and scalp and usually becomes apparent in childhood.
i. Lesions of Mucous Membranes
1. Infection of the mouth (oral thrush) is characterized b. Systemic Candidiasis
by the development of discrete white patches on the 1. It is usually encountered with serous abnormality of the
mucosal surface occurs most frequently in infancy and host and in certain groups of hospitalized patients par-
old age. ticularly in overgrowth of commensal yeasts in mouth
2. Intestinal candidiasis is a sequela of the oral antibiotic and gastrointestinal tract in association with antibiotic
therapy presenting as diarrhoea. and steroid therapy.
3. Vaginal thrush characterized by typical white lesions 2. The infection may be widely disseminated and leading
usually develops on epithelial surfaces of vulva, vagina to infection of kidney and brain associated with a septi-
and cervix. Balanitis in male may occur following sex- caemia.
ual contact.
3 . Candidal endocarditis follows surgery of heart valves. b. Chlamydospores: These develop in a nutritionally
4. In pre-existing diseases like tuberculosis, cancer, inter- poor medium such as cornmeal agar at 28°C.
nal organs like lungs, kidney and other organs may be 3. Biochemical reactions: C. albicans can be identified by
secondarily invaded. the assimilation and fermentation of sugar.
5. Methods used in laboratory diagnosis of candida are as 4. Serology: C. albicans can also be identified by the pre-
follows: cipitation test with a carbohydrate extract of group A
antigens.
5. Antigen detection: It is done by ELISA and RIA which
Direct Examination
detects cell wall manner or cytoplasmic constituents.
Scrapings from the lesions of skin, nails or mucosa are ex- 6. Skin test: Delayed hypersensitivity to candida extracts is
amined in a wet film in KOH or Gram-stained smear. The a useful indicator of functional integrity of CMI.
C. albicans appear as budding yeast cells. 7. Animal inoculation: C. albicans kills the animal (rabbit,
guinea pig and mice) in 4–5 days with typical renal
abscess on intravenous inoculation.
Culture
1. Specimens are inoculated on the Sabouraud’s dextrose
chloramphenicol agar medium at 25–37°C for 24 h.
Treatment
Candida produces creamy white, smooth colonies with 1. Management is mainly by removing the predisposing
a yeasty odour. causes as candida is resistant to all antibiotics.
2. The C. albicans is identified by the following: a. Superficial infections: Topical application of nystatin
a. Germtubes: When candida is grown in human serum or imidazole
at 37°C for 3 h. A wet KOH film shows filamentous b. Systemic infections: Amphotericin B along with
outgrowths (Reynolds Braude phenomenon). 5 fluorocytosine
SHORT ESSAYS
Q. 1. Morphological classification of fungi Dimorphic Fungi
Ans. Depending on cell morphology, fungi can be divided They occur as yeasts in host tissues or cultures at 37°C and
into four classes as follows: as moulds in the soil and in cultures at 22°C, e.g. H. capsu-
latum, Blastomyces dermatitidis.
1 . Yeasts, e.g. Cryptococcus neoformans
2. Yeast like fungi, e.g. C. albicans
3. Moulds, e.g. Dermatophytes Q. 2. Id reaction
4. Dimorphic fungi, e.g. Histoplasma capsulatum Ans.
l Id reaction is also known as dermatophitidis.

Yeasts l In the ringworm disease the fungi and their metabolic
They are unicellular fungi, occurring as spherical or oval products may be responsible for inciting local inflam-
cells and reproduced by budding. In cultures, they form mation.
smooth, creamy colonies, e.g. C. neoformans. l Hypersensitivity to fungus antigens plays a role in
pathogenesis and is responsible for the sterile vesicular

lesions seen in the sites distant from the ringworm.
Yeast like Fungi These lesions are called dermatophitidis or id reaction.
They grow partly as yeast and partly as elongated cells re- l Hypersensitivity can be demonstrated by skin testing
sembling hyphae, forming a pseudomycelium, e.g. C. albi- with the fungus antigen, i.e. trichophyton.
cans.
Q. 3. Rhinosporidiosis
Moulds Ans.
Moulds or filamentous fungi form true mycelia and produce by l Rhinosporidiosis is a chronic granulomatous disease char-
the formation of different types of spores, e.g. Dermatophytes. acterized by the development of friable polyps, usually
confined to the nose, mouth or eye, but rarely seen on the l Histologically the lesion is composed of large numbers
genitalia or other mucous membranes. of fungal spherules embedded in a stroma of connective
l Haematogenous dissemination may occur though the tissue and capillaries. The spherules are 10–200 mm in
disease is generally confined to mucous membranes. diameter and contain thousands of endospores.
l Causative agent is Rhinosporidium seeberi, a fungus. l The causative fungus R. seeberi has not been cultivated
l Pathogenesis: The mode of infection is not known in media, diagnosis is usually established by direct
though infection is believed to originate from stagnant microscopy or histopathological examination.
water or aquatic life.
SHORT NOTES
Q. 1. Candidal infections b. Gram-stained smear shows Gram-positive yeast
cells.
Ans. Lesions produced by C. albicans are as follows:
2. Culture and identifications
l Vaginitis: Characterized by an acidic discharge, found a. On Sabouraud’s dextrose with chloramphenicol
frequently in pregnancy and diabetics. after 1–7 days incubation at 37°C shows creamy
l Oral thrush: White patch on oral/buccal mucosa and white smooth colonies.
tongue occurring commonly in bottle-fed infants and 3. Other laboratory tests are as follows:
aged, diabetic adults with ill fitting dentures, prolonged a. Precipitations test
use of antibiotics. b. Agglutination test
l Skin lesion: Paronychia c. Indirect fluorescent test
l Intestinal lesion is a sequel to antibiotic therapy and
present as diarrhoea not responding to treatment. Q. 4. Thrush

Ans.
Q. 2. Opportunistic fungal infection
l Oral thrush caused by C. albicans is most common fun-
Or,
gal infection of the oral cavity.
Oppurtunistic mycosis l Infection of the mouth (oral thrush) is characterized by
the development of discrete creamy white patches on

Ans.
the mucosal surfaces of tongue or buccal mucosa.
l Opportunistic infections are caused by some sapro- l It occurs most frequently in bottle-fed infants and the
phytic fungi which are ubiquitous in environment. old age and debilitated individuals.
Example: Aspergillus, mucor, penicillium and rhizopus
species Q. 5. Write brief note on superficial mycosis.
l They produce serious and fatal infections in patients Ans.
with AIDS or other debilitating diseases like cancer,
diabetes or in those persons where the physiological 1. Superficial mycosis is of following types:
state has been upset by immunosuppressive drugs, ste- a. Surface infections
roids, X-ray or broad-spectrum antibiotics. b. Cutaneous infections
l Aspergillosis and mucormycosis are important opportu- 2. In superficial mycosis the fungi lie exclusively on the
nistic systemic infections. dead layers of skin and its appendages. They have no
contact with living tissues and have elicited no inflam-
Q. 3. Candida albicans matory response.
Ans. Example: Tinea versicolour, tinea nigra and piedra are
some surface infections.
l C. albicans is an ovoid or spherical budding cell 3. The most important cutaneous infection is dermatophy-
which produces pseudomycelia both in culture and in tosis caused by dermatophytes which infects only super-
tissues. ficial keratinized tissue, i.e. the skin, hair and nails.
l Candidiasis is an opportunistic infection, the common- 4. C. albicans causes cutaneous candidiasis which is an
est predisposing factor being diabetes. infection of skin and mucosa. Common mucosal lesions
l Laboratory diagnosis is done by the following: are vaginitis characterized by an acidic discharge and
1. Direct microscopic examination found frequently in pregnancy and oral thrush, found
a. KOH preparation shows yeast all with budding commonly in bottle-fed infants, characterized by creamy
and pseudohyphae. white patches on the tongue and buccal mucosa.
Part V
Medical Parasitology
Topic 38
Protozoans
LONG ESSAYS
Q. 1. Describe the morphology and life cycle of Ent- 3. Cystic Stage
amoeba histolytica. Write about laboratory diagnosis of
1. The cyst is rounded and is surrounded by a highly retrac-
intestinal amoebiasis.
tile membrane called cyst wall and varies greatly in size.
Ans. Entamoeba histolytica is an important human patho- 2. The cyst begins as uninucleate body, develops into
gen, causing amoebic dysentery as well as hepatic amoe- binucleate and quadrinucleate body. A mature cyst is a
biasis and other extraintestinal lesions. quadrinucleate spherical body having clear and hyaline
cytoplasm.
This parasite is more commonly found in tropics and
3. In the early stage of development, cytoplasm shows
subtropics, although its distribution is worldwide.
chromatoid bars as retractile oblong bars with rounded
ends and glycogen mass which stains brown with
MORPHOLOGY OF E. HISTOLYTICA iodine.
E. histolytica occurs in three forms which are
1. the trophozoite,
LIFE CYCLE
2. precystic stage and
3. cyst. 1. E. histolytica passes its life cycle in only one host, the
man. The methods of reproduction of this parasite are
1. Trophozoite excystation, encystations and multiplication.
2. The mature quadrinucleate cysts are the infective forms
1 . It is the infective form of the parasite.
of the parasite. These cysts are swallowed along with
2. It is irregular in shape, actively motile with single pseu-
contaminated food and drink. The cyst wall is resistant
dopodium. Size ranges from 18 to 40 mm, average size
to the action of trypsin in the intestine.
being 20–30 mm.
3. The excystation occurs when the cyst reaches the
3. The cytoplasm is divisible into two portions, a clear
caecum or the lower part of the ileum. Each cyst lib-
ectoplasm and a granular endoplasm.
erates a single amoeba with four nuclei, a tetranucle-
4. Red blood cells, sometimes leucocytes and tissue debris
ate amoeba which eventually forms eight amoebulae
are usually found in the endoplasm.
by division of nuclei with successive fission of cyto-
5. The nucleus is spherical in shape and contains a central
plasm.
dot-like karyosome. The nucleus is lined with a delicate
4. The trophozoite phase of parasite is responsible for
nuclear membrane.
producing characteristic lesion of amoebiasis.
6. A fine thread-like linen network having a spoke-like
5. After sometime, the parasite finds it difficult to continue
radial arrangement between karyosome and nuclear
the life solely in the trophozoite stage.
membrane are seen.
6. A certain number of these trophozoites are discharged
into the lumen of the bowel and are transformed into the
2. Precystic Stage precystic forms from which the cyst are developed and
1. It is round or slightly oval in shape varying in size from passed in feces.
10 to 20 mm, with a blunt pseudopodium projecting 7. The cysts produced in an infected individual are un-
from the periphery. able to develop in the host in which they are produced
2. The endoplasm is free of red blood cells and other in- and therefore necessitate a transfer to another suscep-
gested food particles. Nucleus will be similar to that of tible host where they can grow and continue their life
trophozoite. cycle.
Pathogenicity EXTRAINTESTINAL LESIONS

1. The infection occurs through ingestion of the cysts. Fae- b. Secondary or Metastatic Lesions
cal contamination of drinking water and food are the (Extraintestinal Amoebiasis)
primary causes. Incubation period varies a great deal but
is generally 4–5 days. i. In amoebic liver abscess: In amoebic liver abscess
2. E. histolytica can cause two types of pathological le-
sions as follows: Trophozoites enter radicals of portal vein from base of ulcer
a. Intestinal amoebiasis or primary lesion
b. Extraintestinal amoebiasis or secondary or meta- Capillary system of liver filters them and traps them
static lesions
Trophozoites multiply and carry on cytolytic action
a. Primary or Intestinal Amoebiasis

Focal necrosis of liver cell
1. The trophozoites liberated after excystation enter
through crypts of Lieberkuhn and penetrate directly Large abscess formed
through the columnar epithelium of the mucous mem-
brane and reach the submucous coat. 1. Amoebae often are transported through the portal
2. Here the amoebae multiply, pass in various directions circulation to the liver. Hepatic invasion is multifo-
destroying the submucous tissue, formation of abscesses cal, right lobe being affected more commonly.
which finally break down leading to development of ul- 2. The amoebae initiate the lytic necrosis and with in-
cers. The ulcers are multiple and confined to the colon. creasing size of the lesion and continuing necrosis,
3. The distribution of ulcers may be generalized or local- there occurs considerable leucocyte infiltration. There
ized at ileocaecal region or sigmoidorectal region. is hepatomegaly which is known as amoebic hepatitis.
4. The typical amoebic ulcer is flask-shaped in cross-sec- 3. The lesions may develop into amoebic abscesses,
tion, multiple ulcers may coalesce to form large necrotic which may vary in size from a few millimetres to
lesions with ragged or undermined edges and covered several centimetres. The centre of the abscess con-
with brownish slough. tains thick chocolate brown pus similar to anchovy
5. The ulcers do not generally extend deeper than the sub- sauce which is liquefied necrotic liver tissue. It does
mucous layer. Occasionally the ulcer may involve the not contain any bacteria or amoebae. The amoebae
deeper tissues and may cause perforation and peritonitis. are located at the periphery.
6. Erosion of a blood vessel may lead to haemorrhage. 4. The liver abscesses may be solitary or may be mul-
7. The superficial lesions generally heal without scarring tiple. It may lead to jaundice.
but the deep ulcers form the scars which may lead to 5. If untreated, some abscesses tend to rupture into ad-
strictures, partial obstruction and thickening of the gut jacent tissues and organs.
wall, occasionally granulomatous growth may develop ii. Lungs: In pulmonary amoebiasis
in the intestinal wall from a chronic ulcer (amoeboma).
Trophozoites
INTESTINAL LESION
Portal circulation
Metacystic trophozoite liberated after excystation

Pulmonary circulation
Penetrate mucous membrane (by amoeboid Pulmonary abscess

activity and proteolytic enzymes)
1. It usually occurs following rupture of hepatic abscess
Reach submucosa and multiply rapidly through diaphragm by direct extension.
2. Rarely, it may occur by direct haematogenous spread
from the colon.
Destroy considerable area of submucosa and
mucous membrane i ii. Brain
1. A rare variety of secondary amoebiasis presenting as
amoebic brain abscess, arising as a complication of
Coagulative necrosis begins and abscess forms
either hepatic or lung abscess or both.
2. Generally a small single abscess most commonly
Flask-shaped ulcer developed located in cerebral hemisphere.
i v. Spleen g. RIA
1. Spleen is occasionally involved in association with the h. Test of Goldman (immunofluorescence)
liver resulting in splenic abscess. 5 . Passive cutaneous anaphylaxis test in guinea pig skin
v. Skin may be positive.
1. Skin of the region adjoining the visceral lesion shows 6. Intradermal test may be positive.
sloughing, necrosis, ulceration, granulomatous masses. 7. Radiographic examination or ultrasound or scanning
It is known as cutaneous amoebiasis. methods show raised right dome of diaphragm.
LAB DIAGNOSIS OF INTESTINAL 2. Diagnosis of Pulmonary Amoebiasis

AND EXTRAINTESTINAL AMOEBIASIS 1. Demonstration of trophozoites in sputum and by sero-
logical tests
1. Stool findings of amoebic dysentery: Stool which is
collected directly into a wide mouthed container and
examined without delay. 3. Diagnosis of other Metastatic Lesions
a. Macroscopic examination
1. In all such cases trophozoites are searched for.
i. Stool is offensive odour.
ii. Dark brown and semifluid Q. 2. Describe the life cycle of malarial parasites. Give a
iii. Acid in reaction brief description of laboratory diagnosis of malarial
iv. Mixed with blood, mucous and much faecal parasites.
matter
b. Microscopic examination Ans.
i. The cellular exudate is scanty, consists of nu- 1. Malaria is a protozoan disease caused by four Plasmo-
clear masses of a few pus cells, macrophages and dium species which are as follows:
epithelial cells. a. Plasmodium vivax
ii. RBC in clumps b. Plasmodium falciparum
ii. Charcot-Leyden crystals are also seen. c. Plasmodium ovale
iv. In acute cases, the amoebic trophozoites can be d. Plasmodium malariae
easily recognized by their characteristics move- Of these vivax and falciparum are important species.
ment and presence of red cells.
v. In chronic patients and carriers the presence of LIFE CYCLE OF MALARIAL PARASITES
cysts can be demonstrated.
The Plasmodium passes its life cycle in two hosts.
2. Examination of blood: Blood shows moderate leucocy-
1. In man: Man is the intermediate host where the parasite
tosis.
resides in the liver cells and red blood cells and repro-
3. Serological tests: In early stages, it is always negative.
duces asexually.
It may be positive in later stages.
2. In female anopheles mosquito: Female anopheles mos-
4. Culture: E. histolytica can be cultivated on the following:
quito is the definitive host. The sexual forms or gameto-
a. modified Boeck and Drbohlav medium
cytes developed in the human host are transferred to
b. Philips medium
insect host where they develop further and transformed
c. Shaffer and Frey medium
into sporozoites, the infective forms for human host.
d. Diamond’s medium
The lab diagnosis of extraintestinal amoebiasis is done by
serological tests including the following:
HUMAN CYCLE OR SCHIZOGONY OR
ASEXUAL CYCLE
1. Diagnosis of Hepatic Amoebiasis l It starts with the introduction of sporozoites by the bite
of an infected female anopheles mosquito.
1. Demonstration of trophozoite stages in aspirated pus l Human cycle comprises of following stages:
and liver biopsy specimens 1. Pre-erythrocytic schizogony
2. Cysts are present in some patients with liver abscess. 2. Erythrocytic schizogony
3. Blood leucocytosis 3. Gametogony
4. Serological tests 4. Exoerythrocytic schizogony
a. CFT
b. Gel diffusion test
a. Pre-erythrocytic Schizogony
c. Indirect haemagglutination
d. ELISA 1 . Occurs inside the parenchyma of hepatocytes.
e. Counter current immunoelectrophoresis 2. The sporozoites enter the liver cells and multiply in
f. Latex agglutination them by asexual reproduction or schizogony which
result in the production of large number of small forms 3. The male and female gametocytes continue sexual cycle
called merozoites or cryptozoites. (sporogony) in the mosquito. First all gametocytes be-
3 . The liver cell ultimately ruptures and releases many come rounded and exflagellation occurs with the forma-
merozoites which attack new liver cells and this stage is tion of filamentous structure.
called pre-erythrocytic or exoerythrocytic cycle. 4. In mosquito gut, from one microgametocyte, 5–7 thin
4. Larger merozoites re-enter fresh liver cells and smaller thread-like filamentous microgametes are formed.
merozoites enter blood circulation and infect erythro- From one macrogametocyte only one macrogamete
cytes. develops.
5. It lasts for 8 days. No pathological changes or clinical 5. The gametocytes fuse together and form zygote. Zygote
symptoms are seen, parasites are not found in the pe- becomes very active and now called ookinete.
ripheral blood. 6. Ookinete penetrates the muscle wall of stomach and
forms oocyst.
7. Oocyst enlarges and matures and divides by meiosis and
b. Erythrocytic Schizogony mitosis to form many sickle-shaped structures called
1. During this phase, parasite resides inside RBC and sporozoites.
passes through stages of trophozoite, schizont and mer- 8. Sporocyst ruptures around 10th day of infection
ozoite. and liberates sporozoites into the body cavity of
2. Parasite feeds on haemoglobin of RBC but cannot me- mosquito.
tabolize completely so leaves behind a residue of hae- 9. Sporozoites have special affinity for salivary gland and
moglobin pigment called hemozoin. get concentrated into its ducts. The mosquito becomes
3. The multiplication of parasite inside RBC is responsible infective at this stage.
for bringing on a clinical attack of malaria.
4. This cycle lasts for 48–72 h in P. vivax and 48 h in
P. falciparum.
1. Microscopic Examination of Blood Film
c. Gametogony a. Blood Examination
1. After the parasite has undergone erythrocytic schizog- 1. The most important method for diagnosis of malaria is
ony for a certain period of time some of the merozoites demonstration of parasite in the blood.
give rise to gametocytes which develop in the RBCs of 2. Two types of blood films are prepared for examination,
capillaries of internal organs like spleen, bone marrow, (a) the thick and (b) the thin films. These films are ex-
etc. and mature in 4 days. amined under oil immersion microscope for detecting
2. Only mature gametocytes are found in peripheral blood. the parasites or their gametocytes.
3. No febrile reaction occurs in the host during gametog- a. Thick film: Parasite quickly detected
ony and person who harbours gametocytes is known as b. Thin film: Species identification
carrier. c. A slide is rated quantitatively as follows:
1–10 parasites/100 thick film fields n 1
c. Exoerythrocytic Schizogony 11–100 parasites/100 thick film fields n 11
1–10 parasites/each thick film fields n 111
1. After the blood infection is established the initial pre- More the 10 parasites/each thick film fields n
erythrocytic phase disappears completely in P. falci- 1111
parum wherever as it persists in the form of local liver 3. About 200 oil immersion fields should be examined
cycle in P. vivax, P. ovale and P. malariae. before declaring a thick film negative.
2. The persistence of this late tissue phase is called exo-
erythrocytic schizogony and is responsible for relapses
in vivax, ovale, and quartan malaria. Merozoites liber- b. Cultural Examination
ated in this phase are called phanerozoites. Trager Jensen successfully cultivated malaria parasites in
RPMI1640 medium consisting of a thin layer of human
LIFE CYCLE IN MOSQUITO OR RBC with human serum under 7% CO2 and low oxygen
about 1–5% in vitro continuous culture technique.
SPOROGONY OR SEXUAL CYCLE Cultures are useful
1. The life cycle in mosquito starts with sucking of blood 1. to obtain erythrocyte stages for the study of antigenic
containing gametocytes from an infected host by female structure.
anopheles mosquito. 2. as a source of antigen for sero-epidemiological study.
2. Both sexual and asexual forms are ingested, but only 3. to study the sensitivity or resistance of the parasite to
mature sexual forms develop and the rest die. various drugs.
4. to observe immunoprophylactic activity. 2. The commonly employed tests are

a. Henry’s melanin flocculation test,
c. Blood count: Moderate leukopenia, b. complement fixation test,
monocytosis c. passive haemagglutination tests,
d. immunofluorescence test,
d. Serological Tests e. ELISA and
1. These are employed most often for sero-epidemiological f. RIA, etc.
surveys.
SHORT ESSAYS
Q. 1. Blackwater fever l Septicaemic malaria is characterized by high continued
temperature, bilious remittent fever, pneumonia and
Ans.
cardiac syncope.
l Blackwater fever is a manifestation of falciparum malaria.
l Blackwater fever is characterized by sudden massive Blackwater Fever
haemolysis followed by fever, haemoglobinemia and
haemoglobinuria. l Blackwater fever is a manifestation of falciparum ma-
l Clinical manifestations are bilious vomiting and pros- laria.
tration with passage of dark red or blackish urine, hence l Blackwater fever is characterized by sudden massive
called blackwater fever. haemolysis followed by fever, haemoglobinaemia and

l Kidneys and liver are particularly involved. There is haemoglobinuria.
excessive deposition of haemosiderin pigment in the l Clinical manifestations are bilious vomiting and pros-
liver, spleen, and kidneys. tration with passage of dark red or blackish urine, hence
l Sequelae of blackwater fever include uraemia, renal called blackwater fever.
failure, circulatory failure, liver failure, anaemia, and l Kidneys and liver are particularly involved.
pigment calculi. Renal failure is the cause of death. l Sequelae of black water fever include uraemia, renal
l In majority of cases parasites may not be detected in pe- failure, circulatory failure, liver failure, anaemia and
ripheral blood smears as they are destroyed by haemolysis. pigment calculi. Renal failure is the cause of death.
Q. 2. Complications of Plasmodium falciparum infection Q. 3. Laboratory diagnosis of kala-azar

Ans. Complications of Plasmodium falciparum infection are Ans. Kala-azar or visceral leishmaniasis is caused by
Leishmania donovani.
1 . pernicious malaria and
2. blackwater fever. Various methods of lab diagnosis of kala-azar are as follows:
Pernicious Malaria Direct Evidences

Demonstration of L. donovani in
l It results from anoxia due to obstruction of capillaries in 1. peripheral blood (thick film)—amastigote form,
various organ followed by necrosis of tissue. 2. blood culture in NNN medium—promastigote forms and
l It may involve
3. biopsy material obtained by
a. nervous system, a. sternal or iliac crest puncture,
b. gastrointestinal system having gastric, choleric and b. splenic puncture and
dysentery and c. lymph node.
c. cardiovascular, respiratory and genitourinary system.
l Pernicious manifestations are seen when .5% RBCs
Indirect Evidences
are infected. Various manifestations of pernicious ma-
1. Progressive leukopenia
laria are grouped into following clinical types:
2. Serum tests
a. Cerebral malaria
a. Aldehyde test (positive after 3 months)
b. Algid malaria
b. Antimony test
c. Septicaemic malaria
c. CFT with WKK antigen
l Cerebral malaria is manifested by hyperpyrexia, coma
d. ELISA (more reliable)
and paralysis.
l Algid malaria is characterized by cold and clammy skin with Microscopic Examination: Reveals presence of amasti-
vascular collapse leading to peripheral circulatory failure. gote forms in thick blood films of kala-azar patients.
Cultivation of L. donovani on NNN medium: In NNN 2 . Cysts are present in some patients with liver abscess.
medium, the amastigote form changes to promastigote 3. Blood leucocytosis
form, which then multiplies actively by longitudinal binary 4. Serological tests
fission to produce numerous flagellates. a. CFT
b. Gel diffusion test
Q. 4. Laboratory diagnosis of Entamoeba histolytica in c. Indirect haemagglutination
brief d. ELISA
e. Counter current immunoelectrophoresis
Ans. Laboratory diagnosis of Entamoeba histolytica con- f. Latex agglutination
sists of demonstration of parasites in the material obtained g. RIA
from a particular lesion like stool, pus and sputum. h. Test of Goldman (immunofluorescence)
5. Passive cutaneous anaphylaxis test in guinea pig skin
may be positive.
LABORATORY DIAGNOSIS OF INTESTINAL 6. Intradermal test may be positive.
AMOEBIASIS 7. Radiographic examination or ultrasound or scanning
methods show raised right dome of diaphragm.
Laboratory diagnosis of intestinal amoebiasis consists of
the following: Diagnosis of pulmonary amoebiasis: Demonstration of
Examination of stool in amoebic dysentery: Stool is col- trophozoites in sputum and by serological tests
lected directly into a wide mouthed container and examined. Diagnosis of other metastatic lesions: In all such cases
trophozoites are searched for.
1. Macroscopic examination
a. Stool is offensive odour. Q. 5. Human cycle of malarial parasite
b. Dark brown and semifluid
c. Acid in reaction Ans.
d. Mixed with blood, mucous and much fecal matter
HUMAN CYCLE OR SCHIZOGONY OR
2. Microscopic examination ASEXUAL CYCLE OF MALARIA PARASITE
a. The cellular exudate is scanty, consists of nuclear masses
of a few pus cells, macrophages and epithelial cells. l It starts with the introduction of sporozoites by the bite
b. RBC in clumps of an infected female anopheles mosquito.
l Human cycle comprises of following stages:
c. Charcot-Leyden crystals are also seen.
d. In acute cases, the amoebic trophozoites can be eas- 1. Pre-erythrocytic schizogony
ily recognized by their characteristics movement and 2. Erythrocytic schizogony
presence of red cells. 3. Gametogony
e. In chronic patients and carriers the presence of cysts 4. Exoerythrocytic schizogony
can be demonstrated.
Examination of blood: Blood shows moderate leucocytosis.
Pre-erythrocytic Schizogony
Serological tests: In early stages, it is always negative. It l Occurs inside the parenchyma of hepatocytes.
may be positive in later stages. l The sporozoites enter the liver cells and multiply in
them by asexual reproduction or schizogony which re-
Culture: E. histolytica can be cultivated on
sults in the production of large number of small forms
a. Modified Boeck and Drbohlav medium,
called merozoites or cryptozoites.
b. Philips medium,
l The liver cell ultimately ruptures and releases many
c. Shaffer and Frey medium and
merozoites which attack new liver cells and this stage is
d. Diamond’s medium.
called pre-erythrocytic or exoerythrocytic cycle.
l Larger merozoites re-enter fresh liver cells and smaller
LAB DIAGNOSIS OF EXTRAINTESTINAL merozoites enter blood circulation and infect erythrocytes.
l It lasts for 8 days. No pathological changes or clinical
AMOEBIASIS
symptoms are seen, parasites are not found in the
The lab diagnosis of extraintestinal amoebiasis is done by peripheral blood.
serological tests including the following:
Diagnosis of Hepatic Amoebiasis Erythrocytic Schizogony

1. Demonstration of trophozoite stages in aspirated pus l During this phase, parasite resides inside RBC and passes
and liver biopsy specimens. through stages of trophozoite, schizont and merozoite.
l Parasite feeds on haemoglobin of RBC and leaves be- l Only mature gametocytes are found in peripheral blood.
hind a residue of haemoglobin pigment called hemo- l No febrile reaction occurs in the host during gametog-
zoin. ony and person who harbours gametocytes is known as
l The multiplication of parasite inside RBC is responsible carrier.
for bringing on a clinical attack of malaria.
l This cycle lasts for 48–72 h in Plasmodium vivax and
Exoerythrocytic Schizogony
48 h in Plasmodium falciparum.
l After the blood infection is established the initial pre-
erythrocytic phase disappears completely in P. falci-
Gametogony parum whereas it persists in the form of local liver cycle
l After the parasite has undergone erythrocytic schizog- in P. vivax, P. ovale and P. malariae.
ony for a certain period of time some of the merozoites l The persistence of this late tissue phase is called exo-
give rise to gametocytes which develop in the RBCs of erythrocytic schizogony and is responsible for relapses
capillaries of internal organs like spleen, bone marrow, in vivax, ovale and quartan malaria. Merozoites liber-
etc. and mature in 4 days. ated in this phase are called phanerozoites.
SHORT NOTES
Q. 1. Amoebic dysentery amoebiasis, amoebic brain abscess and cutaneous
amoebiasis.
Ans.
l Amoebic dysentery is also known as intestinal amoebi- Q. 3. Microfilaria

asis or ulcerative colitis. Ans.
l The term amoebic dysentery refers to a condition in
which the infection is confined to intestine and is char- l Microfilariae are the larvae of nematodes.
acterized by the passage of blood and mucus in the stool. l The female nematodes are viviparous giving birth to
l In acute amoebic dysentery there are multiple ulcers, larvae called microfilariae.
deep and extensive. Complications are pericaecal and l It needs two hosts to complete its life cycle, man and a
pericolic abscess, amoebic appendicitis, perforation, blood sucking insect.

generalized peritonitis, and gangrene of gut and fistulas. l Microfilaria completes its development in the insect
l In chronic intestinal amoebiasis a single latent ulcer host, giving rise to the infective form. The infected in-
is present in the caecum and multiple small superficial sect bites another man and transmits the infection.
ulcers are scattered throughout the large intestine. l Species identification is made by studying the larvae,
Thickened caecum or colon with occasional stricture the adult worms are rarely obtained.
formation. Amoeboma in the caecum and large intestine. l Differentiating features of microfilariae are mentioned
in Table 38.1.
Q. 2. Entamoeba histolytica
Ans.
TABLE 38.1 Features of Microfilariae
l Entamoeba histolytica is an important human pathogen, Features Position Genus
more commonly found in tropics and subtropics, although Location of Sheath of Nuclei Species
its distribution is worldwide.
Blood Sheathed and Nuclei up M. malayi
l Morphology of E. histolytica
periodic to tail tip
E. histolytica occurs in three forms which are M. loa
a. the trophozoite, Tail tip free M. bancrofti
b. precystic stage and from nuclei
c. cyst. Unsheathed and Nuclei up M. perstans
l E. histolytica passes its life cycle in only one host, the man. nonperiodic to tail tip
l The methods of reproduction of this parasite are excys-
Unsheathed and Nuclei-free M. ozzardi
tation, encystations and multiplication. nonperiodic tail tip
l E. histolytica can cause two types of pathological lesions
Skin Unsheathed and Nuclei up M. strepto-
as follows: nonperiodic to tail tip cerca
a. Intestinal amoebiasis or primary lesion
b. Extraintestinal amoebiasis or secondary or meta- Tail tip free M. volvulus
from nuclei
static lesions like amoebic liver abscess, pulmonary
Q. 4. Gametocytes of malaria RBC with human serum under 7% CO2 and low oxygen
about 1–5% in vitro continuous culture technique.
Ans.
3. Blood count: Moderate leukopenia, monocytosis
l Gametogony is a stage in human cycle or asexual cycle
of malaria parasite. 4. Serological Tests
l In gametogony, after the parasite has undergone eryth-
rocytic schizogony for a certain period of time, some of l These are employed most often for sero-epidemiologi-
the merozoites give rise to gametocytes which develop cal surveys.
in the RBCs of capillaries of internal organs like spleen, l The commonly employed tests are
bone marrow etc. and mature in 4 days. 1. Henry’s melanin flocculation test,
l Only mature gametocytes are found in peripheral blood. 2. complement fixation test,
l No febrile reaction occurs in the host during gametog- 3. passive haemagglutination tests,
ony and person who harbours gametocytes is known as 4. immunofluorescence test,
carrier. 5. ELISA and
6. RIA, etc.
Q. 5. Erythrolytic schizogony
Q. 7. Laboratory diagnosis of intestinal amoebiasis
Ans.
Ans. Laboratory diagnosis of intestinal amoebiasis con-
l Human cycle or asexual cycle of malaria parasite com- sists of demonstration of parasites in the material obtained
prises of following stages: from a particular lesion like stool, pus, and sputum.
1. Pre-erythrocytic schizogony
2. Erythrocytic schizogony 1 . Macroscopic and microscopic examination of stool
3. Gametogony 2. Examination of blood reveals moderate leucocytosis.
4. Exoerythrocytic schizogony 3. Serological tests: In early stages, it is always negative.
It may be positive in later stages.
Erythrocytic Schizogony 4. Culture: E. histolytica can be cultivated on various media
like modified Boeck and Drbohlav medium, Philips me-
l During this phase parasite resides inside RBC and dium, Shaffer and Frey’s medium and Diamond’s medium.
passes through stages of trophozoite, schizont and mero-
zoite. Q. 8. Name the species of malarial parasites infecting
l Parasite feeds on haemoglobin of RBC and leaves be- humans.
hind a residue of haemoglobin pigment called hemo- Ans.
zoin.
l The multiplication of parasite inside RBC is responsible l Malaria is a protozoan disease caused by Plasmodium
for bringing on a clinical attack of malaria. species.
l This cycle lasts for 48–72 h in P. vivax and 48 h in l Four Plasmodium species which causes malaria are as
P. falciparum. follows:
1. Plasmodium vivax
Q. 6. Laboratory diagnosis of malaria 2. Plasmodium falciparum
Ans. 3. Plasmodium ovale
4. Plasmodium malariae
Laboratory diagnosis of malaria consists of the following: Of these vivax and falciparum are important species.
1. Microscopic Examination of Blood Film Q. 9. Benign tertian malaria
l The most important method for diagnosis of malaria is
Ans.
demonstration of parasite in the blood.
l Two types of blood films are prepared for examination l Benign tertian malaria is caused by Plasmodium vivax.
as follows: l In vivax malaria (benign tertian malaria) the typical in-
a. Thick film: Parasite quickly detected termittent periodic fever establishes only in later stages,
b. Thin film: Species identification initially there may be continuous or remittent fever.
l Initially two broods of parasites undergo schizogony on
2. Cultural Examination alternate days, thereby releasing two generations of mero-
Trager Jensen successfully cultivated malaria parasites in zoites with a febrile reaction each day. Later one brood
RPMI1640 medium consisting of a thin layer of human drops out and then the febrile curve becomes tertian.
Topic 39
Helminthes
SHORT ESSAYS
Q. 1. Ancylostoma duodenale l When larva reaches the lung multiple haemorrhages and
Ans. transient broncho-pneumonia occur.
l Adult worm causes irritation and petechiae of intestinal
l Ancylostoma duodenale is also known as the Old World mucosa.
hookworm.
l Adult worm when freshly passed is reddish brown due
to ingested blood otherwise they are grayish white, Laboratory Diagnosis

small and cylindrical. l Stool examination for both adult worms and ova
l The anterior end is bent slightly dorsally, hence the
l Study of duodenal contents for adult worm and ova
name hookworm. l Indirect evidences
l The life span of adult worm is 3–4 years. The sexes are
1. Blood examination for anaemia and eosinophilia
easily differentiated. 2. Stool examination for occult blood and Charcot-
1. Male worm is smaller, about 8 mm in length, poste- Leyden crystals
rior end is expanded in an umbrella-like fashion with
copulatory bursa, genital aperture opens posteriorly Q. 2. Write note on life cycle of Echinococcus
with cloaca. granulosus.
2. Female is longer than male and is about 12.5 mm in
length, posterior end is tapering and not expanded. Ans.
Genital opening is at the junction of posterior and
l Echinococcus granulosus is also known as dog tape-
middle third of the body.
worm. It is a cestode and is the causative agent of hyda-
tid disease.
Life Cycle l It is ingested by contaminated food and it releases onco-
l The adult worm lives in small intestine of man, after sphere which penetrates the mesenteric blood vessels
fertilization female lays eggs which are passed out with and gets distributed to various organs like lungs, kidney,
the stool. brain, etc.
l Rupture of cyst gives rise to allergic symptoms and
l Outside the body of the host the larva develops from
eggs. In 24 h rhabditiform larva is liberated and is trans- sign.

l Life cycle of E. granulosus is completed in two hosts as
formed into filariform larva which is infective.
l On coming in contact with skin of foot, it penetrates
follows:
into hair of follicle through intact skin to reach right 1. Definitive host: Dog, fox and wolf
side of heart. Thereafter larva reaches the lung and 2. Intermediate host: Man, sheep and goat
l The gravid proglottids disintegrate in the intestine and
alveolar space. Third moulting occurs at this stage.
l From alveolar space the larvae reach bronchioles, tra-
the eggs are passed out in the stool of dog.
l Ingestion of the contaminated food by the intermediate
chea, larynx and are swallowed back to stomach. In
intestine another moulting occurs and larvae grow to food resulting in hatching out of hexacanth embryo out
mature adult form. of eggs
l This liberated oncospheres penetrate the mesenteric
blood vessels and get distributed to the various organs

Pathogenicity
of the body such as liver, lungs, etc.
l Ancylostomiasis or hookworm disease is characterized l Whenever embryo settles it grows into hydatid cyst
by anaemia. containing thousands of scolices. The hydatid cysts are
l Dermatitis may occur at the site of larva penetration. ingested by the definitive host.
The larva then migrates to subcutaneous vessels and l Lesions produced by Echinococcus granulosus are as
causes creeping eruption. follows:
1. Hydatid disease and echinococcosis 3. Infective eggs are swallowed with raw food mate-
2. Rupture of cyst gives rise to allergic symptoms and rial which passes through stomach into small in-
signs. testine. Outer shell of egg is dissolved and larva
3. Rupture in lung causes chest pain, cough, dyspnoea comes out.
and hemoptasis. 4. The larva penetrate the mucosa and reaches the por-
4. Cyst in the cerebrum may gives rise to epilepsy. tal circulation thereafter to liver, heart and finally to
5. A cyst in kidney may causes hematuria. the lung alveoli.
5. The larvae from alveoli migrate to bronchioles, tra-
Q. 3. Life cycle of Ascaris lumbricoides chea and are swallowed back in the stomach, during
Ans. this period moulting occurs. In the intestine larva
develops into adult worm.
l Ascaris lumbricoides (roundworm) is a nematode. l Lesions produced by Ascaris are as follows:
l The life cycle of Ascaris lumbricoides is as follows: 1. The larva in the lung alveoli causes migrating pneu-
1. The female adult worm liberates fertilized eggs in monitis.
small intestine which are passed with stool. At this 2. Adult worm may cause malnutrition, vague ab-
stage they are noninfective to man. dominal pain, colic pain, poor digestion, diar-
2. In 9–15 days in moist soil rhabditiform larva devel- rhoea, etc.
ops inside the fertilized egg. A moulting occurs 3. Perforation of bowel, appendicitis and diverticulitis
within the egg and the egg becomes infective. may occur.
SHORT NOTES
Q. 1. Hydatid cyst within half an hour, in all positive cases. It shows mul-
tiple pseudopodia and fades in 1 hour or so. For control
Ans.
sterile normal saline 0.2 mL is similarly injected on the
l Embryos of Echinococcus granulosus (dog tapeworm) other arm using a separate needle and syringe.
grows into hydatid cyst and causes hydatid disease. l Hydatid fluid from human cases or from animals is used
l Hydatid cyst consists of the following: as an antigen.

1. Ectocyst
2. Endocyst Q. 3. Ancylostoma duodenale
3. Hydatid fluid Ans.
4. Hydatid sand
l Ectocyst is a hyaline membrane which forms thick, l Ancylostoma duodenale is also known as the Old World
outer, circular layer and is elastic in nature. hookworm.
l Endocyst is cellular inner germinal layer. It has role in l Adult worm when freshly passed is reddish brown due
formation of outer layer secretion of hydatid fluid and to to ingested blood otherwise they are greyish white,
form brood capsule with scolices. small and cylindrical.
l Hydatid fluid is secreted by endocyst. It is clean, colour- l The anterior end is bent slightly dorsally hence the
less, pale yellow fluid, weakly acidic, containing so- name hookworm. The adult worm lives in small intes-
dium chloride, sodium sulphate and sodium phosphate. tine of man, attached to the mucosa.
It provides nutrition for developing scolices and is anti- l The life span of adult worm is 3–4 years. The sexes are
genic and highly toxic. easily differentiated.

l Hydatid sand is granular deposit consisting of liberated 1. Male worm is smaller, about 8 mm in length, poste-
brood capsule-free scolices and loose hooklets. rior end is expanded in an umbrella-like fashion with
copulatory bursa, genital aperture opens posteriorly
Q. 2. Casoni’s test with cloaca.
2. Female is longer than male and is about 12.5 mm in
Ans.
length, posterior end is tapering and not expanded.
l It is an intradermal test introduced by Casoni in 1911, Genital opening is at the junction of posterior and
for testing immediate hypersensitivity in hydatid dis- middle third of the body.
ease. l Pathogenicity: It causes
l Intradermal injection of 0.2 mL of a fresh sterile hydatid 1. ancylostomiasis or hookworm disease characterized
fluid produces a large wheal about 5 cm in diameter by anaemia.
2. dermatitis and creeping eruptions. l Man gets infected in the same way as does pig through
3. multiple haemorrhages in lungs and transient bron- drinking contaminated water or by eating uncooked raw
chopneumonia. vegetables contaminated with eggs.
4. Adult worm causes irritation and petechial intestinal l Effects produced by cysticerci depend upon the organ
mucosa. they are localized in. When they are found in

1. subcutaneous tissues and muscles they cause palpa-
Laboratory Diagnosis ble nodules.
2. the brain they produce severe consequences includ-
l Stool examination for both adult worms and ova ing epilepsy.
l Study of duodenal contents for adult worm and ova 3. the eye they can be visualized by ophthalmoscopy.
l Indirect evidences
1. Blood examination for anaemia and eosinophilia Q. 6. Enumerate parasites which enter through unbro-
2. Stool examination for occult blood and Charcot- ken skin. Draw labelled diagram of three ova found in
Leyden crystals stool. Describe lab diagnosis of guinea worm.
Q. 4. Hookworm infestations Ans. The parasite which enters through unbroken skin is
Ans Various hookworm infestations are as follows: 1 . Trichuris trichiura

2. Trichinella spiralis
l Ancylostomiasis or hookworm disease is characterized 3. Guinea worm
by anaemia. 4. Ascaris lumbricoides
l At the site of larva penetration, dermatitis may occur.
5. Ancylostoma duodenale
The larva then migrates to subcutaneous vessels and 6. Echinococcus granulosus
causes creeping eruptions.
l When larva reaches the lungs, it causes multiple haem- For labelled diagram of ova found in stool refer to the ex-
orrhages and transient broncho-pneumonia. planation of Q. No. 5.
l Adult worm causes irritation and petechial intestinal
mucosa. Q. 7. Laboratory diagnosis of guinea worm

Ans.
Laboratory Diagnosis Laboratory diagnosis of guinea worm includes the fol-
l Stool examination for adult worm (naked eye) and mi- lowing:
croscopic examination of stool for ova 1. Clinical diagnosis: By demonstration of the emerging
l Study of duodenal contents for adult worm and ova adult worm or even before its emergence
l Indirect evidences like 2. Detection of embryo: The part of the body suspected to
a. blood examination for anaemia and eosinophilia and carry the worm may be emerged in water. On contact
b. stool examination for occult blood and Charcot- with water larva will be discharged which can be exam-
Leyden crystals ined under the microscope.
3. X-ray examination: The calcified worm can be detected
Q. 5. Cysticercus cellulosae on X-ray examination.
4. Blood examination: May reveal eosinophilia.
Ans.
5. Immunodiagnosis: Intradermal test and compliment
l Cysticercus cellulosae is the larval stage of Taenia so- fixation test have been tried.
lium developing in the muscles of the pig.
l A mature cyst is opalescent, ellipsoidal measuring Q. 8. Write short note on common ova found in stool.
5 3 8–10 mm. It contains a dense milky white spot at Ans.
the side where the scolex with its hooks and suckers
remains invaginated. The cyst fluid is rich in salt and The common ova found in human faeces are as follows:
albuminous material. 1. Eggs of Ascaris lumbricoides
l It can survive up to 8 months in pig muscles and can 2. Eggs of Ancylostoma duodenale
develop further only after it is ingested by man. 3. Eggs of Echinococcus granulosus
Part VI
Dental Microbiology
Topic 40
Dental Microbiology
SHORT ESSAYS
Q. 1. Cultural methods of Candida albicans Q. 2. Enumerate the clinical features of congenital
syphilis.
Ans. Methods used in laboratory diagnosis of Candida are
as follows: Ans. Congenital syphilis exhibits the following clinical
1. Direct examination: Scrapings from the lesions of skin, features:
nails or mucosa are examined in a wet film in KOH or
Gram-stained smear. The Candida albicans appears as 1. Hutchinson’s teeth (centrally notched, widely-spaced
budding yeast cells. peg-shaped upper central incisors)
2. Culture 2. Mulberry molars
a. Specimens are inoculated on the Sabouraud’s dex- 3. Frontal bossing
trose chloramphenicol agar medium at 25–37°C for 4. Saddle nose
24 h. Candida produces creamy white, smooth colo- 5. Poorly developed maxillae
nies with a yeasty odour. 6. Enlarged liver and spleen
b. The Candida albicans is identified by the following: 7. Anaemia
i. Germ tubes: When Candida is grown in human 8. Lymph node enlargement
serum at 37°C for 3 h a wet KOH film shows 9. Jaundice
filamentous outgrowths (Reynolds Braude phe- 10. Pseudoparalysis
nomenon). 11. Snuffles (rhinitis)
ii. Chlamydospores: These develop in a nutrition-
Q. 3. Name the microorganisms causing dental caries.
ally poor medium such as cornmeal agar at
28°C. Ans. Dental caries is a microbial disease that damages the
iii. Biochemical reactions: Candida albicans can be structure of teeth.
identified by the assimilation and fermentation
of sugar. Aetiology
iv. Serology: Candida albicans can also be identi-
fied by the precipitation test with a carbohydrate The common bacteria causing dental caries are Streptococ-
extract of group A antigens. cus mutans, Lactobacilli and actinomycosis, etc.
v. Antigen detection: It is done by ELISA and RIA
which detects cell wall manner or cytoplasmic Predisposing Factors
constituents. 1 . Poor oral hygiene
vi. Skin test: Delayed hypersensitivity to Candida 2. Carbohydrates (sugars and starches)
extracts is a useful indicator of functional integ- 3. Habit of snacking in between meal time
rity of CMI.
vii. Animal inoculation: Candida albicans kills the
animal (rabbit, guinea pig and mice) in 4–5 days Pathogenesis
with typical renal abscess on intravenous inocu- 1. The bacteria act on all types of foods—especially
lation. sugar and starch and convert them into acids. Bacteria,
acids, food debris, and saliva combine in the mouth to Q. 4. Candida albicans
form a sticky substance called plaque that adheres to
Ans.
the teeth.
2. If this plaque is not removed thoroughly and routinely l Candida albicans is an ovoid or spherical budding cell
from the teeth it mineralizes into calculus. which produces pseudomycelia both in culture and in
3. Plaque and calculus irritate the gums, resulting in gingi- tissues.
vitis and ultimately leading to periodontitis. l Candidiasis is an opportunistic infection, the common-
4. The acids in plaque dissolve the enamel surface of est predisposing factor being diabetes.
the tooth resulting in the loss of tooth substance (cavi- l Laboratory diagnosis is done by the following:
ties). 1. Direct microscopic examination
5. Caries is usually painless until it progresses deeper into a. KOH preparation shows yeast cells with budding
the tooth and destroys the nerve and blood vessels in the and pseudohyphae.
tooth. b. Gram-stained smear shows Gram-positive yeast
6. Untreated tooth decay ultimately causes the loss of the cells.
tooth. 2. Culture and identifications: On Sabouraud’s dextrose
with chloramphenicol, after 1–7 days incubation at
Complications of Caries 37°C shows creamy white smooth colonies.
3. Other laboratory tests are as follows:
1 . Periapical abscess a. Precipitations test
2. Fractured tooth b. Agglutination test
3. Pain c. Indirect fluorescent test.
SHORT NOTES
Q. 1. Oral thrush l Vincent’s angina is a painful condition of the throat
characterized by local ulceration of the tonsils, mouth
Or, and pharynx.
Oral candidiasis l Vincent’s bacillus (fusiform bacillus) is the causative
organism.
Ans. l It may occur as an acute illness with diffuse involve-
l Oral thrush caused by Candida albicans is most com- ment of tissue or as chronic illness consisting of ulcer-
mon fungal infection of the oral cavity. ation of tonsil.
l It is insidious in onset, with less fever and less discom-
l Infection of the mouth (oral thrush) is characterized by
the development of discrete creamy white patches on fort in throat.

l Membrane which usually forms over the tonsil, can be
the mucosal surfaces of tongue or buccal mucosa.
l It occurs most frequently in bottle-fed infants and the
easily removed revealing an irregular ulcer on the
old age and debilitated individuals. tonsil.
Q. 2. Dental plaque
Q. 4. Lactobacilli
Ans.
Ans.
l The bacteria act on all types of foods—especially
sugar and starch and convert them into acids. Bacteria, l Lactobacilli are nonsporing anaerobic Gram-positive ba-
acids, food debris and saliva combine in the mouth to cilli and are acidophilic and grow best at pH of 5 or less.
form a sticky substance called plaque that adheres to l They are normally present in the mouth, intestines and
the teeth. typically in the adult vagina.
l If this plaque is not removed thoroughly and routinely
l Normally those present in mouth cause dental caries.
from the teeth it mineralizes into calculus. They form lactic acid by fermentation of sugars which
l Plaque and calculus irritate the gums, resulting in gingi-
destroys enamel and dentine.
vitis and ultimately leading to periodontitis. l Some species are most common in intestine, e.g.
Lactobacillus acidophilus which are beneficial in

Q. 3. Vincent’s angina
synthesizing vitamins such as biotin, B12 and vitamin
Ans. K, which may be absorbed by the host.
l They constitute the normal flora of vagina and ferment an American pediatrician who first described them
the glycogen deposited in the vaginal epithelial cells, in 1896.
forming lactic acid, which accounts for the highly acidic l Koplik’s spots are bluish white ulcerations seen on the
pH of vagina. buccal mucosa opposite the lower molars.

l Several species of lactobacilli occur in vagina and are l A day or two before the rash begins the Koplik’s spots
collectively known as Doderlein’s bacillus. usually appear on the buccal mucosa and occasionally
on the conjunctiva and intestinal mucosa and can be a
Q. 5. Oral flora useful sign to look for in children known to be exposed
Or, to the measles virus.
Bacteria in oral cavity Q. 8. Oral antiseptics

Or, Ans.
Microbial flora of oral cavity l Oral antiseptics are used to keep the commensal bacte-
Ans. rial flora of the oral cavity in check.
l Some of them also serve the purpose of deodorant. For
l The normal resident flora of the oral cavity occupies example: Thymol, menthol, eugenol, benzoic acid, bo-
available colonization sites which makes it more diffi- ric acid, calcium and magnesium peroxides
cult for other nonindigenous microorganisms to become
established. Q. 9. Laboratory diagnosis of Candida infections in oral
l It also contributes to host nutrition through the synthesis cavity
of vitamins. Ans. Oral thrush caused by Candida albicans is most com-
l It contributes to immunity by inducing low levels of
mon fungal infection of the oral cavity.
circulating and secretory antibodies that may crossreact
with pathogens.
l Finally, the oral bacteria exert microbial antagonism Laboratory Diagnosis of Candida albicans
against nonindigenous species by production of inhibi- 1. Direct examination: Swab from the oral cavity lesion
tory fatty acids, peroxides, bacteriocins, etc. is examined in a wet film in KOH or Gram-stained
smear. The Candida albicans appears as budding yeast
Q. 6. Prevention of dental caries cells.
Ans. 2. Culture
a. Swab is inoculated on the Sabouraud’s dextrose
l Use fluoride toothpastes and mouth rinses to increase chloramphenicol agar medium at 25–37°C for 24 h.
the resistance of host, thorough brushing each day to Candida produces creamy white, smooth colonies
remove plaque. with a yeasty odour.
l In addition to brushing, using dental floss is necessary b. The Candida albicans is identified by germ tubes
to keep the gums healthy. and chlamydospores.
l An antibacterial mouth rinse for the control of oral flora c. Candida albicans can be identified by the assimila-
for prophylaxis of plaque and swollen gums. tion and fermentation of sugar.
l Avoiding compounds with soluble carbohydrates such d. Serology: Candida albicans can be identified by the
as ice cream, sweets, chocolates, etc. as they act as sub- precipitation test with a carbohydrate extract of
strate for bacterial growth reducing the in between eat- group A antigens.
ing habit. e. Antigen detection is done by ELISA and RIA.
f. Skin test: Delayed hypersensitivity to Candida ex-
Q. 7. Koplik’s spots tracts is a useful indicator of functional integrity of
Ans. CMI.
g. Animal inoculation: Candida albicans kills the ani-
l Koplik’s spots are pathognomonic of measles or ru- mal (rabbit, guinea pig and mice) in 4–5 days with
bella infection. They are named after Henry Koplik, typical renal abscess on intravenous inoculation.

Comparison of Prokaryotic and Eukaryotic Cells
Cell type Membrane Membrane bound Ribosome size Nucleic acid location DNA type Replication
enveloped nucleus organelles
Prokaryote No No 70S Nucleoid (cytoplasm) Circular Binary fission
Eukaryote Yes Yes 80S Nucleus Linear Mitosis
Common Sterilization Techniques
Sterilization Techniques Mechanism of Action Common Use Characteristics

Moist heat (autoclaving) Denatures proteins Normal cycle heats to 121°C Most common form of steriliza-
(250°F) for 15–20 minutes, tion. Can corrode or dull
yielding 25 lb/in2 of vapour pres- carbon-steel instruments
sure. Fast cycle heats to 134°C
(270°F) for 3 minutes, yielding
30 lb/in2 of vapour pressure
Dry heat Denatures proteins Heats up to 160°C (320°F) for Does not corrode or dull
2 hours, or 170°C (340°F) for instruments
1 hour
Chemical vapour Denatures and alkylates Heats up to 132°C (270°F) for Uses a combination of alcohol
(chemiclave) nucleic acids and proteins 20–30 minutes, yielding and formaldehyde. Does not
25 lb/in2 of vapour pressure corrode or dull instruments
Ethylene oxide gas Alkylates nucleic acids Sterilization is slow, taking Requires an appropriate cham-
and proteins 8–10 hours ber and ventilation system.
Used mostly in hospitals for
heat-sensitive materials
Formaldehyde Alkylates nucleic acids Commonly used as a 37% Less efficacious compared to
and proteins solution in water (formalin) other methods of sterilization
Glutaraldehyde (2%) Alkylates nucleic acids Sterilization is slow, taking 10 Associated with hypersensitiv-
and proteins hours ity. Used mostly for heat-
sensitive materials
Filtration Physically and electrostati- Commonly uses a nitrocellulose The preferred method of
cally traps microorganisms filter with a 0.22 mm pore size sterilizing liquid solutions
larger than the pore size
Commonly Used Antiseptics Are as Follows

Antiseptic Mechanism of Action Characteristics
Iodine & iodophors Oxidatively inactivates sulphhydryl- Most effective skin antiseptics. Associated with
containing enzymes hypersensitivity
Ethanol & isopropyl alcohol (70–90%) Disrupts cell membranes and Most widely used skin antiseptic. Used on skin
dentures proteins prior to venipuncture or immunization
Hydrogen peroxide Oxidatively inactivates sulphhydryl- Effective only against catalase-negative
containing enzymes organisms
Chlorhexidine gluconate (0.12%) Disrupts cell membranes (due to its Highly substantive. Used as a handwash and a
cationic properties) mouthrinse
Triclosan Disrupts cell membranes Used as a handwash and as an ingredient in

some dentifrices
Methods of Sterilization of Important Materials
Material Method
All suture materials except catgut Autoclave
Catgut Ionizing radiation
Commonly used material as preservative for gut sutures Isopropyl alcohol
Surgical needle and sutures are sterilized in manufacturing units by Gamma radiation
Rubber gloves, surgical instruments and most of culture media Autoclave
Forceps, scalpel, scissors, needles Hot air oven
Disposable syringes Ethylene oxide
Suture materials Glutaraldehyde
Hospital wastes Incinerator
Vaccines/serum/ antibiotic solutions Filtration
Operation theatres Fumigation with formaldehyde
Preparation of the skin for surgery Iodine, spirit, Savlon, chlorhexidine, etc.
Absorbent points, broaches, files and other root canal instruments Hot-salt sterilizer or glass bead sterilizer
Cotton pliers, cement spatulas By passing the working blade quickly through a flame several times
Dappen dishes, glass slab Swabbing the surface with tincture of thimerosal followed by
double swabbing with alcohol
Immunology:
Various Immunoglobulins (Antibodies) with the Proper Description
Immunoglobulin Description
IgA Is the most abundant immunoglobulin
l
It is the only immunoglobulin which crosses the placenta, main defence against various patho-
l
genic organisms
IgD Second most abundant immunoglobulin
l
Synthesized by plasma cells in the mucous membranes of the GI, respiratory, and urinary tracts
l
Occurs in body secretions and protects surface tissues

l
IgE Makes up less than 1% of immunoglobulins

l
Present on membrane of many circulating B-cells

l
Its function is unknown or not fully understood

l
IgG Largest immunoglobulin

l
First antibody produced in response to infection, powerful activator of the complement system
l
IgM Is present in only trace amounts in serum

l
Reaginic activity resides in this immunoglobulin

l
Protects external mucosal surfaces; tightly bound to its receptors on mast cells and basophils;
l
responsible for Type I hypersensitivity reactions like allergic and anaphylactic reactions
Classification of Hypersensitivity Reactions
Type Immunologic Mechanism Examples

Type I (anaphylactic type): Imme- IgE antibody mediated-mast cell activation & ‘Hay fever’, asthma, anaphylaxis
diate hypersensitivity degranulation
Type II (cytotoxic type): Cytotoxic Cytotoxic (IgG, IgM) antibodies formed against cell Autoimmune haemolytic anemiae,
antibodies surface antigens complement is usually involved antibody-dependent cellular cytotox-
icity (ADCC), Goodpasture disease
Classification of Hypersensitivity Reactions—cont’d
Type Immunologic Mechanism Examples

Type II (immune complex type): Antibodies (IgG, IgM, IgA) formed against exogenous or Autoimmune diseases (SLE, rheu-
immune complex disease endogenous antigens. Complement and leucocytes (neu- matoid arthritis), most types of
trophils, macrophages) are often involved glomerulonephritis
Type IV (cell-mediated type): de- Mononuclear cells (T lymphocytes, macrophages) with Granulomatous diseases
layed type hypersensitivity interleukin and lymphokine production (tuberculosis, sarcoidosis)
Some Protein Toxins (Exotoxins) Produced by Microorganisms that Cause Disease in Humans
Organism Exotoxin(s) Disease(s) Action(s)

Streptococcus pyogenes Various Hemolysins Various diseases Lysis of red blood cells; causes symp-
(Group A Streptococcus) Streptolysin -O, Streptolysin- S Rheumatic and Scarlet toms of rheumatic fever; causes rash
and Erythrogenic. fever of scarlet fever
Staphylococcus aureus Enterotoxin Food poisoning Intestinal inflammation
Clostridium botulinum Several neurotoxins Botulism Paralysis, blocks neural transmission
Clostridium perfringens a-Toxin (a lecithinase) Gas gangrene Destroys integrity of cell membranes;
K-Toxin (a collagenase) breaks down fibrous tissue
Clostridium tetani Neurotoxin (tetanospasm) Tetanus Spastic paralysis interferes with motor
neurons
Corynebacterium Diphtheria toxin Diphtheria Blocks protein synthesis at level of
diphtheriae translation
Shigella dysenteriae Neurotoxin Bacterial dysentery Haemorrhage, paralysis
Classification of Viruses
l Viruses are smallest infectious agents containing only one kind of nucleic acid as their genetic material.
DNA viruses are:

l Adeno virus, e.g. swimming pool conjunctivitis (group B -adenovirus), gastroenteritis (group F)
l Pox virus, e.g. smallpox, molluscum contagiosum
l Papova virus, e.g. papilloma, polyoma, vacuolating viruses
l Parvo virus, e.g. erythema infectiosum (fifth disease)
l Herpes virus, e.g. HHV I, II, III, IV, V, VI, VII
l Hepadna virus, e.g. Hepatitis B.
RNA viruses are:

l HIV virus, e.g: Retro virus
l Picorna virus, e.g. Polio, coxsackie, echo, rhino, hepatitis A
l Orthomyxo virus, e.g. Influenza
l Paramyxo virus, e.g. Mumps, measles, respiratory syncytial virus
l Toga virus, e.g. rubella, yellow fever
l Rota virus, e.g. gastroenteritis virus
Various Types of Grafts
Graft Name Origin

Homograft Same species
Heterograft Different species
Isograft Same genetic composition individual (twins)
Autograft Same person
Allograft Other person
Alloplast Inert synthetic material (synthetic bone and implant)
Xenograft From different animal
Some Important Tests
Name of Test Disease

Schick test and Elek test Diphtheria
Schultz-Charlton Scarlet fever
Dick Scarlet fever sarcoidosis
Kveim Infectious mononucleosis
Monospot Infectious mononucleosis
Paul Bunnell AIDS
ELISA (enzyme-linked immunosorbent assay) Syphilis
Kahn Syphilis
VDRL (veneral diseases research laboratory) Syphilis
TPI (treponemal immobilisation) Syphilis
Tzanck test - Herpes Herpes/pemphigus
Mantoux - Tuberculosis Tuberculosis
ASO (antistreptolysin O) Rheumatic fever
Northern blot RNA identification
Southern blot DNA identification
Western blot AIDS
Casoni Hydatids
Gordon’s biological test Chanaoid
Schilling Hodgkin
anaemia (pernicious) Folic acid absorption
FIGLU Capillary fragility
Tournique test RA (rheumatoid arthritis)
Rose Water Ketone bodies in the urine
Rotnera (diabetes mellitus) Carcinoma of cervix
Schiller test Rickettsial infection
Weil Felix Sjogren’s syndrome
Rose Bengal dye test Sjogren’s syndrome
Schirmer test Screening test for syphilis
RPR (Rapid plasma reagin) test - Syphilis
Bacterial Vaccines
Vaccinations can confer two types of acquired immunity.
l Active immunity: Whole bacteria, capsular polysaccharides, or toxoids elicit immunity
l Live attenuated vaccine
l Tuberculosis
l Tularemia
l Killed vaccine
l Cholera
l Typhoid fever
l Pertussis
l Toxoid vaccine: Contains inactivated exotoxin
l Tetanus
l Diphtheria
l Capsular polysaccharide vaccine
l Pneumonia (Strep. pneumoniae)
l Meningitis (N. meningitides and H. influenzae)
l Passive immunity: Preformed antibody preparations elicit immunity
l Antitoxin vaccine: Contains antibodies to bacterial exotoxins
l Tetanus
l Diphtheria
l Botulism
Section IV
Pharmacology
PART I: GENERAL PHARMACOLOGICAL PRINCIPLES

Topic 1 Definitions, Routes of Drug Administration 361
Topic 2 Pharmacokinetics 367
Topic 3 Pharmacodynamics 372
Topic 4 Adverse Drug Effects 378
PART II: DRUGS ACTING ON AUTONOMIC NERVOUS SYSTEM

Topic 5 Cholinergic System and Drugs 383
Topic 6 Anticholinergic Drugs and Drugs Acting on Autonomic
Ganglia 388
Topic 7 Adrenergic System and Drugs 394
Topic 8 Antiadrenergic Drugs 400
PART III: AUTOCOIDS AND RELATED DRUGS

Topic 9 Histamines and Antihistamines 404
Topic 10 5-Hydroxytryptamine, Its Antagonists and Drug Therapy of
Migraine, Prostaglandins, Leukotrienes (Eicosanoids) and
Platelet-Activating Factor 407
Topic 11 Nonsteroidal Anti-inflammatory Drugs and Antipyretic
Analgesics 409
Topic 12 Additional Drugs for Rheumatoid Arthritis and Drugs for Gout 416
PART IV: RESPIRATORY SYSTEM

Topic 13 Drugs for Cough and Bronchial Asthma 417
PART V: HORMONES AND RELATED DRUGS

Topic 14 Anterior Pituitary Hormones, Thyroid Hormone and Thyroid
Inhibitors 420
Topic 15 Insulin, Oral Hypoglycaemics and Glucagon 423

Topic 16 Corticosteroids 431
Topic 17 Gonadal Hormones (Sex Hormones) and Their Antagonists 437
Topic 18 Oxytocin and Drugs Acting on Uterus 438
Topic 19 Drugs Affecting Calcium Balance 438
PART VI: DRUGS ACTING ON PERIPHERAL NERVOUS SYSTEM

Topic 20 Skeletal Muscle Relaxants 442
Topic 21 Local Anaesthetics 446
PART VII: DRUGS ACTING ON CENTRAL NERVOUS SYSTEM

Topic 22
General Anaesthetics 451
Topic 23
Ethyl and Methyl Alcohols 458
Topic 24
Sedatives/Hypnotics 458
Topic 25
Antiepileptic Drugs 464
Topic 26
Antiparkinsonian Drugs 467
Topic 27
Drugs Used in Mental Illness: Antipsychotic
and Antianxiety Drugs 469
Topic 28 Opioid Analgesics and Antagonists 471
Topic 29 CNS Stimulants and Cognition Enhancers 476
PART VIII: CARDIOVASCULAR DRUGS

Topic 30 Drugs Affecting Renin-Angiotensin System and Plasmakinins 477
Topic 31 Cardiac Glycosides and Drugs for CHF 477
Topic 32 Antiarrhythmic Drugs 479
Topic 33 Antianginal and Other Anti-ischaemic Drugs 480
Topic 34 Antihypertensive Drugs 484
PART IX: DIURETICS AND ANTIDIURETICS

Topic 35 Diuretics and Antidiuretics 489
PART X: DRUGS AFFECTING BLOOD AND BLOOD FORMATION

Topic 36 Haematinics and Erythropoietin 494
Topic 37 Drugs Affecting Coagulation, Bleeding and Thrombosis 499
Topic 38 Hypolipoproteinaemic Drugs and Plasma Expanders 507
PART XI: GASTROINTESTINAL DRUGS

Topic 39 Drugs for Peptic Ulcer 509
Topic 40 Emetics, Antiemetics and Other Gastrointestinal Drugs 514
Topic 41 Drugs for Constipation and Diarrhoea 517
PART XII: ANTIMICROBIAL DRUGS

Topic 43 Sulphonamides, Co-trimoxazole and Quinolones 522
Topic 44 Beta-Lactam Antibiotics 526
Topic 45 Tetracyclines and Chloramphenicol 537
Topic 46 Aminoglycoside Antibiotics 541
Topic 47 Macrolide and Other Antibacterial Drugs in Treatment
of Urinary Tract Infections 544
Topic 48 Antitubercular Drugs 546
Topic 49 Antileprotic Drugs 551
Topic 50 Antifungal Drugs 553
Topic 51 Antiviral Drugs 555
Topic 52 Antimalarial Drugs 557
Topic 53 Antiamoebic and Other Antiprotozoal Drugs 558
Topic 54 Anthelmintics 560
PART XIII: CHEMOTHERAPY OF NEOPLASTIC DISEASES

PART XIV: MISCELLANEOUS

Topic 56 Immunosuppressants, Gene Therapy and Drugs Acting
on Skin and Mucous Membranes 564
Topic 57 Antiseptics, Disinfectants and Ectoparasiticides 565
Topic 58 Chelating Agents 567
Topic 59 Vitamins 569
Topic 60 Vaccines and Sera 571
Topic 61 Dental Pharmacology 572
Section IV
Pharmacology
Part I
General Pharmacological Principles
Topic 1
Definitions, Routes of Drug Administration

LONG ESSAYS
Q. 1. Describe the routes of drug administration. Their Various systemic routes of drug administration are as
merits and demerits with suitable examples. follows:
Ans. Drugs can be administered by a variety of routes. The
choice of an appropriate route depends both on the drug as a. Oral Route
well as patient-related factors.
Drugs available in solid dosage forms like capsules, span-
Routes of drug administration can be classified into two sules, dragees, powders, tablets and liquid forms like elixirs,
major categories as follows: syrups, emulsions can be given orally.
1. Systemic
a. Oral Merits
b. Sublingual
c. Rectal i. Safer
d. Cutaneous ii. More convenient
e. Inhalation iii. Noninvasive and painless
f. Parenteral iv. Assistance not required
2. Local v. Cheap
a. Topical vi. May be destroyed by gastric juices, or amount is con-
b. For deeper tissues siderably reduced in first-pass metabolism.
c. Arterial supply
Demerits
SYSTEMIC ROUTES i. Action is slower, not suitable for emergencies.
Drugs intended to directly enter the bloodstream and dis- ii. Unpalatable drugs are difficult to administer.
tributed all over the body through circulation including the iii. Can cause nausea or vomiting, may stain the teeth,
site of action are administered systemically. leave an unpleasant taste.
iv. Certain drugs may not be absorbed, e.g. streptomycin.
361
b. Sublingual Route i ii. The drug is absorbed percutaneously.

iv. Usual sites of application are chest, abdomen, upper
Here the tablet or pellet is placed under the tongue. Drug is
arm, lower back, behind the ear, buttock and mastoid
directly absorbed into the circulation. Example: Glyceryl
region. For example: Glyceryl trinitrate, fentanyl, nico-
trinitrate, buprenorphine, desamino-oxytocin
tine, and oestradiol
Merits Merits
i. First-pass metabolism is bypassed.
i. Rate of drug delivery is constant.
ii. Once desired effect is achieved the drug can be spat out.
ii. Patient compliance is better.
iii. Rapid rate of absorption
iii. Interindividual variations are reduced.
iv. Provides smooth plasma concentrations without fluctuation.
Demerits
i. Only lipid-soluble nonirritating drugs can be used. Demerits
ii. Inconvenient to the patient. i. Mild irritation and erythema is possible that can be
overcome by changing the site.
c. Rectal Route
Certain irritant and unpleasant drugs can be put into the e. Inhalation
rectum as suppositories or retention enema for systemic ef- Volatile liquids and gases are given by this route for systemic
fect. For example: Aminophylline, indomethacin, diazepam effects. For example: General anaesthetic agents
and ergotamine are a few of them.
Merits
Merits
i. Quick onset of action.
i. Used in patients having recurrent vomiting. ii. Very less dose is required.
ii. Bypass first-pass metabolism. iii. We can regulate the amount of drug administered.
Demerits Demerits
i. Highly inconvenient and embarrassing i. Local irritation leading to increased respiratory secre-
ii. Absorption is slow and unpredictable. tions and bronchospasm.
iii. May cause rectal inflammation.
f. Parenteral Route
d. Cutaneous Route
Refers to drugs injected directly into tissue fluid or blood
Highly lipid-soluble drugs are applied over the skin for low without having to cross the intestinal mucosa.
and prolonged action. First-pass metabolism in the liver is
also bypassed. Drug can be incorporated in an ointment and
Merits
applied over specific areas of the skin. For example: Beta-
methasone (Betnovate-C) i. Drug action is faster and surer.
ii. Gastric irritation and vomiting is not provoked.
iii. Can be used in unconscious, uncooperative patients.
Transdermal Patches
iv. First-pass metabolism is bypassed in the liver.
i. These are the recent devices in the form of adhesive
patches of various shapes and sizes which deliver the
Demerits
drug at a constant controlled rate into the systemic cir-
culation. i. Chances of systemic toxicity are very high compared to
ii. The drug is held in between an occlusive backing film the other routes.
and a rate controlling micropore membrane whose un- ii. Invasive, painful procedure
dersurface is smeared with adhesive impregnated with iii. Preparations have to be sterilized and are costlier.
priming dose of drug that is protected by another film iv. Assistance of another individual required in most
to be peeled off just before application. cases.
Section | IV Pharmacology 363
Various routes of parenteral drug administration are as ii. Self-administration is impractical as deep penetration is
follows: necessary.
i. Subcutaneous iii. They may cause injury to the nerves.
ii. Intramuscular
iii. Intravenous
Intravenous
iv. Intradermal
i. Drugs are injected directly into the bloodstream through
a vein.
I. Subcutaneous ii. Drugs are injected as bolus or infused slowly over hours
i. The drug is injected into the loose subcutaneous tissue into superficial veins.
that is rich in nerve supply but is less vascular.
ii. Special forms of administration in this route are as Merits
follows:
a. Dermojet: Needle is not used. Essentially painless i. This route of drug administration is of great value in
procedure. High velocity jet of drug solution is emergencies as the drug directly enters blood stream
projected from microfine orifice using gun-like and effects are produced immediately.
implement and the solution passes through superfi- ii. 100% bioavailability, dosage of drug required is
cial layers and gets deposited in the subcutaneous lesser.
layer.
b. Pellet implantation: Solid pellet is introduced with a
Demerits
trochar and canula. It provides sustained release of
drug over weeks, e.g. DOCA, testosterone. i. Most risky route.
c. Silastic implants: Crystalline drugs packed in biode- ii. Vital organs like brain, heart, etc. get exposed to higher
gradable or nondegradable tubes or capsules im- concentrations of the drug.
planted under the skin for slow uniform leaching of iii. Systemic toxicity is increased.
the drug, e.g. norplant for contraception. iv. Once injected the action of the drug cannot be halted.
Merits Intradermal
1 . Self-administration is possible. Injected into the skin raising a bleb or scarring or multiple
2. Repository (depot) preparations can be inserted into puncture of the epidermis through a drop of the drug is
subcutaneous tissue. done. For example: BCG vaccine, sensitivity tests.
Demerits LOCAL ROUTES

1 . Not suitable for emergency as absorption is slow. They can be used only for localized lesions at accessible
2. Suitable only for nonirritant drugs. sites and for drugs whose systemic absorption from these
sites is minimal, slow or absent.
High concentration is attained at the desired site without
II. Intramuscular exposing the rest of the body to the adverse effects or toxic-
i. Drugs are injected into larger skeletal muscles like ity of the drug.
deltoid, triceps, gluteus, rectus femoris, etc.
ii. A volume of 5–10 mL can be given at a time. For 1. Topical
example: Tetanus toxoid, procaine penicillin.
l Refers to external application of the drug to the surface
of the localized lesion.
Merits l Can be used to deliver the drug to skin, oropharyngeal
i. Absorption is more rapid as the muscles are more vascular. or nasal mucosa, eyes, ear canal, anal canal, vagina, etc.
ii. Depot preparations can be administered by this route. Examples:
1. Inhalation for bronchial mucosa (cromolyn sodium)
2. Irrigating solution or jellies (povidone iodine, lignocaine)
Demerits
3. Paints, toothpastes, mouthwashes, gargles, lozenges,
i. Aseptic conditions are needed. antiseptics, astringents, haemostatics
2. Deeper Tissues Natural Sources

l Can be approached with a syringe and needle. Naturally some drugs can be obtained from the following:
l Care should be taken to see that the systemic absorption i. Plants: Alkaloids like atropine, morphine, quinine, re-
is slow. serpine and glycosides like digoxin and digitoxin
Examples: Injection of local anaesthetic around a nerve, ii. Animals: Insulin, heparin, gonadotropins, antitoxic
intra-articular injection of hydrocortisone acetate sera
iii. Minerals: Magnesium sulphate, aluminium hydroxide,
iron, sulphur, radioactive isotopes
3. Arterial Supply iv. Microorganisms: Penicillin, cephalosporins, tetracy-
Close intra-arterial injections can be used for a contrast media cline, and other antibiotics
in angiography and anticancer drugs used in the femoral or v. Humans: Immunoglobulins from blood, growth hor-
brachial artery to localize the effect for limb malignancies. mone from anterior pituitary, chorionic gonadotropins
from urine of pregnant woman
Q. 2. Describe the various sources of drugs in pharma-
cology with suitable examples.
Synthetic Sources
Ans.
i. Most drugs used now are obtained from synthetic or
According to WHO a drug is any substance or product that is semisynthetic sources, e.g. quinolones, omeprazole.
used or intended to be used to modify or explore physiological ii. Some drugs are obtained by cell cultures, e.g. urokinase
systems or pathological states for the benefit of the recipient. from cultured human kidney cells.
The various sources of drug are as discussed below. iii. Some are produced by recombinant DNA technology,
The source of a drug can be natural or synthetic. e.g. human insulin, tissue plasminogen activator.
SHORT ESSAYS
Q. 1. Discuss merits and demerits of oral and intrave- 2 . Unpalatable drugs are difficult to administer.
nous routes of administration. 3. Can cause nausea or vomiting, may stain the teeth, leave
an unpleasant taste.
Ans. Drugs can be administered by a variety of routes. The
4. Certain drugs may not be absorbed, e.g. streptomycin.
choice of an appropriate route depends both on the drug as
well as patient-related factors.
Intravenous Route
Merits and demerits of oral and intravenous routes of
administration are as discussed below. Intravenous route is a type of parenteral drug administra-
tion where
1. drugs are injected directly into the bloodstream through
Oral Route a vein.
Drugs available in solid dosage forms like capsules, span- 2. drugs are injected as bolus or infused slowly over hours
sules, dragees, powders, tablets and liquid forms like elix- into superficial veins.
irs, syrups, emulsions can be given orally.
Merits
Merits 1. This route of drug administration is of great value in
1 . Safer emergencies as the drug directly enters blood stream
2. More convenient and effects are produced immediately.
3. Noninvasive and painless 2. 100% bioavailability, dosage of drug required is lesser.
4. Assistance not required
5. Cheap Demerits
6. May be destroyed by gastric juices, or amount is consid-
erably reduced in first-pass metabolism. 1 . Most risky route
2. Vital organs like brain, heart, etc get exposed to higher
concentrations of the drug.
Demerits 3. Systemic toxicity is increased.
1. Action is slower, not suitable for emergencies. 4. Once injected the action of the drug cannot be halted.
Q. 2. Describe the routes of administration of drugs Cutaneous

with examples.
For example: Cyclovir 5% skin cream, betamethasone
Ans. (Betnovate-C)
Routes of drug administration can be classified into two
major categories as follows: Transdermal Patches
1. Local For example: Glyceryl trinitrate, fentanyl, nicotine, hyo-
a. For superficial application: Topical scine
b. For deeper tissues: Sublingual, arterial supply
2. Systemic: Oral, rectal, cutaneous, transdermal patches,
parenteral Parenteral
Various routes of parenteral drug administration are as 1. Subcutaneous, e.g. DOCA, testosterone, norplant con-
follows: traceptives
1. Subcutaneous 2. Intramuscular, e.g. tetanus toxoid, procaine penicillin
2. Intramuscular 3. Intravenous, e.g. ampicillin, ribavirin
3. Intravenous 4. Intradermal, e.g. BCG vaccine, sensitivity tests
4. Intradermal
Q. 3. Write briefly about sublingual route of adminis-
tration.
LOCAL
Ans.
Topical
1 . Inhalation for bronchial mucosa—cromolyn sodium
2. Irrigating solution/jellies—povidone iodine, lignocaine Sublingual Route
The tablet or pellet is placed under the tongue. Drug is
Deeper Tissues directly absorbed into the circulation.
For example: Injection of local anaesthetic around a nerve,
intra-articular injection of hydrocortisone acetate Merits
1 . First-pass metabolism is bypassed.
Arterial Supply 2. Once desired effect is achieved the drug can be spat out.
For example: Contrast media in angiography and anticancer 3. Rapid rate of absorption
drugs used in the femoral or brachial artery to localize the
effect for limb malignancies Demerits
1 . Only lipid-soluble nonirritating drugs can be used.
SYSTEMIC 2. Inconvenient to the patient
Oral Example: Glyceryl trinitrate, buprenorphine, desamino-
oxytocin
For example: Drugs available in solid dosage forms like
capsules, spansules, dragees, powders, tablets and liquid
Q. 4. Intravenous route of drug administration
forms (elixirs, syrups, emulsions)
Ans. In the intravenous route drugs are injected directly
Sublingual into bloodsteam through a vein.
For Example: Glyceryl trinitrate, buprenorphine, desamino- Drugs are injected as

oxytocin 1. bolus: single and relatively a large dose of drug injected
rapidly or slowly as a single unit into a vein,
2. slow intravenous (IV) injection, e.g. morphine and
Rectal 3. intravenous infusion, i.e. adding the drug to a bottle
For example: Aminophylline, indomethacin, diazepam, containing dextrose or saline, e.g. dopamine infusion in
ergotamine cardiogenic shock.
Advantages Disadvantages
1. Drug directly enters bloodstream and exhibits quick 1. Most risky route. Vital organs like brain, heart, etc. get
onset of action, great value in emergencies. For exam- exposed to higher concentrations of the drug.
ple: IV diazepam in status epilepticus 2. Systemic toxicity is increased.
2. 100% bioavailability 3. Action cannot be stopped once the drug is injected.
3. Dosage of drug required is lesser. 4. Local irritation may cause phlebitis.
4. Large volume of fluid can be administered. For example: 5. Extravasation of some drugs may cause injury, necrosis
IV fluids in severe dehydrated patients and sloughing of tissues.
5. Hypertonic solutions can be infused by IV route. For
example: 20% mannitol in cerebral oedema
SHORT NOTES
Q. 1. New drug delivery systems Q. 3. Sublingual administration of drug
Ans. Ans.
Special drug delivery systems are used to improve duration 1. Here the tablet or pellet of the drug is placed under the
of action of drug and thereby improve patient compliance. tongue and the drug is directly absorbed into the circulation.
2. It has advantage of
Some forms of newer drug delivery are as follows:
a. bypassing first-pass metabolism.
1. Ocusert: Thin epithelial units containing the drug in a
b. can be spat out once desired effect is achieved.
reservoir. For example: Pilocarpine used in glaucoma
c. rapid rate of absorption.
2. Progestasert: Inserted into the uterus for delivering pro-
3. The disadvantages of this route are
gesterone
a. only lipid-soluble nonirritating drugs can be used.
3. Transdermal patches: The drug is held in between an
b. inconvenient to the patient. For example: Glyceryl
occlusive backing film and a micropore membrane
trinitrate, buprenorphine, desamino-oxytocin
whose undersurface is smeared with adhesive. For ex-
ample: Glyceryl trinitrate, fentanyl, nicotine, hyoscine. Q. 4. Enumerate various routes of drug administration.
4. Prodrug: Inactive form of the drug that gets metabolized to
an active form. For example: Levodopa, esters of penicillin. Ans.
5. Computerized miniature pumps—programmed to release
drugs at a definite rate. For example: Insulin
Local Route
Q. 2. Parenteral administration of drugs l Topical inhalation for bronchial mucosa (cromolyn so-
Ans. dium), irrigating solution or jellies (povidone iodine,
lignocaine)
l Refers to drugs injected directly into tissue fluid or l For deeper tissues through arterial supply, e.g. injection
blood without having to cross the intestinal mucosa. of local anaesthetic around a nerve, intra-articular injec-
l Drug action is faster and surer. Can be used in uncon- tion of hydrocortisone acetate
scious, uncooperative patients. First-pass metabolism is
bypassed in the liver.
Systemic Route
l Chances of systemic toxicity is very high. Invasive,
painful procedure. Assistance of another individual re- 1. Oral solid dosage forms (capsules, spansules, dragees,
quired in most cases. powders, tablets) and liquid forms (elixirs, syrups,
l Various routes of parenteral drug administration are as emulsions)
follows: 2. Sublingual (glyceryl trinitrate, buprenorphine, desamino-
1. Subcutaneous oxytocin)
a. Dermojet 3. Rectal (aminophylline, indomethacin, diazepam, ergot-
b. Pellet implantation, e.g. DOCA, testosterone amine)
c. Silastic implants, e.g. norplant contraceptives 4. Cutaneous (cyclovir 5% skin cream, betamethasone
2. Intramuscular, e.g. tetanus toxoid, procaine penicillin (Betnovate-C))
3. Intravenous, e.g. ampicillin, ribavirin 5. Transdermal patches (glyceryl trinitrate, fentanyl, nico-
4. Intradermal, e.g. BCG vaccine, sensitivity tests tine, hyoscine)
6. Parenteral: Various types of this route of administration Advantages

are as follows:
1 . Instantaneous absorption
a. Subcutaneous (DOCA, testosterone, norplant-
2. Serves as local route in pulmonary disorders, hence is
contraceptives)
more effective and less harmful.
b. Intramuscular (tetanus toxoid, procaine penicillin)
3. First-pass metabolism is avoided.
c. Intravenous (ampicillin, ribavirin)
4. Blood levels can be controlled by controlling absorption
d. Intradermal (ampicillin, ribavirin)
and excretion.
Q. 5. Advantages and disadvantages of oral route
Ans. Disadvantages
1. Irritant gases enhance pulmonary secretions and cause
Advantages bronchospasm.
1. Oral route is used for drugs available in solid dosage
forms like capsules, spansules, dragees, powders, tab- Q. 7. Drug nomenclature
lets and liquid forms like elixirs, syrups, emulsions. Ans.
2. This route is safer, more convenient, noninvasive, pain-
less and cost effective. A drug nomenclature generally has three categories of
names which are as follows:
1. Chemical name: Describes the substance chemically, e.g.
Disadvantages 1-(isopropylamino)-3-(1-naphthyloxy) propan- 2- ol or
1 . Action is slower. propranolol
2. Not suitable for emergencies A code name may be used by the manufacturer instead
3. Unpalatable drugs are difficult to administer. of this long name, e.g. RO 15-1788 for flumazenil
4. Can cause nausea or vomiting. 2. Nonproprietary name: Name accepted by a competent
5. May stain the teeth. scientific body, like the United States Adopted Name
6. Leave an unpleasant taste. (USAN), British Approved Name (BAN), recommended
International Nonproprietary name (rINN), for example
Q. 6. Advantages and disadvantages of inhalation route Aminoglycosides, tricyclic antidepressants
3. Proprietary name: Name assigned by the manufacturer
Ans.
and his property or trademark. One drug may have sev-
Volatile liquids and gases are given by inhalation, e.g. general eral proprietary names. For example: Altol, Atcardil,
anaesthetics, salbutamol. Atecor, Aten for atenolol.
Topic 2
Pharmacokinetics
LONG ESSAYS
Q. 1. Describe the various methods to prolong the duration l drug effect could be maintained overnight without dis-
of action of a drug. turbing sleep.
Ans. Prolonging the duration of action of drug is some- Drugs with half-life (t1/2) less than 4 h are suitable for
times advantageous. controlled release while the drugs with half-life more
than 4 h do not need controlled release formulations.
By prolonging the duration of action
l frequency of drug administration can be reduced, Methods utilized for prolonging drug action are as follows:
l patient compliance can be improved, A. By prolonging the absorption of the drug from the site
l large fluctuations in plasma concentration are avoided of administration
and B. By increasing plasma protein binding
. By retarding the rate of metabolism

C ii. Inhibition of the specific metabolizing enzyme by
D. By retarding renal excretion one drug can prolong the action of another drug. For
example:
l Physostigmine prolongs the action of acetylcholine
A. By Prolonging the Absorption by inhibiting the enzyme cholinesterase.
a. Oral Route l By inhibiting the enzyme peptidase in the renal
tubules the cilastatin prolongs action of imipenem.

Sustained release preparations, coating with resins, plastic
materials or other substances which temporarily disperse
release of the active ingredient in the GIT. Another tech- D. By Retarding Renal Excretion
nique utilizes a semipermeable membrane to control the re- Renal excretion of the drug can be prolonged by competing
lease of drug from tablet or capsules, e.g. iron, deriphyllin. with the same transportation system for the renal tubular
secretion. For example: Probenecid prolongs the action of
b. Parenteral Route penicillin and ampicillin.
The subcutaneous and intramuscular injections of drug in Q. 2. Explain the means of biotransformation of drugs
the following: in the body with examples.
i. Insoluble form and reducing solubility. For example:
Procaine penicillin Ans.
ii. Oily suspensions. For example: Depot progestins
iii. Altering particle size. For example: Insulin zinc sus-
BIOTRANSFORMATION
pension as large crystals that are slowly absorbed.
iv. Pellet implantation—silastic capsules. For example: DOCA Biotransformation is the process of biochemical alteration
v. Reduction in vascularity of the absorbing surface. For of the drug in the body.
example: Adrenaline 1 lignocaine (addition of vaso- l Body treats most drugs as foreign substances and tries
constrictor) to inactivate and eliminate them by various biochemical

vi. Combining with protein. For example: Protamine 1 zinc reactions. These processes convert the drugs into more
1 insulin polar, water-soluble compounds so that they are easily
vii. Chemical alteration—esterification. For example: Oes- excreted through the kidneys.
trogen, testosterone l Some drugs may be excreted largely unchanged in the
urine. For example: Frusemide, atenolol

l The most important site for biotransformation is the
c. Transdermal Drug Delivery Systems liver. But the drugs get metabolized even in the kidneys,
i. The drug impregnated in transdermal adhesive patches. gut mucosa, lungs, blood and skin.
For example: Scopolamine l Though biotransformation generally inactivates the
ii. Ointments. For example: Nitroglycerine. drug, some drugs may be converted to active or more
iii. Ocusert (transmucosal) used in eye. For example: Pilo- active metabolites.
carpine l Biotransformation of drug may lead to the following:
i. Inactivation: where active drug–inactive metabolite

results. For example: Pentobarbitone, morphine,
B. By Increasing Plasma Protein Binding chloramphenicol, propranolol
Few drugs have been prepared which are highly bound to ii. Active metabolite from an active drug: Where there
plasma protein and are slowly released in the free active will be active drug—active metabolite. For exam-
form. Choosing more protein bound member of the group ple: Primidone–phenobarbitone, digitoxin–digoxin,
also favours this mechanism. For example: Sulphonamides diazepam–oxazepam
like sulphamethoxypyridazine, sulphadoxine iii. Activation of inactive drug: where inactive drug
is converted to active metabolite. For example:
Levodopa–dopamine, prednisone–prednisolone,
C. By Retarding Rate of Metabolism enalapril–enalaprilat
i. Small chemical modification markedly affects the rate l When the metabolite of the drug is active, the duration
of metabolism without affecting the biological action. of action of the drug gets prolonged.
For example: Addition of ethinyl group to oestradiol makes l Prodrug is an inactive form of drug which gets con-
it longer acting and suitable to be used as oral contraceptive. verted into the active form in the body.
Enzymes in Biotransformation For example: Choline esters, procaine, lignocaine, pro-

cainamide, pethidine, oxytocin
The biotransformation of a drug can be brought about by
specific enzymes located in iv. Cyclization: Here there is formation of a ring structure
l liver microsomes called microsomal enzymes. from a straight chain compound. For example: Proguanil
l cytoplasm and mitochondria, plasma and other tissues v. Decyclization: Here there is opening up of ring struc-
called nonmicrosomal enzymes. ture of cyclic drug molecule. For example: Barbitu-
rates, phenytoin
Chemical Reactions of Biotransformation B. Phase II or synthetic reactions
Endogenous water-soluble substances like glucuronic acid,
They can be classified into two phases as follows: sulphuric acid, or an amino acid combine with the drug or
A. Phase I reactions or nonsynthetic reactions: Convert the its phase I metabolite to form a highly polar conjugate
drug to a more polar metabolite by oxidation, reduction which is inactive and gets readily excreted by the kidneys.
or hydrolysis. Catalyzed by mono-oxygenase present in Large molecules are excreted through bile.
the liver. Here the metabolite may be active or inactive.
B. Phase II reactions or synthetic reactions or conjugation Various synthetic reactions are as follows:
reactions: If the metabolite is not sufficiently polar to be i. Glucuronide conjugation: This is most important syn-
excreted, they undergo phase II reaction. thetic reaction. Compounds with a hydroxyl or a carbox-
ylic group are easily conjugated with glucuronic acid
A. Phase I reactions or nonsynthetic reactions derived from glucose. For example: Aspirin, morphine,
metronidazole
i. Oxidation ii. Acetylation: Compounds having amino acids or hydra-
l This reaction involves addition of oxygen or nega-
zine residues are conjugated with the help of acetyl
tively charged radical or either removal of hydrogen coenzyme-A. For example: Sulphonamides, isoniazid,
or positively charged radical. PAS, hydralazine
l Oxidations are the most important drug metabolizing
iii. Methylation: The amines and phenols can be methyl-
reactions, various oxidation reactions include hydrox- ated, methionine and cystine acting as methyl donors.
ylation, oxygenation at C, N or S atoms, N or O For example: Adrenaline, histamine and nicotinic
dealkylation, oxidative deamination, etc. acid
l Oxidative reactions are mostly carried out by a
iv. Sulphate conjugation: Phenolic compounds and steroids
group of mono-oxygenases in the liver. For exam- are sulphated by sulphokinases. For example: Chloram-
ple: Barbiturates, phenothiazines, paracetamol, phenicol, adrenal and sex steroids
steroids, phenytoin, benzodiazepines. v. Glycine conjugation: Salicylates and other drugs having
ii. Reduction: This reaction is the converse of oxidation carboxylic acid group are conjugated with glycine, but
and involves cytochrome P450 enzymes working in the this is not a major pathway of metabolism.
opposite direction. For example: Chloramphenicol, vi. Glutathione conjugation: Serves to inactive highly reactive
halothane and warfarin quinone or epoxide intermediates formed during metabo-
iii. Hydrolysis: This reaction involves cleavage of drug lism. For example: Paracetamol
molecule by taking up a molecule of water. Occurs in vii. Ribonucleoside/nucleotide synthesis: It is important for
liver, intestines, plasma and other tissues. activation of many purine and pyrimidine antimetabo-
Ester 1 H2O → acid 1 alcohol lites used in cancer chemotherapy.
SHORT ESSAYS
Q. 1. Drug metabolism excreted largely unchanged in the urine. For example:
Frusemide, atenolol
Ans.
l Biotransformation or drug metabolism is the process of liver. But the drugs get metabolized even in the kidneys,
biochemical alteration of the drug in the body. gut mucosa, lungs, blood and skin.
l Body treats most drugs as foreign substances and tries l The biotransformation of a drug can be brought about
to inactivate and eliminate them by various biochemical by specific enzymes located in the following:
reactions. These processes convert the drugs into more 1. Liver microsomes called microsomal enzymes
polar, water-soluble compounds so that they are easily 2. Cytoplasm and mitochondria, plasma and other tis-
excreted through the kidneys. Some drugs may be sues called nonmicrosomal enzymes
l The chemical reactions of biotransformation can take Certain drugs like anthracene purgatives and heavy met-
place in two phases as follows: als are excreted directly in the colon.
1. Phase I: includes nonsynthetic reactions like
3. Exhaled air: Gases and volatile liquids (general anaes-
a. oxidation, e.g. barbiturates, phenothiazines,
thetics, alcohols) are eliminated by lungs irrespective of the
paracetamol, steroids, phenytoin and benzodiaz-
lipid solubility.
epines
4. Saliva and sweat: Drugs like lithium, potassium iodine,
b. reduction, e.g. chloramphenicol, halothane and
rifampicin are excreted by these routes.
warfarin
5. Milk: The excretion of drug in milk is not important for
c. hydrolysis, e.g. choline esters, procaine, ligno-
the mother, but the suckling infant receives the drug. Milk
caine, procainamide, pethidine and oxytocin
has a lower pH than plasma, hence basic drugs are some-
2. Phase II: includes synthetic reactions like
what more concentrated in it. However the total amount of
a. glucuronide conjugation, e.g. glucuronic acid,
drug reaching the mother is generally small.
sulphuric acid or an amino acid
b. acetylation, e.g. sulphonamides, isoniazid, PAS, Q. 3. Define the term prodrug giving an example.
hydralazine
c. methylation, e.g. adrenaline, histamine and nicotinic Ans.
acid
l Prodrug is an inactive form of the drug that gets me-
d. sulphonate conjugation, e.g. chloramphenicol, adre-
tabolized to the active derivative in the body. A prodrug
nal and sex steroids
may overcome some of the disadvantages of the con-
e. glycine conjugation
ventional forms of the drug administration. For exam-
f. glutathione conjugation, e.g. paracetamol
ple: Levodopa crosses blood-brain barrier and then gets
g. ribonucleoside or nucleotide synthesis, e.g. purine
converted to dopamine.
and pyrimidine antimetabolites used in cancer
l Prodrugs also help to prolong the duration of action of
chemotherapy
the drug. For example: Esters of penicillin
l Various examples of prodrugs and their active forms are
Q. 2. Channels of drug excretion
listed in Table 2.1.
Ans. Drug excretion takes place mainly through five main
channels as follows:
TABLE 2.1 Examples of Prodrugs and Their Active Forms
1 . Urine
Prodrugs Active Forms
2. Faeces
Levodopa Dopamine
3. Exhaled air
4. Saliva and sweat Enalapril Enalaprilat
5. Milk Dipivefrine Epinephrine
1. Renal excretion (urine) is the most important channel of Acyclovir Acyclovir triphosphate
excretion for most of the drugs. It takes place in three steps Bacampicillin Ampicillin
as follows:
1. Glomerular filtration: All nonprotein drugs, whether
lipid soluble or not, they are presented to the glomeru- Q. 4. First-pass metabolism
lus are filtered. The filtration depends on the plasma
protein binding and the filtration rate. Normal filtration Ans.
rate is 120 mL/min and reduces after 50 years of age.
l First-pass metabolism is the metabolism of the drug
2. Tubular reabsorption: Depends on lipid solubility and
during its first passage from the site of absorption into
ionization of the drug at the existing urinary pH.
systemic circulation.
About 99% of lipid-soluble drugs are reabsorbed,
l Orally administered drugs have to pass via gut wall, portal
but drugs like aminoglycoside, quaternary ammonium
vein and liver to enter the systemic circulation. Certain
compounds that are lipid insoluble are not reabsorbed.
drugs during this process of passage get metabolized and
3. Tubular secretion involves active transfer of organic
are removed or inactivated before they reach the systemic
acids and bases by two separate nonspecific mecha-
circulation, this process is known as first-pass effect.
nisms which operate in the proximal tubules.
l It results in decreased bioavailability and therapeutic effect
2. Faeces: Apart from the unabsorbed fraction, most of the of the drug. For example: Propranalol and nitroglycerine
drug present in the faeces is obtained from bile. Organic l Extent of metabolism depends on the individual and the
acids, bases and steroids are actively transported into the drug. Bioavailability is increased in patients with liver
bile by the nonspecific active transport mechanism. disorders due to reduction in hepatic metabolism.
l Consequences of first-pass metabolism: 2. Formulation: Inert substances used with drugs as diluents
a. The dose has to be increased for some drugs, e.g. like starch slow absorption and reduce bioavailability.
propranolol. 3. Particle size: Small particles are easily absorbed than
b. Route of administration has to be changed for drugs bigger particles and there is better bioavailability.
that undergo extensive first-pass metabolism, e.g. 4. Lipid solubility: Lipid-soluble drugs are absorbed
lignocaine, isoprenaline, testosterone. faster and they are more bioavailable.
5. pH and ionization: Ionized drugs are poorly absorbed
Q. 5. Bioavailability. Factors influencing it by oral route compared to unionized drugs. Acidic drugs remain
with examples. unionized in acidic medium and are rapidly absorbed,
e.g. aspirin, barbiturates.
Ans.
6. Area and vascularity of the absorbing surface: The larger
l Bioavailability is the fraction of the drug that reaches the the surfaces are for absorption and more vascularity,
systemic circulation following administration by any route. there will be more absorption and more bioavailability.
l Thus for a drug given intravenously, the bioavailability 7. Gastrointestinal motility: Faster gastric emptying time
is 100%. ensures passage of drug to intestine is fast and more
l For IM/SC injection, drugs are almost completely ab- absorption. Intestinal motility as in diarrhoea reduces
sorbed while by oral route the bioavailability is low due absorption and the amount of drug available is reduced.
to reduced absorption and high first-pass metabolism. 8. Presence of food: Delays gastric emptying and delays
absorption.
Factors influencing bioavailability of drugs are as follows: 9. Metabolism: Some drugs are degraded in the GI tract
1. Disintegration and dissolution time: Oral drugs have to and bioavailability becomes zero.
disintegrated to be absorbed and then dissolved in gastro- 10. Diseases: Bioavailability is increased in patients with
intestinal fluids. Liquids are absorbed faster than solids. liver disorders due to reduction in hepatic metabolism.
Water-soluble drugs like aspirin reduce bioavailability.
SHORT NOTES
Q. 1. Bioavailability Ans.
Ans. l Biotransformation is the process of biochemical altera-
tion of the drug in the body.
l Bioavailability is the fraction of the drug that reaches
l Body treats most drugs as foreign substances and tries
the systemic circulation following administration by
to inactivate and eliminate them by various biochemical
any route.
reactions. These processes convert the drugs into more
l For a drug given intravenously, the bioavailability is
polar, water-soluble compounds so that they are easily
100%. For IM/SC injection, drugs are almost com-
excreted through the kidneys.
pletely absorbed while by oral route the bioavailabil-
l Some drugs may be excreted largely unchanged in the
ity is low due to reduced absorption and high first-
urine. For example: Frusemide, atenolol
pass metabolism.
liver. But the drugs get metabolized even in the kidneys,

Q. 2. Mention the factors which affect bioavailability. gut mucosa, lungs, blood and skin.
Ans. l The biotransformation of a drug can be brought about
by specific enzymes located in liver microsomes called

The factors influencing bioavailability are as follows: microsomal enzymes and those located in cytoplasm,
1. Disintegration and dissolution of time mitochondria, plasma and other tissues called nonmi-
2. Formulation crosomal enzymes.
3. Particle size
4. Lipid solubility Q. 4. Define prodrug and give examples.
5. pH and ionization
Ans.
6. Area and vascularity of the absorbing surface
7. Gastrointestinal motility l Prodrug is an inactive form of the drug that gets me-
8. Presence of food tabolized to the active derivative in the body.
9. Metabolism l A prodrug may overcome some of the disadvantages of
10. Diseases the conventional forms of the drug administration. For
example: Levodopa crosses blood-brain barrier and then
Q. 3. Biotransformation or drug metabolism gets converted to dopamine.
l Prodrugs also help to prolong the duration of action of drugs during this process of passage get metabolized and
the drug. For example: Esters of penicillin. are removed or inactivated before they reach the systemic
l Various examples of prodrugs and their active forms are circulation, this process is known as first-pass effect.
as given in Table 2.2. l It results in decreased bioavailability and therapeutic
effect of the drug. For example: Propranolol and nitro-

TABLE 2.2 Examples of Prodrugs and Their Active Forms glycerine
l Consequences of first-pass metabolism are that the dose
Prodrugs Active Forms has to be increased for some drugs. For example: Pro-
Levodopa Dopamine pranolol or the route of administration has to be changed
Enalapril Enalaprilat for some drugs like lignocaine, isoprenaline, etc.
Dipivefrine Epinephrine Q. 7. Pharmacokinetics
Ans.
Q. 5. Methods of prolonging the effects of a drug
l Pharmacokinetics is the study of the absorption, distri-
Ans. bution, metabolism and excretion of drugs, i.e. move-
ment of the drugs into within and out of the body.
The duration of action of a drug can be prolonged by inter-
l Once the drug is administered, it is absorbed and enters
fering with the pharmacokinetic process by one of the fol-
the blood and is distributed to different parts of the
lowing methods:
body, reaches the site of action and is metabolized and
1. Prolonging the absorption of the drug from the site of
is excreted out of the body.
administration
l Pharmacokinetics examines the movement of a drug
2. Increasing plasma protein binding
over time through the body.
3. Retarding the rate of metabolism
4. Delaying renal excretion Q. 8. What is plasma half-life?
Advantages of prolonging the duration of action of a drug Ans.
are as follows:
1. It helps to reduce the frequency of drug administration. l Plasma half-life (t1/2) of a drug is the time taken for its
2. Improves patient compliance. plasma concentration to be reduced to half its original
3. Large fluctuations in plasma concentrations are avoided. value.
4. Side effects related to high peak plasma concentrations l It takes place in two phases as follows:
can be avoided. 1. Initial rapid phase due to distribution

5. Drug affect can be maintained overnight without dis- 2. Later less declined phase due to elimination
turbing sleep. l Plasma half-life t1/2 5 ln2/k where ln2 is the natural
logarithm of 2 and k is the elimination rate constant of

Q. 6. First-pass metabolism with suitable examples. the drug.
Ans. During
1. first t1/2: 50% of the drug is eliminated,
l Orally administered drugs have to pass via gut wall, por- 2. second t1/2: 75% (50 1 25) is eliminated and
tal vein and liver to enter the systemic circulation. Certain 3. third t1/2: 87.5% (50 1 25 1 12.5) is eliminated.
Topic 3
Pharmacodynamics
LONG ESSAYS
Q. 1. Describe the various factors that modify the dos- Ans.
age and action of drugs.
The same dose of a drug can produce different degrees of
Or, response in different patients and even in the same patient
Discuss factors modifying drug action with examples. under different situations.
Various factors that modify the effects of drugs are as iv. Dose
follows:
The response to drug may be modified by the dose adminis-
A. Drug factors
tered, as the dose is increased magnitude of the response also
i. Route of administration
increases proportionately till the maximum is reached. Further
ii. Presence of other drugs
increase in doses produces adverse effects. For example: The
iii. Cumulation
drugs used in myasthenia enhance muscle power in therapeu-
iv. Dose
tic doses, but in high doses it causes muscle paralysis.
v. Placebo
B. Patient factors
i. Age v. Placebo
ii. Body weight Placebo is the Latin word which means 'I will please'. It is
iii. Sex a dummy medicine having no pharmacological effect.
iv. Species and race Substances such as starch, lactose, etc. are used as placebos.
v. Environment
vi. Genetic factors Uses
vii. Emotional factors l They are used for relief of subjective symptoms like
viii. Pathological state anxiety, headache, tremors, pain and insomnia.

ix. Tolerance l They are used in clinical trials to minimize bias.
x. Drug dependence
PATIENT FACTORS
DRUG FACTORS i. Age
i. Route of Administration l The pharmacokinetics of many drugs change with age.
l In neonates, the metabolizing function of the liver and
Route of administration governs the speed and intensity of
the excretory function of kidney are not fully developed
drug response, e.g. magnesium sulphate given orally acts as
to handle drugs. For example: Chloramphenicol can
a purgative. But given IV causes CNS depression and has
produce grey baby syndrome.
anticonvulsant effects. When topically applied reduces lo-
l Calculation of the appropriate dose is important to avoid
cal oedema. Hypertonic magnesium sulphate used as reten-
toxicity. Formula for calculation of dose for children:
tion enema reduces intracranial tension.
Young’s formula
ii. Presence of Other Drugs Age (years)

Child's dose = × Adult d o se
Drugs may modify the response to each other by pharma- Age + 12
cokinetic or pharmacodynamic interaction between them.
The concurrent use of two or more drugs can influence the l In elderly people the capacity of the liver and kidney to
response of each other. handle the drug is reduced. Hence lower doses are rec-
ommended.
For example:
a. A combination of drugs is used in hypertension— ii. Body Weight
hydralazine 1 propranolol for their beneficial inter-
action. l The recommended dose is usually calculated for medium
b. Penicillin and gentamicin should never be mixed in the built persons whereas for the obese and underweight
same syringe. persons, the dose has to be calculated individually.
c. Succinylcholine is prone to induce arrhythmias in digi- l Formula for calculation of dose according to body
talized patients. weight is as follows:
Body weight (kg)

iii. Cumulation Dose = × Average adult do se
70
When the rate of elimination of the drug is slower than the
rate of administration, the drug may accumulate in the body
causing cumulative toxicity. For example: Drugs like di-
iii. Sex
goxin, emetine, chloroquine are slowly eliminated, so they l Sex can also influence the drug effect.
cumulate and result in toxicity. l The hormonal effects and smaller body size may influ-
Prolonged use of chloroquine causes retinal damage. ence drug response in women. For example: Drugs
like morphine and barbiturates can cause paradoxical ix. Tolerance

response like excitement in females.
l Repeated administration of certain drugs can result in a
decrease in their pharmacological effect. Hence, higher
iv. Species and Race doses of such drugs are needed to produce a given response.
l Tolerance may be of two types as follows:
l Response to drugs may vary with species and race. For
a. Natural tolerance: Some species or races show less
example: Rabbits are resistant to atropine.
sensitivity to certain drugs, e.g. black race is tolerant
l Blacks need higher doses of atropine to produce
to mydriatics.
mydriasis.
b. Acquired tolerance: Develops on repeated adminis-
tration of a drug, e.g. barbiturates, opioids, nitrites.
v. Diet and Environment l Tolerance may develop to some actions of the drug and
not to others. For example:

l Food interferes with the absorption of many drugs. For
i. Morphine—tolerance develops to analgesic euphoric
example: Tetracyclines form complexes with calcium in
effects of morphine but not to its constipating and
the food are poorly absorbed.
miotic effects.
l Certain environmental pollutants like DDT, cigarette
ii. Barbiturates—tolerance develops to sedative but not
smoke, insecticides and alcohol consumption are known to
antiepileptic effects of barbiturates.
induce hepatic microsomal enzymes and increase metabo-
l Tachyphylaxis is the rapid development of tolerance.
lism of drugs like oral contraceptives, theophylline, etc. So
When drugs are administered repeatedly at short inter-
the dose of these drugs administered may be inadequate.
vals, tolerance develops and is known as tachyphylaxis
or acute tolerance. For example: Ephedrine, amphet-
vi. Genetic Factors amine, tyramine
l Variations in an individual’s response to drugs could
genetically be mediated. Difference in response is x. Drug Dependence
due to variations in the amount of drug metabolizing
enzymes. For example: Acetylation of drugs l Drug dependence can be defined as 'a state, psychic
l The rate of drug acetylation differs among individuals
and sometimes also physical, resulting from the inter-
who may be fast or slow acetylators. For example: INH action between a living organism and a drug charac-
sulphonamides and hydralazine are acetylated. terized by behavioural and other response that always
l Slow acetylators treated with hydralazine are more
include a compulsion to take the drug on a continuous
likely to develop lupus erythematosus. or periodic basis in order to experience its psychic
l In G6PD deficiency—use of primaquine, sulfones and
effects and sometimes to avoid the discomfort of its
quinolones can cause hemolysis. absence'. For example: Alcohols, opioids, barbiturates,
amphetamine
l Dependence may be psychological or physical.
vii. Psychological Factors
Q. 2. Describe the principles and mechanism of action of
l The doctor–patient relationship influences the response
drugs with examples. Add a note on enzyme induction.
to a drug often to a large extent by acting on the patient’s
psychology. Ans.
l The patients confidence in the doctor may itself be suf-
ficient to relieve a suffering, particularly the psychoso-

matic disorders. This can be substantiated by the fact PRINCIPLES OF DRUG ACTION
that large number of patients response to placebo.
Drugs produce their effects by interacting with the physio-
logical systems of the organisms. By such interaction,
viii. Diseases (Pathological States) drugs can only modify the rate of functions of the various
a. Presence of certain diseases can also influence the drug systems but they cannot bring about qualitative changes,
responses. For example: i.e. they cannot change the basic functions of any physio-
logical systems.
i. In malabsorption syndrome, drugs are poorly
absorbed. The basic types of drug action can be broadly classified as
ii. In liver diseases, rate of drug metabolism is reduced. follows:
iii. In renal dysfunction, drugs mainly excreted through i. Stimulation
kidneys are likely to accumulate and cause toxicity. ii. Depression
i ii. Irritation I. Physical Action

iv. Replacement
The action of a drug results from its physical properties like
v. Cytotoxic action
the following:
vi. Modification of the immune status
l Adsorption—activated charcoal in poisoning, kaolin
i. Stimulation is the selective enhancement of the level
l Mass of the drug—bulk laxatives like psyllium, bran
of activity of the specialized cells. For example:
and protectives like dimethicone
Adrenaline stimulates the heart.
l Osmotic property—osmotic diuretics, mannitol and
ii. Depression is the selective diminution of activity of
magnesium sulphate
the specialized cells. For example: 131
l Radioactivity—radioiodine I and other radioisotopes
l Quinidine depresses the heart.
l Radio opacity—contrast media like barium sulphate,
l Barbiturates depress the central nervous system.
urografin
l Some drugs stimulate one system but may depress
the other, e.g. morphine depresses the CNS but

stimulates the vagus. II. Chemical Action
iii. Irritation
Drugs interact according to simple chemical reactions.
l This is a nonselective, often noxious effect and is
Examples:
particularly applied to less specialized cells like
l Antacids like AlOH3 and others neutralize gastric HCl.
epithelium, connective tissue, etc.
l Oxidizing agents—potassium permanganate, I2 are ger-
l Mild irritation may stimulate associated func-
micidal and inactivate ingested alkaloids.
tion, e.g. bitters increase salivary and gastric
l Chelating agents—bind heavy metals making them
secretion, counterirritants increase blood flow
nontoxic, e.g. calcium disodium edentate, BAL, peni-
to the site.
cillamine.
l Strong irritation results in inflammation, corro-
sion, necrosis and morphological damage. This

may result in diminution or loss of function. III. Through Enzymes
iv. Replacement: Drugs may act by replacement spe-
l Enzymes are a very important target of drug action.
cifically when there is deficiency of natural sub-
Drugs can either increase or decrease the rate of enzy-
stances like hormones, metabolites or nutrients.
matically mediated reactions.
For example: Insulin in diabetes mellitus, iron in
l Stimulation: Enzyme stimulation is relevant to endoge-
anaemia, vitamin C in scurvy.
nous mediators and modulators.
v. Cytotoxic action
For example:
l Selective cytotoxic action for invading parasites
a. Adrenaline stimulates adenylyl cyclase.
or cancer cells, attenuating them without signifi-
b. Pyridoxine acts as a cofactor and increases.
cantly affecting the host cells is utilized for cure
l Inhibition: Drugs may act by inhibition of various
or palliation of infections and neoplasms.
enzymes, thus altering the enzyme-mediated reactions.
l Drugs may act by specifically destroying infec-
For example:
tive organisms, e.g. penicillin or by cytotoxic
a. Allopurinol inhibits the enzyme xanthine oxidase
effect on cancer cells, e.g. anticancer drugs.
which converts xanthine to uric acid. Allopurinol is
vi. Modification of the immune status: Vaccines act by
used to reduce synthesis of the uric acid in treatment
improving our immunity while immunosuppressants
of chronic gout cases.
act by depressing immunity, e.g. glucocorticoids.
Xanthine Hypoxanthine Uric acid
MECHANISM OF DRUG ACTION
l Most drugs act by binding to specific target proteins like Xanthine oxidase
receptors, enzymes and ion channels. They may act on ↑ (−)
the cell membrane, inside or outside the cell to produce Allopurinol
their effects.
l Fundamental mechanisms of drug action may be distin- b. Disulphiram inhibits aldehyde dehydrogenase en-
guished into four categories: zyme and is used in treatment of chronic alcoholism.
i. Physical action
ii. Chemical action
IV. Through Receptors
iii. Through enzymes
iv. Through receptors l Drugs may act by interacting with receptors in the body.
l Receptors are macromolecules present either on cell l Inverse agonist: After binding to the receptors, some
surface, cytoplasm or in the nucleus where drug binds drugs act opposite to the agonist. They are called
and interacts to bring about cellular change. inverse agonists. It has affinity and intrinsic activity
(0–1).
Drug 1 Receptor I Drug receptor complex n Response
For example: b-carbolines
l Receptors are specific proteins and have specificity and l Ligand is a molecule which binds selectively to a spe-
selectivity. Drugs may have relatively selective action cific receptor.
on one type of receptors like adrenergic receptors (a l Site: The receptors may be present in the cell mem-
and b), cholinergic receptors (muscarinic and nicotinic brane, in the cytoplasm, or in the nucleus.
receptors), opioid receptors, etc.
l Affinity is the ability of the drug to bind to the receptor.
l Intrinsic activity or efficacy is the ability of the drug to

v. Through Ion Channels
elicit a response after binding to the receptor. Drugs may interfere with the movement of ions across spe-
l Agonist: An agonist is a substance that binds to the cific channels, e.g. calcium channel blockers, potassium
receptor and produces a response. It has affinity and channel openers.
intrinsic activity.
l Antagonist: It is a substance that binds to the receptor
and prevents action of agonist on the receptor. It has af-

vi. By Altering Metabolic Processes
finity but no intrinsic activity. Drugs like antimicrobials alter the metabolic pathway in the
l Partial agonist binds to the receptor but has low intrin- microorganisms resulting in the destruction of the microor-
sic activity. It has affinity and less intrinsic activity. ganisms, e.g. sulphonamides interfere with bacterial folic
For example: Pindolol, buprenorphine acid synthesis.
SHORT ESSAYS
Q. 1. Pharmacodynamics penicillin or by cytotoxic effect on cancer cells, e.g.
anticancer drugs.
Ans.
f. Modification of the immune status vaccines act by
1. Pharmacodynamics is the study of actions of the drugs improving our immunity while immunosuppressants
on the body and their mechanisms of action. act by depressing immunity, e.g. glucocorticoids.
2. Drugs produce their effects by interacting with the physi-
ological systems of the organisms. By such interaction, Q. 2. Mention factors modifying drug action.
drugs can merely modify the rate of functions of the vari- Ans.
ous systems. But they cannot bring about qualitative
changes, i.e. they cannot change the basic functions of any The same dose of a drug can produce different degrees of
physiological systems. Thus drugs act by the following: response in different patients and even in the same patient
a. Stimulation is the increase in activity of the special- under different situations. Various factors modify the dos-
ized cells, e.g. adrenaline stimulates the heart. age and action of the drug.
b. Depression is the decrease in activity of the special- Factors that modify the effects of drugs are broadly classi-
ized cells, e.g. quinidine depresses the heart, barbitu- fied as follows:
rates depress the central nervous system. 1. Drug factors
Some drugs stimulate one system but may depress a. Route of administration
the other, e.g. morphine depresses the CNS but b. Presence of other drugs
stimulates the vagus. c. Cumulation
c. Irritation: this can occur on all types of tissues in the d. Dose
body and result in inflammation, corrosion and necrosis. e. Placebo
d. Replacement: Drugs may act specifically when there 2. Patient factors
is deficiency of natural substances like hormones, a. Age
metabolites or nutrients. For example: Insulin in b. Body weight
diabetes mellitus, iron in anaemia, vitamin C in c. Sex
scurvy d. Species and race
e. Anti-infective or cytotoxic action: Drugs may act by e. Environment
specifically destroying infective organisms, e.g. f. Genetic factors
g. Emotional factor b. irreversible antagonism: The antagonist binds so

h. Pathological state firmly by covalent bonds to the receptor that it dis-
i. Tolerance sociates very slowly or not at all. Thus it blocks the
j. Drug dependence action of the agonists and the blockade cannot be
overcome by increasing the dose of the agonist and
Q. 3. Placebo hence it is irreversible. For example: Adrenaline and
Ans. phenoxybenzamine at the a-adrenergic receptors
4 . Noncompetitive inhibition: Here the antagonists block
Placebo is the Latin word for the term 'I will please'. It is a at the level of receptor–effector linkage.
dummy medicine having no pharmacological effect. Sub-
stances such as starch, lactose are used as placebos. Q. 5. Explain three types of drug antagonism with
examples.
Uses of placebo are as follows:
1. They are used for relief of subjective symptoms like Ans.
anxiety, headache, tremors, pain, insomnia.
Antagonism is the condition where one drug opposes or
2. Are used in clinical trials to minimize bias.
inhibits the action of another drug. Based on the mecha-
Factors affecting placebo effect are as follows: nisms, antagonism can be of following types:
1. Patient factors: Patients with neurotic symptoms re- 1. Chemical antagonism
spond to placebos. 2. Physiological antagonism
2. Drug factors: The placebo response can be affected by the 3. Antagonism at receptor level—reversible (competitive),
presentation or route of administration of the drug. For irreversible
example: Colourful tablets such as red, blue, green and 4. Noncompetitive
injectable preparations give better placebo preparation. 1. Chemical antagonism: Two drugs interact chemically
3. Doctor factors: Personality of the doctor, motivation, to result in inactivation of the effect. For example: Che-
process of instruction, doctor–patient relationship are lating agents inactivate heavy metals like lead and mer-
important factors that affect the response to a placebo. cury to form inactive complexes.
2. Physiological antagonism: Two drugs act at different
Q. 4. Drug antagonism sites to produce opposing effects, e.g. histamine action
Ans. on H2 receptors to produce bronchospasm and hypoten-
sion while adrenaline reverses these effects by acting on
One drug inhibiting or opposing the action of another is adrenergic receptors.
antagonism. Based on the mechanisms, antagonism can be 3. Antagonism at receptor level: The antagonists inhibit
of following types: the binding of the agonist to the receptor. It may be
1. Chemical antagonism—Two drugs interact chemically a. reversible/competitive antagonism: The agonist and
to result in inactivation of the effect. For example: Che- antagonist compete for the same receptor. By increas-
lating agents inactivate heavy metals like lead and ing the concentration of the agonist, the antagonism
mercury to form inactive complexes. can be overcome. It is thus reversible antagonism.
2. Physiological antagonism: Two drugs act at different Acetylcholine and atropine compete at muscarinic
sites to produce opposing effects. For example: Hista- receptors.
mine action on H2 receptors to produce bronchospasm b. irreversible antagonism: The antagonist binds so
and hypotension while adrenaline reverses these effects firmly by covalent bonds to the receptor that it dis-
by acting on adrenergic receptors. sociates very slowly or not at all. Thus it blocks
3. Antagonism at receptor level: The antagonists inhibit the action of the agonists and the blockade cannot
the binding of the agonist to the receptor. It may be be overcome by increasing the dose of the agonist
a. reversible/competitive antagonism: The agonist and and hence it is irreversible. For example: Adrena-
antagonist compete for the same receptor. By increas- line and phenoxybenzamine at the a-adrenergic
ing the concentration of the agonist, the antagonism can receptors.
be overcome. It is thus reversible antagonism. Acetyl- 4. Noncompetitive inhibition: The antagonists block at
choline and atropine compete at muscarinic receptors. the level of receptor–effector linkage.
SHORT NOTES
Q. 1. Tachyphylaxis intervals, tolerance develops and is known as tachyphy-
laxis or acute tolerance, e.g. ephedrine, amphetamine,
Ans.
tyramine, and hydroxytryptamine.
1. Tachyphylaxis is the rapid development of tolerance. 2 . These drugs act by displacing noradrenaline from the
When the drugs are administered repeatedly at short sympathetic nerve endings.
3. There may be slow dissociation of the drug from the Based on the mechanisms, antagonism can be of following
receptor, thereby blocking the receptor. For example: types:
Epinephrine given repeatedly in bronchial asthma may 1. Chemical antagonism, e.g. chelating agents inactivate
not give the desired response. heavy metals like lead and mercury to form inactive
complexes.
Q. 2. Drug synergism 2. Physiological antagonism, e.g. histamine action on H2
Ans. receptors to produce bronchospasm and hypotension
while adrenaline reverses these effects by acting on ad-
1. When the action of one drug is enhanced or facilitated renergic receptors.
by another drug, the combination is synergistic. 3. Antagonism at receptor level
2. The total effect of the combination is greater than the sum a. Reversible (competitive): Acetylcholine and atropine
of their independent effects. It is often called potentiation compete at muscarinic receptors.
or supra-additive effect. For example: Acetylcholine b. Irreversible, e.g. adrenaline and phenoxybenzamine
1 physostigmine, levodopa 1 carbidopa at the a-adrenergic receptors
4. Noncompetitive inhibition: The antagonists block at the
Q. 3. Placebo level of receptor–effector linkage.
Ans.
Q. 5. Bioassay
1. Placebo is the Latin word for the term 'I will please'.
Ans.
It is a dummy medicine having no pharmacological
effect. Substances such as starch, lactose are used as Bioassay is the determination or estimation of the amount
placebos. of biological activity in a unit quantity of preparation.
2. Uses
a. They are used for relief of subjective symptoms like Indications of bioassay are as follows:
anxiety, headache tremors, pain, insomnia. 1. When the chemical composition is not known but the
b. Used in clinical trials to minimize bias. substance has a specific action, e.g. long-acting thyroid
3. Factors affecting placebo effect are as follows: stimulator (LATS).
a. Patient factor: Patients with neurotic symptoms 2. When there is no simple chemical means of ensuring a
respond to placebos. product of constant composition.
b. Drug factor: The placebo response can be affected by 3. When the chemical assay method is too complex or
the presentation or route of administration of the drug. insensitive, e.g. adrenaline and histamine can be bioas-
For example: Colourful tablets such as red, blue, sayed in microgram quantities.
green and injectable preparations give better placebo 4. When drugs which differ in composition but have
effect. same pharmacological action, e.g. digitalis glycosides
c. Doctor factor: Personality of the doctor, motivation, obtained from various sources.
process of instruction, doctor–patient relationship are 5. When active principle is unknown or cannot be isolated
important factors that affect the response to a placebo. easily, e.g. peptide hormones.
The important methods of bioassay are as follows:
Q. 4. Drug antagonism
1. Direct comparison on the same tissues
Ans. One drug inhibiting or opposing the action of another 2. Direct assay on several animals
is antagonism. 3. Indirect assays
Topic 4
Adverse Drug Effects

LONG ESSAYS
Q. 1. Write in detail the drug toxicity in men. Adverse drug reactions
Or, Ans.
ADVERSE DRUG REACTIONS l Over dose may be accidental, suicidal or homicidal.

CVS, CNS, lungs, kidneys and liver are the most com-
l WHO has defined an adverse drug reaction as any response
monly affected organs.
to a drug that is noxious and unintended and that occurs at
l Toxicity may result from overdosage of a therapeutic
doses used in men for prophylaxis, diagnosis, or therapy.
drug like barbiturates. Poisoning can occur when the
l Adverse reactions are classified into two types:
dose of the drug crosses the therapeutic index.
l Therapeutic index is the demarcation between therapeu-
tic dose and maximum acceptable dose.
Median lethal dose

Therapeutic dose =
Median effective dose
Predictable type-A reaction Unpredictable type-B reactions
If it is less than or equal to 1 the drug is safe, if it is more

Predictable Type-A Reactions l
than 1 it causes toxicity.

These are based on pharmacological properties of drug. They
are more common, dose related and are mostly preventable.
Treatment of Toxicity
i. Termination of exposure, exposure of patient to fresh
Unpredictable Type-B Reactions
air in case of inhalation poison, induction of emetics,
Based on the peculiarities of the patient and not on drug’s gastric lavage.
known actions. They are less common, nondose related, ii. Preventing absorption of ingested poison. For example:
generally more serious and drug may need to be withdrawn Acidic drugs are absorbed in acidic medium, by making
from the body. the medium basic absorption can be inhibited.
Universal antidote is burnt toast, strong tea and milk of
magnesia in the ratio 2:1:1.
I. Side Effects
A suspension of 20–40 g active charcoal in 200 mL
These are unwanted but unavoidable effects that occur at water may be used.
therapeutic doses. They are predictable reactions. iii. Maintaining airway by adequate ventilation or by arti-
ficial respiration
A side effect may be based on the following:
iv. Maintaining BP and heart rate
i. Same therapeutic effect of the drug itself. For example:
The antisecretory action of atropine used in peptic ulcer
causes dryness of the mouth. IV. Intolerance
ii. Different facet of action
l It is the appearance of characteristic toxic effects of a
For example: drug in an individual at therapeutic doses.
Promethazine causes sedation, that is unrelated to its l It indicates a low threshold of the individual to the action
antiallergic effect. of the drug. For example: Single dose of triflupromazine
Oestrogens cause nausea which is unrelated to their may cause muscular dystonias in some individuals espe-
antiovulatory action. cially children.
II. Secondary Effects V. Idiosyncrasy

These are indirect consequences of primary action of drug. l Idiosyncrasy is a type of intolerance of some patients to
specific drugs.
For example:
l Idiosyncrasy is a genetically determined abnormal reac-
Corticosteroids cause immunosuppression that may
tion to a drug.
lead to latent TB in patients.
Suppression of bacterial flora by tetracyclines paves the For example:
way for superinfections. a. Primaquine and sulphonamides induce haemolysis in
patients with G6PD deficiency.
b. Some patients show excitement with barbiturates.
III. Toxic Effects
c. Chloramphenicol induced agranulocytosis, where no
l These are a result of excessive pharmacological action definite genetic background is known, is also included
due to overdose or prolonged use. under idiosyncrasy.
VI. Allergic Reaction VIII. Addictions/Drug Dependence

Drugs can induce both types of allergic reaction, i.e. humoral- l Addiction can be described as the dependence of a per-
and cell-mediated immunity. son to a certain drug to an extent that the behaviour and
Humoral-mediated immunity causes immediate allergic mood are influenced.
reactions, which are as follows: l The drugs are misused to obtain a pleasurable effect.
1. Type I (anaphylaxis) which occurs due to antigen– l Repeated usage of such drugs results in dependence.
antibody reaction when the drug induces IgE anti- l Drug dependence/addiction is a state of compulsive use
bodies. of drugs in spite of the knowledge of the risks associ-

2. Type II (cytolytic reaction): The drug binds to the pro- ated with its use.
tein and together they act as antigen and induce the l It could be of two types as follows:
formation of antibodies. a. Psychological dependence is a compulsive drug

3. Type III (arthus reaction): The antigen binds to circu- seeking behaviour to obtain its pleasurable effects.
lating antibodies and the complexes are deposited on For example: Cigarette smoking
the vessel wall where it initiates the inflammatory b. Physical dependence is said to be present when with-
response. drawal of the drug produces adverse symptoms. The
Cell-mediated immunity causes the following reaction: body undergoes physiological changes to adapt itself
4. Type IV (delayed hypersensitivity reaction): It is medi- to the continued presence of a drug in the body. Stop-
ated by T-lymphocytes and macrophages. The antigen ping the drug can result in withdrawal symptoms. For
reacts with receptors on T-lymphocytes which produce example: Alcohol, opioids and barbiturates.
lymphokines leading to allergic reaction.
IX. Teratogenicity
VII. Photosensitivity
l Teratogenicity is the ability of the drug to cause fetal
It is a cutaneous reaction resulting from drug-induced abnormality when administered to a pregnant lady.
sensitization of skin to UV rays. There are two types of l Depending on the stage of the pregnancy during which
reaction as follows: the teratogen is administered, it can produce various

a. Phototoxic: Drug or its metabolite accumulate in skin abnormalities.
absorbs light and undergoes photochemical reactions 1. Conception to 16 days: Usually resistant to any tera-
followed by photobiological reactions, resulting in local togenic effects. If affected, abortion occurs.
tissue damage, sunburn, blistering hyperpigmentation, 2. 17–55 days (period of organogenesis): Most vulner-
e.g. tetracyclines, Tar products. able period. Major physical abnormalities occur.
b. Photoallergic: Drug/metabolite-induced cell-mediated 3. 56 days onwards (fetal period): Period of growth and
immune response on exposure to light of longer wave- development. Hence developmental and functional
length like UV. Papular/eczematous contact dermatitis abnormalities result. For example: (a) Thalidomide
is produced, e.g. sulphonamides, sulphonylureas, chlo- causes phocomelia, (b) sodium valproate causes
roquine. spina bifida, (c) tetracyclines cause staining of teeth
and (d) smoking causes cleft palate.
SHORT ESSAYS
Q. 1. Define adverse drug reaction. Describe different Side Effects
types of adverse drug reactions.
l Side effects are the unrelated pharmacological effects
Ans. produced with therapeutic dose of a drug.
l These side effects which might be troublesome in a
An adverse drug reaction is any response to a drug that is particular condition may be useful in other circum-
noxious and unintended and that occurs at doses used in stances. For example: Dryness of mouth produced by
men for prophylaxis diagnosis or therapy (WHO). atropine may be troublesome in peptic ulcer disorders
but is beneficial as preanaesthetic medication.
Types of Adverse Drug Reactions
1 . Side effects Untoward Effects
2. Untoward effects l Untoward effects develop with therapeutic dose of a drug.
3. Toxic effects l They may be so severe and undesirable that they may
4. Allergic and idiosyncratic effects necessitate cessation of the treatment. For example:
Resistant staphylococcal diarrhoea following tetracy- l Drugs can induce both types of allergic reaction, i.e.
cline therapy or vomiting and diarrhoea due to aspirin humoral- and cell-mediated immunity.
therapy l Humoral-mediated immunity causes immediate allergic
reactions, which are as follows:

1. Type I: Anaphylaxis
Toxic Effects
2. Type II: Cytolytic reaction
l These are usually seen when a drug is administered re- 3. Type III: Arthus reaction
peatedly or in large doses.
Cell-mediated immunity causes delayed hypersensitivity
l Drug toxicity is usually the primary attribute of a
reaction.
drug and is dose dependent. For example: Respira-
l In anaphylactic reaction the drug induces synthesis of
tory depression due to morphine or ototoxicity due to
IgE antibodies which are fixed to the mast cells.
aminoglycosides
l On subsequent exposure the antigen–antibody com-
plexes cause degranulation of mast cells releasing the

Allergic and Idiosyncratic Effects mediators of inflammation like histamine, leukotrienes,
prostaglandins and platelet-activating factor.
l These are the qualitative intolerance due to immune or
l These mediators of inflammation are responsible for the
other than immune mechanisms.
characteristic signs and symptoms of anaphylaxis,
l Chloramphenicol causing aplastic anaemia is an exam-
which could be fatal and are as follows:
ple of idiosyncratic reaction. For example: Penicillin
1. Bronchospasm
producing anaphylaxis
2. Laryngeal oedema
Q. 2. Anaphylactic reaction 3. Hypotension
l Allergy develops within minutes and is called immedi-
Ans. ate hypersensitivity reaction. For example: Penicillin
l Skin tests may predict this type of reactions.
SHORT NOTES
Q. 1. Drug resistance l In anaphylactic reaction the drug induces synthesis of
IgE antibodies which are fixed to the mast cells.
Ans.
l On subsequent exposure the antigen–antibody com-
l Drug resistance is unresponsiveness of a microorganism plexes cause degranulation of mast cells releasing the
to an antimicrobial agent. mediators of inflammation like histamine, leukotrienes,
l Types of drug resistance are as follows: prostaglandins and platelet-activating factor.
1. Natural resistance l These mediators of inflammation are responsible for the
2. Acquired resistance characteristic signs and symptoms of anaphylaxis,

l Natural resistance: Some microbes show resistance to which could be fatal and are as follows:
certain antimicrobials because they may lack metabolic 1. Bronchospasm
process or target site which is affected by the particular 2. Laryngeal oedema
drug. For example: Gram-negative bacilli are normally 3. Hypotension
unaffected by penicillins.
l Acquired resistance: It is the development of resistance
Q. 3. Idiosyncrasy
by an organism to an antimicrobial to which it was sus- Ans.
ceptible before due to its use over a period of time. For
example: Gonococci have shown resistance to penicillin. Idiosyncrasy is a type of intolerance of some patients to
l A microorganism becomes resistant to a drug by either specific drugs. It is a genetically determined abnormal reac-
mutation or gene transfer. tion to a drug.
For example:
Q. 2. Anaphylactic reaction 1. Primaquine and sulphonamides induce haemolysis in
Ans. patients with G6PD deficiency.
2. In addition some responses like chloramphenicol induce
l Anaphylactic reaction is a type I humoral-mediated agranulocytosis, where no definite genetic background
immunity. is known, are also included under idiosyncrasy.
Q. 4. Addictions l Adrenaline is the drug of choice (0.3–0.5 mL of 1:1000

solution). It promptly reverses all hypotension, laryn-
Ans.
geal oedema and bronchospasm and is life saving in
l Addictions can be described as the dependence of a anaphylactic shock.
person to a certain drug to an extent that the behaviour l For administration of adrenaline IM route is preferred as
and mood are influenced. absorption through SC route is not reliable.

l Drug dependence/addiction is a state of compulsive use
of drugs in spite of the knowledge of the risks associ- Q. 7. Hypersensitive reaction

ated with its use. Ans.
1. Psychological dependence is a compulsive drug- l Drugs can induce both types of allergic reactions, i.e.
seeking behaviour to obtain its pleasurable effects. humoral- and cell-mediated immunity.
For example: Cigarette smoking. l Humoral-mediated immunity causes immediate allergic
2. Physical dependence: When withdrawal of the drug reactions as follows:

produces adverse symptoms it is known as physical 1. Type I (anaphylaxis) which occurs due to antigen–
dependence. The body undergoes physiological antibody reaction when the drug induces IgE anti-
changes to adapt itself to the continued presence of a bodies.
drug in the body. Stopping the drug can result in 2. Type II (cytolytic reaction): The drug binds to the
withdrawal symptoms. For example: Alcohol, opi- protein and together they act as antigen and induce
oids and barbiturates. the formation of antibodies.
3. Type III (Arthus reaction): The antigen binds to circulat-
Q. 5. Teratogenicity ing antibodies and the complexes are deposited on the
vessel wall where it initiates the inflammatory response.
Ans.
The cell-mediated immunity causes the following reaction:
l Teratogenicity is the ability of the drug to cause fetal 4. Type IV (delayed hypersensitivity reaction): It is me-
abnormality when administered to a pregnant lady. diated by T-lymphocytes and macrophages. The an-
l Depending on the stage of the pregnancy during which tigen reacts with receptors on T-lymphocytes which
the teratogen is administered, it can produce various produce lymphokines leading to allergic reaction.
abnormalities.
1. Conception to 16 days: Usually resistant to any tera- Q. 8. What is drug cumulation?
togenic effects. If affected, abortion occurs.
Ans.
2. 17–55 days (period of organogenesis): Most vulner-
able period. Major physical abnormalities occur. l Drug cumulation is the build-up of sufficiently high
3. 56 days onwards (fetal period): Period of growth and concentration of a drug in the body to produce toxicity
development. Hence developmental and functional on subsequent administration.
abnormalities result. l It is usually seen in the drugs which are excreted slowly,
e.g. digitalis, emetine and heavy metals.
For example: l Sometime, a cumulative effect is desired, e.g. with phe-
1. Thalidomide causes phocomelia. nytoin in the treatment of epilepsy. But most often,
2. Sodium valproate causes spina bifida. however, it is undesirable.
3. Tetracyclines causes staining of teeth. l Substances like lead can remain deposited in bones
4. Smoking causes cleft palate. without producing toxic effects. This is called passive
cumulation. It would produce the toxic manifestations
Q. 6. Adrenaline in anaphylactic shock as soon as it is released into the blood.
l To avoid cumulation
Ans.
a. stop the drug administration at the appearance of the
l Anaphylaxis is a humoral-mediated type I hypersensitiv- first warning symptom.
ity reaction where degranulation of mast cells releases b. carefully select the form in which the drug is to be
the mediators of inflammation like histamines, leukotri- administered.
enes, prostaglandins and platelet-activating factors c. check liver and kidney function before and during
which are responsible for the characteristic signs and drug administration, as even a noncumulative drug
symptoms of anaphylaxis like bronchospasm, laryngeal would produce cumulation in the presence of hepatic
oedema, hypotension, which could be fatal. and renal damage.
Part II
Drugs Acting on Autonomic Nervous System
Topic 5
Cholinergic System and Drugs
LONG ESSAY
Q. 1. Classify cholinergic drugs with examples. Write Cholinergic drugs are those which produce actions similar
the mechanism of action, uses and adverse effects of to that of acetylcholine (ACh), either by directly interacting
neostigmine. with cholinergic receptors or by increasing availability of
ACh at these sites.
Ans.
Classification of cholinergic drugs is as follows:
Cholinergic drugs
Directly-acting Indirectly-acting
(anticholinesterases)
Choline esterases Alkaloids

(acetylcholine (pilocarpine
bethanechol muscarine
carbachol) arecoline)
Reversible Irreversible
a. arbamates b. Acridine a. Organophosphates b. Carbamates

(physostigmine (tacrine) (dyflos (carbaryl
neostigmine echothiophate propoxur)
pyridostigmine parathion
edrophonium malathion
rivastigmine diazinon
donepezil) tabun, sarin, soman)
Click here to Visit - www.thedentalhub.org.in Repetitive firing

Twitching and fasciculations
NEOSTIGMINE Force of contraction in partially curarized and myasthenic

muscle is increased
Mechanism of Action
i. Neostigmine is a synthetic reversible anticholinesterase
Higher doses cause persistent depolarization of endplates
agent.
resulting in blockade of neuromuscular transmission
ii. Reversible anticholinesterases reversibly inhibit both true
and pseudocholinesterases. Thus ACh gets accumulated
and produces cholinergic effects. Hence, anticholinester-
Weakness and paralysis
ases are called indirectly-acting cholinergic drugs. Direct action of neostigmine and its congeners at muscle end
iii. Its actions are more pronounced on NMJ, GIT and blad- plates results in augmentation of these features
der than on CVS or eye. On skeletal muscles, it has both
direct and indirect actions.
iv. Indirect actions: By inhibiting cholinesterases, neostig- Pharmacokinetics
mine increases the ACh concentration at NMJ.
v. Direct actions: Because of structural similarity with Neostigmine is
ACh, neostigmine also directly stimulates the NM re- l poorly absorbed orally.
ceptors at NMJ. Thus it improves muscle power in pa- l does not penetrate cornea or cross blood-brain barrier.
tients with myasthenia gravis. l partially hydrolyzed and partially excreted unchanged
in urine.
Pharmacological Actions
Lipid-insoluble agents like neostigmine and other quater- Adverse Effects
nary ammonium compounds produce more marked effects a. Muscarinic: Salivation, lacrimation, urination, defaeca-
on skeletal muscles, stimulate ganglia but muscarinic ef- tion, GI distress and emesis (SLUDGE)
fects are less prominent and produce no CNS effects. b. Nicotinic: Muscular fasciculation, cramps, weakness,
areflexia, muscle paralysis, hypertension, tachycardia,
a. Ganglia pallor, mydriasis
l It stimulates ganglia primarily through muscarinic c. CNS: Restlessness, emotional lability, headache, tremors,
receptors. drowsiness, confusion, slurred speech, ataxia, generalized
l High doses cause persistent depolarization of the gangli-
weakness, coma, convulsions, depression of respiratory
onic nicotinic receptors and blockade of transmission. and cardiovascular centres.
b. Cardiovascular System Contraindications

l Bradycardia and hypotension through muscarinic action. Sick sinus, AV conduction defects, hypotensive states, peptic
l Tachycardia and hypertension through ganglionic ulcer, asthma, COPD and seizure patients.
stimulation.
Therapeutic Uses
c. Skeletal Muscles (Direct Action)
a . As miotic
After treatment with anticholinesterases the acetylcho- i. In glaucoma
line released by a single nerve impulse is not immediately ii. To counteract effect of mydriatics after refraction
destroyed
testing
iii. To prevent formation of adhesions between iris and
lens or iris and cornea—physostigmine (0.1 %) is
It rebinds to same receptors and diffuses to act on neigh-
bouring receptors and activates prejunctional fibres
used only to supplement pilocarpine.
b. Myasthenia gravis: Neostigmine 15 mg orally 6 hourly
c. Postoperative paralytic ileus or urinary retention: Neo-
Repetitive firing stigmine 0.5–1 mg SC
d. Postoperative decurarization: Neostigmine 0.5–2 mg IV
e. Cobra bite: Neostigmine along with atropine
Twitching and fasciculations f. Belladona poisoning
g. Alzheimer’s disease
Force of contraction in partially curarized and myasthenic
muscle is increased
Higher doses cause persistent depolarization of endplates

resulting in blockade of neuromuscular transmission
SHORT ESSAYS
Q. 1. Irreversible anticholinesterases l Indirect actions: By inhibiting cholinesterases, neostig-
mine increases the ACh concentration at NMJ.
Ans.
l Direct actions: Because of structural similarity with
l Irreversible anticholinesterases are powerful inhibitors ACh, neostigmine also directly stimulates the NM recep-
of ACh enzyme. They bind with the enzyme perma- tors at NMJ. Thus it improves muscle power in patients
nently by covalent bonds. with myasthenia gravis.
l Their actions are similar to ACh as ACh accumulates in
the tissues. They are lipid soluble and are highly absorb- Pharmacokinetics
able by all routes including intact skin.
l They include the following: Neostigmine is
1. Organophosphates: Dyflos, echothiophate, parathion, l poorly absorbed orally.
malathion l do not penetrate cornea or cross blood-brain barrier.
2. Carbamates: Carbaryl, propoxur (Baygon) l partially hydrolyzed and partially excreted unchanged
l Organophosphates are used as agricultural and domestic in urine.

insecticides. Organophosphorus poisoning can result as
accidental, suicidal or homicidal result. Therapeutic Uses
l Symptoms include muscarinic, nicotinic and central
effects: vomiting, abdominal cramps, diarrhoea, miosis, l Myasthenia gravis: Neostigmine 15 mg orally 6 hourly
sweating, increased salivary, tracheobronchial and gastric l Postoperative paralytic ileus or urinary retention: Neo-
secretions. Hypotension, muscular twitching, weakness, stigmine 0.5–1 mg SC
convulsions and coma may occur. l Postoperative decurarization: Neostigmine 0.5–2 mg IV
l Death occurs due to respiratory paralysis. l Cobra bite: Neostigmine along with atropine is given.
Q. 3. Compare neostigmine and physostigmine.

Treatment
Ans. Neostigmine and physostigmine are compared based
l If poisoning is through skin, remove clothes and wash skin on following parameters:
thoroughly. If by oral route, gastric lavage is necessary.
l Maintain BP and patent airway. Comparison
l Atropine is used in the treatment of organophosphorus Parameters Physostigmine Neostigmine
poisoning and mushroom poisoning. 1. Source Natural alkaloid Synthetic
l Atropine is highly effective in counteracting the musca- obtained from Physo-
rinic symptoms produced by the organophosphorus stigma venenosum
compounds. 2. Chemistry Tertiary amine Quaternary ammo-
l In high doses it antagonizes the central effects also. derivatives nium compound
l Pralidoxime and obidoxime are used in the treatment of
3. Oral absorption Good Poor
organophosphorus poisoning. The compounds combine
with cholinesterase organophosphate complex release 4. Lipid solubility Soluble Insoluble
the binding and set free AChE enzyme. They should be 5. CNS actions Present Absent
given within a few hours (, 24 h) after poisoning, pref- 6. Applied to eye Penetrates cornea Poor penetration
erably immediately because the complex undergoes
7. Direct action on Absent Present
ageing and then the enzyme cannot be released.
cholinoceptors
Q. 2. Neostigmine 8. Prominent Autonomic effectors Skeletal muscles

effect on
Ans.
9. Important uses As miotic in glau- Postoperative uri-
l Neostigmine is a synthetic reversible anticholinesterase coma and atropine nary retention and
poisoning paralytic ileus, my-
agent. asthenia gravis and
l Reversible anticholinesterases reversibly inhibit both true curare poisoning
and pseudocholinesterases. Thus ACh gets accumulated
10. Dose 0.5–1 mg oral/ 0.5–2.5 mg IM/SC,
and produces cholinergic effects. Hence, anticholinester- parenteral, 0.1–1.0% 15–30 mg orally
ases are called indirectly-acting cholinergic drugs. eye drops
l Its actions are more pronounced on NMJ, GIT and blad-
11. Duration of Systemic 4–6 h 3–4 h
der than on CVS or eye. On skeletal muscles, it has both action Ocular 6–24 h
direct and indirect actions.
Q. 4. Therapeutic uses of atropine Reversible Anticholinesterases

Ans. 1. Carbamates: Physostigmine, neostigmine, pyridostig-
mine, edrophonium, rivastigmine, donepezil
Therapeutic uses of atropine are as follows:
2. Acridine: Tacrine
As Antisecretory Therapeutic Uses

l Preanaesthetic medication: Prior use of atropine (anti- l As miotic
cholinergics) is must to check increased salivary and 1. In glaucoma
tracheobronchial secretions when irritant general anaes- 2. To counteract effect of mydriatics after refraction testing
thetics like ether are used. It also prevents laryngospasm 3. To prevent formation of adhesions between iris and
by reducing respiratory secretions and also prevents lens or iris and cornea: Physostigmine (0.1%) is used
vasovagal attack. only to supplement pilocarpine
l Peptic ulcer: Atropine reduces gastric secretion in fast- l Myasthenia gravis: Neostigmine 15 mg orally 6 hourly
ing and neurogenic phase and affords symptomatic l Postoperative paralytic ileus or urinary retention: Neo-
relief in peptic ulcer. stigmine 0.5–1 mg SC
l Pulmonary embolism: Atropine benefits by reducing l Postoperative decurarization: Neostigmine 0.5–2 mg IV
reflex secretions. l Cobra bite: Neostigmine along with atropine
l To check excess seating salivation as in parkinsonism. l Belladonna poisoning: Physostigmine 0.5–2 mg IV
l Drug overdosages of tricyclic antidepressants, pheno-
thiazines, many antihistamines

As Antispasmodic
l Alzheimer’s disease: Rivastigmine
l Intestinal and renal colic, abdominal cramps: In absence
of mechanical obstruction, atropine offers symptomatic Q. 6. What is the organophosphorus poisoning? Describe
relief but is less effective in biliary colic. the treatment.
l Nervous and drug-induced diarrhoea, functional diar-
Ans.
rhoea but not effective in infective diarrhoeas
l Spastic constipation, irritable colon l Organophosphates are used in agricultural and domestic
l Pylorospasm, gastric hypermotility, gastritis, nervous insecticides. Organophosphorus poisoning can result as
dyspepsia accidental, suicidal or homicidal result.
l Dysmenorrhoea l Symptoms include muscarinic, nicotinic and central ef-
fects: vomiting, abdominal cramps, diarrhoea, miosis,

sweating, increased salivary, tracheobronchial and gas-
In Bronchial Asthma, Asthmatic tric secretions. Hypotension, muscular twitching, weak-
Bronchitis, COPD ness, convulsions and coma may occur.
l Atropine dries up secretions in the respiratory tract lead l Death occurs due to respiratory paralysis.
to its inspissations and plugging of bronchioles.

Treatment
As Mydriatics and Cycloplegic l If poisoning is through skin, remove clothes and wash skin
thoroughly and if by oral route, gastric lavage is necessary.
l Atropine is very valuable in treatment of iritis, iridocy- l Maintain BP and patent airway.
clitis, choroiditis, keratitis and corneal ulcer. l Atropine is used in the treatment of organophosphorus
l It affords rest to intraocular muscles and cuts down their
poisoning and mushroom poisoning.
painful spasm. l Atropine is highly effective in counteracting the muscarinic
l Atropine prevents adhesions between iris and lens or
symptoms produced by the organophosphorus compounds.
iris and cornea and may even break them if already l In high doses it antagonizes the central effects also.
formed. l Pralidoxime and obidoxime are used in the treatment of
l As cardiac vagolytic: Atropine is useful in counteracting
organophosphorus poisoning. The compounds combine
bradycardia and partial heart block in patients where in- with cholinesterase organophosphate complex, release
creased vagal tone is responsible as in MI, digitalis toxicity. the binding and set free AChE enzyme. They should be
given within a few hours (, 24 h) after poisoning, pref-
Q. 5. Therapeutic uses of reversible anticholinesterases
Ans. ageing and then the enzyme cannot be released.
SHORT NOTES
Q. 1. Role of atropine in organophosphorus poisoning given within a few hours (, 24 h) after poisoning, pref-
Ans.
ageing and then the enzyme cannot be released.
l Atropine is used in the treatment of organophosphorus
poisoning and mushroom poisoning. Q. 4. Neostigmine in myasthenia gravis
l Atropine is highly effective in counteracting the musca- Ans.
rinic symptoms produced by the organophosphorus
compounds. l Myasthenia gravis is a chronic autoimmune disease
l In high doses it antagonizes the central effects also. For characterized by progressive weakness with rapid and
these reasons atropine is used in organophosphorus easy fatigability of skeletal muscles. Antibodies to nico-
poisoning. tinic receptors are found, resulting in the number of
these receptors at NMJ.
Q. 2. Neostigmine l Neostigmine (15mg tab, 6 hourly) or pyridostigmine or
a combination of both may be used.

Ans.
l They enhance the levels of ACh at the NMJ by prevent-
l Neostigmine is a synthetic reversible anticholinesterase ing its destruction. Thus they increase the force of con-
agent. traction and improve muscle power.
l Its actions are more pronounced on NMJ, GIT and blad-
der than on CVS or eye. On skeletal muscles, it has both Q. 5. Neostigmine—uses and adverse effects
direct and indirect actions. Ans. Therapeutic uses and adverse effects of neostigmine
are as follows:
Pharmacokinetics l As miotic in glaucoma
l Myasthenia gravis
Neostigmine l Postoperative paralytic ileus or urinary retention
l is poorly absorbed orally.
l Postoperative decurarization
l does not penetrate cornea or cross blood-brain barrier.
l Cobra bite: Neostigmine along with atropine
l is partially hydrolyzed and partially excreted unchanged
l Belladona poisoning
in urine. l Alzheimer’s disease
Therapeutic Uses Adverse Effects

l Myasthenia gravis: Neostigmine 15 mg orally 6 hourly
l Muscarinic: Salivation, lacrimation, urination, defec-
l Postoperative paralytic ileus or urinary retention: Neo-
tion, GI distress and emesis
stigmine 0.5–1 mg SC
l Nicotinic: Muscular fasciculation, cramps, weakness,
l Postoperative decurarization: Neostigmine 0.5–2 mg SC
areflexia, muscle paralysis, hypertension, tachycardia,
l Cobra bite: Neostigmine along with atropine is given.
pallor and mydriasis
l CNS: Restlessness, emotional lability, headache, tremors,
Q. 3. Pralidoxime
drowsiness, confusion, slurred speech, coma, convulsions,
Or, depression of respiratory and cardiovascular centres
Oximes in organophosphorus poisoning
Q. 6. Therapeutic uses of atropine
Ans.
Ans. Therapeutic uses of atropine are as follows:
l Oximes are reactivators of cholinesterase which are 1. As antisecretory
used to restore neuromuscular transmission in cases of l preanaesthetic medication,
organophosphorus poisoning. l peptic ulcer and
l But its use is secondary to atropine. l pulmonary embolism
l Pralidoxime and obidoxime are used in the treatment of 2. As antispasmodic

organophosphorus poisoning. The compounds combine l Intestinal and renal colic, abdominal cramps
with cholinesterase organophosphate complex, release l Nervous and drug-induced diarrhoea
the binding and set free AChE enzyme. They should be l Spastic constipation, irritable colon
l Pylorospasm, gastric hypermotility, gastritis, nervous Treatment

dyspepsia
l If poisoning is through skin, remove clothes and wash
l Dysmenorrhoea
skin thoroughly and if by oral route, gastric lavage is
3 . Bronchial asthma, asthmatic bronchitis, COPD: Atro-
necessary.
pine dries up secretions in the respiratory tract, leading
l Maintain BP and patent airway.
to its inspissations and plugging of bronchioles.
l Atropine is used in the treatment of organophosphorus
4. As mydriatics and cycloplegic: Atropine is very valu-
poisoning and mushroom poisoning.
able in treatment of iritis, iridocyclitis, choroiditis, kera-
titis and corneal ulcer.
organophosphorus poisoning.
Q. 7. Irreversible anticholinesterases
Q. 8. Name few oximes.
Ans.
Ans.
l They are powerful inhibitors of ACh enzyme. They bind
with the enzyme permanently by covalent bonds. l Oximes are reactivators of cholinesterase which are used
l Their actions are similar to ACh. They are lipid soluble and
to restore neuromuscular transmission in cases of organo-
are highly absorbable by all routes including intact skin. phosphorus poisoning, but its use is secondary to atropine.
l Few examples of oximes are as follows:
l They include the following:
1. Organophosphates, e.g. dyflos, echothiophate, para- 1. Pralidoxime (2-PAM)

thion, malathion, etc. 2. Obidoxime
2. Carbamates, e.g. carbaryl, propoxur 3. Diacetyl monoxime (DAM)
l Organophosphates are used in agricultural and domestic
insecticides. Organophosphorus poisoning can result as organophosphorus poisoning.

l They should be given within a few hours (, 24 h) after
accidental, suicidal or homicidal result. Death occurs
due to respiratory paralysis. poisoning, preferably immediately.
Topic 6
Anticholinergic Drugs and Drugs

Acting on Autonomic Ganglia
LONG ESSAY
Q. 1. Classify anticholinergic drugs. Discuss the phar- Classification
macology and uses of atropine. Mention the symptoms
of atropine poisoning and line of treatment. I. Natural alkaloids
i. Atropine
Or, ii. Hyoscine (scopolamine)
Classify anticholinergic drugs. Discuss the adverse II. Semisynthetic derivatives
effects and uses of atropine. i. Homatropine
ii. Atropine methonitrate
Or, iii. Hyoscine butyl bromide
Discuss the pharmacological actions of atropine. Men- iv. Ipratropium bromide
tion some atropine substitutes and their uses in the v. Tiotropium bromide
therapy. III. Synthetic compounds
a. Mydriatics
Ans. i. Cyclopentolate
Anticholinergic drugs are those which block actions of ii. Tropicamide
acetylcholine on autonomic effectors and in the CNS ex- b. Antisecretory: Antispasmodic
erted through muscarinic receptors. i. Quaternary compounds: Propantheline, oxyphe-
nonium, clidinium, pipenzolate methyl bromide,
isopropamide, glycopyrrolate, tertiaryamines, l Cycloplegia due to paralysis of ciliary muscle (blockade

dicyclomine, oxybutynin, flavoxate, pirenzepine, M3 receptors)
telenzepine l Ciliary muscles recover earlier than sphincter pupillae.
c. Antiparkinsonian: Trihexy phenidyl (benzhexol),

procyclidine, biperiden, benztropine, cycrimine, v. Smooth Muscles
ethopropazine
Through M3 blockade atropine relaxes all visceral smooth
muscles that receive parasympathetic innervation.
ATROPINE a. GIT: Atropine decreases tone and motility of the gut, but
l Atropine is the prototype drug and the chief alkaloid of bel- increases the sphincter tone and may cause constipation.
ladonna. It is an anticholinergic drug that acts as an antago- It also relaxes the smooth muscle of the gallbladder.
nist of muscarinic receptors and is parasympatholytic. b. Urinary bladder: Atropine relaxes the detrusor muscle
l Mechanism of action: Atropine acts by antagonizing the of the bladder but increases the tone of the trigonal
muscarinic receptors. It blocks the action of ACh on sphincter and may cause urinary retention, especially in
autonomic effectors and in the CNS. elderly men with enlarged prostate.
c. Bronchi: Atropine relaxes the bronchial smooth muscle.
Pharmacological Actions It also reduces the secretions and mucociliary clearance
resulting in the mucus plug that may block the airway.
Pharmacological actions of atropine are as follows: Atropine causes bronchodilatation and reduces airway
resistance especially in COPD and asthma patients.
i. CNS
l Atropine has overall CNS stimulant action. In therapeu- vi. Body Temperature
tic doses, atropine has mild CNS-stimulant effect. l At high doses body temperature rises due to inhibition
l It suppresses tremors and rigidity of parkinsonism by of sweating and stimulation of temperature regulating
blocking the relative cholinergic overactivity in basal centres in the hypothalamus.
ganglia and extrapyramidal tracts and thus produces l Children are highly susceptible to atropine fever.
antiparkinsonian effect.
l It suppresses vestibular disturbances and produces anti-
vii. Local Anaesthetics
motion sickness effect.
l Large doses can produce excitement, restlessness, agita- Atropine has a mild anaesthetic action on the cornea.
tion, hallucinations, medullary paralysis, coma and death.
THERAPEUTIC USES
ii. CVS
a. As Antisecretory
l At low doses, atropine causes initial bradycardia due to
i. Preanaesthetic medication
the blockade of presynaptic muscarinic autoreceptors
l Prior use of atropine (anticholinergics) is must to check
(M1) on vagal nerve endings.
increased salivary and tracheobronchial secretions
l In therapeutic doses, tachycardia is seen due to block-
when irritant general anaesthetics like ether are used.
ade of M2 receptors of the heart and it also improves
l It also prevents laryngospasm by reducing respira-
A–V conduction.
tory secretions and also prevents vasovagal attack.
l In high doses, flushing of the face and hypotension may
ii. Peptic ulcer: Atropine reduces gastric secretion in fast-
occur due to cutaneous vasodilatation.
ing and neurogenic phase and affords symptomatic re-
lief in peptic ulcer.
iii. Glands
iii. Pulmonary embolism: Atropine benefits by reducing
l All secretions under cholinergic influence are reduced reflex secretions.
due to blockade of M3 receptors, i.e. sweat, salivary, iv. In bronchial asthma, asthmatic bronchitis and COPD,
nasal, throat, bronchial, gastric, lacrimal, etc. The milk atropine dries up secretions in the respiratory tract,
and bile secretions are not affected. The skin and mu- leading to its inspissations and plugging of bronchioles.
cous membranes become dry. v. To check excess seating salivation as in parkinsonism
iv. Eye b. As Antispasmodic

Topical instillation of atropine causes the following: i. Intestinal and renal colic, abdominal cramps: In absence
l Passive mydriasis due to paralysis of constrictor pupillae of mechanical obstruction, atropine offers symptomatic
(blockade of M3 receptors), lasting 7–10 days relief but less effective in biliary colic.
ii. It is effective in nervous and drug-induced diarrhoea, func- e. Poisoning

tional diarrhoea but not effective in infective diarrhoeas.
l In organophosphorus poisoning, atropine is the life-
iii. Spastic constipation, irritable colon
saving drug.
iv. Pylorospasm, gastric hypermotility, gastritis, nervous
l In some types of mushroom poisoning (Inocybe spe-
dyspepsia
cies) atropine is the drug of choice.
v. Dysmenorrhoea
l Atropine is used in curare poisoning with neostigmine
to counteract the muscarinic effects of neostigmine.

c. As Mydriatics and Cycloplegic
i. Atropine, homatropine, cyclopentolate or tropicamide ADVERSE EFFECTS AND
are used topically for producing mydriasis and cyclo- CONTRAINDICATIONS
plegia during refraction testing.
ii. Atropine is very valuable in treatment of iritis, iridocy- Adverse effects are due to the extension of pharmacological
clitis, choroiditis, keratitis and corneal ulcer. actions.
iii. It affords rest to intraocular muscles and cuts down i. GIT: Dryness of mouth and throat, difficulty in swal-
their painful spasm. lowing, constipation, etc.
iv. Atropine prevents adhesions between iris and lens or iris ii. Eye: Photophobia, headache, blurring of vision and in
and cornea and may even break them if already formed. elderly persons with shallow anterior chamber, they
v. In children, atropine is preferred because of its greater may precipitate acute congestive glaucoma. Hence,
efficacy. anticholinergics are contraindicated in glaucoma.
iii. Urinary tract: Difficulty in micturition and urinary re-
tention especially in elderly men with enlarged prostate
d. As Cardiac Vagolytic iv. CNS: With large doses produce restlessness, excite-
Atropine is useful in counteracting bradycardia and par- ment, muttering delirium and hallucinations
tial heart block in patients where increased vagal tone is v. CVS: Tachycardia, palpitation and hypotension
responsible as in MI, digitalis toxicity. It improves A–V vi. Acute belladonna poisoning: It is more common in chil-
conduction by vagolytic effect. dren. Convulsions and coma occur in severe poisoning.
SHORT ESSAYS
Q. 1. Compare atropine and cocaine. Q. 2. Atropine
Ans. Ans.
Comparison between atropine and cocaine is given in Table 6.1. l Atropine is an anticholinergic drug that acts as an
antagonist of muscarinic receptors and is parasympa-
TABLE 6.1 Comparison between Atropine and Cocaine tholytic.
Comparable l Mechanism of action: Atropine acts by antagonizing the
Points Atropine Cocaine muscarinic receptors. It blocks the action of ACh on

Acts on Autonomic nervous Central nervous
autonomic effectors and in the CNS.
system system
Action Anticholinergic drug Surface anaesthetic Pharmacological Actions
Causes Antispasmodic, Used earlier for
1. Central nervous system: Atropine stimulates many
mydriatic, cycloplegic, ocular anaesthesia
preanaesthetic medullary centres—vagal, respiratory, vasomotor. It
medication, organo- depresses vestibular excitation and has antimotion sick-
phosphorus poisoning, ness property.
in bronchial asthma 2. Cardiovascular system
and motion sickness
l Heart: Most prominent effect is tachycardia.
Adverse Blurring of vision, dry Causes constriction l Blood pressure: Atropine by itself does not have any
effects mouth and skin dys- of corneal vessels, consistent or marked effect on blood pressure. How-
phagia, fever, constipa- clouding and
ever indirectly through tachycardia and stimulation
tion, urinary retention sloughing of cornea
of vasomotor centre it raises BP.
3. Eye: Topical instillation of atropine causes mydriasis, l Dry as a bone: The skin and mucous membranes be-
abolition of light reflex and cycloplegia lasting 7–10 come dry because of blockade of secretions.
days. This results in photophobia and blurring of near l Blind as a bat: Mydriasis and cycloplegia result in pho-
vision. tophobia and severe blurring of vision.

4. Smooth muscle l Mad as a hatter: Restlessness, excitement, confusion,
l Tone and amplitude of contractions of stomach and disorientation and hallucinations.

intestine are reduced and it relieves spasms and pas- l Severe poisoning: It may cause respiratory depression,
sage of chyme is slowed resulting in constipation. cardiovascular collapse, convulsions, coma and death.
l Atropine causes bronchodilatation and reduces air- Treatment of belladonna poisoning (atropine poisoning)
way resistance especially in COPD and asthma l Mainly symptomatic
patients. l Hospitalization
5. Body temperature: At high doses body temperature rises l Gastric lavage in case of ingested poisoning
due to inhibition of sweating and stimulation of tem- l Tepid sponging to control hyperpyrexia
perature regulating centres in the hypothalamus. Chil- l Diazepam to control convulsions
dren are highly susceptible to atropine fever. l The antidote for severe atropine poisoning is physo-
6. Local anaesthetics: Atropine has a mild anaesthetic stigmine.

action on the cornea. l Physostigmine (1–4 mg) is injected slowly intrave-
nously. It is a tertiary amine, counteracts both peripheral

as well as central effects of atropine poisoning. Hence,
Uses physostigmine is preferred over neostigmine.
Atropine can be used as
l antispasmodic, Q. 5. Uses and adverse effects of atropine
l mydriatic,
Ans.
l cycloplegic,
l preanaesthetic medication,
Uses
l organophosphorus poisoning, in bronchial asthma and
l motion sickness. Atropine can be used as

l antispasmodic,
Q. 3. Homatropine l mydriatic,
l cycloplegic,
Ans.
l preanaesthetic medication,
l Belladonna alkaloids lack the selectivity and exert a l organophosphorus poisoning, in bronchial asthma and
wide range of effects, thus producing many side effects. l treatment for motion sickness.
To overcome this, several synthetic and semisynthetic Adverse effects of atropine are common but not serious,
derivatives with selective action were introduced. they are as follows:
l Homatropine is an atropine substitute that is used on l Atropine increases heart rate and in large doses may
the eye. cause hypotension.
l It causes mydriasis and cycloplegia that last for about l Atropine has an antisecretory effect on all glands and
6–24 h. They have shorter action than atropine. hence secretion is reduced from gastric glands, salivary
l Homatropine can be used in case of atropine intolerance. gland and sweat glands. It causes dry mouth, dry skin,
dysphagia, etc.
Q. 4. Atropine poisoning l It reduces GI motility and causes constipation.
l Atropine causes mydriasis due to which the iris may

Ans.
block the drainage of aqueous humour leading to raise
Acute belladonna poisoning: It is more common in in intraocular pressure. It causes blurring of vision and
children. may also cause glaucoma in some patients.
Cohen described the effects as follows:
l Hot as a hare: The body temperature is increased Q. 6. Atropine and scopolamine
(hyperpyrexia) due to the suppression of sweating Ans.
(atropine fever).
l Red as a beetroot: Hot, red and flushed skin is due to Comparison between atropine and scopolamine is given in
cutaneous vasodilatation (atropine flush). Table 6.2.
TABLE 6.2 Comparison between Atropine and Scopolamine l Some of them may also possess significant nicotinic
blocking property.
Comparable Scopolamine
Points Atropine (Hyoscine)
1. Chief Atropa belladonna, Hyoscyamus
Classification
source Datura stramonium niger Quaternary Compounds
2. Alkaloidal Tropic acid with Tropic acid with
ester of tropine scopine
l Hyoscine butyl bromide
l Atropine methonitrate
3. CNS effect
l Ipratropium bromide
a. Low dose Mild excitation Depression l Tiotropium bromide
l Propantheline
b. High dose Strong excitation Excitation
l Oxyphenonium
4. Anticholinergic More potent on More potent on
l Clidinium
property heart, bronchial eye and secretory
muscle and glands l Pipenzolate methyl bromide
intestines l Isopropamide
l Glycopyrrolate
5. Duration of Longer Shorter
action
6. Antimotion 11 111
Tertiaryamines
sickness l Dicyclomine
l Oxybutynin
l Flavoxate
Q. 7. Atropine substitutes
l Pirenzepine
Ans. l Telenzepine
l Atropine substitutes are semisynthetic derivatives of
Mydriatics
belladonna alkaloids and synthetic compounds.
l They are antagonists of muscarinic receptors and are l Homatropine
parasympatholytics. They differ only marginally from l Cyclopentolate
the atropine. l Tropicamide
SHORT NOTES
Q. 1. Atropine Uses
Ans. Atropine can be used as antispasmodic, mydriatic, cyclo-
plegic, preanaesthetic medication and in treating motion
Atropine is an anticholinergic drug that acts as an antago- sickness.
nist of muscarinic receptors and is parasympatholytic.
Q. 2. Atropine derivatives
Pharmacological Actions Ans.
1. Central nervous system: Atropine stimulates many med- Semisynthetic and synthetic antimuscarinic agents or atro-
ullary centres. pine derivatives are as follows:
2. Cardiovascular system: On the heart, most prominent 1. Atropine derivatives used as mydriatic: Homatropine,
effect is tachycardia. cyclopentolate, tropicamide
3. Eye: Topical instillation of atropine causes mydriasis, 2. Atropine derivatives used in chronic obstructive pul-
abolition of light reflex and cycloplegia. monary disease (COPD) and bronchial asthma: Ip-
4. Smooth muscle: Tone and amplitude of contractions of ratropium bromide, tiotropium bromide, oxitropium
stomach and intestine are reduced resulting in constipation. bromide
5. Body temperature: At high doses body temperature 3. Atropine derivatives used in peptic ulcer: Pirenzepine,
rises. telenzepine
6. Local anaesthetics: Atropine has a mild anaesthetic 4. Atropine derivatives used as antispasmodics: Dicyclo-
action on the cornea. mine, flavoxate, oxybutynin, tolterodine
5. Atropine derivative used as a preanaesthetic agent: Q. 6. Scopolamine

Glycopyrrolate
Ans.
6. Atropine derivatives used in parkinsonism: Benzhexol
(trihexyphenidyl), benztropine, biperidin. l Scopolamine is an anticholinergic drug which is a bel-
ladonna alkaloid.
Q. 3. Mention two atropine substitutes. l It acts by competing with the acetylcholine for musca-
Ans. rinic receptors and block these receptors. They are

muscarinic antagonists.
Belladonna alkaloids lack the selectivity and exert a wide l Chief source: It is derived from Hyoscyamus niger.
range of effects; thus producing many side effects. To over- l It forms an alkaloidal ester of tropic acid with scopine.
come this, several synthetic and semisynthetic derivatives l In low doses it depresses CNS activity and high doses it
with selective action were introduced. causes excitation.
1. Homatropine: Instilled in eye, it produces mydriasis in l It has a shorter duration of action compared to atropine.
45–60 min lasting 1–3 day but accommodation recovers l It is mainly used for antimotion sickness: Given 30 min
in day or two. before the journey. Transdermal patches of hyoscine are
2. Cyclopentolate: It produces mydriasis and cycloplegia applied behind the ear for prolonged action.
in 30–60 min lasting about a day. It is preferred for cy-
cloplegic refraction and is also used in iritis and uveitis. Q. 7. Uses of hyoscine in motion sickness
3. Tropic amide: It acts quickly in 20–40 min and duration
Ans.
of action is short lasting (3–6 h). It is used for refraction
testing and as short-acting mydriatic for fundoscopy. l Hyoscine or scopolamine acts as antiemetic by blocking
the conduction of nerve impulses across a cholinergic
Q. 4. Therapeutic uses of atropine. link in the pathway leading from the vestibular appara-
Ans. tus to the vomiting centre. Therefore, scopolamine is
used in motion sickness.
Atropine can be used as l Scopolamine has more prominent actions on eyes and
l antispasmodic, secretory glands. By blocking cholinergic activity, sco-
l mydriatic, polamine suppresses vestibular disturbances and pro-
l cycloplegic, duces antimotion sickness effect.
l preanaesthetic medication, l Scopolamine is the drug of choice for motion sickness.
l organophosphorus poisoning, It can be administered orally or as a transdermal patch.
l in bronchial asthma and l It is given minimum 30 min before the journey. Trans-
l treatment for motion sickness. dermal patches of hyoscine are applied behind the ear
for prolonged action.
Q. 5. Atropine poisoning
Ans. Q. 8. Mention four adverse effects of atropine.
Ans.
l Acute belladonna poisoning is more common in children.
l Cohen described the effects as hot as a hare, red as a Adverse effects of atropine are as follows:
beetroot, dry as a bone, blind as a bat and mad as a 1. Atropine increases heart rate and in large doses may
hatter. cause hypotension.
l Severe poisoning: It may cause respiratory depression, 2. Atropine has an antisecretory effect on all glands and
cardiovascular collapse, convulsions, coma and death. hence it causes dry mouth, dry skin, dysphagia.
l Treatment of belladonna poisoning (atropine poisoning) 3. It reduces GI motility and causes constipation.
1. Mainly symptomatic 4. Atropine causes mydriasis.
2. Hospitalization
3. Gastric lavage in case of ingested poisoning Q. 9. Rationale of using atropine in preanaesthetic
4. Tepid sponging to control hyperpyrexia medication
5. Diazepam to control convulsions Ans.
l The antidote for severe atropine poisoning is physostig-
mine. Physostigmine (1–4 mg) is injected slowly intra- Atropine is used as a preanaesthetic medication.
venously. It counteracts both peripheral as well as cen- 1. When administered 30 min before anaesthesia, atropine
tral effects of atropine poisoning. Hence, physostigmine reduces salivary and respiratory secretions. This pre-
is preferred over neostigmine. vents the development of laryngospasm.
2 . It prevents bradycardia during surgery. l For these reasons atropine is used in treatment of
3. It acts as a bronchodilator, reduces risk of asthma re- organophosphorus poisoning.
lated to anaphylactic shock. For example, glycopyrro-
late is used mostly as a preanaesthetic medication. Q. 11. Explain the rationale of using pralidoxime in
Q. 10. Rationale of using atropine in organophosphorus
Ans.
poisoning
Ans. l Pralidoxime and obidoxime are used in the treatment of
l Atropine is used in the treatment of organophosphorus l These compounds combine with cholinesterase organo-
poisoning and mushroom poisoning. phosphate complex, release the binding and set free
l Atropine is highly effective in counteracting the musca- AChE enzyme. They should be given within a few
rinic symptoms produced by the organophosphorus hours (, 24 h) after poisoning, preferably immediately
compounds. because the complex undergoes ageing and then the
l In high doses it antagonizes the central effects also. enzyme cannot be released.
Topic 7
Adrenergic System and Drugs

LONG ESSAYS
Q. 1. What are sympathomimetics? Classify them. De- 3. Mixed-action sympathomimetics: They act directly as well
scribe pharmacological actions, therapeutic uses and as indirectly, e.g. ephedrine, amphetamine, mephentermine.
side effects of adrenaline.
Or, II. On the Basis of Their Chemical
Discuss the pharmacological actions and some impor- Structure
tant uses of sympathomimetic drugs. 1. Catecholamines: Sympathomimetics with catechol nu-
Or, cleus are called catecholamines, e.g. adrenaline, nor-
adrenaline, dopamine, isoprenaline and dobutamine.
Classify sympathomimetics. Write the therapeutic uses 2. Noncatecholamines: Sympathomimetics that lack catechol
and adverse effects of adrenaline. nucleus are called noncatecholamines, e.g. tyramine,
Ans. ephedrine, amphetamine, phenylephrine, salbutamol, etc.
Sympathomimetics are also known as adrenergic drugs. III. On the Basis of Their Therapeutic Use
These are drugs with action similar to that of adrenaline or
sympathetic stimulation. i. Drugs that raise blood pressure (pressor agents): Nor-
adrenaline, ephedrine, phenylephrine, methoxamine
mephentermine and dopamine
CLASSIFICATION OF ADRENERGIC DRUGS ii. As cardiac stimulants or inotropic agents: Adrenaline,
(SYMPATHOMIMETICS) isoprenaline, dopamine or dobutamine
iii. Drugs used as bronchodilators: Adrenaline, isoprena-
I. On the Basis of Their Mechanism of Action
line, orciprenaline, salbutamol, terbutaline, salmeterol,
1. Direct-acting sympathomimetics: They act directly as formoterol
agonists on a and/or b adrenoreceptors, e.g. adrena- iv. As CNS stimulants: Ephedrine, amphetamine, dexam-
line, noradrenaline, isoprenaline, phenylephrine, meth- phetamine
oxamine, xylometazoline, salbutamol, etc. v. As anorexiants: Dextroamphetamine, phentermine,
2. Indirect-acting sympathomimetics: They act on adrener- fenfluramine
gic neurone to release NA which then acts on the adre- vi. As uterine relaxants and vasodilators: Isoxsuprine,
noreceptors, e.g. tyramine. salbutamol, terbutaline and ritodrine
vii. Nasal decongestants: Phenylephrine, xylometazoline, VI. CNS

oxymetazoline pseudoephedrine and naphazoline
In therapeutic doses, adrenaline does not cross the BBB and
viii. For allergic reactions (anaphylactic shock): Adrenaline
hence CNS effects are very minimal.
ix. For local vasoconstrictor effect: Adrenaline
PHARMACOLOGICAL ACTIONS THERAPEUTIC USES

OF ADRENALINE Therapeutic uses of adrenaline are as follows:
i. Anaphylactic shock: Adrenaline is a life-saving drug in
I. Cardiovascular System anaphylactic shock and other type-I hypersensitive re-
i. Heart actions. It rapidly reverses the manifestations of severe
allergic reactions. Given as adrenaline 0.3–0.5 mL of
l Adrenaline is a powerful cardiac stimulant. 1:1000 solution (1 mg/mL) IM.
l It increases heart rate (positive chronotropic). ii. Allergic disorders: It rapidly reverses the manifesta-
l Increases myocardial contractility (positive inotropic). tions of severe allergic reactions.
l Increase in conduction velocity (positive dromotropic) iii. Along with local anaesthetics it increases duration of
l Thus increases cardiac output and oxygen consumption. action of anaesthesia.
l Increase in the excitability and tendency to cause car- iv. Control epistaxis and other capillary oozing: Adrena-
diac arrhythmias. line is used as a local haemostatic to control bleeding
following tooth extraction and during surgical proce-
ii. Blood Vessels and Blood Pressure dures in nose, throat, larynx, etc. because of its vaso-
constrictor effect.
l Adrenaline constricts blood vessels of skin and mucous v. Bronchial asthma: Adrenaline is a powerful broncho-
membranes which predominantly contain a1 receptors. dilator and has rapid onset but short duration of action.
l It also constricts renal, mesenteric, pulmonary and It is useful for acute attack. Adrenaline 0.3–0.5 mL of
splanchnic vessels but dilates blood vessels of skeletal 1:1000 solution is given subcutaneously. It can be
muscles and coronary vessels which contain b2 receptors. given by nebulization (as inhalation).
l Intravenous administration of adrenaline in moderate vi. Cardiac resuscitation: In the treatment of cardiac arrest
doses produces typical biphasic effect. There is an due to drowning or electrocution, adrenaline is injected
initial rise in blood pressure due to a1 (blood vessels) intravenously in 1:10000 (0.1 mg/mL) concentration
and a1 (heart) actions, followed by a fall in BP due to along with other supportive measures such as external
b2-mediated vasodilation in skeletal muscle. cardiac massage, as a part of advanced life support (ALS).
vii. Blood pressure: Adrenaline increases systolic blood
II. Respiratory System pressure and decreases diastolic BP.
viii. Glaucoma: Adrenaline has poor penetration when ap-
l Adrenaline rapidly relaxes (b2) bronchial smooth muscle. It plied locally into the eye, hence it is administered as a
is a potent bronchodilator but has short duration of action. prodrug.
l It inhibits the release of inflammatory mediators from
mast cells (b2).

SIDE EFFECTS OF ADRENALINE
l It reduces secretions and relieves mucosal congestion
by vasoconstrictor effect (a1). The adverse effects are due to the extension of pharmaco-
logical actions, they are as follows:
i. Tachycardia, palpitation, headache, restlessness, tremor
III. GIT and rise in BP
Adrenergic drugs cause gut relaxation, decrease motility ii. The serious side effects are cerebral haemorrhage and
and constrict sphincters. cardiac arrhythmias.
iii. In high concentrations, adrenaline may cause acute
pulmonary oedema due to the shift of blood from the
IV. Bladder systemic to the pulmonary circulation.
Adrenergic drugs cause detrusor muscle relaxation (b2) and iv. Adrenaline is contraindicated in most of the cardiovascu-
contract the trigone sphincter (a1). As a result it may cause lar diseases such as hypertension, angina, cardiac arrhyth-
inhibition or difficulty of micturition. mias, CCF, etc. and also in patients on b-blockers, because
it may cause hypertensive crisis and cerebral haemorrhage
due to unopposed action on vascular a1 receptors.
V. EYE v. On intravenous administration adrenalin rapidly causes
Adrenaline has poor penetration through cornea when applied sudden rise in BP, ventricular tachycardia, angina, myo-
topically into the eye. Hence, it is administered as a prodrug. cardial infarction and stroke.
vi. Metabolic side effects of adrenaline include hypergly- A. Therapeutic Uses of Adrenaline
caemia, hyperlactacidemia and hypokalaemia.
i. Anaphylactic shock
Q. 2. Describe the differences in action of adrenaline, nor- ii. Allergic disorders
adrenaline and isoprenaline. Write their uses indicating iii. Used along with local anaesthetics to increase dura-
the routes of administration. tion of action of anaesthesia.
iv. They control local bleeding from skin, mucous mem-
Ans. brane, epistaxis, tooth socket.
v. Cardiac arrest: IV adrenaline to stimulate heart.
Sympathomimetics are also known as adrenergic drugs.
vi. Bronchial asthma
These are drugs with action similar to that of adrenaline or
vii. Mydriatics: Decreases intraocular tension in glau-
sympathetic stimulation.
coma.
The differences in pharmacological actions of adrena-
viii. Route of administration of adrenaline: 0.2–0.5 mg can
line, noradrenaline and isoprenaline are given in Table 7.1.
be given SC, IM or 0.5% by aerosol.
TABLE 7.1 Differences in Action of Adrenaline,

Noradrenaline and Isoprenaline
B. Therapeutic Uses of Other Adrenergic
Drugs (Noradrenaline and Isoprenaline) Are
Site of Action Adrenaline Noradrenaline Isoprenaline as Follows:
1. Heart Increases Does not Powerful
heart rate increase heart cardiac stimu- i. Anaphylactic shock and allergic disorders
rate lant increases ii. Hypotensive state: Vasopressor agent can be used.
heart rate iii. Neurogenic or cardiogenic shock: Dopamine or dobuta-
2. BP Systolic BP, Both systolic Systolic and mine is preferred.
diastolic BP and diastolic diastolic BP iv. Congestive heart failure: Short-term use in decompen-
BP sated state, i.e. dopamine and dobutamine.
3. Respiration Causes No bronchodi- Causes bron- v. Partial or complete heart block: Ephedrine or isoprena-
bronchodilation chodilation line can be used as cardiac stimulant.
lation vi. Control local bleeding from skin and mucous mem-
4. GIT Causes gut brane, e.g. epistaxis. NA 8 mg in 100–200 mL saline
relaxation controls bleeding from gastric erosions and stress ulcers
and decrease when put in the stomach through a tube.
in motility
vii. Route of administration of noradrenaline or isoprena-
and cause
constipation line is as follows:
a. Noradrenaline 2–4 µg/min IV infusion
5. Blood
b. Isoprenaline 20 mg sublingual, 1–2 mg IM,
sugars
5–10 µg/min IV infusion
SHORT ESSAYS
Q. 1. Adrenaline l Thus increases cardiac output and oxygen consumption.
Ans.
Blood Vessels and Blood Pressure
Sympathomimetics are also known as adrenergic drugs.
These are drugs with action similar to that of adrenaline or l Adrenaline constricts blood vessels of skin and mucous
sympathetic stimulation. membranes which predominantly contain a 1 receptors
but dilates blood vessels of skeletal muscles and coro-
nary vessels which contain b2 receptors.
PHARMACOLOGICAL ACTIONS l Intravenous administration of adrenaline in moderate
OF ADRENALINE doses produces typical biphasic effect. There is an ini-

tial rise in blood pressure due to a1 (blood vessels) and
Cardiovascular System b1 (heart) actions, followed by a fall in BP due to
Heart a2-mediated vasodilation in skeletal muscle.
Adrenaline is a powerful cardiac stimulant.

Respiratory System
l
l It increases heart rate (positive chronotropic), myocar-

dial contractility (positive inotropic) and also conduc- l Adrenaline rapidly relaxes (b2) bronchial smooth muscle. It
tion velocity (positive dromotropic). is a potent bronchodilator but has short duration of action.
l It reduces secretions and relieves mucosal congestion Therapeutic uses

by vasoconstrictor effect (a1).
1. Cardiogenic and septic shock: DA is the drug of
choice because it increases BP as well as selectively
GIT dilates renal, mesenteric, coronary blood vessels and
improves blood flow to the vital organs. Hence dopa-
l Adrenergic drugs cause gut relaxation, decrease mo-
mine is preferred.
tility and constrict sphincters.
2. Severe heart failure with renal impairment: DA im-
proves both cardiac and renal functions.
Bladder
Q. 3. Compare adrenaline and ephedrine.
l Adrenergic drugs cause detrusor muscle relaxation (b2)
and contract the trigone sphincter (a1), as a result it may Ans.
cause inhibition or difficulty of micturition.
Comparison between adrenaline and ephedrine is given in
Table 7.2.
EYE
TABLE 7.2 Comparison between Adrenaline and Ephedrine
l Adrenaline has poor penetration through cornea when
applied topically into the eye. Hence, it is administered Comparable
as a prodrug. Points Adrenaline Ephedrine
Type Directly-acting sympa- Mixed-acting
thomimetics medulla sympathomimet-
CNS ics medulla
l In therapeutic doses, adrenaline does not cross the BBB Source Natural Natural: Ephedra
vulgaris
and hence CNS effects are very minimal.
Action on Acts on a1, a2, b1, b2 Mainly acts indi-
Q. 2. Dopamine receptors receptors but no D rectly but acts on
action a and b receptors
Ans.
Heart rate Increases followed by Increases
l Dopamine (DA) is a catecholamine and the immediate reflex bradycardia
metabolic precursor of NA. It is a directly-acting sym- Cardiac output Increases Increases
pathomimetic that acts on the receptors of the medulla. Total periph- Decreases Increases
l DA, like adrenaline and noradrenaline (NA), is not ef- eral resistance
fective orally. DA is rapidly inactivated by COMT and
Mean blood Increases followed by Increases
MAO and is administered by IV infusion. pressure decrease (Dale’s vaso-
l It is a D1 and D2 as well as adrenergic a and b1 (but not motor phenomenon)
b2) agonist.
Blood vessels Vasoconstriction Vasoconstriction
l The D1 receptors in renal and mesenteric blood vessels
are the most sensitive. Adverse effects Transient restlessness, Insomnia, tachy-
palpitation, anxiety, cardia, palpita-
l IV infusion of low dose of DA dilates these vessels in-
tremors. Marked rise tion, difficulty in
creasing GFR and Na1 excretion. in BP leading to cere- urination and
l At doses normally infused IV doses, it raises cardiac bral haemorrhage, tachyphylaxis on
output and systolic BP with little effect on diastolic BP. ventricular tachycar- repeated adminis-
l Moderately high doses produce a positive inotropic ef-
dia, angina, MI tration
fect on heart. Route of ad- SC, IM Orally
l Vasoconstriction (a1 action) occurs only when large doses ministration
are infused. This is useful in cardiogenic and septic shock. Therapeutic Shock, along with lo- Mild chronic
l Adverse effects: The adverse effects seen are mainly due uses cal anaesthetics styp- asthma and for
to sympathetic stimulation. They are nausea, vomiting, tics, cardiac arrest, hypotension
headache, hypertension, tachycardia, cardiac arrhyth- allergic disorders, during spinal
bronchial asthma anaesthesia
mias and anginal pain.
Q. 4. Pharmacotherapy of shock Points to be

Ans. Compared Adrenaline Noradrenaline
Cardiac output Increased Decreased
Drugs used in shock are as follows:
1. Sympathomimetic amines: Noradrenaline, adrenaline, Systolic BP Increased Increased
dopamine and dobutamine. These drugs maintain perfu- Diastolic BP Decreased Increased
sion of vital organs by increasing myocardial contractil- Mean BP Increased Increased
ity and cardiac output, constricting vessels, venules and
Total peripheral Decreased Increased
dilating arterioles in vital organs. resistance
2. Alpha adrenoceptor blocking agents: Phenoxybenza-
mine is used in surgical shock after loss of adequate Blood vessels Constriction of Vasoconstrictor
some but dilata-
fluid volume by reducing vasoconstriction by reflex tion of blood
release of noradrenaline. vessels in mus-
3. Oxygen: It is used in patients in cardiogenic shock, cles, liver and
reduces cyanosis due to arterial hypoxemia. heart
4. Dextran and other plasma expanders: High molecular Respiration Stimulated and Stimulated but
weight dextran and low molecular weight dextran are used bronchodilata- no bronchodila-
in hypovolaemic shock. They increase plasma volume tion tion
temporarily and drawing fluid in vascular space and Uterus (in vivo) Inhibits in late Stimulates
improve blood flow. pregnancy and contractions
5. Glucagon: It increases myocardial contractility and during labour
and puerperium
improve haemodynamic status.
6. Corticosteroids: They are used in anaphylactic shock, Uses For anaphylactic As a pressor
septic shock and shock due to acute adrenal insufficiency. shock agent but rarely
used nowadays
Q. 5. Adrenaline and noradrenaline
Ans. Q. 6. List at least two drugs from b adrenoceptor stimu-
lants. Describe pharmacological actions.
Comparison between adrenaline and noradrenaline is given
in Table 7.3. Ans.
b Adrenoceptor Stimulants
TABLE 7.3 Comparison between Adrenaline and
Noradrenaline b adrenoceptor stimulants are as follows:
1. Adrenaline
Points to be
2. Noradrenaline
Compared Adrenaline Noradrenaline
Site of synthesis Only in adrenal In adrenergic
cells medulla neurons Pharmacological Actions
Action on a1 1 a 2 1 b1 1 a 1 1 a 2 1 b1 Heart
b2 and weak b3 1 b3 but no b2
action action l Adrenaline: It increases heart rate, force of contraction,
Pharmacological conduction; thus increases the cardiac output.
action on various l Noradrenaline: It does not increase the heart rate but
systems produces bradycardia due to reflex mechanism.
Cardiovascular system
Heart rate Increased Decreased BP
Force of contraction Increased Decreased l Adrenaline: It increases systolic BP and decreases dia-
Excitability of Increased No change stolic BP.
increased heart l Noradrenaline: It increases systolic and diastolic BP
muscle because b2 action is very weak.
Respiration Bladder
l Adrenaline: It is a potent bronchodilator. l They cause muscle relaxation, constriction of sphincter
l Noradrenaline: It does not cause bronchodilatation. and inhibition of micturition.
GIT Eye
l Adrenaline and noradrenaline cause gut relaxation, l Contraction of radial muscle of iris causes mydriasis
decrease motility and cause constriction of sphincter.
SHORT NOTE
Q. 1. Ephedrine l Prazocin is used as an antihypertensive, in LVF not
controlled by diuretics and digitalis, Raynaud’s syn-
Ans.
drome and prostatic hypertrophy.
l Ephedrine is an alkaloid obtained from Ephedra vul-
garis. Q. 4. Write the rationale of combining xylocaine with
l Mainly acts indirectly but has some direct action on
adrenaline for local anaesthesia.
a and b receptors. Ans.
l Repeated injections produce tachyphylaxis primarily
because the neuronal pool of NA available for displace- l Adrenaline combined with xylocaine is used in dental
ment is small. practice for anaesthesia.
l It is resistant to MAO therefore effective orally. l Adrenaline causes vasoconstriction and prolongs dura-
l It crosses to brain and is a CNS stimulant. tion of action of local anaesthetic, reduces blood loss
l It has vasoconstrictor, cardiac stimulant, nasal decon- after an extraction and surgical procedures and also
gestant, bronchodilator and mydriatic actions. decreases the toxicity.
l Ephedrine is now replaced by more selective drugs and
is occasionally used in mild chronic bronchial asthma Q. 5. What is dopamine? Mention one use and route of
and for hypotension during spinal anaesthesia. administration.
Ans.
Q. 2. Amphetamine
l Dopamine (DA) is a catecholamine and the immediate
Ans.
metabolic precursor of NA. It is a directly-acting sym-
l Amphetamine is a synthetic compound having the same pathomimetic that acts on the receptors of the medulla.
pharmacological profile as ephedrine. l DA is not effective orally as it is rapidly inactivated by
l Orally active with long duration (4–6 h). COMT and MAO and is administered by IV infusion.
l The CNS actions are more prominent, maximal selec- l It is a D1 and D2 as well as adrenergic a and b1 (but not
tivity is exhibited by dextroamphetamine and metham- b2) agonist.

phetamine, which in the usual doses produce few l The D1 receptors in renal and mesenteric blood vessels
peripheral effects. are the most sensitive IV infusion of

l The central effects include alertness, increased concen- l low dose of DA dilates these vessels increasing GFR
tration and attention span, euphoria, talkativeness and and Na1 excretion.
increased work capacity. l normal dose raises cardiac output and systolic BP
with little effect on diastolic BP.

Q. 3. Prazocin l moderately high doses produce a positive inotropic
effect on heart.
Ans.
l vasoconstriction (a 1 action) occurs only when large
l Prazocin is first of the highly selective a1 blockers hav- doses are infused.
ing a1: a2 selectivity ratio 1000:1. l Adverse effects: Nausea, vomiting, headache, hyperten-
l It blocks sympathetically-mediated vasoconstriction sion, tachycardia, cardiac arrhythmias and anginal pain
and produces fall in BP which is attended by only mild l Therapeutic uses
tachycardia. l Cardiogenic and septic shock
l Prazocin dilates arterioles more than veins. l Severe heart failure with renal impairment
Q. 6. Adrenaline in anaphylactic shock l Dopamine is an adrenergic a and b1 but not b2 agonist.

l In IV low dose dopamine dilates the blood vessel and
Ans.
increase GFR and sodium secretion.
l Adrenaline is the drug of choice in anaphylaxis (ana- l At normal dose it increases the cardiac output and sys-
phylactic shock). tolic blood pressure with little effect on diastolic blood
l Adrenaline is the physiological antagonist of histamine pressure.
which is an important mediator of anaphylactic shock. l The dopamine increases blood pressure and causes
l It also raises BP, counteracts accompanying broncho- urine outflow, hence it is used in the shock.
spasm or laryngeal oedema, therefore adrenaline is used l Dopamine is the drug of choice in cardiogenic and sep-
in anaphylaxis. tic shock because it increases BP as well as selectively

dilates renal, mesenteric, coronary blood vessels and
improves blood flow to the vital organs.
Q. 7. Write basis of use of dopamine in shock.
l Dopamine can be used in all types of shocks and in
Ans. severe CHF. Its normal dose is 0.2–1 mg/min IV.
Topic 8
Antiadrenergic Drugs
LONG ESSAY
Q. 1. Enumerate b-blockers. Write their pharmacological l Blood pressure falls. The effect is more pronounced in
actions and adverse effects of propranolol. presence of increased sympathetic tone than in a normal
Or, situation.
l AV conduction is delayed.
Classify b-blockers. Describe the pharmacological action, l Myocardial oxygen requirement is reduced due to
therapeutic uses and adverse effects of propranolol. reduced cardiac work.
l It also improves exercise tolerance in angina patients.
Ans.
l High dose produces membrane stabilizing activity.
b-blockers are drugs that block the actions of catechol-
amines mediated through the b-receptors.
B. Respiratory Tract
l Blockade of b2 receptors in the bronchial smooth mus-
Classification cle causes increase in airway resistance. Many precipi-
I. Nonselective b-adrenergic blockers tate acute attack in asthmatics.
a. with intrinsic sympathomimetic activity: Proprano-
lol, nadolol, timolol, sotalol C. Eye
b. with intrinsic sympathomimetic activity: Partial
agonists: Pindolol, oxprenolol Many b-blockers reduce intraocular pressure by decreased
II. Cardioselective (b 1) adrenergic blockers: Metoprolol, secretion of aqueous humour.
atenolol, acebutolol, esmolol
III. b-blockers with additional vasodilatory effect: Labet- D. Metabolic
alol, carvedilol, celiprolol
b antagonists and glycogenolysis induced by sympathetic
stimulation. Plasma triglycerides may increase and HDL
Pharmacological Action levels decrease in some patients.
A. CVS
l b -blockers depress all the cardiac properties. E. CNS
l b -blockers decrease heart rate, force of contraction and No overt central effects are produced by the propranolol.
cardiac output. However, subtle behavioural changes, forgetfulness, increased
dreaming and nightmare have been reported with long-term vii. Pheochromocytoma: b-blockers may be added to
use of relatively high doses. b-blockers to control cardiac manifestations like
tachycardia and arrhythmias.
viii. Thyrotoxicosis: Propranolol rapidly controls symptoms
F. Local Anaesthetic
(palpitation, nervousness, tremors, severe myopathy
Propranolol is as potent a local anaesthetic as lignocaine, and sweating) without significantly affecting thyroid
but is not used because of its irritant property. status.
ix. Migraine: Propranolol is the most effective drug for
chronic migraine.
G. Skeletal Muscle
x. Anxiety: Propranolol exerts an apparent antianxiety
Propranolol inhibits adrenergically provoked tremor. This effects especially under conditions which provoke
is a peripheral action exerted directly on muscle fibre nervousness and panic, e.g. examination, unaccus-
through b2 receptors. tomed public appearances, etc.
xi. Essential tremors: Oral propranolol may be used in
treatment of essential tremors.
Uses
xii. Glaucoma: b-blockers decrease IOP by reducing the
i. Hypertension: Propranolol is used as a mild antihyper- production of aqueous humour.
tensive. They are the first drugs of choice as patient xiii. Hypertrophic obstructive cardiomyopathy: The sub-
acceptability is good. aortic region is hypertrophic. Propranolol improves
ii. Prophylaxis of angina pectoris: It benefits angina of cardiac output in these patients during exercise, by
effort. Taken over a period of time, they decrease fre- reducing left ventricular outflow.
quency of attacks and increase exercise tolerance.
iii. Cardiac arrhythmias: It suppresses extrasystoles and
tachycardias, especially those mediated adrenergically.
Adverse Effects
iv. Myocardial infarction: In cases of MI, propranolol is i. Propranolol can accentuate myocardial insufficiency
used for two purposes. and worsen CHF.
l Secondary prophylaxis of MI: Long-term use after ii. Bradycardia: Resting HR may be reduced to 60 min or
recovery from MI has been found to decrease sub- less.
sequent mortality. iii. Propranolol worsens chronic obstructive lung disease
l Myocardial salvage during evolution of MI—ad- can precipitate life-threatening bronchial asthma;
ministered IV within 4–6 h of an attack followed by hence contraindicated in asthmatics.
continued oral therapy. It helps to iv. Carbohydrate tolerance may be impaired in prediabetics.
1. limit the size of the infarct. v. Withdrawal of propranolol after chronic use should be
2. prevent arrhythmias including ventricular fibril- gradual, otherwise rebound hypertension, worsening
lation. of angina and sudden death can occur.
v. Congestive cardiac failure: Introduced gradually and vi. Propranolol is contraindicated in partial and complete
maintained for long term, it can retard progression of heart block, arrest may occur.
congestive heart failure and prolong life, e.g. carve- vii. Cold hands and feet due to blockade of vasodilatory
dilol, metoprolol and bisoprolol. b2 receptors
vi. Dissecting aortic aneurysm: b -blockers help by reduc- viii. Side effects not overtly due to b blockade are—GIT
ing cardiac contractile force and aortic pulsation as well upset, lack of drive, nightmares, forgetfulness, rarely
as the rate of development of pressure during systole. hallucinations.
SHORT ESSAYS
Q. 1. Adrenergic a-blockers 2 . Equilibrium type (competitive)
3. Nonselective
Ans.
a. Ergot alkaloids: Ergotamine, ergotoxine
These drugs inhibit adrenergic responses mediated through b. Hydrogenated ergot alkaloids: Dihydroergotamine
the a-adrenergic receptors, without affecting those medi- (DHE), dihydroergotoxine
ated through b-receptors. c. Imidazolines: Tolazoline, phentolamine
d. Miscellaneous: Chlorpromazine, ketanserin
4. a1 selective: Prazosin, terazosin, doxazosin, tamsu-
Classification losin
1. Nonequilibrium type: b-haloalkylamines, phenoxyben- 5. a2 selective: Yohimbine
zamine
Pharmacological Actions l CNS: No overt central effects are produced by the

propranolol. However, subtle behavioural changes,
l Blockade of vasoconstrictor a1 receptors reduces periph-
forgetfulness, increased dreaming and nightmare have
eral resistance, causes pooling of blood in capacitance
been reported with long-term use of relatively high doses.
vessels, venous return and cardiac output is reduced and
l Local anaesthetic: Propranolol is as potent a local an-
there is a fall in BP.
aesthetic as lignocaine, but is not used because of its
l Reflex tachycardia occurs due to fall in mean arterial
irritant property.
pressure and increased release of NA due to blockade of
l Skeletal muscle: Propranolol inhibits adrenergically
presynaptic a 2 receptors.
provoked tremor. This is a peripheral action exerted
l Nasal stiffness and miosis result from blockade of a
directly on muscle fibre through b2 receptors.
receptors in nasal blood vessels and in radial muscles of
iris respectively. Q. 3. Uses and adverse effects of propranolol
l Intestinal motility is increased—diarrhoea occurs.
l Tone of smooth muscle is reduced in bladder, sphincter Ans.

and prostate.
Propranolol is a first generation nonselective b-blocker
with intrinsic sympathomimetic activity.
Uses They are the drugs that block the actions of catechol-
amines mediated through the b receptors.
l Pheochromocytoma
l Hypertension
l Secondary shock Uses
l Peripheral vascular diseases
l Hypertension: Propranolol is used as a mild antihy-
l Benign hypertrophy of prostate
pertensive. b-blockers are the first drugs of choice as
Q. 2. Classification and pharmacological actions of patient acceptability is good.
l Prophylaxis of angina pectoris: It benefits angina of effort.
b-adrenergic blocking drugs.
l Cardiac arrhythmias: It suppresses extrasystoles and
Ans. tachycardias, especially those mediated adrenergically.
l Myocardial infarction: In cases of MI, propranolol is
used for two purposes.

Classification 1. Secondary prophylaxis of MI: Long-term use after
1. Nonselective b-adrenergic blockers recovery from MI has been found to decrease subse-
a. with intrinsic sympathomimetic activity: Propranolol, quent mortality.
nadolol, timolol, sotalol 2. Myocardial salvage during evolution of MI: Admin-
b. with intrinsic sympathomimetic activity: Partial istered IV within 4–6 h of an attack followed by
agonists (indolol, oxprenolol) continued oral therapy.
2 . Cardioselective b 1-adrenergic blockers: Metoprolol, l Congestive cardiac failure: Introduced gradually and
atenolol, acebutolol, esmolol maintained for long term, it can retard progression of
3. b-blockers with additional vasodilatory effect: Labet- congestive heart failure and prolong life, e.g. carvedilol,
alol, carvedilol, celiprolol metoprolol and bisoprolol.
l Pheochromocytoma: b-blockers may be added to
b-blockers to control cardiac manifestations like tachy-

Pharmacological Actions cardia and arrhythmias.
l CVS: b-blockers depress all the cardiac properties. It l Thyrotoxicosis: Propranolol rapidly controls symptoms
improves exercise tolerance in angina patients. High (palpitation, nervousness, tremors, severe myopathy
dose produces membrane stabilizing activity. and sweating) without significantly affecting thyroid
l Respiratory tract: Blockade of b2 receptors in the bron- status.
chial smooth muscle causes increase in airway resis- l Anxiety: Propranolol exerts an apparent antianxiety
tance. Many precipitate acute attack in asthmatics. effects especially under conditions which provoke
l Eye: Most of the b-blockers reduce intraocular pressure nervousness and panic.
by decreased secretion of aqueous humour. l Essential tremors: Oral propranolol may be used in
l Metabolic: b-antagonists and glycogenolysis induced treatment of essential tremors.

by sympathetic stimulation. Plasma triglycerides may l Glaucoma: b-blockers decrease IOP by reducing the
increase and HDL levels decrease in some patients. production of aqueous humour.
Adverse Effects l Carbohydrate tolerance may be impaired in prediabetics.

l Withdrawal of propranolol after chronic use should be
l Propranolol can accentuate myocardial insufficiency gradual, otherwise rebound hypertension, worsening
and worsen CHF. of angina and sudden death can occur.
l Bradycardia l Propranolol is contraindicated in partial and complete
l Propranolol worsens chronic obstructive lung disease heart block, arrest may occur.
can precipitate life-threatening bronchial asthma; hence l Cold hands and feet due to blockade of vasodilatory b2
contraindicated in asthmatics. receptors
SHORT NOTES
Q. 1. Classify b-adrenergic receptor blockers. l Propranolol worsens chronic obstructive lung disease
can precipitate life-threatening bronchial asthma; hence
Or, contraindicated in asthmatics.
Classification of b-blockers. l Withdrawal of propranolol after chronic use should be
gradual, otherwise rebound hypertension, worsening of

Ans. angina and sudden death can occur.
b-blockers are drugs that block the actions of catechol-
Q. 3. Timolol
Ans.
Classification l Timolol is a nonselective b-blocker with intrinsic sym-
1. Nonselective b-adrenergic blockers pathomimetic activity.
a. with intrinsic sympathomimetic activity: Proprano- l Its ocular hypotensive action is smooth and well sus-
lol, nadolol, timolol, sotalol tained; hence is used as a topical agent in the eye.
b. with intrinsic sympathomimetic activity: Partial ago- l Used in the treatment of glaucoma.
nists (pindolol, oxprenolol) l Orally it is a potent b-blocker and has been used in
2. Cardioselective b1-adrenergic blockers: Metoprolol, hypertension, angina and prophylaxis of myocardial

atenolol, acebutolol, esmolol infarction.
3. b-blockers with additional vasodilatory effect: Labet-
alol, carvedilol, celiprolol Q. 4. Name few cardioselective b-blockers.
Ans.
Q. 2. Propranolol
l b-blockers are drugs that block the actions of catechol-
Ans.
Propranolol is a first generation nonselective b-blocker l Cardioselective b1-adrenergic blockers are as follows:
with intrinsic sympathomimetic activity. 1. Metoprolol

2. Atenolol
3. Acebutolol
Uses 4. Esmolol
l Hypertension
l Prophylaxis of angina pectoris Q. 5. Classify a-adrenergic blocking agents.
l Cardiac arrhythmias Ans.
l Myocardial infarction
l Congestive cardiac failure These drugs inhibit adrenergic responses mediated through
l Pheochromocytoma the a-adrenergic receptors, without affecting those medi-
l Thyrotoxicosis ated through b receptors.
l Essential tremors
l Glaucoma Classification
1. Nonequilibrium type: b-haloalkylamines (phenoxyben-
Adverse Effects
zamine)
l Propranolol causes bradycardia and can accentuate 2. Equilibrium type (competitive)
myocardial insufficiency and worsen CHF. a. Nonselective
i. Ergot alkaloids: Ergotamine, ergotoxine l However the potency of blocking b receptor is

ii. Hydrogenated ergot alkaloids: Dihydroergota- five times more compared to a receptors.
mine (DHE), dihydroergotoxine
iii. Imidazolines: Tolazoline, phentolamine
Pharmacological Action
iv. Miscellaneous: Chlorpromazine, ketanserin
b. a1 selective: Prazosin, terazosin, doxazosin, tamsulosin l Causes vasodilatation and fall in both systolic and dia-
c. a2 selective: Yohimbine stolic BP.
l Reduction in both cardiac output and total peripheral
Q. 6. Propranolol is contraindicated in bronchial resistance.
asthma. Why?
Ans. Pharmacokinetics
l Blockade of b2 receptors in the bronchial smooth mus- l Effective orally but has high first-pass metabolism.
cle causes increase in airway resistance. Many precipi- l Metabolized by conjugation with glucuronic acid and
tate acute attack in asthmatics. excreted in the urine.
l Propranolol worsens chronic obstructive lung disease,
can precipitate life-threatening bronchial asthma; hence

is contraindicated in asthmatics.
Therapeutic Uses
l Pheochromocytoma
Q. 7. Labetalol l Essential hypertension
Ans.
Side Effects
l Labetalol is the first adrenergic antagonist of both a and
b receptors. Most important side effect is postural hypotension.
Part III
Autocoids and Related Drugs
Topic 9
Histamines and Antihistamines

SHORT ESSAYS
Q. 1. Mention four newer nonsedative antihistamines 1 . They do not impair psychomotor performance.
with four advantages. 2. Produce no subjective effects.
Ans. Newer nonsedative antihistamines are as follows: 3. No sleepiness
1. Fexofenadine 4. Do not potentate alcohol or benzodiazepines.
2. Loratadine
3. Cetirizine Q. 2. Mention therapeutic uses of H1 blockers.
4. Azelastine
Ans.
5. Mizolastine
6. Terfenadine Therapeutic uses of H1 blockers are as follows:
Advantages of newer nonsedative antihistaminics are as l Allergic diseases: H1 antihistamines are used to prevent
follows: as well as to treat the symptoms of allergic reactions, e.g.

pruritus, urticaria, dermatitis, rhinitis, conjunctivitis and Q. 3. Autocoids

angioneurotic oedema respond to these drugs. Type I
Ans.
hypersensitivity to drugs is suppressed.
l Common cold: They produce symptomatic relief by Autocoids are substances formed in various tissues, have
sedative and anticholinergic actions. complex physiological and pathological actions and act lo-
l Preanaesthetic medication: Promethazine is used for its cally at the site of synthesis. They have brief action and are
sedative and anticholinergic effects. destroyed locally. Hence they are called local hormones.
l Motion sickness: Promethazine, diphenhydramine, But they differ from true hormones which are produced by
dimenhydrinate, etc. are useful especially for pro- specific cells and act at target sites.
phylaxis of motion sickness because of their anticho- Autocoids include the following:
linergic action. They act probably on the vestibular 1. Histamine (H1 and H2)
apparatus or cortex. Sedative effect also contributes a. H1 blockers: Diphenhydramine, chlorphenamine,
to their beneficial effect. These drugs are also useful cetrizine, loratadine
in morning sickness, drug-induced and postoperative b. H2 blockers: Ranitidine, famotidine, roxatidine
vomiting. 2. 5-HT or serotonin
l As sedative, hypnotic and anxiolytic a. Agonists: Sumatriptan, buspirone, dexfenfluramine
l Antihistaminics with CNS depressant action are used as b. Blockers: Cyproheptadine, ketanserin, ondansetron
sedative and to induce sleep especially in children, e.g. 3. Prostaglandins
promethazine and diphenhydramine. a. Analogues: Misoprostol, dinoprostine, carboprost
l Hydroxyzine is used in anxiety associated with auto- b. Synthesis inhibitors: Aspirin, indomethacin,
nomic manifestations. paracetamol
l Parkinsonism 4. Kinins: Bradykinin, kallidin
l Imbalance between dopamine and acetylcholine in 5. Leukotrienes
the basal ganglia produces parkinsonism. a. Antagonists: Montelukast, zafirlukast
l Promethazine, diphenhydramine or orphenadrine are b. Lipoxygenase inhibitors: Zileuton
used to control tremors, rigidity and sialorrhoea of 6. Angiotensin
parkinsonism due to their anticholinergic and seda- a. Blockers: Losartan
tive properties. b. ACE inhibitors: Captopril, enalapril, ramipril
l They are also useful to treat extrapyramidal side
effects caused by phenothiazines or metoclopramide. Q. 4. Antihistamines

l H1 antihistamines are used to control mild blood trans-
Ans.
fusion and saline infusion reactions (chills and rigors)
and as adjunct in anaphylaxis. H1 receptor antihistaminics are the drugs which competi-
l Vertigo: Cinnarizine is widely used in vertigo because tively antagonize the action of histamine at H1 receptors.
of its additional anticholinergic, anti-5-HT sedative and
vasodilator properties.
l Dimenhydrinate and meclizine are effective to control
Classification
vertigo in Meniere’s disease and in other types of 1. Highly sedative
vertigo. l Diphenhydramine
l Appetite stimulant: Buclizine is used in underweight l Dimenhydrinate
children because of its appetite stimulating effect. l Promethazine
l Cough: Chlorpheniramine, diphenhydramine and pro- l Hydroxyzine
methazine are used in cough due to respiratory allergic 2. Moderately sedative

states as they offer symptomatic relief because of their l Pheniramine
sedative and anticholinergic properties. l Cyproheptadine
l Acute muscle dystonia: Parenteral promethazine or hy- l Meclizine
droxyzine promptly relieves the acute muscle dystonia l Buclizine
caused by antiemetic or antipsychotic drugs. l Cinnarizine
l Other conditions involving histamine are as follows: 3. Mild sedative

l Symptomatic relief is obtained in insect bite and ivy l Chlorpheniramine
poisoning. l Methdilazine
l Abnormal dermographism is suppressed. l Mepyramine
l If used in blood or saline infusion-induced rigor, it l Dimethindene
has prophylactic value. l Triprolidine

l Mebhydroline l Motion sickness: Promethazine, diphenhydramine,

l Cyclizine dimenhydrinate, etc. are useful especially for prophy-
l Clemastine laxis of motion sickness because of their anticholiner-
4 . Nonsedative (second generation) gic action. They act probably on the vestibular
l Terfenadine apparatus or cortex. Sedative effect also contributes to
l Fexofenadine their beneficial effect. These drugs are also useful in
l Astemizole morning sickness, drug-induced and postoperative
l Loratadine vomiting.
l Desloratadine l As sedative, hypnotic and anxiolytic
l Cetirizine l Antihistaminics with CNS depressant action are used
l Azelastine as sedative and to induce sleep especially in children,

l Mizolastine e.g. promethazine and diphenhydramine.
l Hydroxyzine is used in anxiety associated with auto-
nomic manifestations.
Therapeutic Uses l Parkinsonism
l Allergic diseases: H1 antihistamines are used to pre- l Imbalance between dopamine and acetylcholine in
vent as well as to treat the symptoms of allergic the basal ganglia produces parkinsonism.
reactions, e.g. pruritus, urticaria, dermatitis, rhinitis, l Promethazine, diphenhydramine or orphenadrine are
conjunctivitis and angioneurotic oedema respond to used to control tremors, rigidity and sialorrhoea of
these drugs. Type I hypersensitivity to drugs is sup- parkinsonism due to their anticholinergic and seda-
pressed. tive properties.
l Common cold: They produce symptomatic relief by l They are also useful to treat extrapyramidal side
sedative and anticholinergic actions. effects caused by phenothiazines or metoclopramide.

l Preanaesthetic medication: Promethazine is used for its l H1 antihistamines are used to control mild blood trans-
sedative and anticholinergic effects. fusion and saline infusion reactions (chills and rigors)
and as adjunct in anaphylaxis.
SHORT NOTES
Q. 1. Autocoids H1 receptor antihistaminics are the drugs which competi-
tively antagonize the action of histamine at H1 recep
Ans.
tors.
l Autocoids are substances formed in various tissues, They are classified as follows:
have complex physiological and pathological actions 1. Highly sedative: Diphenhydramine, promethazine and
and act locally at the site of synthesis. hydroxyzine
l They have brief action and are destroyed locally; hence 2. Moderately sedative: Pheniramine, cyproheptadine, cin-
they are called local hormones. But they differ from true narizine
hormones which are produced by specific cells and act 3. Mild sedative: Chlorpheniramine, mepyramine, cycli-
at target sites. zine and clemastine
l Autocoids include the following: 4. Nonsedative (second generation): Terfenadine, fexofen-
1. Histamine (H1 and H2) blockers, e.g. diphenhydr- adine, astemizole, loratadine, cetirizine
amine, chlorphenamine, cetirizine, ranitidine, roxati-
dine, etc. Therapeutic uses of H1 receptor antihistaminics are as
2. 5-HT or serotonin agonists (dexfenfluramine) and follows:
blockers (cyproheptadine) 1. Allergic disorders
3. Prostaglandins: Misoprostol, indomethacin, 2. Other conditions involving histamine
paracetamol, etc. 3. Pruritus
4. Kinins: Bradykinin, kallidin 4. Common cold
5. Leukotrienes: Both antagonists (montelukast, zafir- 5. Motion sickness
lukast) and lipoxygenase inhibitors (zileuton) 6. Appetite stimulant
6. Angiotensin blockers: Losartan and ACE inhibitors 7. Vertigo
(captopril, enalapril, ramipril) 8. Preanaesthetic medication
9. Cough
Q. 2. H1 blockers 10. Parkinsonism
11. Acute muscle dystonia
Ans.
Q. 3. Cyproheptadine l Cetirizine does not have sedative property.
Ans.
Pharmacological Action
l Cyproheptadine is a serotonin antagonist.
l It blocks 5-HT2 receptors and cholinergic receptors. It
l Antagonism of histamine
increases appetite and is used to promote weight gain, l Antiallergic action
especially in children.
l It is also used in carcinoid tumours. Pharmacokinetics
Q. 4. Nonsedative antihistamines l Well absorbed orally, not metabolized
l Attains high and longer lasting concentration in skin.
Ans.
l CNS penetration is poor.
Newer nonsedative antihistamines are as follows:

1. Terfenadine Therapeutic Uses
2. Fexofenadine
3. Astemizole l In a daily dose of 10 mg cetrizine is used in upper respira-
4. Loratadine tory allergies, pollinosis, urticaria and atopic dermatitis.
5. Cetirizine l Seasonal asthma as adjuvant
6. Azelastine
7. Ebastine Q. 6. Mention therapeutic uses of promethazine.
Advantages of newer nonsedative antihistaminics are as follows: Ans.

1. They do not impair psychomotor performance. Promethazine is a highly sedative H1 antagonist and it is
2. Produce no subjective effects. used in daily dose of 25–50 mg orally or IM.
3. No sleepiness
4. Do not potentate alcohol or benzodiazepines.
Therapeutic Uses
Q. 5. Cetirizine Promethazine is used in cases of
l allergic disorders,
Ans.
l pruritus,
l Cetirizine is a second generation antihistaminic. It is l common cold,
a metabolite of hydroxyzine with marked affinity for l preanaesthetic medication and
peripheral H1 receptors. l parkinsonism.
Topic 10
5-Hydroxytryptamine, Its Antagonists and Drug

Therapy of Migraine, Prostaglandins, Leukotrienes
(Eicosanoids) and Platelet Activating Factor
SHORT ESSAYS
Q. 1. Prostaglandins PGs from arachidonic acid is cyclooxygenase (COX).
Ans. Another class of substances obtained from arachidonic
acid by the action of lipoxygenase is leukotrienes.
i. Prostaglandins (PGs) are products of long-chain fatty
acids. They are widely distributed in the body.
The main PGs in man are PGE2, PGF2a and PGI2.
Pharmacological Actions and Uses
ii. Arachidonic acid is the precursor for the biosynthesis i. GI tract: PGE2 and PGI2 reduce acid secretion and increase
of all PGs. The enzyme involved in the formation of the secretion of mucus in the stomach (cytoprotective
action). Misoprostol (PGE1 analogue) is useful in the i. Ergometrine or ergonovine is an amine ergot alkaloid.
prevention of nonsteroidal anti-inflammatory drug ii. It has a very weak agonistic and no antagonistic action
(NSAID)-induced ulcers. on a-adrenergic receptors.
ii. CVS and blood vessels It has partial agonistic action on 5-HT receptors
a. PGE1 (alprostadil) is used to maintain the patency of in uterus, placental and umbilical blood vessels and in
ductus arteriosus before surgery. certain brain areas. It is a moderately potent 5-HT2 an-
b. Prostacyclin (PGI2) decreases peripheral, pulmonary tagonist in GI smooth muscles and a weak dopaminer-
and coronary resistance, it is used to treat pulmonary gic agonist on the pituitary lactotropes as well as CTZ.
hypertension. iii. Emetic potential is low. The most prominent action is
c. PGI 2 inhibits platelet aggregation. Hence, it is contraction of myometrium and is used exclusively in
used during haemodialysis to prevent platelet obstetrics.
aggregation. iv. Ergometrine and methylergometrine are rapidly and
i ii. Eye: PGF2a has been found to decrease intraocular nearly completely absorbed from the oral route.
tension. Its analogue, e.g. latanoprost is used in glau- v. Onset of uterine action is 15 min by oral route, 5 min by
coma. IM, almost immediately by IV route.
iv. Uterus vi. They are partly metabolized in liver and excreted in
a. PGF2a and low concentration of PGE2 contract preg- urine. Plasma t1/2 is 1–2 h. It is available as 0.25, 0.5 mg
nant uterus. PGs are mainly used in mid-term abor- tab, 0.5 mg/mL inj.
tion, missed abortion and in molar pregnancy.
b. Induction of labour
PGE2 and PGF2a can induce labour at term. But, they
Adverse Effects
are used only when oxytocin is contraindicated-renal i. They are less toxic and hardly any complications arise
failure, toxemia of pregnancy, etc. when correctly used in obstetrics.
v. Impotence: PGE1 (alprostadil) is useful in the treatment ii. Nausea, vomiting and rise in BP occur occasionally.
of erectile dysfunction. iii. Ergometrine should be avoided in patients with vascu-
lar disease, hypertension, toxaemia. It should also be
avoided in presence of sepsis and as well as liver and
Adverse Effects: kidney diseases.
l Nausea, vomiting, diarrhoea, fever and backache due to
uterine contractions.
Uses
l Injections are painful due to sensitization of nerve endings.
i. To control and prevent postpartum haemorrhage

Q. 2. Ergometrine ii. After caesarean section or instrumental delivery to pre-
Ans. vent uterine atony
iii. To ensure normal involution
SHORT NOTE
Q.1. Uses of ergot alkaloids Ergot Alkaloid Uses
Ans. i. Ergotamine Acute migraine
Ergot alkaloids occur naturally in fungus. Ergot contains ii. Ergometrine Postpartum haemorrhage
many active substances. The most important compounds iii. Dihydroergotoxine Alzheimer's dementia
and their therapeutic uses are as follows: iv. Bromocriptine Suppression of lactation and
parkinsonism
Topic 11
Nonsteroidal Anti-inflammatory Drugs

and Antipyretic Analgesics
LONG ESSAYS
Q. 1. What are analgesics? Classify analgesics. Describe A. Analgesic Action
pharmacological action, therapeutic uses and side
l Analgesic effect of NSAIDs is mainly used for relieving
effects of acetyl salicylic acid.
musculoskeletal pain, dysmenorrhoea and pain associ-
Ans. ated with inflammation or tissue damage.
l Mechanisms by which NSAIDs exhibit the analgesic
Analgesics are drugs that relieve pain without affecting action are as follows:
consciousness. 1. Inhibition of COX enzyme which is responsible for
Classification of analgesics is as follows: synthesis of prostaglandins
2. By sensitizing the free nerve endings to pain stimuli
and also increasing pain threshold by acting at sub-
Analgesics
cortical site
↓ 3. By irreversible acetylation of COX enzyme
l These drugs relieve pain without causing sedation, tol-
Opioids NSAIDs erance or drug dependence.
A. Natural opium A. Nonselective COX inhibitors l Acetyl salicylic acid is effective against pain with
B. Semisynthetic opiates B. Preferential COX-2 inhibitors inflammation, e.g. dental pain and rheumatic pain.
C. Diacetylmorphine and phenol C. Selective COX-2 inhibitors
codeine B. Anti-inflammatory Action
D. Synthetic Opioids D. Analgesic, antipyretic, poor l The anti-inflammatory action of NSAIDs is mainly due
anti-inflammatory to inhibition of PG synthesis at the site of injury. They
also affect other mediators of inflammation (bradykinin,
histamine, serotonin, etc) and thus inhibit granulocyte
ACETYL SALICYLIC ACID OR ASPIRIN adherence to the damaged vasculature.
l NSAIDs also cause modulation of T-cell function, stabi-
Acetyl salicylic acid is a derivative of nonselective COX lization of lysosomal membrane and inhibition of che-
inhibitors. motaxis.
l Anti-inflammatory effect is seen at high doses (aspirin:
Pharmacological Actions 4–6 g/day in divided doses). These drugs produce only
symptomatic relief.
Pharmacological actions of acetyl salicylic acid or aspirin l It suppresses signs and symptoms of inflammation such
are as follows: as pain, tenderness, swelling, vasodilatation and leuco-
A. Analgesic action cyte infiltration but does not affect the progression of
B. Anti-inflammatory action underlying disease.
C. Antipyretic action
D. Antiplatelet (antithrombotic) effect
E. Acid-base and electrolyte balance C. Antipyretic Action
F. Action on gastrointestinal tract l The antipyretic effect is mainly due to inhibition of PGs
G
. Action on respiration in the hypothalamus.
H
. Action on CVS l Aspirin blocks action of pyrogens due to which prosta-
I. Action on urate excretion glandin synthesis in hypothalamus is inhibited.
l The thermoregulatory centre is situated in the hypo- action of uricosuric drug and hence it is avoided in gout
thalamus. Fever occurs when there is a disturbance in patients.
hypothalamic thermostat.
l NSAIDs reset the hypothalamic thermostat and reduce
the elevated body temperature during fever. They pro- Therapeutic Uses or Indications of Aspirin or
mote heat loss by causing cutaneous vasodilatation and Acetyl Salicylic Acid
sweating. l As analgesics: It is used in headache, toothache, joint
pain, dysmenorrhoea and myalgia in dosage 0.3–0.6 g
D. Antiplatelet (Antithrombotic) Effect per day.
l As antipyretic: It is used in fever of any origin.
l A COX enzyme formed irreversibly in platelets. Thus, l It is first drug to be used in acute rheumatic fever.
platelet aggregation is prevented and bleeding time is l It is used in rheumatoid arthritis and osteoarthritis.
prolonged. l In myocardial infarction and stroke: Aspirin inhibits plate-
l Aspirin in low doses (50–325 mg) irreversibly inhibits
let aggregation by blocking COX enzymes in platelets,
platelet TXA2 synthesis and produces antiplatelet effect. thus it prevents clot formation and lowers the incidence of
Aspirin in high doses (2–3 g/day) inhibits both PGI2 and reinfarction.
TXA2 synthesis, hence beneficial effect of PGI2 is lost. l In patent ductus arteriosus aspirin can bring about
closure and prevent surgery.

E. Acid-base and Electrolyte Balance l Aspirin is used in pregnant women to delay labour.
l Aspirin is useful in pregnancy-induced hypertension.

l In therapeutic doses, salicylates cause respiratory alka-
losis, which is compensated by excretion of alkaline Side effects of acetyl salicylic acid or aspirin are as follows:
urine (compensated respiratory alkalosis). i. Aspirin causes nausea, vomiting, hypersensitivity reac-
l In toxic doses, the respiratory centre is depressed and tion, epigastric distress, gastritis, peptic ulcer, precipita-
can lead to respiratory acidosis. Later, there is uncom- tion of asthma.
pensated metabolic acidosis. ii. Anti-inflammatory doses: A syndrome called salicylism
is produced.
iii. In salicylism: Dizziness, vertigo, tinnitus, reversible
F. Action on GIT impairment of hearing and of vision, hyperventilation
l Aspirin is unionized in GIT at gastric pH and is ab- and electrolytic imbalance
sorbed in mucosal cell where it gets ionized and cannot iv. Aspirin use in children with viral infections causes
diffuse back, this causes gastric mucosal damage. Reye’s syndrome.
l Aspirin also inhibits COX-1 which cause decrease in v. Aspirin causes acute salicylate poisoning in adults.
PGE2 and PGI2 synthesis which decreases mucus barrier
and causes gastric mucosal damage. Q. 2. Classify nonsteroidal anti-inflammatory, analgesic
agents. Discuss mode of action, toxicities and contrain-
dications of aspirin.
G. Action on Respiration
Ans.
At anti-inflammatory doses salicylates increase oxygen
consumption by a skeletal muscle, which causes increase in Nonsteroidal anti-inflammatory drugs (NSAIDs) are classi-
CO2 production and there is hyperventilation due to which fied as follows:
CO2 is washed out and hence results in respiratory alkalosis A. Nonselective COX inhibitors
and at higher doses metabolic acidosis. i. Salicylate derivatives: Aspirin
ii. Propionic acid derivatives: Ibuprofen, ketoprofen,
naproxen
H. Action on CVS
iii. Anthranilic acid derivatives: Mephenamic acid
Aspirin at large doses increases oxygen demand and in- iv. Arylacetic acid derivatives: Diclofenac, aceclofenac
creases cardiac output. v. Oxicam derivatives: Piroxicam, tenoxicam
vi. Pyrrolopyrrole derivatives: Ketorolac
vii. Indole derivatives: Indomethacin, sulindac
I. Action on Urate Excretion
viii. Pyrazolone derivatives: Phenyl butazone
Aspirin at small dose inhibits uric acid secretion by DCT B. Preferential COX-2 inhibitors: Nimesulide, meloxicam,
due to which plasma urate level is increased. It also blocks nobumetone
C. Highly selective COX-2 inhibitors: Celecoxib, rofe- Toxicities of Aspirin

coxib, valdecoxib, etoricoxib
l Aspirin causes acute salicylate poisoning in adults.
D. Analgesic, antipyretic with poor anti-inflammatory
l Acute salicylate poisoning is more common in children.
action
Fatal dose in adults is estimated to be 15–30 g, but is
i. Para-aminophenol derivatives: Paracetamol (acet-
considerably lower in children.
aminophen)
l Serious toxicity is seen when serum salicylate levels
ii. Pyrazolone derivatives: Metamizol, propyphena-
are . 50 mg/dL. Manifestations are vomiting, dehy-
zone
dration, acid-base and electro-imbalance, hyperpnoea,
iii. Benzoxazocine derivative: Nefopam
restlessness, confusion, coma, convulsions, cardiovas-
cular collapse, pulmonary oedema, hyperpyrexia and
Mode of Action death.
l COX is the enzyme responsible for the biosynthesis
of various PGs. The COX-1 and COX-2 are well- Contraindications of Aspirin
recognized isoforms of COX enzyme.
l COX-2 is induced during inflammation by cytokines l The aspirin is contraindicated in hypertensive patients,
and endotoxins and is responsible for the production of asthmatic, peptic ulcer patients and patients with bleed-
prostanoid mediators of inflammation. ing disorders.
l Aspirin and most of the nonsteroidal anti-inflamma- l Aspirin is contraindicated in children suffering from
tory drugs (NSAIDs) inhibit both COX-1 and COX-2 viral syndrome, i.e. Reye’s syndrome.
isoforms, thereby decrease PG and thromboxane syn- l Aspirin is contraindicated in hepatic necrosis.
thesis. l It causes premature closure of ductus arteriosus.
l Anti-inflammatory effect of NSAIDs is mainly due to l During pregnancy it should not be given near or at term
inhibition of COX-2. Aspirin causes irreversible inhibi- because it causes delayed labour and greater postpartum
tion of COX activity whereas rest of the NSAIDs cause blood loss.
reversible inhibition the enzyme. l It should be avoided by breastfeeding mothers.
SHORT ESSAYS
Q. 1. List at least two drugs from NSAIDs. Describe Analgesic Action
pharmacological actions and therapeutic uses of this
l Analgesic effect of NSAIDs is mainly used for relieving
class of drugs.
musculoskeletal pain, dysmenorrhoea and pain associ-
Ans. ated with inflammation or tissue damage.
l NSAIDs exhibit the analgesic action mainly by inhibi-
The two drugs from NSAIDs are as follows: tion of COX enzyme which is responsible for synthesis
1. Nonselective COX inhibitor: Salicylates (aspirin) of prostaglandins.
2. Selective COX inhibitor: Paracetamol l Anti-inflammatory action: The anti-inflammatory action of
NSAIDs is mainly due to inhibition of PG synthesis at the

SALICYLATES (ACETYL SALICYLIC site of injury. They also affect other mediators of inflam-
ACID OR ASPIRIN) mation like bradykinin, histamine, serotonin, etc. and thus
inhibit granulocyte adherence to the damaged vasculature.
Pharmacological Actions l Antipyretic action: Aspirin blocks action of pyrogens
Pharmacological actions of acetyl salicylic acid or aspirin and the antipyretic effect is mainly due to inhibition of
are as follows: PGs in the hypothalamus.
l NSAIDs reset the hypothalamic thermostat and reduce the
1. Analgesic action
2. Anti-inflammatory action elevated body temperature during fever. They promote heat
3. Antipyretic action loss by causing cutaneous vasodilatation and sweating.
4. Antiplatelet (antithrombotic) effect
5. Acid-base and electrolyte balance Antiplatelet (Antithrombotic) Effect
6. Action on gastrointestinal tract
7. Action on respiration l A COX enzyme formed irreversibly in platelets. Thus,
8. Action on CVS platelet aggregation is prevented and bleeding time is
9. Action on urate excretion prolonged.
l Aspirin in low doses (50–325 mg) irreversibly inhibits thus it prevents clot formation and lowers the incidence
platelet TXA2 synthesis and produces antiplatelet of reinfarction.
effect. l In patent ductus arteriosus aspirin can bring about
l Aspirin in high doses (2–3 g/day) inhibits both PGI2 closure and prevent surgery.
and TXA2 synthesis; hence beneficial effect of PGI2 l Aspirin is used in pregnant women to delay labour.
is lost. l Aspirin is useful in pregnancy-induced hypertension.
Acid- base and Electrolyte Balance PARACETAMOL

In therapeutic doses, salicylates cause respiratory alkalosis, Pharmacological Actions of Paracetamol
which is compensated by excretion of alkaline urine (com-
pensated respiratory alkalosis). l Analgesic: Paracetamol inhibits COX in brain and it
also raises pain threshold.
l Antipyretic: It decreases fever of any origin due to inhi-
Action on GIT bition of COX enzyme.
l Urate excretion: Paracetamol does not effect urate
Aspirin is unionized in GIT at gastric PH and is absorbed
in mucosal cell where it gets ionized and cannot diffuse excretion and is given in gout patients.
back, this causes gastric mucosal damage.
Aspirin also inhibits COX-1 which causes decrease in Therapeutic Uses of NSAIDs
PGE2 and PGI2 synthesis which decreases mucus barrier
and causes gastric mucosal damage. l It is one of the best antipyretic drugs.
l It is an analgesic for headache, dysmenorrhoeal and
musculoskeletal pain.
Action on Respiration l It has negligible anti-inflammatory action as it poorly
At anti-inflammatory doses salicylates increase oxygen inhibits COX enzyme.

consumption by a skeletal muscle, which causes increase
Q. 2. Differences between paracetamol and aspirin
in CO2 production and there is hyperventilation due to
which CO2 is washed out and hence results in respiratory Ans.
alkalosis and at higher doses metabolic acidosis.
Paracetamol differs from aspirin in the following aspects
given in Table 11.1.
Action on CVS
Aspirin at large doses increases oxygen demand and in- TABLE 11.1 Differences between Paracetamol and Aspirin
creases cardiac output. Paracetamol Aspirin
It does not stimulate It causes hyperventilation
Action on Urate Excretion respiration
Aspirin at small dose inhibits uric acid secretion by DCT due It does not affect acid-base It affects acid-base balance
balance
to which plasma urate level is increased. It also blocks action
of uricosuric drug and hence it is avoided in gout patients. It does not increase cellular It increases cellular metabo-
metabolism lism
It has no effect on CVS It causes increased output in
Therapeutic Uses or Indications of Aspirin CVS
or Acetyl Salicylic Acid
It is safer in asthmatics It precipitates asthma in
l As analgesics: It is used in headache, toothache, joint sensitive individuals
pain, dysmenorrhoea and myalgia in dosage 0.3–0.6 g
per day.
l As antipyretic: It is used in fever of any origin. Q. 3. Write briefly on selective COX-2 inhibitors.
l It is first drug to be used in acute rheumatic fever.
Ans.
l It is used in rheumatoid arthritis and osteoarthritis.
l In myocardial infarction and stroke: Aspirin inhibits plate- Highly selective COX-2 inhibitors are as follows:
let aggregation by blocking COX enzymes in platelets, l Celecoxib, rofecoxib, valdecoxib, etoricoxib
l COX-2 inhibitors reduce whole body PGI2 production l If dental analgesia is given during pregnancy, paracetamol
without affecting platelet thromboxane A2 synthesis. is the safest drug to be given.
l Parecoxib is a prodrug of valdecoxib and is adminis- l If dental analgesia is in diabetic, CHF and in epileptics,
tered parenterally. Etoricoxib is given by enteral route. physician should be consulted before giving the drug
during analgesia.
Celecoxib Q. 5. Write briefly on the adverse effects produced by
l It exerts anti-inflammatory, analgesic and antipyretic aspirin. How would you treat a case of salicylate (aspirin)
action with low ulcerogenic potential. poisoning?
l It is approved for use in osteoarthritis and rheumatoid
Ans.
arthritis in a dose of 100–200 mg BD.
l Platelet aggregation in response to collagen exposure Adverse effects produced by aspirin are as follows:
remains intact in celecoxib recipients and serum TXB2 1. GIT: Nausea, vomiting, dyspepsia, epigastric pain,
levels were not reduced. acute gastritis, ulcers and GI bleeding. Ulcerogenic
effect is the major drawback of NSAIDs.
2. Hypersensitivity: It is relatively more common with
Rofecoxib aspirin. The manifestations are skin rashes, urticaria,
l It is the most common COX-2 selective inhibitor. rhinitis, bronchospasm, angioneurotic oedema, rarely
l It is effective in osteoarthritis, rheumatoid arthritis as anaphylactoid reaction.
well as in dysmenorrhoea, dental pain, postoperative 3. Bronchospasm (aspirin-induced asthma) is due to in-
and acute musculoskeletal pain. creased production of leukotrienes. Incidence of hyper-
l Used in the dose of 12.5–25 mg OD. sensitivity is high in patients with asthma, nasal polyps
l Occurrence of peptic ulcer is rare and it has no effect on recurrent rhinitis or urticaria. Therefore, aspirin should be
TXA2 production by platelets. avoided in such patients.
l It should be avoided in presence of severe hepatic or 4. With G6PD deficiency, administration of salicylates
renal disease. may cause haemolytic jaundice. Use of salicylates in-
terferes with action of vitamin K in the liver and
causes decreased synthesis of clotting factors resulting
Valdecoxib in hypoprothrombinemia.
l Recently marketed drug with similar efficacy and toler- 5. Reye’s syndrome is a rare form of hepatic encepha-
ability as that of rofecoxib. lopathy. Use of salicylates in children with viral infec-
l Used in the dose of 10 mg once daily in osteoarthritis tion like varicella, influenza, etc. may cause damage to
and rheumatoid arthritis. liver with fatty infiltration and encephalopathy. Hence
salicylates are contraindicated in children with viral
Q. 4. Write brief account on drugs in dental pain. illness.
Ans. 6. Pregnancy: These drugs inhibit PG synthesis, thereby
delaying onset of labour and increasing chances of PPH.
l NSAIDs are main drugs for management of acute den- In the newborn, inhibition of PG synthesis results in
tal pain. The nature of pain, risk factors and individual premature closure of the ductus arteriosus.
preference are to be considered while prescribing an 7. Analgesic nephropathy: Slowly progressive renal fail-
NSAID. ure occurs on chronic use of high doses of NSAIDs.
l For mild to moderate pain with little inflammation: Renal failure is usually reversible on stoppage of ther-
Paracetamol or low dose ibuprofen is preferred. apy but rarely NSAIDs may cause irreversible renal
l Postextraction or acute short-lasting pain: Ketorolac, damage.
diclofenac and nimesulide
l Gastric intolerance or peptic ulcer patients: Paracetamol
Salicylism
or selective COX-2 inhibitor
l During dental analgesia if patient is with history of Salicylate intoxication may be mild or severe. The mild
asthma or anaphylactic reaction to aspirin, then other form is called salicylism. The effects include headache,
NSAID (nimesulide) is given. tinnitus, vertigo, confusion, nausea, vomiting, diarrhoea,
l If dental analgesia is present in paediatric patient hyperpnoea, electrolyte imbalance, etc. These symptoms
paracetamol, ibuprofen or naproxen is given. are reversible on stoppage of therapy.
Salicylate Poisoning l It is useful for short-lasting painful inflammatory condi-

tions, e.g. dental surgery, ear, nose and throat.
l Acute salicylate poisoning is more common in children.
l While aspirin as anti-inflammatory produces a syn-
Fatal dose in adults is estimated to be 15–30 g, but is
drome called salicylism.
considerably lower in children.
l Aspirin therapy in children with rheumatoid arthritis
l Serious toxicity is seen when serum salicylate levels are
has been found to raise serum level indicating liver
. 50 mg/dL.
damage.
l Manifestations are vomiting, dehydration, acid-base and
l In adult long-term therapy with high dosage can cause
electro-imbalance, hyperpnoea, restlessness, confusion,
hepatic injury.
coma, convulsions, cardiovascular collapse, pulmonary
l Aspirin is contraindicated with patients of peptic ulcer,
oedema, hyperpyrexia and death.
bleeding tendencies and in children suffering from
chickenpox or influenza.
Treatment l It is also contraindicated in chronic liver diseases and is
avoided in diabetes and in breastfeeding mothers.

There is no specific antidote for salicylate poisoning. Treat-
ment is symptomatic and supportive. Normally the treat- Q. 7. Compare the action and uses of morphine and
ment includes the following: aspirin.
1. Hospitalization
2. Gastric lavage to remove unabsorbed drug followed by Ans.
administration of activated charcoal, the activated char-
Comparison between the action and uses of morphine and
coal adsorbs the toxic material-physical antagonism.
aspirin is given Table 11.2.
3. Fluid and electrolyte and acid-base balance restoration.
4. Intravenous sodium bicarbonate to treat metabolic aci-
dosis. It also alkalinizes the urine and enhances renal TABLE 11.2 Comparison between Morphine and Aspirin
excretion of salicylates as the salicylates exist in ionized
form in alkaline pH. Morphine Aspirin
5. Most important is external cooling. Morphine is an opioid Aspirin is an NSAID
6. Forced alkaline diuresis or haemodialysis in severe analgesic
cases to remove absorbed drug. Morphine has central action Aspirin has peripheral action
7. Vitamin K and blood transfusion is given if bleeding and it decreases perception and it decreases sensitization
occurs. of pain of nerve endings by inhibit-
ing prostaglandin secretion
Q. 6. Explain why nimesulide is preferred over aspirin Morphine can be used in Aspirin relieves pain better in
as anti-inflammatory agent. severe pain of any type, i.e. conditions associated with in-
trauma, burn, cancer, pain, etc. flammation like dental pain
Ans.
Morphine is also used in Aspirin is not used in prean-
l Nimesulide is a newer NSAID and is relatively weaker preanaesthetic medication aesthetic medication
inhibitor of prostaglandin synthesis and exhibits relative On GIT morphine causes On GIT aspirin causes gastric
COX-2 selectivity. spasm of sphincters and ulcer, bleeding may occur
l Nimesulide is completely absorbed orally and is 99%
increases muscle tone
plasma bounded. Its t1/2 is 2–5 h. Inhibition of platelet Morphine has no antipyretic Aspirin has antipyretic
activated factor synthesis, so acts as an anti-inflammatory action action, thus reduces body
temperature
agent.
l Its anti-inflammatory action is exerted by mainly reduc- Morphine does not show Aspirin shows antiplatelet
ing generation of superoxide by neutrophils. antiplatelet activity activity. It prevents platelet
aggregation by blocking COX
l Other mechanisms involved in anti-inflammatory action
and preventing formation of
of nimesulide are that it also acts as free radical scaven- thromboxane A2
ger and as well inhibits metalloproteinase activity in
Morphine induces sedation It does not cause euphoria,
cartilage. The anti-inflammatory activity of nimesulide
or euphoria sedation and sleep
is superior to other NSAIDs.
SHORT NOTES
Q. 1. Enumerate the contraindications of aspirin. l The antiplatelet effect of low dose aspirin is marked of
in the prophylactic treatment of various thromboem-
Ans. bolic disorders like myocardial infarction (MI)
l to reduce the incidence of recurrent MI.
Contraindications of aspirin are as follows:
l to decrease mortality in post-MI patients.
The aspirin is contraindicated in the following:
1. Hypertensive patients, asthmatic, peptic ulcer patients Q. 4. Nimesulide
and patients with hepatic necrosis and bleeding disorders.
Ans.
2. Children suffering from viral diseases as they may
develop Reye’s syndrome on aspirin usage. l Nimesulide is a newer NSAID and is relatively weaker
3. During pregnancy it should not be given near or at term inhibitor of prostaglandin synthesis and exhibits relative
because it may cause delayed labour and greater postpartum COX-2 selectivity.
blood loss. It also causes premature closure of ductus l Nimesulide is completely absorbed orally and is 99%
arteriosus. plasma bounded. Its t1/2 is 2–5 h. Excreted primarily in urine.
4. It should be avoided by breastfeeding mothers. l The analgesic, antipyretic and anti-inflammatory activity
of nimesulide has been rated comparable to other NSAIDs.

Q. 2. Paracetamol l It is useful for short-lasting painful inflammatory condi-
Ans. tions, e.g. dental surgery, ear, nose and throat.

l Considering that it has not been marketed in many
Paracetamol is a demethylated active metabolite of phenac- countries like the UK, USA, Australia and Canada, the
etin. It is effective by oral and parenteral (IM) routes. It is overall safety of the drug especially in children has been
well absorbed, distributed all over the body, metabolized questioned.
in the liver by sulphate and glucuronide conjugation. The l Most asthmatics and those patients who develop bron-
metabolites are excreted in urine. chospasm or intolerance to aspirin and other NSAIDs
do not crossreact with nimesulide and it appears to be
Uses safer in these patients.
1 . As antipyretic, to reduce body temperature during fever Q. 5. Enumerate and write mode of action of COX-2
2. As analgesic, to relieve headache, toothache, myalgia, inhibitors as NSAIDs.
dysmenorrhoea, etc.
Ans.
3. Preferred analgesic and antipyretic in patients with pep-
tic ulcer, haemorrhage, bronchial asthma and children The COX-2 inhibitors are as follows:
l Preferential COX-2 Inhibitors: Nimesulide, meloxicam,
Adverse Effects nobumetone

l Selective COX-2 Inhibitor: Celecoxib, rofecoxib, valde-
1 . Nausea and rashes occur occasionally. coxib
2. Leukopenia is rare.
Q. 3. Rationale of using aspirin in postmyocardial Mode of Action

infarction l Preferential COX-2 inhibitor: The COX-2 inhibitors re-
Ans. duce generation of superoxide by neutrophils, inhibition
of platelet activating factor synthesis and tumour necrosis
l Aspirin in low doses (50–325 mg) irreversibly inhibits factor a, free radical scavenging, inhibition of metallopro-
platelet TXA2 synthesis and produces antiplatelet ef- teinase activity in cartilage. In this way it acts as NSAID.
fect. Aspirin in high doses (2–3 g/day) inhibits both l Selective COX-2 inhibitor: These drugs cause inhibition
PGI2 and TXA2 synthesis; hence beneficial effect of of COX-2 without affecting the function of COX-1 and
PGI2 is lost. hence act as NSAID.
Topic 12
Additional Drugs for Rheumatoid Arthritis

and Drugs for Gout
SHORT NOTES
Q. 1. Action of probenecid and penicillin in chemotherapy l Dosage: Orally starting with a dose of 7.5 mg once
Or weekly and increased by 2.5 mg weekly. Maximum
weekly dose is 30 mg.
Rationale of using probenecid with penicillin l It acts probably by inhibiting aminoimidazole carbox-
Ans. amide (AICAR) transformylase and thymidylate enzymes.

l It has immunosuppressant and potent antirheumatoid
l Probenecid and penicillin (b-lactum antibiotics) are effects.
excreted by active tubular secretion. l It can also be used in the treatment of psoriasis, poly-
l When both are administered simultaneously, probenecid myositis, giant cell arteritis, dermatomyositis, etc.
competes with penicillin and blocks the tubular secre- l Adverse effects: Nausea, vomiting, mucosal ulcers and
tion of b-lactum antibiotics and their duration of action dose-dependent hepatotoxicity
increases. Thus treatment becomes more effective. l It is contraindicated in pregnancy.
Q. 2. D-penicillamine Q. 4. Role of glucocorticoids in rheumatic arthritis

Ans. Ans.
l D-penicillamine is a degradation product of penicillin l Glucocorticoids (steroids) are used as adjunct to nonste-
and has cross-reactivity with penicillins. roidal anti-inflammatory drugs (NSAIDs) and disease
l It is effective in treating copper, mercury, zinc and lead
modifying antirheumatic drugs (DMARDs) in the treat-
poisoning. It is also useful in treating Wilson’s disease, ment of rheumatoid arthritis.
scleroderma, cystinuria and rheumatoid arthritis. l Their effects are prompt and they suppress inflamma-
l D-penicillamine is used in Wilson’s disease as it chelates
tion quickly. They produce an immediate and dramatic
copper and promotes its excretion. Life-long therapy is symptomatic relief in rheumatoid arthritis, but do not
required. halt the progression of the disease.
l Adverse effects: Skin rashes, pruritus, urticaria, pemphi-
goid lesions, pyrexia, etc.

Mechanism of Action
Q. 3. Methotrexate
1. Glucocorticoids induce a protein called lipocortin which
Ans. inhibits phospholipase A2 and so PGs, leukotrienes and
PAF are not formed.
l Methotrexate is the preferred disease modifying anti- 2. TNFa is inhibited by glucocorticoids which are necessary
rheumatic drugs (DMARDs) in the treatment of rheu- for initiating inflammatory process.
matoid arthritis. 3. Glucocorticoids stabilize the lysosomal membrane and
l It is a folate antagonist and has more rapid onset of
prevent the release of inflammatory mediators.
action than other DMARDs.
l The dose of methotrexate used in rheumatoid arthritis is Intra-articular injection is preferred only if one or two joints
much lower than the dose used in cancer chemotherapy. are involved.
Part IV
Respiratory System
Topic 13
Drugs for Cough and Bronchial Asthma

SHORT ESSAYS
Q. 1. Salbutamol l Other routes of administration are oral, IM, IV.
Ans. l The proper technique for inhalation is to be taught.
Spacers should be used in children and adults who do
l Salbutamol is a sympathomimetic, selective b2-adrenergic not know proper inhalational technique.
agonist drug acting as bronchodilator. l It is not suitable for round-the-clock prophylaxis.
l It is the fastest-acting bronchodilator, convenient to use
and relatively safe.

l On inhalation salbutamol has rapid onset within 1–5 min
Side Effects
and short duration of action, preferred for acute attack of l Cardiac side effects like tachycardia and palpitation are
asthma. less prominent.
l Muscle tremors due to stimulation of b2 receptors of
skeletal muscle. Tolerance develops to this effect on

Pharmacology
continued administration.
l Pharmacological actions of salbutamol are as follows: l Restlessness, nervousness, throat irritation and ankle
l Bronchodilatation oedema can occur.
l Relaxation of pregnant uterus l On parenteral administration hyperglycaemia may oc-
l Dilatation of blood vessels supplying the skeletal cur in diabetics.
muscles l Hypokalaemia is due to shift of K into the cell.
1
l Promote hepatic glycogenolysis and uptake of potas-
sium (K1) into the cells Q. 2. Disodium cromoglycate

Ans.
Therapeutic Use
Disodium cromoglycate is a mast cell stabilizer belonging
Therapeutic uses of salbutamol are as follows: to group of antiasthmatic drugs. It is a synthetic chromone
l In bronchial asthma it is usually administered as aero- derivative.
sol. It produces prompt bronchodilatation with mini-
mum systemic side effects.
l Salbutamol is used to delay the premature labour on oral
Mechanism of Action
or parenteral administration. It relaxes pregnant uterus l It inhibits the degranulation of mast cells by trigger
by interacting with b2 receptors. stimuli and prevents the release of chemical mediators
l It is useful in hyperkalaemia as it increases the uptake like histamine, leukotrienes, prostaglandins, platelet-
of K1 into the cells. activating factors, interleukins, etc. from mast cells by
stabilizing the mast cell membrane.
Route and Dose
l Inhalation salbutamol 100–200 mcg every 6 h or as
and when required through metered dose inhaler l Inhibition of chemotaxis of inflammatory cells
(MDI) l Cellular inflammatory response is decreased on long-
l It is available as metered dose inhalers, nebulizers, tab- term treatment.
lets for oral use. l Bronchial hyperreactivity is reduced to variable extent.
l Prevents bronchospasm induced by allergens, irritants, l Rashes

cold air and exercise. l Dysuria rarely
l Antigen–antibody reaction is not interfered with. Therapeutic uses
l Does not antagonize bronchoconstrictor action of hista- 1. Allergic asthma
mine, acetylcholine, leukotrienes, etc. l As long-term prophylactic agent to prevent broncho-
spasm induced by allergens and irritants

l Frequency and severity of asthma is reduced and
Pharmacokinetics lung function is improved.
l Not absorbed orally l Benefits extrinsic and exercise-induced asthma espe-
l Administered as an aerosol through metered dose cially in younger patients

inhaler delivering 1 mg/dose l Used as an alternative to inhaled steroids in mild to
l Only a small fraction is absorbed systemically. moderate asthma

l Excreted rapidly unchanged in urine and bile 2. Allergic rhinitis
l Regular four times daily prophylactic used as nasal
spray produces symptomatic improvement after 4–6

Adverse Effects weeks thus reducing need for nasal decongestants. Two
l Bronchospasm squeezes in each nostril of 2% solution four times a day.
l Throat irritation and cough 3. Allergic conjunctivitis
l Nasal congestion, headache, dizziness l Regular use may benefit chronic cases. One drop
l Arthralgia each eye of 2% solution four times a day.
SHORT NOTES
Q. 1. Noscapine l It is third or fourth line of drugs in the treatment of
asthma due to its narrow margin of safety.
Ans.
l Noscapine is an opium alkaloid, central cough suppres- Pharmacological Actions

sant having potent antitussive effect.
l It acts by inhibiting cough centre in the medulla.
l CNS: It is a CNS stimulant.
l It is a potent antitussive with minimal CNS effects.
l CVS: It directly stimulates heart.
l Smooth muscle: All smooth muscles are relaxed; the prom-
l It rarely causes any side effect though nausea may be
seen in a few cases. inent effect is exerted on bronchi, especially in asthma.

l Kidney: It is a mild diuretic.
l Dose: 15–30 mg every 6 h
l Stomach: It enhances secretion of acid and pepsin.
l Side effects: Nausea and headache
l Mast cell and inflammatory cell: It inhibits the release
Q. 2. Salbutamol of histamine and other mediators of asthma from mast

cells and activated inflammatory cells.
Ans.
l Salbutamol is a sympathomimetic, selective b2-adrenergic Uses

agonist drug acting as bronchodilator.
l Inhaled salbutamol produces rapid onset of bronchodi-
l Bronchial asthma and COPD: Aminophylline benefits
latation in 1–5 min. Its action lasts for 2–4 h. Short by causing bronchodilatation and by reducing release of
duration of action, preferred for acute attack of asthma. inflammatory mediators.
l Apnoea in premature infants: It reduces the frequency
l It is used to abort or terminate attack of asthma. It is not
suitable for round-the-clock prophylaxis. and duration of episodes of apnoea.

l Side effect: Cardiac side effects are less prominent,
muscle tremor, palpitation, restlessness, nervousness, Adverse Effects

throat irritation and ankle, oedema can occur.
l They have narrow margin of safety.
Q. 3. Aminophylline l Tachycardia, palpitation, hypotension and sudden death
due to cardiac arrhythmias
Ans.
Q. 4. Mention two drugs used to suppress dry cough.
l Aminophylline is one of the methylxanthines used as
bronchodilator. Ans.
1. Opioids l It cannot be used to treat asthma but is used as prophy-

l Codeine lactic drug to prevent acute attacks of asthma, bronchial
l Pholcodine hypersensitivity and effectively controls symptoms.
l Ethylmorphine l It is available as nasal spray for allergic rhinitis and as
l Morphine ointment for skin and mucous membrane lesions. HPA

2. Nonopioids axis suppression is minimal.
l Noscapine l Dose: Beclate inhaler—50, 100, 200 µg, metered dose—
l Dextromethorphan 1–2 puffs 3–4 times a day.

l Oxeladin l Adverse effects: Hoarseness of voice, sore throat, oropha-
l Chlophedianol ryngeal candidiasis

3. Antihistaminics
l Chlorpheniramine Q. 8. List three groups of drugs used in bronchial
l Diphenhydramine asthma with an example.
l Promethazine Ans.
Q. 5. Nasal decongestants Drugs used in chronic bronchial asthma are as follows:
1. Bronchodilators
Ans.
a. Sympathomimetics: Adrenaline, isoprenaline, salbu-
l Nasal decongestants stimulate the a receptors and cause tamol
vasoconstriction in the nasal mucous membrane and b. Anticholinergic: Atropine, ipratropium bromide
thus relieve nasal congestion. 2. Mast cell stabilizers: Sodium cromoglycate, ketotifen
l The commonly used a agonists as nasal decongestants are 3. Glucocorticoids: Beclomethasone, budesonide, hydro-
naphazoline, pseudoephedrine, phenylephrine, imidazo- cortisone, prednisolone
line compounds like xylometazoline and oxymetazoline.
l They are used either topically or systemically in allergic
Q. 9. Describe the mechanism of action of sodium
rhinitis, common cold, sinusitis etc. cromoglycate.
l They have longer duration of action than ephedrine. Ans.
l Atrophic rhinitis, anosmia and local irritation are the other
adverse effects seen with topical decongestants. On sys- l It is a synthetic chromone derivative.
temic absorption these drugs may aggravate hypertension. l Mechanism of action: It inhibits the degranulation of
mast cells by trigger stimuli and prevents the release of
Q. 6. Rationale of using salbutamol in bronchial asthma. chemical mediators like histamine, leukotrienes, prosta-
glandins, platelet-activating factors, interleukins, etc.
Ans.
from mast cells by stabilizing the mast cell membrane.
l Salbutamol is a sympathomimetic bronchodilator.
Q. 10. Pharmacotherapy of status asthmaticus
l It is highly selective b2 agonist.
l Salbutamol has b2: b1 ratio of about 10. Thus it causes Ans.
b2-mediated bronchodilatation in bronchial asthma.
l Inhaled salbutamol produces bronchodilatation in 5 min. l When an attack of asthma is prolonged with severe in-
Its action lasts 2–4 h, therefore salbutamol is used pri- tractable wheezing it is known as status asthmaticus or
marily in bronchial asthma. acute severe asthma.
l It may be triggered by an acute respiratory infection,
Q. 7. Beclomethasone abrupt withdrawal of steroids, allergens, anaphylaxis,

emotional stress.
Ans.
l Beclomethasone is a long-acting glucocorticoid. Treatment of Status Asthmaticus

l Beclomethasone is an inhalational steroid that largely l Humidified oxygen inhalation
minimizes the adverse effects caused by steroids. l Nebulized b2-adrenergic agonist (salbutamol 5 mg or
l It has local action, inhaled steroids suppress bronchial
terbutaline 10 mg) 1 anticholinergic agent (ipratropium
inflammation and hence used in bronchial asthma. bromide 0.5 mg), intermittent inhalations every 30 min.
l It does not cause bronchodilation but is an anti-
l Systemic glucocorticoids: Hydrocortisone hemisucci-
inflammatory drug, hence suppresses the inflammatory nate 200 mg IV stat followed by 100 mg every 6 hours
response to antigen–antibody reaction and thereby re- or prednisolone 30–60 mg/day depending on patient's
duces mucosal oedema and hyperirritability. condition.
l Intravenous fluids to correct dehydration Rationale of Using Adrenaline in the

l Potassium supplements to correct hypokalaemia pro- Treatment of Bronchial Asthma
duced by repeated doses of salbutamol or terbutaline
l Sodium bicarbonate to treat acidosis
l Adrenaline acts as a powerful bronchodilator through its
l Antibiotics to treat chest infections
action on b2 receptors. This action is more marked when
l Artificial ventilation may be necessary for extreme
the bronchi are constricted.
l Effects of adrenaline in bronchial asthma are depicted
cases.
as follows:
Q. 11. Mention two drugs used in acute bronchial
asthma. Write the rationale of using anyone drug. Adrenaline
Ans.
Drugs Used in Bronchial Asthma It inhibits the release of inflammatory Causes

mediators from mast cells. ↓
1. Bronchodilators (Histamine, bradykinin, Bronchodilatation (β2)
a. Sympathomimetics: Adrenaline, ephedrine, isopren- LTs, PAF, PGF 2α) Vasoconstriction (α1)
aline, salbutamol, terbutaline, salmeterol, formoterol ↓
b. Methylxanthines: Theophylline, aminophylline, eto- Decreases secretions
phylline ↓
c. Anticholinergics: Atropine methonitrate, ipratro- Relieves mucosal oedema
pium bromide, tiotropium bromide and congestion
2. Leukotriene receptor antagonist: Montelukast, zafirlukast
3. Mast cell stabilizers: Sodium cromoglycate, nedocromil l It has rapid onset but short duration of action hence use-
sodium, ketotifen ful for acute asthmatic attacks.
4. Glucocorticoids l Adrenaline given by aerosols additionally decongests
a. Systemic: Hydrocortisone, prednisolone bronchial mucosa by its action and also stimulates respi-
b. Inhalational: Beclomethasone dipropionate, ratory centre.
budesonide, fluticasone propionate l Adrenaline 0.3–0.5 mL of 1:1000 solution is given sub-
cutaneously. It can be given by nebulization.
Part V
Hormones and Related Drugs
Topic 14
Anterior Pituitary Hormones, Thyroid

Hormone and Thyroid Inhibitors
LONG ESSAY
Q. 1. Enumerate the antithyroid drugs. Explain the ac- Ans.
tion of the thioamides giving the indications, advantages
and adverse effects of each of them. Hyperthyroidism is caused due to excess of circulating
thyroid hormone.
Drugs used in the treatment of hyperthyroidism are classi- ii. Hypothyroidism due to overtreatment is common but
fied as follows: reversible on stopping the drug.
i. Thyroid hormone synthesis inhibitors or antithyroid iii. Important side effects are GI intolerance, joint pain,
drugs (thioamides or thiourea derivatives): Propylthio- hepatitis, nephritis, etc.
uracil, methimazole, carbimazole iv. Rare complications include loss or greying of hair, loss
ii. Inhibitors of iodide trapping (inhibitors): Thiocyanates of taste, fever and liver damage.
and perchlorates v. A less common but most dangerous adverse effect is
iii. Hormone release inhibitors: Iodine, iodides of Na1 and agranulocytosis. It is mostly reversible.
K1 and organic iodide
iv. Thyroid tissue destroying agent: Radioactive iodine
Uses
(131I, 125I, 123I)
v. Others: Propranolol, atenolol, diltiazem, dexamethasone They are used in the long-term treatment of thyrotoxicosis
where surgery is contraindicated or not feasible and radio-
The mechanism of action of thioamides (thiourea derivatives),
active iodine is contraindicated.
e.g. propylthiouracil, methimazole, carbimazole are as follows:
i. Graves’ disease is diffuse toxic goitre and needs treat-
l Thioamides act by reducing hormone synthesis.
ment for long term (1–5 years).
l They inhibit thyroid peroxidase enzyme, which converts
ii. Toxic nodular goitre as an alternative when surgery is
iodide to iodine.
not indicated as in elderly patients.
l They inhibit iodination of tyrosine residues in thyro-
iii. Preoperatively, hyperthyroid patients are made euthy-
globulin.
roid with antithyroid drugs and then operated.
l They inhibit coupling of iodotyrosine residues (MIT
l They are used along with radioactive iodine to hasten
and DIT).
recovery in thyrotoxicosis.
l They are used for treatment of thyrotoxic crisis along
Propylthiouracil with iodide and propranolol.
l Propylthiouracil is less potent and most rapidly absorbed. iv. Thyroid storm or thyrotoxic crisis is sudden, severe
It has short half-life and needs to be given every 6–8 h. exacerbation of thyrotoxicosis and can be life threaten-
l It also inhibits the peripheral deiodination of T4 to T3. Other
ing. Propylthiouracil, oral or rectal potassium iodide,
thioamides inhibit this process to a much lesser extent. IV hydrocortisone and supportive therapy are needed
Dose: 50–150 mg TDS followed by 25–50 mg BD or immediately.
TDS for maintenance
l Available as PTU 50 mg Advantages
Advantages of antithyroid drugs over surgery or 131I are as
Carbimazole follows:
l Carbimazole is a commonly used drug as it is more i. No surgical risks and no chances of injury to parathy-
potent and long acting. Carbimazole acts largely by get- roids or recurrent laryngeal nerve.
ting converted to methimazole in the body. ii. Hypothyroidism, if induced, is reversible.
l Dose: 5–15 mg TDS initially, maintenance dose is iii. Can be used in children and young adults also.
2.5–10 mg daily in 1–2 divided doses.
l Available as Neomercazole, Thyrozol and Antithyrox
Disadvantages
5 mg tab.
Disadvantages of antithyroid drugs are as follows:
i. Prolonged treatment is needed as relapse rate is high.
Adverse Effects ii. Not useful in uncooperative or unintelligent patients.
i. Allergic reactions or skin rashes are most common. iii. Drug toxicity
SHORT ESSAY
Q. 1. Radioactive iodine l Radioiodine 131I is used therapeutically while sodium
iodide 123I is used for diagnostic scan.
Ans. l
131
I given is rapidly absorbed and is concentrated
l Radioactive iodine (131I, 125
I, 123
I) is a thyroid tissue by the thyroid in the follicles. It emits g rays and
destroying agent. b particles.
l The b particles which penetrate up to 0.5–2 mm of the Advantages

tissue, destroys only the thyroid tissues and does not
l Treatment is simple and convenient.
damage the surrounding structures.
l Cost effective
l They cause destruction of the follicular cells leading to
l No risk of surgery
fibrosis and correction of hyperthyroid state.
l Hyperthyroidism is permanently cured.
The indications or uses of radioactive iodine are as fol-
lows: Disadvantages
l They are most commonly used as sodium salts and l Slow acting, long-time treatment necessary for maxi-
taken orally as solution or capsules in hyperthyroidism. mum response (3 months)
l It emits b particles which destroy thyroid cells, so they l High incidence of hypothyroidism
are used in carcinoma of thyroid. l Not suitable for pregnant women, children and young
l It is used for diagnostic purposes. patients
SHORT NOTES
Q. 1. Lugol’s iodine l As an antiseptic and expectorant
Ans. Q. 3. Carbimazole
l Lugol’s iodine is a solution containing 5% iodine and Ans.
10% potassium iodide solution.
l A daily dose of 5–15 drops can be used. l Carbimazole is a thioamide, acting as thyroid hormone
synthesis inhibitor.
It can be used l It is a commonly used drug as it is more potent and long
l as an expectorant.
acting. Carbimazole acts largely by getting converted to
l as prophylaxis in endemic goitre.
methimazole which is active in the body.
l as an antiseptic.
l Less protein bound and is 10 times more potent than
l for preoperative preparation for thyroidectomy.
propylthiouracil.
l in patients with thyroid storm.
l Crosses placental barrier and causes fetal hypothy-
roidism.
Q. 2. Iodine
Ans.
Adverse Effects
l Iodine is used in the treatment of hyperthyroidism. It l Allergic reactions
includes usage of iodides and radioactive iodine. l Hypothyroidism
l Iodides inhibit the release of thyroid hormone and in
l GI intolerance, joint pain, hepatitis, nephritis, etc.
thyrotoxic patients; symptoms subside in 1–2 days. The l A less common but most dangerous adverse effect is
gland becomes firm and shrinks in size over a period of agranulocytosis.
10–14 days. Effects are transient and decrease after
15 days
l Adverse effects: Allergic reactions like skin rashes, con- Uses
junctivitis, swelling of the lips and salivary glands, fever l They are used in the long-term treatment of thyro-
and lymphadenopathy. toxicosis where surgery is contraindicated or not
l Uses
feasible and radioactive iodine is contraindicated.
l Preoperative preparation for thyroidectomy
l They are used along with radioactive iodine to hasten
l In thyroid storm iodine is used to reduce release of
recovery in thyrotoxicosis.
thyroid hormone. l They are used for treatment of thyrotoxic crisis along
l Prophylaxis to prevent endemic goitre
with iodide and propranolol.
Topic 15
Insulin, Oral Hypoglycaemics and Glucagon

LONG ESSAYS
Q. 1. Classify antidiabetic drugs and write about the levels. They are noninvasive drugs as the necessity of injec-
oral antidiabetic drugs. tions is avoided here.
Ans.
l Diabetes mellitus is a chronic metabolic disorder char-

CLASSIFICATION
acterized by hyperglycaemia and altered metabolism of I. Sulphonylureas
carbohydrates.
Sulphonylureas were the first oral hypoglycaemic drugs to
i. Type I insulin-dependent diabetes mellitus (IDDM) be introduced. They are divided into two generations. All
ii. Type II noninsulin-dependent diabetes mellitus these drugs have same mechanism of action, but differ in
(NIDDM) potency and duration of action. The second generation drugs
are about 100 times more potent than first generation drugs.
Usually type I IDDM is treated with insulin supplements while
type II NIDDM is treated with oral hypoglycaemic agents.
Mechanism of action
ANTIDIABETIC DRUGS Sulphonylureas
They are classified as follows:
A. Insulin
I. Ultra short-acting (rapid acting) Bind to specific receptors on β cells of islets of pancreas
i. Insulin lispro (lysine 1 proline)
ii. Insulin aspart
Block the ATP-sensitive potassium channels
II. Short-acting (rapid acting)
i. Regular crystalline insulin (rapid action)
ii. Insulin zinc suspension (semilente amorphous) Depolarization and influx of Ca2+ ions into β cells
III. Intermediate-acting
i. Isophane insulin suspension (NPH)
ii. Insulin zinc suspension (lente) Degranulation and increased release of stored insulin from
iii. Biphasic insulin (ready-made PPN) β cells
iv. Glargine (clear, no buffer, no protein)
IV. Long-acting
They are metabolized in the liver and mainly excreted in urine.
i. Glargine
ii. Extended insulin zinc suspension (ultralente)
iii. Protamine zinc suspension (PZT) Use
B. Oral hypoglycaemics
Sulphonylureas are useful in patients with type II diabetes
I. Sulphonylureas
mellitus.
i. First generation: Tolbutamide, chlorpropamide
ii. Second generation: Glibenclamide (glyburide), Various drugs included in sulphonylureas are as follows:
glipizide, gliclazide, glimepiride A. First generation
II. Biguanides: Phenformin, metformin i. Tolbutamide
III. Meglitinide analogues: Repaglinide, Nateglinide l Weaker, short acting, safer in patients prone to
IV. Thiazolidinediones: Rosiglitazone, Pioglitazone hypoglycaemia
V. a -Glucosidase inhibitors: Acarbose, Miglitol l Daily dose: 0.5–3 g; half-life: 6–8 h; duration of
action: 6–8h
ii. Chlorpropamide
ORAL HYPOGLYCAEMIC DRUGS
l Longest acting, can cause prolonged hypoglycae-
These drugs are used in cases of early and mild noninsulin- mia, potentiates ADH action, more cholestatic jaun-
dependent diabetes mellitus as they lower blood glucose dice, alcohol flush.
l Daily dose: 0.1–0.5 g; half-life: 30–36 h; duration Repaglinide

of action: 36–48 h l Acts similar to sulphonylureas, by binding to their re-
B. Second generation ceptors and other distinct receptors, causing closure of
Glibenclamide (glyburide) ATP dependent K1 channels. This causes depolarization
l Potent but slow acting, marked initial insulinaemic action and there is insulin release.
in urine as well as bile, single dose is sufficient despite l It is indicated only in type II diabetes as an alternate to
short half-life. sulphonylureas or to supplement metformin. It is given

l Daily dose: 5–15 mg; half-life: 4–6 h; duration of action: half an hour before a meal to control postprandial hyper-
18–24 h glycaemia.
Glipizide
Nateglinide
l Fast acting, insulinaemic action persists even after pro-
l It has more rapid onset and shorter duration of hypogly-
longed use, can be given once daily despite short half-life.
l Daily dose: 5–20 mg; half-life: 3–5 h; duration of action:
caemic action than repaglinide. There is little effect on
12–18 h fasting blood glucose level. Episodes of hypoglycaemia
are less frequent.
Gliclazide
l Daily dose: 180–480 mg; half-life: 1.5 h; duration of
l Has antiplatelet action, reduces free radicals, delays dia-
action: 2–3 h
betic retinopathy, less weight gain.
l Daily dose: 40–240 mg; half-life: 8–20 h; duration of
action: 12–24 h IV. Thiazolidinediones

l Stronger extrapancreatic action, less hyperinsulinaemia
They are selective agonists for the nuclear peroxisome prolif-
erator-activated receptor g which enhances the transcription
24 h
of several insulin responsive genes. Hepatic gluconeogenesis
is also suppressed. They are well tolerated. Weight gain, head-
II. Biguanides ache, myalgia and mild anaemia are common.
They are used to supplement sulphonylureas or metformin.
Metformin is the only biguanide used clinically.
Rosiglitazone
Mechanism of Action
Reverses insulin resistance. No hypoglycaemia
They inhibit hepatic gluconeogenesis and enhance insulin- occurs.
mediated glucose disposal from muscles and fat. They pro- l Daily dose: 4–8 mg; half-life: 4 h; duration of action:
mote peripheral glucose utilization by enhancing anaerobic 12–24 h
glycolysis and inhibit alimentary absorption of glucose.
Metformin is taken orally, well absorbed through GIT Pioglitazone
and is excreted mostly unchanged in urine. l Reverses insulin resistance. No hypoglycaemic action
occurs.
l It may cause failure of oral contraceptives.
Use
Metformin is useful in obese patients with type II DM ei- 24 h
ther alone or in combination with sulphonylureas.
Phenformin Glucosidase Inhibitors

Lactic acidosis is more common. Drug usage is withdrawn Acarbose is a complex oligosaccharide which irreversibly
in many countries. inhibits a-glucosidases, the final enzymes for the metabo-
lism of carbohydrates in the small intestines. It slows down
Metformin
digestion and absorption of polysaccharides and sucrose. It
l It is not metabolized in the body at all. Lactic acidosis is a mild antihyperglycaemic and not a hypoglycaemic. It is
is less common. Very high doses can cause hypoglycae- used as an adjuvant to diet in obese diabetics.
mia or vitamin B12 deficiency.
l Daily dose: 0.5–2 g; half-life: 1.5–3 h; duration of action: Q. 2. Describe the different preparations of insulin. Add
6–8 h a note on their merits and demerits.
Or,
III. Meglitinide Analogues
Mention the various insulin preparations with their
Recently developed quick and short-acting insulin releases. advantages and disadvantages.
Or, iii. Human Insulin

Mention insulin preparations and discuss their pharma- It is prepared either by enzymatic modification of porcine
cological actions and adverse effects. insulin (semisynthetic human insulin) or by DNA recombi-
nant technology. Human insulin is least immunogenic.
Ans.
Insulin is a hormone synthesized in the beta cells of pancreatic Mechanism of Action

islets from a single chain polypeptide precursor called prepro-
insulin. It maintains blood glucose levels by oxidizing it. Insulin binds with specific receptors
(insulin receptors) on cell membrane
Various preparations of insulin are as follows (Table 15.1):
The conventional commercial preparations of insulin
are derived from beef and pork pancreas. It has been modi- Activates the tyrosine protein kinase enzyme
fied by adding zinc with or without protamine.
The tyrosine gets autophosphorylated to each insulin

TABLE 15.1 Insulin Preparations Based on Onset and receptor substrate proteins (IRS-1, IRS-2, etc)
Duration of Action
Onset Duration of
The cascade of phosphorylation and
Class Type of Insulin (h) Action (h)
dephosphorylation reactions results in
1. Ultra short- Insulin lispro (lysine 0.25 2–6
acting (rapid 1 praline)
acting)
Activation or inhibition of enzymes involved in
Insulin aspart 0.25 3–6 rapid metabolic actions of insulin.
2. Short-acting Regular crystalline 0.5–1 6–8
(rapid acting) insulin (rapid action)
Actions of Insulin
Insulin zinc suspen- 1 12–16
sion (semilente i. Carbohydrate metabolism: Insulin decreases blood glu-
amorphous) cose level by inhibiting hepatic glycogenolysis, gluco-
3. Intermediate- Isophane insulin 1–2 18–24 neogenesis and lipolysis in adipose tissue. It promotes
acting suspension (NPH1) glycogenesis in muscle and liver and increases rate of
utilization of glucose.
Insulin zinc suspen- 1–2 18–24
sion (lente) ii. Protein metabolism: It promotes protein synthesis and
inhibits protein breakdown.
4. Long-acting Protamine zinc 4–6 24–36
insulin (PZI)
iii. Fat metabolism: Insulin promotes synthesis of free fatty
acids and triglyceride and inhibits lipolysis.
Extended insulin 4–6 24–36 iv. It increases potassium entry into the cells and decreases
zinc suspension
(ultralente)
urea output from liver.
Glargine 2–5 20–24

Uses or Indications for Insulin
i. In juvenile diabetes, it is essential.
ii. In noninsulin-dependent diabetes mellitus, it is required
INSULIN PREPARATIONS BASED ON when diabetes is not controlled by diet or exercise.
SOURCE AS BOVINE, PORCINE AND iii. When oral hypoglycaemics fail
HUMAN INSULINS iv. Stress of surgery, infections, trauma, pregnancy and labour
v. Gangrene of extremities
i. Bovine (Beef) Insulin vi. Diabetic ketoacidosis (diabetic coma)
It differs from human insulin by three amino acid residues
and is more antigenic to man.
Adverse Effects of Insulin
i. Hypoglycaemia
ii. Porcine (Pig) Insulin l It is the most common and dangerous complication.
It differs from human insulin by only one amino acid resi- Prolonged hypoglycaemia may cause permanent brain
due and is less immunogenic. damage. Hypoglycaemia can occur in any diabetic
and may be due to delay in taking food, too much of i. Insulin

physical activity or excess dose of insulin.
l Insulin is a hormone which maintains normal levels of
l Treatment: All these manifestations are relieved by
blood glucose. It is synthesized in the beta cells of pan-
administration of glucose. If patient is conscious,
creatic islets.
oral glucose or if hypoglycaemia is severe (uncon-
l It facilitates glucose transport across cell membrane and
scious patient) 50 mL of 50% glucose is injected IV.
alters the activity of enzymes involved in metabolism of
l Glucagon 1 mg IV or adrenaline 0.2 mg SC may be
carbohydrates, fats and proteins in liver, muscle and
given for severe hypoglycaemia.
adipose tissue to lower blood glucose levels.
ii. Hypersensitivity
l It prevents rise in free fatty acid level, ketone body pro-
l Allergic reactions are rare; they may cause local skin
duction and protein breakdown of diabetic state.
reactions at the site of injection.
l Rashes, photosensitivity, purpura, transient leukope-
nia, rarely agranulocytosis. ii. Glucagon

iii. Local reactions
l The alpha cells secrete glucagon which is a hyperglycae-
l Swelling, erythema, and stinging can occur some-
mic hormone. It increases the force and rate of contraction.
time, especially in the beginning. Lipodystrophy at
l It activates adenyl cyclase and increases cAMP in liver,
the site of injection after long use
fat cells, heart and other tissues. It is used to counteract
l Lipodystrophy may be avoided by using purified insu-
the actions of insulin hypoglycaemia and occasionally
lin preparations and changing injection site by rotation.
to stimulate the heart in cardiogenic shock.
iv. Nonspecific side effects
l Nausea, vomiting, flatulence, diarrhoea, or constipa-
tion, headache, paraesthesia and weight gain Diabetic Coma

l Oedema due to salt and water retention
l Diabetic coma is seen in insulin-dependent diabetes
v. Insulin resistance
mellitus and less in noninsulin diabetes mellitus.
l It may be acute or chronic. Acute insulin resistance
l The symptoms of diabetic coma are hyperglycaemia,
develops rapidly and is due to stressful conditions like
acidosis, hyperventilation, dehydration, hypotension,
trauma, infection, surgery, psychological stress, etc.
shock and impaired consciousness.
l Chronic insulin resistance is common in patients on
prolonged conventional beef or pork insulins. Such

patients should be treated with highly purified newer Management of Diabetic Coma
insulins.
l Regular insulin is given 0.1–0.2/kg IV followed by
Q. 3. Mention the hormones secreted by pancreas. What is 0.14 kg/h infusion till 4–6 h. Rate of infusion is de-
diabetic coma? What are the principles of treatment? creased in blood glucose level.
l IV fluids are given as normal saline IV l L/h.
Ans. The pancreas has small cells on it called the islets of l IV KCl infusion is given to correct the hypokalaemia.
Langerhans that secrete two hormones which are l Sodium bicarbonate is given to correct acidosis.
l Antibiotics and other symptomatic and supportive treat-

i. insulin and
ment are given.
ii. glucagon.
SHORT ESSAYS
Q. 1. Mention different insulin preparations. 2 . Lente insulin: SC
3. Isophane insulin: SC
Ans.
The various preparations of insulin are as follows: Highly Purified Insulin Preparation
They are nonantigenic and are indicated in insulin resis-
Conventional Insulin Preparations tance, allergy to conventional preparations, diabetics
Conventional commercial preparations of insulin are derived undergoing surgery, trauma and infection. According to
from beef and pork pancreas. Zinc and protamine are added purification method used preparations are of two types, i.e.
for slow absorption and longer duration of action. Insulin is 1. Single peak insulin: It is purified by gel filtration and re-
degraded in GIT and hence not given orally. Commonly used peated crystallization. They contain 50–200 ppm proinsulin.
preparations are as follows: 2. Monocomponent insulin: After gel filtration it is further
1. Regular insulin: SC, IV, IM purified by ion exchange chromatography.
Human Insulin Various drugs included in sulphonylureas are as follows:

1. First generation: Tolbutamide and chlorpropamide
They were produced by recombinant DNA technology in
2. Second generation: Glibenclamide, glipizide, gliclazide
Escherichia coli.
and glimepiride
Insulin preparations based on onset and duration of action
are as follows:
1. Ultra short-acting (rapid acting)
a. Insulin lispro (lysine 1 proline) l These drugs lower blood sugar level on oral and paren-
b. Insulin aspart teral administration.
2 . Short-acting (rapid acting) l They lower blood sugar level in some of the diabetics
a. Regular crystalline insulin (rapid action) and all nondiabetic patients.

b. Insulin zinc suspension (semilente amorphous) l They are effective only in presence of functional pancreas.
3 . Intermediate-acting l They produce increase in body weight.
a. Isophane insulin suspension (NPH1)

b. Insulin zinc suspension (lente) Q. 3. Oral antidiabetic drugs
4. Long-acting Ans.
a. Protamine zinc insulin (PZI)
b. Extended insulin zinc suspension (ultralente) Oral antidiabetic drugs or hypoglycaemic drugs are the
c. Glargine drugs used in cases of early and mild noninsulin-dependent
diabetes mellitus as they lower blood glucose levels. They
Q. 2. Antidiabetic action of sulphonylureas are noninvasive drugs as the necessity of injections is
Ans. avoided here.
Classification of oral antidiabetic drugs is as follows:
Sulphonylureas were the first oral hypoglycaemic drugs to
1. Sulphonylureas
be introduced. They are divided into two generations. All
a. First generation: Tolbutamide and chlorpropamide
these drugs have same mechanism of action, but differ in
b. Second generation: Glibenclamide, glipizide, glicla-
potency and duration of action. The second generation drugs
zide and glimepiride
are about 100 times more potent than first generation drugs.
2. Biguanides: Phenformin, metformin
3. Meglitinides: Repaglinide, nateglinide
Mechanism of Action 4. Thiazolidinediones: Rosiglitazone, pioglitazone
5. a-glucosidase inhibitors: Acarbose, miglitol
Sulphonylureas
Mechanism of Action
Bind to specific receptors on β cells of islets of pancreas l Sulphonylureas: They act by blocking ATP sensitive po-
tassium channels on the pancreatic b cell membrane. This
Block the ATP-sensitive potassium channels
increases calcium influx and increases insulin release.
l Biguanides: They suppress gluconeogenesis in liver and
promote peripheral utilization of glucose. They also in-

Depolarization and influx of Ca2+ ions into β cells hibit intestinal absorption of glucose, amino acid and
vitamin B12.
Degranulation and increased release of stored insulin from

β cells Uses of Oral Antidiabetic Drugs
l Sulphonylureas are used in treatment of maturity on-
Absorption, Fate and Excretion set diabetes, insulin-resistant diabetes and diabetes
insipidus.
Sulphonylureas are rapidly absorbed from gastrointestinal
l Biguanides are used in obese mild diabetics, nondia-
tract. They are partly bound to plasma proteins. They are
betic obese patients and in patients allergic to sulpho-
metabolized in liver and are excreted in urine.
nylureas.
Therapeutic Uses Q. 4. Insulin and sulphonylureas

Sulphonylureas are used in treatment of maturity onset dia- Ans. Comparison between insulin and sulphonylureas is
betes, insulin-resistant diabetes and diabetes insipidus. given in Table 15.2.
TABLE 15.2 Comparison between Insulin and Sulphonylureas 5. Insulin resistance

l It may be acute or chronic. Acute insulin resistance
Insulin Sulphonylureas
develops rapidly and is due to stressful conditions like
The insulin is used in insulin- Sulphonylurea is used in non- trauma, infection, surgery, psychological stress, etc.
dependent diabetes mellitus dependent-diabetes mellitus
l Chronic insulin resistance is common in patients on
and noninsulin-dependent
diabetes mellitus prolonged conventional beef or pork insulins. Such
patients should be treated with highly purified newer
The insulin should be given It is given either parenterally
parenterally, i.e. SC/IM or orally insulins.
For functioning of insulin For functioning of sulphonyl- Q. 6. Mention four advantages of newer insulins.
b cells are not required urea b cells are required
It is used in therapy of It is not used in therapy of
Ans.
diabetic coma diabetic coma
l Insulin is a hormone which helps to maintain normal
Insulin can be given to Sulphonylurea is not given to blood glucose levels by oxidizing it.
nursing mothers nursing mothers because it is l It is synthesized in the beta cells of pancreatic islets. It
secreted in milk
facilitates glucose transport across cell membrane and
Q. 5. Mention four adverse effects of insulins. carbohydrates, fats and proteins in liver, muscle and
Ans. adipose tissue to lower blood glucose levels and prevent
rise in free fatty acid level, ketone body production and
l Insulin is a hormone which helps in maintenance of protein breakdown of diabetic state.
normal blood glucose levels by oxidizing it. It is synthe- l Conventional insulins are obtained from pork and beef
sized in the beta cells of pancreatic islets. pancreas. It has to be injected 2–3 times a day.
l It facilitates glucose transport across cell membrane and l Newer insulins are derived from human pancreas.
Advantages of newer insulin over conventional prepara-
carbohydrates, fat and protein in liver, muscle and adi-
tions are as follows:
pose tissue to lower blood glucose levels.
l The risk of antigen–antibody reactions are avoided
Adverse effects of insulin are as follows: since it is derived from human pancreas. Thus allergies
1. Hypoglycaemia caused by conventional preparations can be overcome.
l It is the most common and dangerous complication. l They are highly purified preparations.
Prolonged hypoglycaemia may cause permanent l They can be used in cases of insulin resistance.
brain damage. Hypoglycaemia can occur in any dia- l They can be used during pregnancy without fear of af-
betic and may be due to delay in taking food, too fecting the mother or the fetus.
much of physical activity or excess dose of insulin. l They can be used in case of injection site lipodystrophy
l Treatment: All these manifestations are relieved by caused by conventional preparations.
administration of glucose. If patient is conscious,
oral glucose or if hypoglycaemia is severe (uncon- Q. 7. Give reason—glibenclamide is not useful in treating
scious patient) 50 mL of 50% glucose is injected IV. childhood diabetes mellitus.
Glucagon 1 mg IV or adrenaline 0.2 mg SC may be Ans.
given for severe hypoglycaemia.
2. Hypersensitivity l Glibenclamide is a second generation sulphonylurea.
l Allergic reactions are rare, they may cause local skin l Sulphonylureas provoke a brisk release of insulin from
reactions at the site of injection. pancreas.
l Rashes, photosensitivity, purpura, transient leukope- l They act on the so-called sulphonylurea receptors on the
nia, rarely agranulocytosis. pancreatic beta cell membrane—cause depolarization
3. Local reactions by reducing conductance of ATP sensitive K1 channels.
l Swelling, erythema and stinging can occur some- This enhances Ca21 influx degeneration and insulin
time, especially in the beginning. Lipodystrophy at release.
the site of injection after long use. l Sulphonylureas cannot cause hypoglycaemia in pancre-
l Lipodystrophy may be avoided by using purified insu- atectomized animals or in type I diabetes mellitus.
lin preparations and changing injection site by rotation. l Since type I diabetes mellitus occurs in children (at an
4. Nonspecific side effects early age) glibenclamide cannot be used to treat it.
l Nausea, vomiting, flatulence, diarrhoea, or constipa-
tion, headache, paraesthesia and weight gain. Oedema Q. 8. Compare and contrast conventional insulin with
due to salt and water retention. newer insulin.
Ans. Comparison between conventional insulin and newer TABLE 15.4 Comparison between Sulphonylurea
insulin is listed in Table 15.3. or Tolbutamide and Biguanides or Metformin
TABLE 15.3 Comparison between Conventional Insulin Sulphonylurea or

and Newer Insulin Tolbutamide Biguanides or Metformin
They lower blood sugar levels Biguanides lower blood
Conventional Insulin Newer Insulin in some of diabetic and all sugar levels only in diabetic
They are derived from beef They are produced by recom- noninsulin-dependent diabetic individual but not in normal
and pork pancreas binant DNA technology individuals individuals
They are less water soluble They are more water soluble For action of sulphonylureas For action of biguanide the
the release of insulin is from insulin is not released from
It has slow SC absorption It has more rapid SC absorption b cells of Langerhans b cells of Langerhans
It has more duration of action It has less duration of action They are rapidly absorbed They are well absorbed from
It produces local reactions Local reactions are not present from gastrointestinal tract gastrointestinal tract
They are metabolized in liver They are eliminated through
Q. 9. Compare and contrast sulphonylureas and bigu- and excreted in urine urine in 24 h
anides. They cause increase in body They cause decrease in body
weight weight
Or,
They are used in treatment They are used in obese mild
Compare and contrast tolbutamide and metformin. of maturity onset diabetes, diabetics and nondiabetic
insulin-resistant diabetes and obese patients
Ans. Comparison between sulphonylurea or tolbutamide diabetes insipidus
and biguanides or metformin is listed in Table 15.4.
SHORT NOTES
Q. 1. Mention four advantages of newer insulins. l Types of sulphonylureas
1. First generation: Tolbutamide and chlorpropamide
Or,
2. Second generation: Glibenclamide, glipizide, glicla-
Newer insulins are preferred to conventional insulins. zide and glimepiride
Why? l Mechanism of action: Sulphonylureas act by blocking
ATP-sensitive potassium channels on the pancreatic

Ans.
b cell membrane. This increases calcium influx and in-
Advantages of newer insulin over conventional prepara- creases insulin release.
tions are as follows: l Uses: Sulphonylureas are used in treatment of maturity
l Conventional insulin preparations are derived from beef onset diabetes, insulin-resistant diabetes and diabetes
and pork pancreas; hence the risk of antigen–antibody insipidus.
reaction is very high whereas newer insulins are derived
from human pancreas, the risks of antigen–antibody Q. 3. Give reason—glibenclamide is not useful in treating
reactions are avoided. Thus allergies caused by conven- childhood diabetes mellitus.
tional preparations can be overcome. Ans.
l Newer insulins are highly purified preparations.
l Newer insulins can be used in cases of insulin resistance. Glibenclamide is a second generation sulphonylurea; they
l They can be used during pregnancy without fear of provoke a brisk release of insulin from pancreas.
affecting the mother or the fetus. They act on the so-called sulphonylurea receptors on
l Newer insulins can be used in case of injection site lipo- the pancreatic beta cell membrane and cause depolariza-
dystrophy caused by conventional preparations. tion by reducing conductance of ATP-sensitive K1 chan-
nels. This enhances Ca21 influx, degeneration and insulin
Q. 2. Sulphonylurea release.
Sulphonylureas cannot cause hypoglycaemia in pancre-
Ans.
atectomized animals or in type I diabetes mellitus. Since
l Sulphonylureas were the first oral hypoglycaemic drugs type-I diabetes mellitus occurs in children (at an early age)
to be introduced. They are divided into two generations. glibenclamide cannot be used to treat it.
All these drugs have same mechanism of action, but dif-
fer in potency and duration of action. Q. 4. Tolbutamide
Ans. 1. Ultra short-acting (rapid acting)

a. Insulin lispro (lysine 1 proline)
l Tolbutamide is an oral hypoglycaemic drug that is cat- b. Insulin aspart
egorized under first generation sulphonylureas. 2. Short-acting (rapid acting)
l It is weaker, short acting, safer in patients prone to
a. Regular crystalline insulin (rapid action)
hypoglycaemia. b. Insulin zinc suspension (semilente amorphous)
l Daily dose: 0.5–3 g; half-life: 6–8 h; duration of action:
3. Intermediate-acting
6–8 h a. Isophane insulin suspension (NPH1)
l They provoke a brisk release of insulin from pancreas
b. Insulin zinc suspension (lente)
and act on the so-called sulphonylurea receptors on the 4. Long-acting
pancreatic beta cell membrane. a. Protamine zinc insulin (PZI)
l They cause depolarization by reducing conductance of
b. Extended insulin zinc suspension (ultra lente)
ATP sensitive K1 channels. c. Glargine
21
l This enhances Ca influx, degranulation and insulin
release. Q. 8. Compare insulin and sulphonylurea.
l They are used only in type II diabetes mellitus.
Ans.
Q. 5. Glibenclamide
Ans. Insulin Sulphonylureas
l Glibenclamide (glyburide) is an oral hypoglycaemic Administered by parenteral Oral hypoglycaemic drugs

route
drug that is categorized under second generation sul-
phonylureas. Used in type I diabetes Affective only in type II
l Potent but slow acting, marked initial insulinaemic
mellitus diabetes
action in urine as well as bile They act on insulin receptors They act on sulphonylurea
l Single dose is sufficient despite short half-life. Daily receptors
dose: 5–15 mg; half-life: 4–6 h; duration of action: They act by reducing blood They provoke brisk release of
18–24 h glucose level insulin from pancreas
l They provoke a brisk release of insulin from pancreas.
They act on the so-called sulphonylurea receptors on the

pancreatic beta cell membrane and cause depolarization
by reducing conductance of ATP-sensitive K1 channels. Q. 9. Write basic use of insulin in type I diabetes.
This enhances Ca21 influx degranulation and insulin Ans.
release.
l They are used only in type II diabetes mellitus. Insulin is needed in type I diabetic cases in the following
conditions:
Q. 6. Newer insulins l When diabetes is not controlled by diet or exercise
l Primary or secondary failure of oral hypoglycaemics or

Ans.
when these drugs are not tolerated
l Newer insulins are derived from human pancreas. l In underweight patients
l Since they are derived from human pancreas, the risk of l Temporarily to tide over infections, trauma, surgery, etc.
antigen–antibody reactions are avoided. Thus allergies

caused by conventional preparations can be overcome. Q. 10. Write the drug treatment of juvenile diabetes.
l They are highly purified preparations. Ans.
l They can be used in cases of insulin resistance.
l They can be used during pregnancy without fear of af- l Juvenile diabetes is an insulin-dependent diabetes mel-
fecting the mother or the fetus. litus. It is immune-mediated and there is destruction of
b cells due to which deficiency of insulin occurs.
Q. 7. Mention preparations of insulin based on duration l Treatment of juvenile diabetes consists of insulin ther-
of action. apy along with diet.
l Insulin therapy is generally started with regular insulin
Ans.
administered parenterally before each major meal. The
Insulin preparations based on onset and duration of action requirement is assessed by testing urine or blood glucose
are as follows: level.
Topic 16
Corticosteroids
LONG ESSAY
Q. 1. Classify glucocorticoids. Describe the mechanism Steroid hormone enters the cells of target organ
of action, adverse effects and therapeutic uses.
Or, In the cytoplasm it binds to specific receptors
Enumerate glucocorticoids. Describe therapeutic uses
and adverse effects of any one of them. Steroid receptor complex becomes activated
Or,
Enters the nucleus
Describe the therapeutic uses and adverse effects of
glucocorticoids. Binds to specific site on the DNA
Ans.
Protein synthesis regulation
Corticosteroids are the hormones produced by the cortex of
the adrenal gland. They are
i. glucocorticoids—cortisol, Shows response
ii. mineralocorticoids—aldosterone and
i ii. a small amount of androgens. THERAPEUTIC USES OF
The secretion of adrenal cortex is under the control of GLUCOCORTICOIDS
ACTH secreted by the anterior pituitary which in turn is Endocrinal Uses
regulated by corticotropin releasing factor (CRF). This is
termed as hypothalamic pituitary-adrenal axis. A. Replacement Therapy
i. Acute adrenal insufficiency: This is an emergency con-
CLASSIFICATION OF CORTICOSTEROIDS dition that could be precipitated by an infection or
sudden withdrawal of steroids. Hydrocortisone hemis-
A
. Short-acting (8–12 h)
uccinate 100 mg bolus followed by infusion is given
i. Hydrocortisone
immediately.
ii. Cortisone
ii. Chronic adrenal insufficiency (Addison’s disease): Oral
B
. Intermediate-acting (18–36 h)
hydrocortisone 20–40 mg dialysis the most commonly
i. Prednisolone
used drug along with adequate salt and water allow-
ii. Methylprednisolone
ance. Some patients may need additional fludrocorti-
iii. Triamcinolone
sones or DOCA are added.
C
. Long-acting (36–54 h)
i. Paramethasone
ii. Dexamethasone Nonendocrinal Uses
iii. Betamethasone B. Pharmacotherapy
i. Arthritides
MECHANISM OF ACTION a. Rheumatoid arthritis: In progressive disease steroids
are given as one of the last resort drugs in conjunction
Corticosteroids bind to specific receptors in the cytoplasm, with nonsteroidal anti-inflammatory drugs (NSAIDs).
the drug-receptor complex is transported into the nucleus If one or two joints are involved, intra-articular injec-
where it binds to specific sites on DNA and regulates the tions are preferred.
synthesis of new proteins that bring about the hormone b. Osteoarthritis: Intra-articular injections are given to
effects. patients with osteoarthritis.
c. Rheumatic fever: Only in severely ill patients with xi. Cerebral oedema: A steroid without salt and water
fever, carditis and congestive heart failure (CHF) and retaining activity, e.g. large dose of dexamethasone is
not responding to NSAIDs require glucocorticoids. preferred.
d. Acute gout: When treatment with NSAIDs has not xii. Lung diseases: Glucocorticoids are used in the treat-
been successful, prednisolone is used as an adjuvant. ment of aspiration pneumonia and prevention of infant
ii. Severe allergic reactions respiratory distress syndrome.
l Corticosteroids may be used for short periods in an- xiii. Organ transplantation: For prevention and treatment
gioneurotic oedema, hay fever, serum sickness, con- of graft rejection, high doses of prednisolone are given
tact dermatitis and anaphylaxis. at the time of surgery with immunosuppressive agents.
l They are slow acting and in less severe cases, antihis- xiv. Other uses include Bell’s palsy, acute polyneuritis and
tamines should be preferred. myotonia.
iii. Bronchial asthma
Glucocorticoids may be used either for
ADVERSE EFFECTS OF GLUCOCORTICOIDS
a. status asthmaticus—intravenous hydrocortisone
hemisuccinate or Most of the adverse effects of glucocorticoids are extension
b. severe chronic asthma—steroids are used as supple- of pharmacological actions and are dependent on dose,
ment to bronchodilators. duration of therapy and the relative potency of additional
Inhalational steroids are used and in more severe cases low mineralocorticoid effects.
dose oral prednisolone is indicated. i. Cushing’s syndrome: Abnormal fat distribution causes
iv. Collagen diseases moon face, buffalo hump, truncal obesity, muscle
l Most cases of polyarthritis nodosa, lupus erythemato- wasting, thinning of limbs and skin, easy bruising,
sus, polymyositis, Wegener’s granulomatosis, and purple striae and acne.
other rheumatoid disorders respond to glucocorticoids. ii. Hyperglycaemia: Precipitation of diabetes mellitus or
l They may be life saving. Therapy is generally started aggravation of pre-existing diabetes.
with high doses which are tapered to maintenance iii. Susceptibility of infection: Long-term therapy with
dose when remission occurs. steroids leads to immunosuppression, which makes
v. Eye diseases the patient more vulnerable to various opportunistic
l Corticosteroids are used in a large number of inflam- infections like fungal, viral and bacterial, etc.
matory ocular diseases and may prevent the blindness. iv. Osteoporosis: Especially of the vertebrae is more
l Allergic conjunctivitis, uveitis, optic neuritis, and common in the elderly.
other inflammatory conditions are treated with ste- v. Avascular necrosis: Avascular necrosis of the bone
roids. due to restriction of blood flow through bone capillar-
vi. Renal diseases: Glucocorticoids are the first line of ies may cause pain and restriction of movement.
drugs in nephrotic syndrome. Growth in children may be suppressed.
vii. Skin diseases vi. Peptic ulceration: This may sometimes occur on pro-
l Atopic dermatitis, seborrhoeic dermatitis, inflamma- longed therapy especially when other ulcerogenic
tory dermatoses and other local conditions are treated drugs are (e.g. NSAIDs) used concurrently.
with topical steroids. vii. Mental disturbance: Euphoria, psychosis, depression
l Systemic therapy is needed and may be life saving in viii. Eye: Cataract and glaucoma may occur on prolonged
pemphigus vulgaris, exfoliative dermatitis, Stevens- therapy.
Johnson syndrome and other severe afflictions. ix. Delayed wound healing
viii. Gastrointestinal diseases: Mild inflammatory bowel x. Other effects: Raised intracranial pressure, convul-
diseases are treated with steroids and in severe cases sions, hypercoagulability of the blood and menstrual
oral prednisolone may be used. disorders
ix. Liver diseases: Steroids are used in chronic active and xi. Mineralocorticoid effects: This includes salt and water
alcoholic hepatitis. retention, oedema, hypokalaemia and hypertension
x. Haematologic disorders are rare with selective glucocorticoids.
l Autoimmune haemolytic anaemias usually respond xii. Thinning of muscles: Steroid treatment can cause hypo-
to glucocorticoids. kalaemia leading to muscle weakness and fatigability.
l Because of their lympholytic action, glucocorticoids Long-term steroid therapy leads to steroid myopathy.
are used usually in combination with antineoplastic xiii. HPA axis suppression: The most undesirable and dan-
drugs to treat certain malignancies, leukaemia, lym- gerous outcome of long-term steroid therapy leads
phomas, Hodgkin’s disease, multiple myeloma, etc. HPA axis suppression.
SHORT ESSAYS
Q. 1. Synthetic corticosteroids 1. Cushing’s syndrome: Abnormal fat distribution causes
moon face, buffalo hump, truncal obesity, muscle
Ans.
wasting, thinning of limbs and skin, easy bruising,
l Synthetic corticosteroids are more selective corticoste- purple striae and acne.
roids. They do not have mineralocorticoid action. 2. Hyperglycaemia: Precipitation of diabetes mellitus or
l They are more potent than the natural corticoids. They aggravation of pre-existing diabetes.
generally have intermediate to long duration of action. 3. Susceptibility of infection: Long-term therapy with
l Synthetic glucocorticoids include the following: steroids leads to immunosuppression, which makes the
1. Prednisolone: It is more selective glucocorticoid and patient more vulnerable to various opportunistic infec-
is four times more potent than hydrocortisone. Used tions like fungal, viral and bacterial, etc.
for allergic, inflammatory, autoimmune diseases and 4. Osteoporosis: Especially of the vertebrae is more com-
in malignancies. mon in the elderly.
For example: Available as Deltacortril, Hostacortin- 5. Avascular necrosis: Avascular necrosis of the bone due
H, 5, 10 mg tab., 20 mg/mL for IM, intra-articular to restriction of blood flow through bone capillaries
injection, Wysolone, Nucort, 5, 10, 20 mg tab. may cause pain and restriction of movement. Growth
2. Methylprednisolone: Slightly more potent and more in children may be suppressed.
selective than prednisolone; 4–32 mg/day oral. 6. Peptic ulceration: This may sometimes occur on pro-
For example: Available as Solu-Medrol methylpred- longed therapy especially when other ulcerogenic
nisolone (as sodium succinate) 0.5 g (8 mL) and 1.0 g drugs (e.g. NSAIDs) are used concurrently.
(16 mL) inj. for IM, slow IV inj. 7. Mental disturbance include euphoria, psychosis,
3. Triamcinolone: Slightly more potent but highly selec- depression.
tive glucocorticoid than prednisolone. 4–32 mg/day 8. Eye: Cataract and glaucoma may occur on prolonged
oral, 5–40 mg IM, intra-articular injection. Also used therapy.
topically. 9. Delayed wound healing
For example: Available as Kenacort, Tricort 1, 4, 8 mg 10. Other effects: Raised intracranial pressure, convul-
tab, 10 mg/mL, 40 mg/mL (as acetonide) for IM, sions, hypercoagulability of the blood and menstrual
intra-articular injection Ledercort 4 mg tab. disorders
4. Dexamethasone: Very potent and highly selective 11. Mineralocorticoid effects: This includes salt and water
glucocorticoid than prednisolone. It is used for in- retention, oedema, hypokalaemia and hypertension are
flammatory and allergic conditions in a dose of rare with selective glucocorticoids.
0.5–5 mg/day oral. 12. Thinning of muscles: Steroid treatment can cause
In shock, cerebral oedema, etc 4–20 mg/day IV, IM, hypokalaemia leading to muscle weakness and fatiga-
injection. Also used topically. bility. Long-term steroid therapy leads to steroid
For example: Available as Decadron, Dexona 0.5 mg myopathy.
tab, 4 mg/mL (as sodium phosphate) for IV, IM inj., 13. HPA axis suppression: The most undesirable and dan-
0.5 mL oral drops, etc. gerous outcome of long-term steroid therapy leads
5. Betamethasone: Same as that of dexamethasone. HPA axis suppression.
0.5–5 mg/day oral, 4–20 mg/day IV, IM, injection or
infusion, also topical. Q. 3. Therapeutic uses of glucocorticoids
For example: Available as Betnesol, Betacortril, Ans.
Celestone 0.5 mg, 1 mg tab, 4 mg/mL (as sodium
phosphate) for IV, IM inj., 0.5 mL oral drops, etc. Therapeutic uses of glucocorticoids are as follows:
Q. 2. Adverse effects of corticosteroids

Endocrinal Uses
Or,
Replacement Therapy
Side effects of glucocorticoids
1. Acute adrenal insufficiency: This is an emergency con-
Ans. Most of the adverse effects of glucocorticoids are dition that could be precipitated by an infection or
extension pharmacological actions and are dependent on sudden withdrawal of steroids. Hydrocortisone hemi-
dose, duration of therapy and the relative potency of addi- succinate 100 mg bolus followed by infusion is given
tional mineralocorticoid effects. immediately.
2. Chronic adrenal insufficiency (Addison’s disease): Oral 9. Haematologic disorders: Autoimmune haemolytic
hydrocortisone 20–40 mg during dialysis is the most anaemiae usually respond to glucocorticoids.
commonly used drug along with adequate salt and water 10. Cerebral oedema: A steroid without salt and water re-
allowance. Some patients may need additional fludro- taining activity, e.g. large dose of dexamethasone is
cortisones or DOCA are added. preferred.
11. Organ transplantation: For prevention and treatment
of graft rejection, high doses of prednisolone are given
Nonendocrinal Uses at time of surgery with immunosuppressive agents.
Pharmacotherapy 12. Other uses include Bell’s palsy, acute polyneuritis and
myotonia.
1. Arthritides
a. Rheumatoid arthritis: In progressive disease steroids Q. 4. Mention the actions and adverse effects of
are given as one of the last resort drugs in conjunc- dexamethasone.
tion with NSAIDs. If one or two joints are involved,
Ans.
intra-articular injections are preferred.
b. Osteoarthritis: Intra-articular injections are given to Dexamethasone is a synthetic corticosteroid. It is a potent
patients with osteoarthritis. and highly selective glucocorticoid.
c. Rheumatic fever: Only in severely ill patients with It is used in cases of inflammatory and allergic condi-
fever, carditis and CHF and not responding to tions, shock and cerebral oedema.
NSAIDs require glucocorticoids.
d. Acute gout: When treatment with NSAIDs has not Actions of dexamethasone are as follows:
been successful, prednisolone is used as an adjuvant. 1. Anti-inflammatory action: It suppresses the inflamma-
2. Severe allergic reactions tory response, mainly by suppressing the recruitment of
l Corticosteroids may be used for short periods in an-
inflammatory cells at cellular level. Production of pros-
gioneurotic oedema, hay fever, serum sickness, con- taglandins (PGs) and other inflammatory regulators like
tact dermatitis and anaphylaxis. lymphotoxins (LTs), platelet-activating factor (PAF), tu-
l They are slow acting and in less severe cases, antihis-
mour necrosis factor a (TNF a) and cytokines are inter-
tamines should be preferred. fered. It reduces increased capillary permeability, local
3. Bronchial asthma: Glucocorticoids may be used either exudation, cellular infiltration, phagocytic activity and
for late response like capillary proliferation, collagen depo-
a. status asthmaticus: intravenous hydrocortisone sition, fibroblastic activity and finally scar formation. It
hemisuccinate or also produces anti-inflammatory protein lipocortin.
b. Severe chronic asthma: steroids are used as supple- 2. Antiallergic action: It impairs immunological compe-
ment to bronchodilators. tence and suppresses all types of hypersensitization and
Inhalational steroids are used and in more severe allergic phenomena. It suppresses the recruitment of
cases low dose oral prednisolone is indicated. leucocytes at the site of contact with antigen and of in-
4. Collagen diseases: Most cases of polyarthritis nodosa, flammatory response to immunological injury.
lupus erythematosus, polymyositis, Wegener’s granulo- Adverse effects include the following:
matosis and other rheumatoid disorders respond to glu- 1. Cushing’s syndrome: Moon face, buffalo hump, trun-
cocorticoids. They may be life saving. Therapy is gener- cal obesity, muscle wasting, thinning of limbs and
ally started with high doses which are tapered to skin, easy bruising, purple striae and acne.
maintenance dose when remission occurs. 2. Hyperglycaemia: Diabetes mellitus
5. Eye diseases and renal diseases: Glucocorticoids are 3. Susceptibility to infection: It is increased and sensitiv-
the first line of drugs in nephrotic syndrome. ity of any injection is more due to immunosuppression.
6. Skin diseases: May be used either topically as in atopic 4. Osteoporosis: Especially more common in the elderly.
dermatitis, seborrhoeic dermatitis and other local condi- 5. Avascular necrosis: Avascular necrosis of the bone due
tions or systemically may be as life-saving drugs in to restricted blood flow through bone capillaries.
pemphigus vulgaris, Stevens-Johnson syndrome and 6. Peptic ulceration: This may sometimes occur on pro-
other severe afflictions. longed therapy especially when other ulcerogenic
7. Gastrointestinal diseases: Mild inflammatory bowel drugs (e.g. NSAIDs) are used concurrently.
diseases treated with steroids and in severe cases oral 7. Mental disturbance: Euphoria, psychosis, depression
prednisolone may be used. 8. Cataract and glaucoma
8. Liver diseases: Steroids are used in chronic active and 9. Delayed wound healing
alcoholic hepatitis. 10. HPA axis suppression
Q. 5. Explain why glucocorticoid therapy should not be l Precipitation or flaring up of the underlying disease be-
stopped abruptly. ing treated and can cause reactivation of the disease.
l Withdrawal symptoms like fever, myalgia, arthralgia,
Or,
malaise, etc.
Abrupt cessation of prolonged administration of gluco- l Subjected to stress, these patients can go to acute adrenal
corticoids is hazardous. Explain. insufficiency manifesting as anorexia, nausea, vomiting,

abdominal pain, hypotension, dehydration, hyponatrae-
Ans.
mia, hyperkalaemia, etc.
Glucocorticoid therapy should be gradually decreased be- l Any patient who has received more than 20–25mg/day
fore stopping it completely. of hydrocortisone should be put on the scheme of

gradual withdrawal.
Sudden cessation of the drug may cause suppression of l Such patients may need protection with steroids if a stress-
hypothalamic pituitary adrenal axis which leads to the ful situation develops up to 1 year after withdrawal.
following:
SHORT NOTES
Q. 1. Side effects of glucocorticoids l Used for allergic, inflammatory, autoimmune diseases
and in malignancies. For example: Available as Deltacor-
Or, tril, Hostacortin-H, 5, 10 mg tab, 20 mg/mL for IM, intra-
Adverse effects of glucocorticoids articular injection, Wysolone, Nucort, 5, 10, 20 mg tab
Or, Q. 3. Betamethasone
Adverse effects of adrenocorticosteroids Ans.
Ans. l Betamethasone is a long-acting, potent and highly selec-
Adverse effects of glucocorticoids include the following: tive glucocorticoid. It causes marked pituitary-adrenal
1. Cushing’s syndrome: Moon face, buffalo hump, trun- suppression.
l Does not cause water retention and hence can be used in
cal obesity, muscle wasting, thinning of limbs and
skin, easy bruising, purple striae and acne cerebral oedema, can also be used in inflammatory and
2. Hyperglycaemia: Diabetes mellitus allergic conditions, shock, etc.
l It is same as that of dexamethasone—0.5–5 mg/day oral,
3. Susceptibility to infection
4. Osteoporosis 4–20 mg/day IV, IM, injection or infusion, also topical.
l For example: Available as Betnesol, Betacortril, Cele-
5. Avascular necrosis of the bone due to restricted blood
flow through bone capillaries stone 0.5 mg, 1 mg tab, 4 mg/mL (as sodium phosphate)
6. Peptic ulceration: This may sometimes occur on pro- for IV, IM inj., 0.5 mL oral drops, etc.
longed therapy especially when other ulcerogenic
drugs (e.g. NSAIDs) are used concurrently. Q. 4. Hydrocortisone
7. Mental disturbance: Euphoria, psychosis, depression Ans.
8. Cataract and glaucoma
9. Delayed wound healing l Hydrocortisone is a short-acting corticosteroid.
10. HPA axis suppression l May be natural or synthetic. It has mineralocorticoid
action.
Q. 2. Prednisolone l Normal rate of secretion in man is 10 mg/day of which
more than half is secreted during morning hours.

Ans.
l It has anti-inflammatory, antiallergic action. Delays
l Prednisolone is synthetic glucocorticoid, more selective wound healing.

and is four times more potent than hydrocortisone.
l Has intermediate duration of action. Q. 5. Uses of glucocorticoids
l Fluid retention occurs with high doses.
Ans.
l Causes less pituitary-adrenal suppression when a single
morning dose or alternate day treatment is given. Therapeutic uses of glucocorticoids are as follows:
Endocrinal Uses c. Rheumatic fever: Only in severely ill patients with

fever, carditis and CHF and not responding to
As a replacement therapy in acute adrenal insufficiency and
NSAIDs require glucocorticoids.
chronic adrenal insufficiency (Addison’s disease).
d. Acute gout: When treatment with NSAIDs has not
been successful, prednisolone is used as an adjuvant.
Nonendocrinal Uses 2 . Severe allergic reactions: Corticosteroids may be used
for short periods in angioneurotic oedema, hay fever,
1. In various arthritides like rheumatoid arthritis, osteoar-
serum sickness, contact dermatitis and anaphylaxis.
thritis, rheumatic fever and acute gout.
3. Bronchial asthma: Glucocorticoids may be used either
2. In severe allergic reactions like angioneurotic oedema,
for status asthmaticus or severe chronic asthma. Ste-
hay fever, serum sickness, contact dermatitis and ana-
roids are used as supplement to bronchodilators.
phylaxis, corticosteroids may be used for short periods.
4. Collagen diseases: Most cases of polyarteritis nodosa,
3. Bronchial asthma: Glucocorticoids may be used either
lupus erythematosus, polymyositis, Wegener’s granulo-
for status asthmaticus or severe chronic asthma.
matosis and other rheumatoid disorders respond to
4. Collagen diseases, e.g. polyarteritis nodosa, lupus ery-
glucocorticoids. They may be life saving.
thematosus, etc.
5. Eye diseases, renal diseases and gastrointestinal diseases Q. 8. Two differences between hydrocortisone and dexa-
6. Haematologic disorders, e.g. autoimmune haemolytic methasone
anaemiae
7. Cerebral oedema Ans.
8. Organ transplantation for prevention and treatment of
Differences between hydrocortisone and dexamethasone
graft rejection
are given in Table 16.1.
9. Other uses include Bell’s palsy, acute polyneuritis,
myotonia, etc. TABLE 16.1 Differences between Hydrocortisone and
Dexamethasone
Q. 6. ACTH
Hydrocortisone Dexamethasone
Ans.
Short-acting corticosteroid Long-acting corticosteroid
l Adrenocorticotropic hormone (ACTH) is secreted in the Has mineralocorticoid It is highly selective glucocorti-
anterior pituitary gland. It regulates the release of corti- activity coid
costeroid from the adrenal gland. Natural and synthetic Synthetic
l Adrenal steroidogenesis takes place under the influence
Used mostly in replace- Used more as anti-inflammatory,
of ACTH which makes more cholesterol available for
ment therapy antiallergic, in shock and cere-
conversion to pregnenolone and induces steroidogenic bral oedema
enzymes.
Q. 9. Name four glucocorticoids.
Therapeutic Uses Ans.
l It mainly serves as a diagnostic tool for differentiating
between primary and secondary adrenal insufficiency. l Glucocorticoids are secreted in the adrenal cortex.
l ACTH is used in the treatment of infantile spasm (West
l Two glucocorticoids secreted naturally are: hydrocorti-
syndrome). sone and aldosterone.
l Synthetic glucocorticoids include prednisolone, meth-
Q. 7. Mention four nonhormonal uses of glucocorticoids. ylprednisolone, triamcinolone, dexamethasone and

betamethasone.
Ans.
Q. 10. Synthetic corticosteroids
Nonendocrinal uses or nonhormonal uses of glucocorti-
coids are as follows: Ans.
1. Arthritides
a. Rheumatoid arthritis: In progressive disease steroids l Synthetic corticosteroids are more selective corticoste-
are given as one of the last resort drugs in conjunc- roids. They are more potent than the natural corticoids.
l They do not have mineralocorticoid action.
tion with NSAIDs. If one or two joints are involved,
l They generally have intermediate to long duration of action.
intra-articular injections are preferred.
l Examples of synthetic glucocorticoids include prednis-
b. Osteoarthritis: Intra-articular injections are given to
patients with osteoarthritis. olone, methylprednisolone, triamcinolone, dexametha-
sone and betamethasone.
Topic 17
Gonadal Hormones (Sex Hormones)

and Their Antagonists
SHORT ESSAYS
Q. 1. Anabolic steroids Contraindications
Ans. 1 . Pregnancy
Anabolic asteroids are synthetic androgens with higher 2. Carcinoma of prostate or breast in males
anabolic and low androgenic activity. They are believed 3. Infants and children
to enhance protein synthesis and increase muscle mass. 4. Renal/cardiac/liver disease
But with higher doses, the relative anabolic activity is
Q. 2. Combination of oestrogen and progesterone in oral
lost.
contraceptives
Ans.
Uses
1 . In catabolic states: It corrects negative nitrogen balance l Combined pill contains low doses of an oestrogen and a
and gives a state of well-being. Anabolic steroids may progestin.
l They are highly efficacious (success rate: 98%). Ethinyl
benefit patients following surgery, trauma, prolonged
illness and debilitating conditions. estradiol or mestranol (in the dose of 30–50 mg) are the
2 . Senile osteoporosis: Older males respond by formation oestrogens used.
l Newer progestins like desogestrel and norgestimate
of new bone tissue.
3 . Growth stimulation in children: Anabolic steroids pro- cause least effects.
l The pill is started on fifth day of the menstrual cycle,
mote vertical growth in prepubertal boys.
4 . Anabolic steroids are used for benefit in refractory taken daily for 21 days followed by a gap of 7 days dur-
anaemiae. ing which bleeding occurs. This is monophasic regimen.
l They are also available as biphasic or triphasic prepa-
5 . Abuse in athletes: Anabolic steroids are abused in
athletes to achieve an improvement in athletic perfor- rations.
l This reduces the amount of hormones needed and more
mance.
closely mimics menstrual cycles.
SHORT NOTES
Q. 1. Oral contraceptives to lower doses needed and lesser side effects reported.
The pill should be started within 72 h of coitus and has
Ans. Various types of oral contraceptives are as follows:
an efficacy of 90–98%. It is advocated as an emergency
1. Combined pill: They contain low doses of an oestrogen method in situations following rape or failure of regular
and a progestin. They are highly efficacious (success rate: contraceptive methods.
98%). Ethinyl estradiol or mestranol (in the dose of
30–50 mg) are the oestrogens used. Newer progestins like Q. 2. Anabolic steroids
desogestrel and norgestimate causes least effects. The pill Ans.
is started on fifth day of the menstrual cycle, taken daily
for 21 days followed by a gap of 7 days during which Anabolic steroids are synthetic androgens with higher
bleeding occurs. This is monophasic regimen. They are anabolic and low androgenic activity. They are believed to
also available as biphasic or triphasic preparations. enhance protein synthesis and increase muscle mass. But
2. Mini pill: A low dose progestin is taken daily without gap. with higher doses, the relative anabolic activity is lost.
Oestrogen and its accompanied long-term adverse effects
are also eliminated. But efficacy is lower, menstrual cycles Uses
may be irregular and is therefore not popular.
3. Postcoital contraceptives: High dose of an oestrogen 1. Used in catabolic states to correct negative nitrogen bal-
was used earlier. The combination is now preferred due ance and give a state of wellbeing.
2. Senile osteoporosis: Older males respond by formation 4. Anabolic steroids are used for benefit in refractory
of new bone tissue. anaemias.
3. Growth stimulation in children: Anabolic steroids pro- 5. Abuse in athletes: Anabolic steroids are abused in ath-
mote vertical growth in prepubertal boys. letes to achieve an improvement in athletic performance.
Topic 18
Oxytocin and Drugs Acting on Uterus

Q. 1. Oxytocin Uses
Ans. l It is used before delivery to induce labour in case of
postmaturity or to augment it in case of uterine inertia.
Oxytocin is an octapeptide secreted by the posterior pitu-
l It is also used to control postpartum haemorrhage as an
itary gland.
alternative to ergometrine.
Actions Adverse Effects
l It increases the force and the frequency of uterine con-
tractions. With low doses full relaxation occurs between Improper administration or overdosage causes too strong
contractions. contractions forcing the presenting part through incom-
l It contracts myoepithelium of mammary glands and pletely dilated birth canal, causing maternal and fetal soft
helps in milk ejection. tissue injury, rupture of uterus, fetus asphyxia and death.
Topic 19
Drugs Affecting Calcium Balance

LONG ESSAYS
Q. 1. Write drugs acting on calcium metabolism. De- i ii. Vitamin D
scribe the pharmacological actions of parathyroid iv. Calcitonin
hormone. v. Bisphosphonates: Etidronate, pamidronate, alendronate
Ans.
l Calcium is essential for tissue excitability, muscular PARATHYROID HORMONE

excitation-contraction coupling, secretion from glands, l Parathyroid hormone (PTH) is a polypeptide hormone
myocardial contractility and formation of bone and secreted by the parathyroid gland. It is also known as
teeth. It also maintains the integrity of mucous mem- parathormone.
branes and cell membrane. Calcium is essential for l Secretion of PTH is regulated by concentration of free
normal blood coagulation. plasma Ca21 concentration. A low plasma Ca21 stimu-
l Calcium is absorbed from the small intestines by a carrier- lates PTH release, while high levels inhibit secretion.
mediated active transport. Normal plasma calcium level is l Parathormone maintains plasma concentration levels by
9–11 mg/dL. It is excreted in faeces, urine and sweat. mobilizing calcium from the bones, promoting reabsorption
Drugs acting on calcium metabolism are as follows: of Ca21 levels from the kidneys and by stimulating the
i. Phosphate synthesis of calcitriol which in turn enhances calcium ab-
ii. Parathyroid hormone sorption from the intestines.
l PTH activates the adenylyl cyclase enzyme present in the iv. Cataract
cell membrane, via G-protein coupled receptors, which in v. Anxiety and depression
turn increases the intracellular cAMP concentration and
the intracellular Ca1, leading to various effects.
Hyperparathyroidism
l PTH also promotes phosphate excretion.
Hyperparathyroidism which is most commonly due to para-

Actions of PTH can be summarized as follows:
thyroid tumour produces hypercalcaemia and deformities
of the bone.
PTH is not therapeutically used. It is used for the diag-
↓Plasma Ca2+ ↑Plasma Ca2+
nosis of pseudohypoparathyroidism.
+ –
Q. 2. What is normal plasma calcium level in the body?
Describe the role of different hormones and vitamins
PTH release
influencing body calcium levels.
Ans.
Bone Kidney l Calcium is essential for tissue excitability, muscular

excitation-contraction coupling, secretion from glands,
Helps in the conversion
↑ resorption of bone of inactive calcifediol to promotes myocardial contractility and formation of bone and
active calcitriol teeth. It also maintains the integrity of mucous mem-
calcium reabsorp-
tion in the renal branes and cell membrane. Calcium is essential for
tubules, inhibition normal blood coagulation.
of phosphate reab- l Calcium is absorbed from the small intestines by a car-
GIT
sorption in the renal rier-mediated active transport. Normally about 30% of
↑ Ca2+ absorption in the butt tubules the dietary calcium is absorbed.
l Normal plasma calcium level is 9–11 mg/dL. It is
excreted in faeces, urine and sweat.

↑ Plasma calcium Drugs acting on calcium metabolism are as follows:
↓ Plasma phosphate
i. Parathyroid hormone
ii. Vitamin D
Hypoparathyroidism iii. Calcitonin
iv. Bisphosphonates: Etidronate, pamidronate, alendronate
Hypoparathyroidism is characterized by low plasma cal-
cium levels with its associated manifestations. The role of different hormones and vitamins influencing
body calcium levels are as follows:
Aetiology
Parathyroid Hormone
i. Following thyroidectomy
ii. Idiopathic l Parathyroid hormone (PTH) is a polypeptide hormone
iii. Genetic secreted by the parathyroid gland. It is also known as
iv. Autoimmune parathormone.
l Secretion of PTH is regulated by concentration of free
Clinical features of acute hypoparathyroidism are as plasma Ca21 concentration. A low plasma Ca21 stimu-
follows: lates PTH release, while high levels inhibit secretion.
i. Hypocalcaemia l Parathormone maintains plasma concentration levels by
ii. Tetany mobilizing calcium from the bones, promoting reab-
iii. Carpopedal spasm sorption of Ca21 levels from the kidneys and by stimu-
iv. Laryngospasm lating the synthesis of calcitriol which in turn enhances
v. Tingling of lips, hands, muscles calcium absorption from the intestines.
vi. Convulsions l PTH activates the adenylyl cyclase enzyme present in the
Clinical features of chronic hypoparathyroidism are as cell membrane, via G-protein coupled receptors, which in
follows: turn increases the intracellular cAMP concentration and
i. Loss of hair the intracellular Ca1, leading to various effects.
ii. Brittle finger nails
l Role of PTH in influencing body calcium levels can be
iii. Caries of the teeth
summarized as follows:
Actions
↓Plasma Ca2+ ↑Plasma Ca2+
i. It enhances calcium and phosphate absorption from the
+ – intestine.
ii. Calcitriol enhances mobilization of calcium from bone
PTH release by promoting osteoclastic activity.
iii. Increases tubular reabsorption of Ca21 and phosphate in
the kidney tubules, but the action is less marked than
that of PTH.
Bone Kidney iv. Calcitriol is essential for normal bone mineralization
and for skeletal muscles, cellular growth and differen-
Helps in the conversion
↑ resorption of bone of inactive calcifediol to promotes tiation.
active calcitriol calcium reabsorp-
tion in the renal Calcitonin
tubules,
inhibition of phos- The role of calcitonin influencing body calcium levels is as
GIT
phate reabsorption follows:
↑ Ca2+ absorption in the butt in the renal tubules 1. Calcitonin is a peptide hormone secreted by the parafol-
licular C cells of the thyroid gland. Secretion is regu-
lated by plasma concentrations—high plasma levels of
Ca21 levels stimulating calcitonin release.
↑ Plasma calcium
↓ Plasma phosphate
Actions
i. The chief effects of calcitonin are to lower serum cal-
Vitamin D cium level and phosphate by its action on the bones and
The role of vitamin D in influencing body calcium levels is kidney.
as follows: ii. It inhibits osteoclastic bone resorption and in the kid-
It is a fat-soluble vitamin, prehormone produced in the ney, reduces both calcium and phosphate reabsorption.
skin from 7-dehydrocholesterol under the influence of UV iii. In general the effects are opposite to parathormone.
rays and gets converted to active metabolites in the body Calcitonin is used to control hypercalcaemia, Paget’s
which regulates plasma calcium level and various functions disease, metastatic bone cancer and osteoporosis and to
of the cells. increase bone mineral density.
SHORT ESSAY
Q. 1. Agonists influencing calcium metabolism l PTH activates the adenylyl cyclase enzyme present in the
cell membrane via G-protein coupled receptors, which in
Ans.
turn increases the intracellular cAMP concentration and
The agonists influencing calcium metabolism are as follows: the intracellular Ca1, leading to various effects.
Hypoparathyroidism is characterized by low plasma calcium

Parathyroid Hormone levels with its associated manifestations. Hyperparathyroid-
l Parathyroid hormone (PTH) is a polypeptide hormone ism which is most commonly due to parathyroid tumour
secreted by the parathyroid gland. It is also known as produces hypercalcaemia and deformities of the bone.
parathormone. PTH is not therapeutically used. It is used for the diagnosis
l Secretion of PTH is regulated by concentration of free
of pseudohypoparathyroidism.
plasma Ca21 concentration. A low plasma Ca21 stimu-
lates PTH release, while high levels inhibit secretion. Vitamin D
l Parathormone maintains plasma concentration levels by
Vitamin D is a fat-soluble vitamin and is a prehormone
mobilizing calcium from the bones, promoting reab- produced in the skin from 7-dehydrocholesterol under the
sorption of Ca21 levels from the kidneys and by stimu- influence of UV rays and gets converted to active metabo-
lating the synthesis of calcitriol which in turn enhances lites in the body which regulates plasma calcium level and
calcium absorption from the intestines. various functions of the cells.
Actions 3. Increases tubular reabsorption of Ca21 and phosphate in

the kidney tubules, but the action is less marked than
1. It enhances calcium and phosphate absorption from the
that of PTH.
intestine.
4. Calcitriol is essential for normal bone mineralization and
2. Calcitriol enhances mobilization of calcium from bone
for skeletal muscles, cellular growth and differentiation.
by promoting osteoclastic activity.
5. Dose required: 400 IU (10 mg)
SHORT NOTES
Q. 1. Calcium carbonate 4. Calcitriol is essential for normal bone, mineralization and
for skeletal muscles, cellular growth and differentiation.
Ans.
Calcium carbonate (40% Ca) is insoluble, tasteless and Deficiency

nonirritating.
It has been used as an antacid, reacts with HCl to form Results in low plasma calcium and phosphate levels with
chloride which may be absorbed from intestine. abnormal mineralization of the bone, causes rickets in chil-
dren and osteomalacia in adults.
Side Effects Q. 3. Parathyroid hormone

Only GI side effects like constipation, bloating and excess Ans.
gas have been reported.
l Parathyroid hormone (PTH) is a polypeptide hormone
Some combined formulations are as follows: secreted by the parathyroid gland. It is also known as
1. Calcinol-RB: It contains calcium carbonate 0.375 g, parathormone.
calcium phosphate 75 mg, vitamin D 250 IU tab. l Secretion of PTH is regulated by concentration of
2. Shelcal: It contains calcium carbonate 625 mg, vitamin free plasma Ca21 concentration. A low plasma Ca21
D3 125 IU tab. stimulates PTH release, while high levels inhibit se-
cretion.
Q. 2. Vitamin D l Parathormone maintains plasma concentration levels by
Ans. mobilizing calcium from the bones, promoting reab-

sorption of Ca21 levels from the kidneys and by stimu-
Vitamin D is a fat-soluble vitamin. lating the synthesis of calcitriol which in turn enhances
Prehormone, produced in the skin from 7-dehydrocho- calcium absorption from the intestines.
lesterol under the influence of UV rays is converted to ac- l PTH also promotes phosphate excretion.
tive metabolites in the body which regulates plasma Ca l Hypoparathyroidism is characterized by low plasma
level and various functions of the cells. calcium levels with its associated manifestations.
l Hyperparathyroidism which is most commonly due to
Source parathyroid tumour produces hypercalcaemia and de-

formities of the bone.
1 . Diet as ergocalciferol (vitamin D2) from plants PTH is not therapeutically used. It is used for the diagnosis
2. Cholecalciferol (vitamin D3) is synthesized in skin from of pseudohypoparathyroidism.
7-dihydrocholesterol.
Q. 4. Vitamin D deficiency
Dose Required Ans.
400 IU (10 mg) l Vitamin D is a fat-soluble vitamin.
l Prehormone, produced in the skin from 7-dehydrocho-
Actions lesterol under the influence of UV rays is converted to
active metabolites in the body which regulates plasma
1. Stimulates calcium and phosphate absorption in the calcium level and various functions of the cells.
intestine. l Deficiency of vitamin D results in low plasma calcium
2. Mobilizes calcium from bone by promoting osteoclastic and phosphate levels with abnormal mineralization of
activity. the bone causes rickets in children and osteomalacia in
3. Increases reabsorption of Ca21 from kidney tubules. adults.
Part VI
Drugs Acting on Peripheral Nervous System
Topic 20
Skeletal Muscle Relaxants

LONG ESSAYS
Q. 1. Classify skeletal muscle relaxants. Describe the B. Centrally Acting Skeletal Muscle Relaxants
pharmacological actions, therapeutic uses and adverse
effects of d-tubocurarine. These drugs reduce skeletal muscle tone by acting on selec-
tive areas of CNS without loss of consciousness.
Ans. i. Mephenesin group: Mephenesin, carisoprodol, chlor-
l Skeletal muscle relaxants are drugs that act peripherally zoxazone, chlormezanone and methocarbamol
at the neuromuscular junction or muscle fibre itself or ii. Benzodiazepines: Diazepam and others
centrally in cerebrospinal axis to reduce muscle tone iii. GABA derivatives: Baclofen
and/or cause paralysis. iv. Central a2 agonist: Tizanidine
l The neuromuscular blocking agents are used in con-
junction with the general anaesthetics to provide muscle D-tubocurarine

relaxation for surgery and centrally acting agents are
used primarily for painful muscle spasm and spastic l D-tubocurarine is a peripherally acting skeletal muscle
neurological diseases. relaxant.
l It is a long-acting, nondepolarizing, competitive neuro-
muscular blocking agent.

CLASSIFICATION l It acts at the neuromuscular junction preventing the combi-
nation of acetylcholine released from the motor nerve end-

A. Peripherally Acting Skeletal Muscle ings with its receptors to generate the end plate potential.
Relaxants
I. Neuromuscular blocking agents Therapeutic Uses
a. Nondepolarizing (competitive) blockers: Agent which Once d-tubocurarine was used
block acetylcholine at muscle end plate i. as adjuvant to general anaesthetics.
i. Long-acting: D-tubocurarine, pancuronium, doxa- ii. to promote skeletal muscle relaxation during abdominal
curium, pipecuronium surgery and in dentistry for setting of mandibular fractures.
ii. Intermediate-acting: Atracurium, vecuronium, cisa- iii. in severe cases of tetanus and status epilepticus.
tracurium, rocuronium, rapacuronium
iii. Short-acting: Mivacurium
b. Depolarizing blockers: Agents which persistently depo- Adverse Effects
larize motor end plate Now d-tubocurarine (d-TC) is no longer used because of its
l Succinylcholine (SCh) or suxamethonium prominent histamine releasing, ganglion blocking and car-
l Decamethonium diovascular actions as well as long duration and need for
pharmacological reversal.
II. Directly Acting Agents
Q. 2. List two classes of skeletal muscle relaxants acting
a . Dantrolene sodium at neuromuscular junction. Mention two therapeutic
b
. Quinine uses of peripherally acting muscle relaxants.
Ans. i. Long-acting: D-tubocurarine, pancuronium, doxa-

curium, pipecuronium
l Skeletal muscle relaxants are drugs that act peripherally ii. Intermediate-acting: Atracurium, vecuronium, cisa-
at the neuromuscular junction or muscle fibre itself or tracurium, rocuronium, rapacuronium
centrally in cerebrospinal axis to reduce muscle tone iii. Short-acting: Mivacurium
and/or cause paralysis. II. Depolarizing blockers: Agents which persistently depo-
l The neuromuscular blocking agents are used in con- larize motor end plate
junction with the general anaesthetics to provide muscle l Succinylcholine (SCh) or suxamethonium
relaxation for surgery and centrally acting agents are l Decamethonium
used primarily for painful muscle spasm and spastic
neurological disease. Therapeutic uses of peripherally acting skeletal muscle
l Skeletal muscle relaxants acting at neuromuscular junc-
relaxants are as follows:
tion are called neuromuscular blocking agents. i. As adjuvant to general anaesthetics
ii. They are used to promote skeletal muscle relaxation
The two classes of neuromuscular blocking agents are as during abdominal surgery and in dentistry for treating
follows: of mandibular fractures.
I. Nondepolarizing (competitive) blockers: Agents which iii. They are used in severe cases of tetanus and status
block acetylcholine at muscle end plate epilepticus.
SHORT ESSAYS
Q. 1. Compare d-tubocurarine and succinylcholine. TABLE 20.2 Comparison between Succinylcholine and
Pancuronium
Ans. The comparison between d-tubocurarine and succi-
nylcholine is listed in Table 20.1. Parameters to
Be Compared Succinylcholine Pancuronium
Type Depolarizing Nondepolarizing
TABLE 20.1 Comparison between d-tubocurarine and
blocker blocker
Succinylcholine
Onset of action 1–1.5 min 4–6 min
Parameters
Duration of Short, 3–6 min Long, 60–120 min
Compared D-tubocurarine Succinylcholine action
Type of muscle Nondepolarizing Depolarizing
Histamine Present May or may not be
relaxant blocker blocker
release present
Onset of action 4–6 min 1–1.5 min
Action on Fasciculations— Spastic contractions
Duration of action Long, 30–60 min Short, 3–6 min vagus flaccid
Histamine release Present Present Order of Neck, limbs or face, Fingers, eyes, limbs,
paralysis jaw, eyes, pharynx, neck, face, trunk and
Action on ganglion Blockade Stimulation trunk and respira- respiratory function
Action on vagus Blockade Stimulation tory function
Order of paralysis Fingers, eyes, Neck, limbs, face, Therapeutic Manipulative proce- Prolonged operations
limbs, neck, jaw, eyes, pharynx , uses dures of short dura- like neurosurgery
face, trunk trunk, respiratory tion like endotra-
cheal intubation
Neostigmine Antagonizes No effect
block
Ether anaesthesia Synergistic No effect

Q. 3. Describe the uses of centrally and peripherally acting
skeletal muscle relaxants.
Q. 2. Compare succinylcholine and pancuronium. Ans. Therapeutic uses of centrally acting skeletal muscle
Ans.
1. During acute muscle spasm diazepam or other muscle
The comparison between succinylcholine and pancuronium relaxants are combined with analgesic.
is listed in Table 20.2. 2. They are used to cure torticollis, backache and neuralgia.
3. These are used in spastic neurological disorders like 2 . Benzodiazepines: Diazepam and others
hemiplegia and paraplegia. 3. GABA derivatives: Baclofen
4. During tetanus IV diazepam is given. 4. Central a 2 agonist: Tizanidine
5. During electroconvulsive therapy diazepam may be
void to suppress convulsions. Q. 5. Succinylcholine
6. Orthopaedic manipulations may be performed under Ans.
diazepam influence.
l Succinylcholine is peripherally acting skeletal muscle
Therapeutic uses of peripherally acting skeletal muscle
relaxant.
l It is a depolarizing neuromuscular blocking agent.
1. As adjuvant to general anaesthetics
2. They are used to promote skeletal muscle relaxation
during abdominal surgery and in dentistry for treating of Mechanism of Action
mandibular fractures.
l Succinylcholine has affinity for nicotinic cholinoceptors.
3. They are used in severe cases of tetanus and status epi-
It depolarizes muscle end plates by opening Na1 chan-
lepticus.
nels and initially produces twitching and fasciculations.
l These drugs do not dissociate rapidly from the receptors
Q. 4. Classify skeletal muscle relaxants.
n Induce prolonged partial depolarization of the region
Ans. around muscle end plate n Inactivation of Na1 chan-
nels nACh released from motor nerve ending is unable
Skeletal muscle relaxants are drugs that act peripherally at to generate propagated MAP n Flaccid paralysis n In
the neuromuscular junction or muscle fibre itself or cen- other words a zone of inexcitability is created round the
trally in cerebrospinal axis to reduce muscle tone and/or end plate preventing activation of muscle fibres.
cause paralysis.
They are classified as follows: Uses
1 . It is used as adjuvant in general anaesthesia.
PERIPHERALLY ACTING SKELETAL MUSCLE 2. It is the commonly used skeletal muscle relaxant for
RELAXANTS passing endotracheal tube.
3. It is employed for brief procedures like laryngoscopy,
Neuromuscular Blocking Agents bronchoscopy, oesophagoscopy, reduction of fracture
Nondepolarizing (competitive) blockers: Agent which block and dislocation, etc.
acetylcholine at muscle end plate 4. It can be used to avoid convulsions and trauma from
1. Long-acting: D-tubocurarine, pancuronium, doxacu- electroconvulsive therapy without decreasing therapeutic
rium, pipecuronium benefit.
2. Intermediate-acting: Atracurium, vecuronium, cisatra-
curium, rocuronium, rapacuronium Adverse Effects
3. Short-acting: Mivacurium
1 . It causes increase in intraocular pressure.
Depolarizing blockers: Agents which persistently depolar- 2. It causes increase in postoperative muscle pain.
izes motor end plate 3. It may cause apnoea in patient with atypical plasma
1. Succinylcholine (SCh) or suxamethonium cholinesterase by prolonged neuromuscular block by
2. Decamethonium succinylcholine.
Directly acting agents Q. 6. Uses of diazepam
1 . Dantrolene sodium Ans.

2. Quinine Diazepam is a benzodiazepine used for the following
purposes:
Centrally Acting Skeletal Muscle Relaxants 1. As hypnotics—used to shorten sleep latency, reduce
nocturnal awakening or to provide anxiolytic effect the
These drugs reduce skeletal muscle tone by acting on selec- day after
tive areas of CNS without loss of consciousness. 2. As anxiolytic and for daytime sedation
1. Mephenesin group: Mephenesin, carisoprodol, chlor- 3. As anticonvulsants—benzodiazepines increase seizure
zoxazone, chlormezanone and methocarbamol threshold and can be used as an anticonvulsant.
4 . As centrally acting muscle relaxant l They enhance the levels of acetylcholine (ACh) at the
5. As IV anaesthetic used for inducing, maintaining and NMJ by preventing its destruction. Thus they increase
supplementing anaesthesia the force of contraction and improve muscle power.
6. As preanaesthetic medication
7. Before electroconvulsive therapy, electrical cardiover- Q. 8. Write rationale of using neostigmine in d-tubocu-
sion of arrhythmias, cardiac catheterization, endosco- rarine poisoning.
pies in obstetrics and many minor procedures Ans.
8. Alcohol withdrawal
l D-tubocurarine acts at the neuromuscular junction pre-
Q. 7. Rationale of using neostigmine in myasthenia venting the combination of acetylcholine released from
gravis the motor nerve endings with its receptors to generate
Ans. the end plate potential.
l This antagonism can be overcome only by increasing
l Myasthenia gravis is a chronic autoimmune disease the concentration of the acetylcholine at the neuromus-
characterized by progressive weakness with rapid and cular junction by anticholinesterase.
easy fatigability of skeletal muscles. l Neostigmine (anticholinesterase) is lipid soluble and
l Antibodies to nicotinic receptors are found, resulting in produces more marked effect on the skeletal muscles,
the number of these receptors at NMJ. i.e. they have direct action on the muscle end plate cho-
l Neostigmine (15 mg tab, 6 hourly) or pyridostigmine or linoceptors. Therefore neostigmine is used in treatment
a combination of both may be used. of diaphragmatic paralysis caused by d-tubocurarine.
SHORT NOTES
Q. 1. Skeletal muscle relaxants l D-tubocurarine is a peripherally acting skeletal muscle
relaxant.
Ans.
l Skeletal muscle relaxants are drugs that act peripherally muscular blocking agent.
at the neuromuscular junction or muscle fibre itself or l It acts at the neuromuscular junction preventing the combi-
centrally in cerebrospinal axis to reduce muscle tone nation of acetylcholine released from the motor nerve end-
and/or cause paralysis. ings with its receptors to generate the end plate potential.
l The peripherally acting agents (neuromuscular blocking l Used as an adjuvant to general anaesthetics, to promote
agents) are used in conjunction with the general anaes- skeletal muscle relaxation during abdominal surgery
thetics to provide muscle relaxation for surgery, e.g. and in treatment of mandibular fractures. They are also
d-tubocurarine, pancuronium, doxacurium, etc. used in severe cases of tetanus and status epilepticus.
l The centrally acting agents are used primarily for
painful muscle spasm and spastic neurological diseases, Q. 4. Lioresal

e.g. diazepam, mephenesin, baclofen, carisoprodol and Ans.
chlorzoxazone.
l Lioresal is the trade name of baclofen, which is an ana-
Q. 2. Pancuronium logue of inhibitory transmitter GABA.
l The primary site of action is considered to be in spinal
l Pancuronium is a peripherally acting skeletal muscle
cord where it depresses both polysynaptic and mono-
relaxant.
synaptic reflexes, as such it produces muscle weakness.
l It reduces spasticity in many neurological disorders like
muscular blocking agent.
multiple sclerosis, amyotrophic lateral sclerosis, spinal
injuries and flexor spasms.
Uses l It has also been tried in trigeminal neuralgia and tardive
dyskinesia. Intrathecal injection of baclofen is used in

1 . As adjuvant to general anaesthetics
severe spasticity of spinal cord origin.
2. They are used to promote skeletal muscle relaxation during
l It is well-absorbed orally and excreted primarily through
abdominal surgery and treatment of mandibular fractures.
urine. Usual recommended dosage is 10 mg BD to 25 mg
3. They are used in severe cases of tetanus and status
TDS.
epilepticus.
l Side effects are drowsiness, mental confusion, weak-
Q. 3. D-tubocurarine ness and ataxia. Sudden withdrawal after chronic use

may cause hallucinations, tachycardia and seizures.
Topic 21
Local Anaesthetics
LONG ESSAY
Q. 1. Classify local anaesthetics and write in detail Class C Agents acting by a re- Benzocaine
about xylocaine. ceptor-independent
physical-chemical
Or, mechanism
Classify local anaesthetics. Describe their mechanism of Class D Agents acting by combi- Most clinically useful
action. Mention the types of local anaesthetics. nation of receptor and local anaesthetic
receptor-independent agents, e.g. articaine,
Ans. Local anaesthetics are the agents which cause revers- mechanisms lidocaine, mepiva-
ible loss of sensation caused by either depression in excita- caine, prilocaine
tion of conducting nerve or suppression of excitation of
peripheral nerves.
MECHANISM OF ACTION
The main site of action of local anaesthetics (LA) is the cell
CLASSIFICATION OF LOCAL ANAESTHETICS membrane. The LA in unionized form easily penetrates the
nerve sheath and axon membrane within the axoplasm. The
I. Based on Chemical Structure molecules become ionized and block the voltage-gated Na1
i. Amides: Lignocaine, mepivacaine, bupivacaine and channels as shown in the flowchart below (Fig. 21.1):
ropivacaine
i i. Esters
Local anaesthetics
a. Esters of benzoic acid: Butacaine, cocaine, tetracaine
b. Esters of para-aminobenzoic acid: Chloroprocaine, ↓
procaine, propoxycaine Block the voltage-gated Na+ channels
i ii. Quinolones: Centbucridine ↓
No entry of Na+ ions into the cell
II. Based on Duration of Action ↓

No depolarization
A . Injectable anaesthetics ↓
i. Low potency and short duration: Procaine, chloropro-
No generation of action potential
caine
i i. Intermediate potency and duration: Lignocaine and ↓
prilocaine No generation and conduction of impulse to CNS
i ii. High potency and long duration: Tetracaine, bupiva- ↓
caine, ropivacaine and dibucaine Local anaesthesia
B. Surface anaesthetic FIGURE 21.1 Mechanism of action of local anaesthetics.
a. Soluble: Cocaine, lignocaine, tetracaine, benoxinate
b. Insoluble: Benzocaine and butyl aminobenzoate,
oxethazaine
l The local anaesthetics block nerve conduction by
decreasing the entry of Na1 ions during upstroke of
III. Based on Biological Site and Mode of action potential.
Action l Conduction is slowed as the concentration of local an-
aesthetic rises and as the rate of rise of action potential

Class A Agents acting at recep- Biotoxins, e.g. tetrodo- and maximum depolarization decreases. Finally local
tor site on external sur- toxins, and saxitoxins depolarization fails to reach the threshold potential and
face of nerve membrane
conduction block ensures.
Class B Agents acting at recep- Quaternary ammonium l The local anaesthetics interact with the local anaesthetic
tor sites on internal sur- analogues of lidocaine, receptor located within the channel in its intracellular
face of nerve membrane scorpion venom
half of the voltage sensitive Na1 channel.
l The cationic form of local anaesthetic can approach c. All local anaesthetics are cardiac depressants but not at
the receptor only when the channel is open at the inner conventional doses. Higher dose or on inadvertent IV
face and it binds more avidly to the inactive state of the injection decreases automaticity and excitability, hence
channel. lignocaine is useful in ventricular arrhythmias.
l On binding to the receptors, they raise the threshold of B. Blood vessels
channel opening and thus Na1 permeability fails to in- l Local anaesthetics produce hypotension due to vaso-
crease in response to an impulse or stimulus. dilatation and myocardial depression.

l A resting nerve is rather resistant to blockade and blockade l The fall in BP is due to sympathetic blockade or
develops rapidly then the nerve is stimulated repeatedly. direct relaxation of arteriolar smooth muscles at
l Degree of blockade is frequency dependent, i.e. greater higher doses.
blockade at higher frequency of stimulation.
21
l Exposure to higher concentration of Ca reduces inac-
Pharmacokinetics
tivation of Na1 channels and lessens the degree of block.
l Local anaesthetics with lower pKa (76–78) are fast act- i. Most of the ester-linked local anaesthetics are hydrolyzed
ing, e.g. lignocaine and those with higher pKa (81–89) by plasma cholinesterase and amide-linked local anaes-
are slow acting. The time of onset of blockade varies thetics are metabolized mainly in liver by microsomes.
with the pKa of the local anaesthetic. ii. Soluble surface anaesthetics are rapidly absorbed from
mucosa and abraded areas but absorption is poor from
intact skin.
Pharmacological Actions iii. Local anaesthetics like procaine, lignocaine, etc. are not
A. Local Actions effective orally because of high first-pass effect.
iv. In liver diseases, the metabolism of lignocaine may be
i. It blocks the sensory nerve endings, nerve trunks, neu- impaired hence dose must be reduced accordingly.
romuscular junction, ganglionic synapses and receptors.
ii. Reduces release of acetylcholine from motor nerve endings
and it can cause anaesthesia of skin and paralysis of volun- Adverse Effects
tary muscles supplied by mixed nerve if injected around it. i. CNS effects: Local anaesthetics initially stimulation
iii. The order of nerve fibres affected is autonomic fibres— followed by depression. The stimulatory symptoms are
pain-touch–temperature deep pressure and motor fibres. drowsiness, mental clouding, altered taste and tinnitus.
Overdoses produce muscle twitching, convulsions,
B. Systemic Actions cardiac arrhythmias, fall in BP, coma and respiratory
i. Nervous System (CNS) arrest.
ii. CVS effects are bradycardia, hypotension, cardiac
l All local anaesthetics initially cause stimulation followed
arrhythmias and vascular collapse. Bupivacaine is
by depression. more cardiotoxic.
l Most of the local anaesthetics cross the blood-brain bar-
iii. Injections are painful and may delay the wound healing.
rier (BBB) and they initially cause CNS stimulation and
then depression in higher doses.
l Sequence of events are euphorianexcitement—mental Therapeutic Uses
confusion—restlessness—tremors and twitching of
a. Anaesthesia
muscles—convulsions—unconsciousness—respiratory
depression—coma and death. Local anaesthetics are used for surface application, infiltra-
tion, nerve blocks, epidural, spinal and intravenous regional
ii. Cardiovascular System (CVS) block anaesthesia.
A. Heart
Local anaesthetics by blocking Na1 channels, decrease
b. Antiarrhythmic
abnormal pacemaker activity, contractility, conductivity,
excitability, heart rate, cardiac output and increase effective l Lignocaine is also a popular antiarrhythmic. It is a first
refractory period. choice drug for acute therapy for ventricular extrasysto-
a. At higher concentrations, the intravenous administra- les, ventricular tachycardia.
tion of LA may precipitate cardiac arrhythmias. l It is an alternative for acute therapy for ventricular
b. Bupivacaine is more cardiotoxic when compared to fibrillation.

other local anaesthetics and may precipitate cardiovas- l 50–100 mg bolus IV followed by 20–40 mg every
cular collapse and death. 10–20 min or 1–3 mg/min infusion

SHORT ESSAYS
Q. 1. Lignocaine Ans.
Lignocaine is most commonly used anaesthetic that can be
used as an infiltration, surface anaesthetic, nerve block, Advantages
spinal anaesthetic and epidural anaesthetic. Addition of vasoconstrictor or adrenaline to local anaes-
thetic, i.e. lignocaine has following advantages:
Mechanism of Action 1. It prolongs duration of action of local anaesthetics by
decreasing their rate of absorption from the site into
l The main site of action of local anaesthetics is the cell systemic circulation.
membrane. It acts by blocking sodium channels due to 2. It increases the intensity of nerve block.
which there is no entry of sodium and generation of ac- 3. Adrenaline provides bloodless field for surgery.
tion potential. 4. It reduces systemic toxicity of local anaesthetic by
l This action affects process of depolarization, leading to
reducing rate of absorption of local anaesthetics.
failure of propagation of impulse without affective rest-
ing potential also known as membrane stabilizing effect.
l Brief description of mechanism of action of local anaes- Disadvantages
thetics is shown in the flowchart (Fig. 21.2): Disadvantages and contraindications of addition of vaso-
constrictor or adrenaline to local anaesthetic, i.e. lignocaine
are as follows:
Local anaesthetics
1. Intense vasospasm and ischaemia in the tissues with end
↓ arteries may cause gangrene of the part either of fingers,
Block the voltage-gated Na+ channels toes, penis, tip of the nose, etc.
↓ 2. Absorption of adrenaline may cause systemic toxicity.
No entry of Na+ ions into the cell Hence combined preparation of LA with adrenaline is
↓ contraindicated in patients with cardiovascular disor-
No depolarization ders like hypertension, congestive cardiac failure (CCF),
↓ arrhythmias and ischaemic heart disease.
No generation of action potential 3. It may delay wound healing by reducing the blood flow
↓ to the affected area.
No generation and conduction of impulse to CNS
Q. 3. Compare lidocaine and mepivacaine.
↓
Local anaesthesia Ans. Comparison between lidocaine and mepivacaine is
FIGURE 21.2 Mechanism of action of local anaesthetics. listed in Table 21.1.
TABLE 21.1 Comparison between Lidocaine and Mepivacaine

Uses of Lignocaine
Points to Compare Lidocaine Mepivacaine
l It is used in nerve block, e.g. tooth extraction by giving Duration of action Intermediate-acting Long-acting
a nerve block.
Onset of action Fast Faster than lig-
l It is given subcutaneously in field block and mainly
nocaine
used in dental procedures.
l It is used in surface anaesthesia, epidural anaesthesia Uses Infiltration, surface Injectable
anaesthetic, spinal anaesthetic
and in spinal anaesthesia.
and epidural
l It is used as antiarrhythmic agent.
anaesthetic
Q. 2. Advantages and disadvantages of addition of

adrenaline to local anaesthesia Q. 4. Differentiate general anaesthetics and local anaes-
Or, thetics.
Write the rationale of combining xylocaine with adren- Ans. The differences between general anaesthetics and
aline for local anaesthesia. local anaesthetics are listed in Table 21.2.
TABLE 21.2 Differences between General Anaesthetics Q. 5. Compare ester and amide local anaesthetics.
and Local Anaesthetics
Ans. Comparison between ester and amide local anaesthetics
Parameters to Be General is listed in Table 21.3.
Compared Anaesthetic Local Anaesthetic
Site of action CNS Peripheral nerves TABLE 21.3 Comparison between Ester and Amide Local
Area of body involved Whole body Site of administration Anaesthetics
Consciousness Lost Unaltered Ester Local Anaesthetics Amide Local Anaesthetics
Care of vital functions Essential Not needed usually They include cocaine, They include lignocaine,
procaine, chloroprocaine, mepivacaine, bupivacaine and
Physiological trespass High Low
benzocaine and tetracaine ropivacaine
In medically compro- Risky to use Safe to use
Short acting and low potency Intermediate acting and potency
mised and patient with
poor health Slow onset of action Rapid onset of action
Use in noncooperative Possible Not possible Metabolized by plasma Metabolized by liver micro-
patient cholinesterase somal enzymes
Uses Major surgical Minor surgical No surface anaesthetic effect Has surface anaesthetic effect
procedures procedures due to poor tissue penetrability due to good tissue penetrability
SHORT NOTES
Q. 1. Mention some uses of lignocaine or xylocaine. l It is ineffective when applied topically thus not used as
surface anaesthetic.
Ans. Lignocaine is most commonly used anaesthetic.
Q. 4. Topical local anaesthetics
Uses of lignocaine are as follows:
1. It is used in nerve block, e.g. tooth extraction by giving Ans.
a nerve block.
2. It is given subcutaneously in field block and mainly l Topical anaesthetics are also known as surface anaes-
used in dental procedures. thetics and are available as solutions, ointment, gel,
3. It is used in surface anaesthesia, epidural anaesthesia cream, spray lozenges, etc.
l Commonly used drugs for topical application are: ligno-
and in spinal anaesthesia.
4. It is used as antiarrhythmic agent. caine 2–10%, tetracaine 2%, benzocaine 1–2%, cocaine
1–4%, etc.
Q. 2. Toxicity of lignocaine
Ans. Toxic effects of lignocaine are manifested as follows: Therapeutic Uses
1. CNS effects are drowsiness, mental clouding, altered 1. Topical anaesthetics are applied on the mucous mem-
taste and tinnitus. brane of the nose, mouth, eyes, throat, upper respiratory
2. CVS effects are bradycardia, hypotension, cardiac tract, oesophagus and urethra.
arrhythmias and vascular collapse. 2. It is also used in many diagnostic procedures like
3. Injections are painful and may delay the wound healing. tonometry in eye and during endoscopes.
4. Overdoses produce muscle twitching, convulsions,
cardiac arrhythmias, fall in BP, coma and respiratory Q. 5. Adrenaline in local anaesthetics
arrest. Ans.
Q. 3. Procaine hydrochloride Addition of vasoconstrictor or adrenaline to local anaes-
thetic, i.e. lignocaine has following advantages:
Ans.
1. It prolongs duration of action of local anaesthetics.
l It is a synthetic injectable ester type of local anaesthetic. 2. It increases the intensity of nerve block.
l It has low potency and short duration of action. 3. Adrenaline provides bloodless field for surgery.
l It forms poorly soluble salts with benzyl penicillin. 4. It reduces systemic toxicity of local anaesthetic by
l It is rapidly absorbed following parenteral administration. reducing rate of absorption of local anaesthetics.
Q. 6. Cocaine l Here the local anaesthesia (LA) is injected into the

vein of upper limb whose blood flow is occluded by
Ans.
tourniquet.
l It is a natural alkaloid derived from leaves of erythroxy- l Lignocaine 0.5% and prilocaine 0.5% are commonly
lon coca. used drugs.

l It is a surface anaesthetic that is rapidly absorbed. l It is mainly used in anaesthetizing the upper limb.
l It is used in ocular anaesthesia.
l It is never injected as it is a protoplasmic poison and

Q. 9. Lidocaine and mepivacaine
causes tissue necrosis. Ans. Comparison between lidocaine and mepivacaine is
listed in Table 21.4.
Adverse Effects
TABLE 21.4 Comparison between Lidocaine and
It stimulates Mepivacaine
1. vagal centre—causes bradycardia.
Parameters Lidocaine Mepivacaine
2. vasomotor centre—causes rise in BP.
3. vomiting centre—causes nausea and vomiting. Duration of action Intermediate acting Long acting
4. temperature regulating centre—causes pyrexia. Onset Fast Faster than ligno-
caine
Q. 7. Mention different types of techniques of local Uses Infiltration, surface an- Injectable anaes-
anaesthesia. aesthetic, spinal and thetic
epidural anaesthetic
Ans.
Various techniques of local anaesthetics (LA) are as Q. 10. Classification of local anaesthetic agents
follows:
1. Surface anaesthesia (topical anaesthesia): Here the LA Ans. Local anaesthetics are the agents which cause revers-
is applied on mucous membranes, e.g. lignocaine ible loss of sensation caused by either depression in excita-
2–10%, cocaine 1–4%. tion of conducting nerve or suppression of excitation of
2. Infiltration anaesthesia: LA is injected directly into tis- peripheral nerves.
sues to be operated; it blocks sensory nerve endings,
e.g. lignocaine 0.5–1%.
3. Nerve block anaesthesia: LA is injected very close Classification of Local Anaesthetics
to or around the peripheral nerve or nerve plexuses.
It produces larger areas of anaesthesia, e.g. ligno-
Based on Chemical Structures
caine 2%. 1 . Amides, e.g. lidocaine
4. Spinal anaesthesia: Here the LA is injected into sub- 2. Esters
arachnoid space to anaesthetize spinal roots usually at a. Esters of benzoic acid, e.g. butacaine, cocaine, tetra-
level of L2–3 or L3–4 below the lower end of spinal cord. caine
5 Epidural anaesthesia: LA is injected into epidural space b. Esters of para-aminobenzoic acid, e.g. chloropro-
where it acts on spinal nerve roots. Commonly used caine, procaine, propoxycaine
drugs are lignocaine and bupivacaine. It is mainly useful 3. Quinolones: Centbucridine
in obstetric analgesia.
6. Intravenous regional anaesthesia (Bier’s block): Here
the LA is injected into the vein of upper limb whose
Based on Duration of Action
blood flow is occluded by tourniquet. Lignocaine and 1. Injectable anaesthetics
prilocaine are commonly used. It is mainly used in an- l Low potency and duration: Procaine
aesthetizing the upper limb. l Intermediate potency and duration: Lignocaine and pri-
locaine
Q. 8. Intravenous anaesthetics l High potency and long duration: Tetracaine, bupiva-
caine, ropivacaine and dibucaine

Ans.
2. Surface anaesthetics
l Intravenous regional anaesthesia is also known as Bier’s l Soluble: Cocaine, lignocaine, tetracaine, benoxinate
block. l Insoluble: Benzocaine and butyl aminobenzoate

Part VII
Drugs Acting on Central Nervous System
Topic 22
General Anaesthetics
LONG ESSAYS
Q. 1. Enumerate stages of general anaesthesia. Describe CLASSIFICATION
the pharmacological actions, merits and demerits of
nitrous oxide as a sole general anaesthetic agent. I. Inhalational
a. Gases: Nitrous oxide, cyclopropane
Or, b. Liquids: Ether, halothane, enflurane, isoflurane,
Classify general anaesthetics. Write pharmacology of methoxyflurane
nitrous oxide. II. Intravenous
a. Inducing agents: Thiopentone sodium, methohexi-
Ans. tone, propofol, etomidate
General anaesthetics are agents that bring about reversible b. Dissociative anaesthesia: Ketamine
loss of sensation and consciousness. There are different c. Neuroleptanalgesia: Fentanyl-droperidol
stages of general anaesthesia. d. Benzodiazepines: Diazepam, lorazepam, midazolam
General anaesthetics are also classified as follows:
STAGES OF GENERAL ANAESTHESIA
i. Stage of analgesia: This stage is the beginning of inha-
lation to loss of consciousness. General anaesthetics
i i. Stage of delirium: This stage is from loss of conscious-
ness to beginning of surgical anaesthesia. It may be with
excitement, shouting, crying and violent behaviour.
Inhalational general anaesthetics Parenteral general anaesthetics
i ii. Stage of surgical anaesthesia
a. Passes to deeper planes
b. Respiratory depression
c. Gradual loss of reflexes Volatile liquids Gas
d. Relaxation of skeletal muscles
i. Ether i. Nitrous oxide Inducing drugs Slow-acting drugs
i v. Stage of medullary paralysis: This is due to the over-
ii. Halothane i. Thiopentone i. Benzodiazepines,
dose. It is the stage of medullary depression, followed
e.g. diazepam
by cessation of breathing, circulatory failure and death.
iii. Enflurane ii. Propofol ii. Ketamine, e.g. dis-
sociative anaesthesia
IDEAL ANAESTHESIA iv. Isoflurane iii. Etomidate iii. Opioids, e.g.
i. It should be pleasant and nonirritating. fentanyl
i i. It should provide adequate analgesia, immobility and v. Desflurane
muscle relaxation. vi. Sevoflurane
i ii. It should be noninflammable.
i v. Administration should be easy, controllable and wide
Nitrous Oxide
margin of safety.
v. Induction and recovery should be smooth. It is a slightly sweetish odour gas and produces light anaes-
v i. It should not affect cardiovascular function and should thesia without significant depression of respiration or vaso-
be inexpensive. motor centre.
Actions Ans.
l Moderate increase in pain threshold l Preanaesthetic medication is used before administration
l Slight amnesia effect of an anaesthetic agent.
l Euphoria is frequent. l It helps to
l Decreased sense of smell a. reduce anxiety and fear.
l Improved hearing b. reduce secretions.
l Slight myocardial depression c. enhance the hypnotic effect of GA agents.
l Minimal effect on respiration d. reduce postoperative nausea and vomiting.
l Reduces MAC of other gaseous agents by 50% e. produce amnesia.
f. reduce the volume and pH of gastric contents.
Metabolism g. attenuate vagal reflexes.
h. attenuate sympathoadrenal responses.
Exhaled primarily unchanged via lungs.
Small amounts are excreted through skin, sweat glands, Drugs used for premedication are as follows:
urine, etc. a. Benzodiazepines: Diazepam, midazolam, oxazepam,
lorazepam
b. Opioid analgesics: Morphine, fentanyl, pethidine, pen-
Side Effects of N2O tazocine
l Postoperative nausea and vomiting c. Anticholinergic agents: Atropine, glycopyrrolate, sco-
l Chronic use causes bone marrow depression, vitamin polamine
B12 and folate metabolic disturbances.
l Teratogenic effects in the first trimester of pregnancy a. Benzodiazepines
l It augments the respiratory depressant effect of thiopen-
tone and opiates. They produce anxiolysis, sedation and amnesia. Reversal
agent is flumazenil.
Four Zones of N2O Anaesthesia

b. Opioid Analgesics
I. Moderate analgesia (6–25%): 25% N2O is more potent
than 10 mg morphine. They produce sedation and analgesia.
II. Dissociative analgesia (26–45%): Psychological symp-
toms and lack of ability to concentrate. c. Anticholinergic Agents
III. Analgesic anaesthesia (46–65%): Near complete anal-
gesia. Patient may respond to commands. i. Vagolytic effect: It increases the heart rate by blocking
IV. Light anaesthesia (66–80%): Complete analgesia and the action of acetylcholine on muscarinic receptors in
amnesia. SA node. Atropine is very useful in preventing intraop-
erative bradycardia resulting from stimulation of carotid
sinus or vagal stimulation.
Advantages of N2O ii. Antisialagogue action: It includes drying of secretions
i. Strong analgesic of salivary, gastric, tracheobronchial and sweat glands.
ii. Induction is rapid and smooth. iii. Glycopyrrolate is more potent and long-acting drying
iii. It is nonirritating and noninflammable. agent and is likely to increase the heart rate.
iv. Recovery is rapid. iv. Scopolamine is more effective antisialagogue than
v. No postoperative nausea. atropine.
vi. It has little effect on respiration and cardiovascular v. Sedation and amnesia: Glycopyrrolate does not cross
function. blood-brain barrier and hence does not cause sedation or
vii. It is nontoxic to liver, kidney, brain and quickly amnesia. Scopolamine has good sedative and amnesic
removed from lungs. effect. Atropine causes delirium in elderly individuals,
so glycopyrrolate is better than atropine for elderly indi-
viduals.
Disadvantages
i. It is less potent and should be used with other agents.
Side Effects
ii. Poor muscle relaxant
i. Papillary dilatation
Q. 2. Preanaesthetic medication ii. Tachycardia
i ii. Delirium, confusion and restlessness B. Gastrokinetic Drugs (Metoclopramide)

iv. Increase in body temperature
l It is a dopamine antagonist that stimulates the upper GI
motility, increases gastroesophageal sphincter tone and
Dosage relaxes pylorus and duodenum.
l It reduces the volume of gastric fluids and thus reduces
Atropine: 0.12 mg/kg
Glycopyrrolate: 0.44 mg/kg the risk of aspiration.
l Its rapid injection can cause abdominal cramping.
Dosage: 10 mg orally, 30–60 min prior to surgery or

Aspiration Prophylaxis 5–20 mg parenterally, 15–30 min prior to surgery.
Several pharmaceutical agents have been used to alter gas-
tric pH and fluid volume. It includes the following: C. Antacid
a. Histamine receptor (H2 receptor) blocking agents
b. Gastrokinetic drugs l It is used to neutralize the pH of gastric fluid.
c. Antacids l A single dose of clear antacid given 15–30 min prior to
d. Anticholinergic agents anaesthesia is effective in raising gastric pH above 2.5,
e.g. 30 mL of 0.3 mg sodium citrate solution can be used.
Aspiration prophylaxis is indicated in
A. Histamine Receptor (H2 Receptor) l obesity,
Blocking Agents (Cimetidine, Ranitidine and l pregnancy,
Famotidine) l diabetic patients,
l alcoholics,
l The drugs raise the gastric pH by blocking histamine- l patients on long-term steroid therapy,
mediated secretions of gastric hydrogen ion. l ascites,
l They reduce the acidity, but have no effect on volume of
l hiatus hernia and
gastric secretions or stomach emptying time. l patients with gastroesophageal reflex.
Dosage D. Antiemetics

i. Cimetidine: 150–300 mg orally or parenteral, 60–90 min Example: Droperidol, metoclopramide, phenothiazines
prior to surgery and should be repeated 8 hourly. (like ondansetron, prochlorperazine)
ii. Ranitidine: 50–100 mg orally or parenterally. It can be l It can be given as a premedication or just prior to the
given 1 night before surgery and 1 hour prior to surgery. emergence from GA or during recovery period.
Duration of action: 9–10 h. Ranitidine will prolong the l Some amount of blood enters the stomach during sur-
sedative effect of midazolam. gery and can cause irritation to the stomach mucosa to
iii. Famotidine: 40 mg one night before surgery and 40 mg induce vomiting postoperatively.
on the morning of surgery, orally. Onset of action: 1 h l To prevent this antiemetic can be used.
and duration of action: 10–12 h.
SHORT ESSAYS
Q. 1. Ether first increase due to stimulation of respiratory centre and
later on they decrease as the anaesthesia deepens.
Or,
l It stimulates salivation, so atropine premedication is
Mention advantages and disadvantages of ether as advised. It is irritating to the respiratory tract and pro-
general anaesthetic. duces cough and laryngeal spasm.
l On induction it induces analgesia followed by excite-
Ans.
ment and then anaesthesia.
l Ether is a highly volatile and colourless liquid. As it is l It increases CSF pressure and blood glucose levels. It pro-
inflammable in air and explosive with oxygen, it should duces postoperative nausea and vomiting in 50% of patients.
not be used when cautery is being used for surgery.
About 85–90% of the drug will get excreted through the Advantages of Ether
lungs.
l It stimulates the sympathetic system yielding to increase l Potent and reliable good anaesthetic.
in heart rate and to depress the vagus nerve. BP falls in the l Effect on cardiovascular, respiratory functions are not
deeper planes of anaesthesia. The respiratory movement’s significant. Reflexes are well maintained.
l It is a bronchodilator. Q. 3. Compare nitrous oxide and halothane.

l Provides full muscle relaxation.
Ans. Comparison between nitrous oxide and halothane is
l Does not sensitize the heart to adrenaline.
l Easy to administer and inexpensive.
TABLE 22.2 Comparison between Nitrous Oxide and
Disadvantages of Ether Halothane
l It is inflammable. Nitrous oxide Halothane
l Highly soluble in body. Induction is slow and unpleasant. It is an inhalational gas It is an inhalational liquid
l It is irritating, so enhances respiratory secretions. Pre-
medication with atropine is essential. Laryngeal spasm It is colourless, odourless, It is volatile, noninflammable,
noninflammable with sweet odours
may occur during induction.
l Postoperative nausea and vomiting are frequent. It produces good analgesia but It is neither a good analgesic
poor muscle relaxation nor a muscle relaxant, but it
l Recovery is slow.
potentiates competitive neuro-
muscular blocking
Status in Anaesthesia Onset is rapid, it is short act- Induction is intermediate and
ing, and recovery is fast and pleasant, recovery is smooth
Ether is not preferred because of flammability and irri- smooth
tant property. But is used in developing countries like
No marked postanaesthetic Postanaesthetic effects include
India because it is cheap, easy to administer and rela- nausea shivering, malignant hyper-
tively safe. thermia, but nausea and
vomiting rarely occur
Q. 2. Compare nitrous oxide and diethyl ether.
Used in obstetrics, dental Mostly used anaesthetic in
Ans. Comparison between nitrous oxide and diethyl ether practice, to produce conscious dental and surgical
is given in Table 22.1. sedation, and along with an- procedures
other general anaesthetic in
major surgeries
Economical Expensive
TABLE 22.1 Comparison between Nitrous Oxide and
Diethyl Ether
Nitrous oxide Diethyl ether Q. 4. Benzodiazepine

It is an inhalational gas It is an inhalational liquid Ans.
It is colourless, odourless, It is highly volatile, inflamma-
noninflammable ble and produces irritating l Benzodiazepines are one of the drugs used for premedi-
vapours cation, e.g. diazepam, midazolam, oxazepam, lorazepam.
l They produce anxiolysis, sedation and amnesia.
It produces good analgesia It is a good analgesic and a
but poor muscle relaxation muscle relaxant l Site of action: Thalamus, hypothalamus, gamma-ami
nobutyric acid (GABA) receptors

Onset is rapid, it is short Highly soluble in blood
acting and recovery is fast hence induction is prolonged,
recovery is slow Action
Recovery is smooth. No Postanaesthetic nausea,
marked postanaesthetic vomiting and retching are 1. Mild decrease in BP by decreasing anxiety and causing
nausea marked muscle relaxation
2. Minimal changes in respiration when given slowly in
Used in obstetrics, dental Rarely used in developed
practice, to produce con- countries. It is used in small doses
scious sedation and along developing countries be- 3. Antiemetic property is present.
with another general anaes- cause it is cheap. Used to 4. It produces amnesia which increases as the dose
thetic in major surgeries produce general anaesthesia increases.
for dental and surgical
5. It produces emotional responses in adolescent females.
procedures
6. Metabolizes in the liver as desmethyldiazepam.
Uses Site of Action

1. Benzodiazepines are used as slow-acting general anaes- Thalamus, hypothalamus, gamma-aminobutyric acid (GABA)
thetics. receptors
2. They are used to induce conscious sedation in small re-
peated doses or by slow infusion. This state lasts for about
Actions
1 h and psychomotor impairment persists for 6–24 h.
3. They are used as sedative hypnotics, antianxiety drugs. 1. Mild decrease in BP by decreasing anxiety and causing
4. They are used as centrally acting skeletal muscle muscle relaxation
relaxants. 2. Minimal changes in respiration when given slowly in
5. Combined with analgesics they can be used for the treat- small doses
ment of rheumatic disorders associated with muscle spasms. 3. Antiemetic property is present.
6. They are used as antiepileptic drugs. 4 . It produces amnesia which increases as the dose
increases.
Q. 5. Two advantages and two disadvantages of 5. It produces emotional responses in adolescent females.
halothane 6. Metabolizes in the liver as desmethyldiazepam.
Ans.
Uses
Halothane is a colourless, volatile liquid with sweet odour,
which is nonirritating and noninflammable. 1 . Diazepam is used as a slow-acting general anaesthetic.
2. It is used to induce conscious sedation in small repeated
doses or by slow infusion. This state lasts for about 1 h
Advantages and psychomotor impairment persists for 6–24 h.
1 . It is potent, noninflammable. 3. It is used as a sedative hypnotic, antianxiety drug.
2. Induction is smooth and rapid. 4. It is used as a centrally acting skeletal muscle relaxant.
3. Nonirritant 5. Combined with analgesics it can be used for the treat-
4. Recovery is rapid and postoperative nausea and vomit- ment of rheumatic disorders associated with muscle
ing is low. spasms.
6. It is used as an antiepileptic drug.
Disadvantages Q. 7. Compare ether and halothane.
1 . It is neither a good analgesic nor muscle relaxant. Ans. Comparison between ether and halothane is given in
2. It is a direct myocardial depressant. As cardiac output Table 22.3.
and BP start falling, heart rate may decrease. It sensitizes
the heart to the arrhythmogenic action of adrenaline.
3. It causes some respiratory depression. TABLE 22.3 Comparison between Ether and Halothane
4. Malignant hyperthermia: Intracellular release of calcium
Diethyl ether Halothane
from the sarcoplasmic reticulum causes muscle contraction
and increased heat production. It is treated with dantrolene. It is an inhalational liquid It is an inhalational liquid
5. It is expensive. It is highly volatile, inflamma- It is volatile, noninflammable
ble and produces irritating with sweet odours
vapours
Status of Anaesthesia It is a good analgesic and a It is neither a good analgesic
Halothane is most popular anaesthetics. Analgesics and muscle relaxant nor a muscle relaxant, but it
potentiates competitive neuro-
muscle relaxants are used as adjuvants.
muscular blocking
Q. 6. Diazepam and its uses Highly soluble in blood, Induction is intermediate and
hence induction is prolonged, pleasant, recovery is smooth
Ans. recovery is slow
Diazepam belongs to the benzodiazepine group. Postanaesthetic nausea, Postanaesthetic effects include
vomiting and retching are shivering, malignant hyper-
marked thermia, but nausea and
Dosage vomiting rarely occur
Economical Expensive
0.2–0.5 mg/kg
SHORT NOTES
Q. 1. Classify general anaesthetics. Actions
Ans. Actions of nitrous oxide are as follows:
l Moderate increase in pain threshold
General anaesthetics are agents that bring about reversible l Slight amnesia effect
loss of sensation and consciousness. They are classified as l Euphoria is frequent.
follows: l Decreased sense of smell
1. Inhalational l Improved hearing
a. Gases: Nitrous oxide, cyclopropane l Slight myocardial depression and minimal effect on
b. Liquids: Ether, halothane, enflurane, isoflurane, respiration
methoxyflurane
2. Intravenous
a. Inducing agents: Thiopentone sodium, methohexi- Metabolism
tone, propofol, etomidate Exhaled primarily unchanged via lungs. Small amounts are
b. Dissociative anaesthesia: Ketamine excreted through skin, sweat glands, urine, etc.
c. Neuroleptanalgesia: Fentanyl 1 droperidol
d. Benzodiazepines: Diazepam, lorazepam, midazolam Q. 4. Uses of diazepam
Q. 2. Ether Ans.
Or, Diazepam belongs to the benzodiazepine group.

Uses of diazepam are as follows:
Diethyl ether 1. It is used to induce conscious sedation in small repeated
Ans. doses or by slow infusion.
2. It is used as a sedative hypnotic, antianxiety drug.
This is a highly volatile and colourless liquid. About 85–90% 3. It is used as a centrally acting skeletal muscle relaxant.
of the drug will get excreted through the lungs. 4. Combined with analgesics it can be used for the treat-
ment of rheumatic disorders associated with muscle
Advantages spasms.
5. It is used as an antiepileptic drug.
1 . Potent and reliable anaesthetic
2. Effect on cardiovascular, respiratory functions are not Q. 5. Ketamine
significant. Ans.
3. Provides full muscle relaxation.
4. Does not sensitize the heart to adrenaline. l It produces dissociative anaesthesia characterized by
5. Easy to administer and economical. profound analgesia, immobility, amnesia with light
sleep and feeling dissociation from one’s own body and
surroundings.
Disadvantages
l Primary site of action: Cortex and subcortical area
1. As it is inflammable in air and explosive with oxygen, l Respiration is not depressed, reflexes are not abolished
it should not be used when cautery is being used for and muscle tone increases.
surgery. l Heart rate, cardiac output and BP are elevated due to
2. Highly soluble in body. Induction is slow and unpleas- sympathetic stimulation.
ant and recovery is also slow. l Ketamine is available as 100 mg and 500 mg/10 mL
3. Postoperative nausea and vomiting are frequent. injection and is used in dosage of 1–4 mg/kg IV or
6.5–15 mg/kg IM.
Q. 3. Actions of nitrous oxide l Children tolerate the drug well.
l Onset of action: Within 1–3 min and recovery starts

Ans.
after 10–15 min
Nitrous oxide is a slightly sweetish odour gas and produces l It is indicated in surgeries on the head and neck.
light anaesthesia without significant depression of respira- l It is contraindicated in hypertensive and ischaemic heart
tion or vasomotor centre. disease patients.
Q. 6. Halothane 2 . Shivering and delirium during recovery

3. Pain in the postoperative period
Ans.
It is colourless, volatile liquid with sweet odour which is Q. 9. Preanaesthetic medication

nonirritating and noninflammable. Ans.
Preanaesthetic medication is used before administration

Advantages l
of an anaesthetic agent.
1 . Induction is smooth and rapid. l It helps to
2. Recovery is rapid. 1. reduce anxiety and fear.

3. Postoperative nausea and vomiting is low. 2. reduce secretions.
3. enhance the hypnotic effect of GA agents.
Disadvantages 4. reduce postoperative nausea and vomiting.
5. produce amnesia.
l It is neither a good analgesic nor a muscle relaxant. 6. reduce the volume and pH of gastric contents.
l It is a direct myocardiac depressant. 7. attenuate vagal reflexes.
l It causes some respiratory depressions, severe hepatitis
8. attenuate sympathoadrenal responses.
and malignant hyperthermia. l Drugs used for premedication are
l It is expensive.
1. Benzodiazepines: Diazepam, midazolam, oxazepam,
lorazepam
Q. 7. Methohexitone
2. Opioid analgesics: Morphine, fentanyl, pethidine,
Ans. pentazocine
3. Anticholinergic agents: Atropine, glycopyrrolate,
l Methohexitone is three times more potent than thiopentone. scopolamine
Quicker and brief actions. Unconsciousness is usually in-
duced in 15–30 s. Consciousness will regain within 2–3 min. Q. 10. Benzodiazepine
Ans.
Actions
1 . Less hypotensive compared to thiopentone Benzodiazepines are now frequently used for inducing,
2. Slight increase in heart rate and moderate hypoventilation maintaining and supplementing anaesthesia, e.g. diazepam,
3. Short period of apnoea may be seen after IV injection. lorazepam, midazolam.
4. This drug is contraindicated in epileptic patients.
Actions
Q. 8. Thiopentone sodium
l Mild decrease in BP by decreasing anxiety and causing
Ans. muscle relaxation
l Antiemetic property is present.
1. Thiopentone sodium is an ultra short-acting thiobar-
l It produces amnesia which increases as the dose
biturate.
2. If given intravenously it produces unconsciousness in increases.
l It produces emotional responses in adolescent fe-
15–20 s and consciousness will be regained in 10–20 min.
3. It produces CNS depression which persists for more males.
than 12 h.
4. This is a poor analgesic and weak muscle relaxant. Respi- Uses
ratory depression with inducing doses of thiopentone is
generally transient, but with large dose it will be severe. l Benzodiazepines are used as slow-acting general anaes-
thetics.
l They are also used to induce conscious sedation and
Adverse Effects also as sedative hypnotics, antianxiety drugs.
1. Laryngospasm occurs generally when respiratory secre- l They are used as centrally acting skeletal muscle
tions or other irritants are present, or when intubation is relaxants.

attempted while anaesthesia is light. l They are used as antiepileptic drugs.
Topic 23
Ethyl and Methyl Alcohols

SHORT ESSAY
Q. 1. Ethyl alcohol is used in methyl alcohol poisoning. l Since ethyl alcohol is an antidote for methyl alcohol
Write the rationale. which counteracts the effect of methanol poisoning it is
Ans. used in treating methyl alcohol poisoning.
l Ethanol 10% is given intravenously. It competes with
l Methanol is a mild CNS depressant. It is metabolized to methanol for metabolic enzymes and saturates them,
formaldehyde and formic acid which in turn causes thus preventing the formation of toxic metabolites like
metabolic acidosis, retinal damage and blindness. formaldehyde and formic acid. Methanol gets excreted
l The signs and symptoms of methanol poisoning are unchanged in urine and breath.
nausea, vomiting, abdominal pain, headache, vertigo,
confusion, hypotension, convulsions and coma.
SHORT NOTES
Q. 1. Clinical uses of ethyl alcohol Methanol is a CNS depressant, but it is less potent than
ethanol.
Ans.
The steps in treating methyl alcohol poisoning are as
l Ethyl alcohol is a hydroxy derivative of aliphatic hydro- follows:
carbons. 1. Patient should be kept in dark room to protect the eyes
l Medicinal uses of ethanol are as follows: from light.
1. As antiseptic 2. Maintain air way, breathing and circulation.
2. Rubefacient and counterirritant for sprains, joint 3. Gastric lavage is done after endotracheal intubation.
pains, etc. 4. Sodium bicarbonate is given intravenously to correct
3. Alcoholic sponges may be used to reduce body tem- acidosis.
perature during fever. 5. Ethanol 10% is given intravenously.
4. As appetite stimulant and carminative 6. Haemodialysis is done to promote excretion of metha-
5. In treating intractable neuralgias like trigeminal neu- nol and its toxic metabolites.
ralgia and also in severe cancer pain, etc. 7. Fomepizole is a specific inhibitor of alcohol dehydroge-
6. In treating methanol poisoning nase and retards methanol metabolism.
8. Folate therapy: Calcium leucovorin injected repeatedly
Q. 2. Treatment of methyl alcohol poisoning to reduce blood formate levels by enhancing its metabo-
lism. This is a promising adjuvant approach.
Ans.
Topic 24
Sedatives/Hypnotics
LONG ESSAYS
Q. 1. Classify hypnotics. Mention the pharmacological Classify hypnotics. Describe the uses, adverse effects
actions, management of poisoning of barbiturates. and treatment of barbiturate poisoning.
Or, Ans.
l Sedative is a drug that produces a calming effect and Barbiturates

reduces excitability. It may induce drowsiness.
l Hypnotic is a drug that induces sleep resembling natural Bind to GABAA receptor Cl− channel complex
sleep.
Potentiate GABAergic inhibition
Classification of hypnotics is as follows:
Benzodiazepines The duration of Cl− channel kept open is increased

Hypnotic Antianxiety Anticonvulsant
Diazepam Diazepam Diazepam Increased chloride conductance
Flurazepam Chlordiazepoxide Clonazepam

Membrane hyperpolarization
Nitrazepam Oxazepam Clobazam
Triazolam Alprazolam
CNS depression
Midazolam Lorazepam
Temazepam
Barbiturates
i. Barbiturates depress all excitable tissues. The CNS is
Long-acting Short-acting Ultra short-acting
most sensitive and effect is dose dependent; with in-
Phenobarbitone Pentobarbitone Thiopentone crease in dose there is sedation n sleep n anaesthesia
Mephobarbitone Secobarbitone Methohexitone n coma.
ii. Barbiturates have an anticonvulsant action in a subhyp-
Newer nonbenzodiazepine drugs
notic dose and are used in the treatment of status epi-
Zopiclone lepticus and generalized tonic-clonic seizures.
Zolpidem iii. Respiration: Increase in dose causes depression of respi-
Zaleplon
ratory centre.
iv. CVS: At hypnotic doses there is slight fall in BP and
decrease in heart rate.
v. Kidney: Barbiturate anaesthesia results in decrease in
BARBITURATES urinary output.
l All barbiturates are the drugs derived from barbituric vi. Barbiturates induce microsomal enzyme and increase the
acid. They are nonselective CNS depressants. rate of their own metabolism as well as for other drugs.
l They were the longest group of drugs in use till newer
drugs like benzodiazepines were discovered in about

Uses
1960.
i. Phenobarbitone is used in epilepsy.
ii. As preanaesthetic and anaesthetic medication
Classification iii. Now they are seldom used as sedatives and hypnotics.
l Long-acting: Phenobarbitone, mephobarbitone iv. They are used in treating congenital nonhaemolytic
l Short-acting: Pentobarbitone, secobarbitone, butobarbitone jaundice due to enzyme-inducing property of phenobar-
l Ultra short-acting: Thiopentone sodium, methohexitone bitone, which is utilized to hasten clearance of con-
genital nonhaemolytic jaundice and kernicterus.
v. They are occasionally employed as adjuvants in psy-
Mechanism of Action chosomatic disorders.
l Barbiturates bind to specific site on the GABA receptor
Cl2 channel complex.
Adverse Effects
l They facilitate inhibitory neurotransmission by opening
chloride ion channels and hyperpolarize the neural i. The common side effects are drowsiness, hangover,
membrane. mental confusion, impaired performance and judgement.
l Mechanism of action of barbiturates can be summa- ii. Nausea, vomiting, diarrhoea
rized as follows: iii. Idiosyncrasy—excitement
iv. Hypersensitivity reactions like skin rashes, itching and Classification of hypnotics is as follows:
swelling of face, especially eyelids may occur.
v. Tolerance and dependence develop due to their sedative Benzodiazepines
and hypnotic actions on repeated use.
Hypnotic Antianxiety Anticonvulsant
vi. Physical and psychological dependence develop on
repeated use. Diazepam Diazepam Diazepam
vii. Prolonged use of phenobarbitone may cause megalo- Flurazepam Chlordiazepoxide Clonazepam
blastic anaemia by interfering with absorption of folic
Nitrazepam Oxazepam Clobazam
acid from gut.
Triazolam Alprazolam
Midazolam Lorazepam
Barbiturate Poisoning
Temazepam
Dosage of barbiturates above 6–10 g causes acute barbitu-
rate poisoning. Barbiturates
Long-acting Short-acting Ultra short-acting
Manifestations Phenobarbitone Pentobarbitone Thiopentone
l Respiratory depression with slow shallow breathing Mephobarbitone Secobarbitone Methohexitone

l Hypotension Newer nonbenzodiazepine drugs
l Skin eruptions Zopiclone
l Swelling of eyelids
Zolpidem
l Cardiovascular collapse
l Renal failure Zaleplon
Management of Acute Barbiturate Poisoning BENZODIAZEPINES

i. Maintain airway, breathing and circulation l All benzodiazepines have a benzene ring fused to a
ii. Gastric lavage using activated charcoal to prevent fur- seven-membered diazepine ring.
ther absorption of the drugs l Their sites of action are midbrain, limbic system, ascend-
iii. Vasopressors, i.e. noradrenaline, dopamine, ephedrine. ing reticular activating system (ARAS).
iv. Haemodialysis should be done especially in severe
cases of renal failure and is highly effective in remov-
ing long-acting barbiturates. Mechanism of Action
v. Forced alkaline diuresis with mannitol, frusimide or so- The benzodiazepines have no GABA-mimetic action.
dium bicarbonate and administration of IV fluids will help l Mechanism of action of benzodiazepines can be summa-
in faster excretion of the drug, since they are acidic drugs. rized as follows:
Q. 2. Classify hypnosedatives. Discuss the pharmacologi- Benzodiazepines
cal actions, uses and adverse effects of benzodiazepines.
What are the advantages of benzodiazepines over barbi-
Bind to specific site on GABAA–BZD receptor
turates as sedative hypnotics?
Cl− channel complex
Or, Potentiate the inhibitory effect of GABA

Classify benzodiazepines. Explain their mechanism of
action and therapeutic uses. Mention their advantages Increase in frequency of opening Cl− channels
over barbiturates as sedative hypnotics.
Ans. Increased chloride conductance
l Sedative is a drug that produces a calming effect and

Membrane hyperpolarization
reduces excitability. It may induce drowsiness.
t
l Hypnotic is a drug that induces sleep resembling natural
sleep. CNS depression

Pharmacological Actions and Therapeutic e. As IV anaesthetic: Benzodiazepines can be used for

Uses inducing, maintaining and supplementing anaesthesia,
e.g. diazepam, lorazepam, midazolam.
The most important actions of benzodiazepines are on CNS f. As preanaesthetic medication: These drugs are used
and include the following: as preanaesthetic medication because of their seda-
1. Sedation and hypnotic action: At larger doses diazepam tive-amnesic and anxiolytic effects, e.g. diazepam,
produces sleep, decreases awakening during sleep, in- lorazepam.
creases total sleep time, shorter REM (rapid eye movement) g. Diagnostic (endoscopies) and minor operative proce-
sleep. dures: Benzodiazepines are used before electroconvul-
2. Benzodiazepines are one of the most prescribed drugs. sive therapy, electrical cardioversion of arrhythmias,
a. As hypnotics cardiac catheterization, endoscopies in obstetrics and
l At present benzodiazepines are the hypnotics of
many minor surgical procedures.
choice. h. To treat alcohol withdrawal symptoms in dependent
l They are used to shorten sleep latency, reduce noctur-
subjects to reduce intensity of withdrawal symptoms.
nal awakening or to provide anxiolytic effect the day
after.
l The benzodiazepines are chosen depending on their
Adverse Effects
onset and duration of action. Benzodiazepines (BDZ) have a wide margin of safety. They
i. Chronic insomnia (. 3 weeks) are generally well tolerated.
l Intermittent use of hypnotics is tried like once every
The common side effects are as follows:
3 days.
i. Drowsiness, dizziness, vertigo, ataxia, amnesia and
l A slowly eliminated drug is preferable because re-
prolongation of reaction time
bound insomnia and withdrawal symptoms are least
ii. Blurring of vision
marked.
iii. Dry mouth and sweating
l There is increased risk of tolerance and abuse.
iv. Tolerance, cross-tolerance and drug dependence
ii. Short-term insomnia (3–21 days)
v. Drug abuse: Flunitrazepam
l Generally a benzodiazepine free of residual effects is
vi. Newborn infants show withdrawal if mother used BDZs
selected.
during pregnancy.
l When anxiety is the dominant feature, benzodiaze-
vii. BDZs during labour can have effects on newborn like
pines with longer duration of action are better. In
a. depressed respiration and feeding and
elderly, short-acting benzodiazepines are preferred.
b. floppy baby syndrome.
l The use of benzodiazepines should be limited to
2–3 weeks. Benzodiazepines are preferred to barbiturates as hypnosed-

iii. Transient insomnia (1–3 days) atives because of following reasons:
l Rapidly eliminating or widely distributing benzodi- i. Benzodiazepines have high therapeutic index.
azepines are preferred to avoid residual effect next ii. Even at the hypnotic doses, there is no loss of conscious-
morning. ness and respiration is not depressed. Hypnotic doses do
b. As anxiolytic and for daytime sedation not affect respiration or cardiovascular functions.
l Benzodiazepines reduce anxiety and aggression and iii. They have practically no action on other body sys-
thus produce a calming effect. tems.
c. As anticonvulsants iv. They cause less distortion of sleep architecture.
l Benzodiazepines increase seizure threshold and can v. They do not alter disposition of other drugs by micro-
be used as anticonvulsants. somal enzyme induction.
l Diazepam is used in situations like status epilepticus, vi. They have lower abuse liability.
febrile convulsions. vii. They have a specific antagonist (flumazenil) which
l Clonazepam is used in absence seizures and myo- can be used in case of poisoning whereas in phenobar-
clonic seizures in children. bitone poisoning there is no specific antagonist.
d. As centrally acting muscle relaxants viii. Rebound phenomenon on discontinuation of drug is
l Benzodiazepines reduce muscle tone by central action. less marked.
l Increased muscle tone and aches associated with ix. Tolerance is mild and psychological and physical
anxiety can be reduced using benzodiazepines. dependence and withdrawal syndrome is less marked.
SHORT ESSAYS
Q. 1. Classify barbiturates and write their uses. l Rebound phenomenon on discontinuation of drug is less
marked with diazepam.
Ans. l Tolerance of diazepam is mild.
l Psychological and physical dependence and withdrawal

Barbiturates syndrome is less marked compared to phenobarbitone.
l Barbiturates are drugs derived from barbituric acid.
l They were the longest group of drugs in use till newer Q. 3. Therapeutic uses of benzodiazepine
drugs like benzodiazepines were discovered in about 1960. Ans.
The therapeutic uses of benzodiazepines are as follows:

Classification 1. As hypnotics
1 . Long-acting: Phenobarbitone, mephobarbitone l At present benzodiazepines are the hypnotics of
2. Short-acting: Butobarbitone, secobarbitone, pentobarbi- choice.

tone l They are used to shorten sleep latency, reduce noc-
3. Ultra short-acting: Thiopentone, methohexitone, hexo- turnal awakening or to provide anxiolytic effect the
barbitone day after.
l The benzodiazepines are chosen depending on their
onset and duration of action.

Uses 2. As anxiolytic and for daytime sedation: Benzodiaze-
1 . Phenobarbitone is used in epilepsy. pines reduce anxiety and aggression and thus produce a
2. As preanaesthetic anaesthetic medication calming effect.
3. Now they are seldom used as sedatives and hypnotics. 3. As anticonvulsants
4.
They are used in treating congenital nonhaemolytic jaundice l Benzodiazepines increase seizure threshold and can
due to enzyme-inducing property of phenobarbitone, which be used as an anticonvulsant.

is utilized to hasten clearance of congenital nonhaemolytic l Diazepam is used in situations like status epilepticus,
jaundice and kernicterus. febrile convulsions.

5 . They are occasionally employed as adjuvants in psycho- l Clonazepam is used in absence seizures and myo-
somatic disorders. clonic seizures in children.

4. As centrally acting muscle relaxants
Q. 2. Mention few advantages of diazepam over pheno- l Benzodiazepines reduce muscle tone by central action.
barbitones as hypnotic. l Increased muscle tone and aches associated with
Ans. anxiety can be reduced using benzodiazepines.

5. As IV anaesthetic: Benzodiazepines can be used for
Diazepam is preferred to phenobarbiturate as hypnotic due inducing, maintaining and supplementing anaesthesia,
to following advantages: e.g. diazepam, lorazepam, midazolam.
l Diazepam has a higher therapeutic index compared to 6. As preanaesthetic medication: These drugs are used
phenobarbitone. as preanaesthetic medication because of their seda-
l Even at hypnotic doses, there is no loss of conscious- tive-amnesic and anxiolytic effects, e.g. diazepam,
ness and respiration is not depressed. It causes less dis- lorazepam.
tortion of sleep architecture. 7. Diagnostic (endoscopies) and minor operative proce-
l Hypnotic doses do not affect respiration or cardiovascu- dures: Benzodiazepines are used before electroconvul-
lar functions. sive therapy, electrical cardioversion of arrhythmias,
l Diazepam practically has no action on other body systems. cardiac catheterization, endoscopies in obstetrics and
l It does not alter disposition of other drugs by micro- many minor surgical procedures.
somal enzyme induction. 8. To treat alcohol withdrawal symptoms in dependent
l Diazepam has lower abuse liability. subjects to reduce intensity of withdrawal symptoms.
l It has a specific antagonist (flumazenil) which can be
used in case of poisoning whereas in phenobarbitone Q. 4. Benzodiazepines as preanaesthetic medication

poisoning there is no specific antagonist. Activated Ans.
charcoal is used to stop absorption and forced alka-
line diuresis is used to facilitate excretion of pheno- l Antianxiety agents like benzodiazepines are used exten-
barbitone. sively as preanaesthetic medication.
l Diazepam 5–10 mg is given orally. 4. to make anaesthesia safer.

l It is given in order to 5. to reduce side effects of anaesthetics like gastric acidity.
1. decrease anxiety.
Barbiturates are not preferred as preanaesthetic medication
2. provide amnesia for preoperative period.
as they produce respiratory depression.
3. to relieve preoperative pain.
SHORT NOTES
Q. 1. Adverse effects of barbiturates 1. reverse the action of benzodiazepine sedation or an-
aesthesia and
Ans.
2. in benzodiazepine overdose or poisoning.
Adverse effects of barbiturates are as follows:
1. The common side effects are drowsiness, hangover, Q. 4. Classify barbiturates. Discuss thiopentone sodium.
mental confusion, impaired performance and judgement. Ans.
2. Nausea, vomiting, diarrhoea
3. Idiosyncrasy—excitement All barbiturates are the drugs derived from barbituric acid.
4. Hypersensitivity reactions like skin rashes and swelling They are nonselective CNS depressants.
in eyelids
5. Tolerance and dependence Classification
6. Physical and psychological dependence
7. Prolonged use of phenobarbitone may cause megalo- 1 . Long-acting: Phenobarbitone, mephobarbitone
blastic anaemia. 2. Short-acting: Pentobarbitone, secobarbitone, butobar-
bitone
Q. 2. Uses of benzodiazepine 3. Ultra short-acting: Thiopentone sodium, methohexitone
Ans.
Thiopentone Sodium
Benzodiazepines can be used as
1. hypnotics—used to shorten sleep latency, reduce noc- l It is an ultra short-acting barbiturate.
turnal awakening. l Highly soluble in water, produces unconsciousness in
2. anxiolytic and for daytime sedation. 15–20 s.
3. anticonvulsants. l Injected IV dosage: 3–5 mg/kg, as 2.5% solution.
4. centrally acting muscle relaxant. l Produces CNS depression which persists for more
5. IV anaesthetic used for inducing, maintaining and sup- than 12 h.

plementing anaesthesia. l Poor analgesic and weak muscle relaxant
6. preanaesthetic medication. l Respiratory depression with inducing doses of thiopen-
7. before electroconvulsive therapy, cardiac catheterization, tone is generally transient, but with large dose it will be
endoscopies in obstetrics and many minor procedures. severe.
8. alcohol withdrawal therapy. l Thiopentone is the commonest inducing agent used. It
can be used as the sole anaesthetic for short nonpainful

Q. 3. Flumazenil operations.
l It may be occasionally used to control convulsions.
Ans.
l Flumazenil is a benzodiazepine antagonist. Q. 5. Define sedatives, hypnotics and tranquilizers.

l It acts by competing with benzodiazepines for the re- Ans.
ceptor and reverses the depressant or stimulant actions.
l It abolishes the hypogenic, psychomotor, cognitive and l Sedative is a drug that reduces excitability and calms the
EEG effects of benzodiazepines. patient without inducing sleep though it may induce
l The action starts seconds after IV administration and drowsiness.
lasts for 1–2 h. l Sedation refers to decreased responsiveness to any level
l Mainly used to of stimulation.

l Hypnotic is a drug that induces or maintains sleep re- Uses

sembling natural arousable sleep. A hypnotic at lower
1 . Epilepsy
dose acts as a sedative.
2. Preanaesthetic and anaesthetic medication
l Tranquilizer is an old term meaning a drug which re-
3. Seldom as sedatives and hypnotics
duces mental tension and produces calmness without
4. Congenital nonhaemolytic jaundice
inducing sleep or depressing mental faculties. It was
mainly used to describe the effects of reserpine.
Dose
Q. 6. Indications of diazepam
Dose depends on lipid solubility. Higher lipid solubility indi-
Ans. cates for lower dose. Highly lipid-soluble agents like short-
acting barbiturates have a dose as low as 1–2 g. Phenobarbitone
Diazepam may be indicated is less lipid soluble and has a dose threshold up to 5 g.
a. as hypnotic—used to shorten sleep latency, reduce noc-
turnal awakening. Q. 8. Urine should be alkalized in acute barbiturate
b. as anxiolytic and for daytime sedation. poisoning. Why?
c. as anticonvulsant.
d. as centrally acting muscle relaxant. Ans.
e. as IV anaesthetic used for inducing, maintaining and l Dosage of barbiturates above 6–10 g causes acute bar-
supplementing anaesthesia. biturate poisoning.
f. as preanaesthetic medication. l Forced alkaline diuresis is done in acute barbiturate
g. before electroconvulsive therapy, cardiac catheteriza- poisoning with mannitol, sodium bicarbonate and
tion, endoscopies in obstetrics and many minor pro- frusemide because it helps in the rapid elimination of
cedures. long-acting barbiturates like phenobarbitone, which are
h. in treatment of alcohol withdrawal. eliminated primarily by renal excretion.
l Alkaline diuresis is the main treatment for acute barbi-
Q. 7. Write the uses and doses of barbiturates. turate poisoning as there is no specific antidote for bar-
Ans. biturate poisoning. Intravenous NaHCO3 alkalinizes
urine. Barbiturates are weakly acidic drugs. In alkaline
Barbiturates are drugs derived from barbituric acid. They urine, barbiturates exist in ionized form, so they are not
were the longest group of drugs in use till newer drugs like reabsorbed while passing through renal tubules and are
benzodiazepines were discovered in about 1960. rapidly excreted in urine.
Topic 25
Antiepileptic Drugs
LONG ESSAY
Q. 1. Classify the drugs used in epilepsy. Write the A. Barbiturate: Phenobarbitone, mephobarbitone
mechanism of action and adverse effects of diphenyl B. Deoxybarbiturate: Primidone
hydantoin sodium. C. Hydantoin: Phenytoin, mephenytoin
Or, D. Iminostilbene: Carbamazepine
E. Succinimide: Ethosuximide
Enumerate the antiepileptic drugs belonging to differ- F. Aliphatic carboxylic acid: Valproic acid (sodium val-
ent groups. Explain the actions of phenytoin. How will proate), Divalproex
you manage a case of convulsion precipitated during G. Benzodiazepines: Diazepam, clonazepam, clobazam,
tooth extraction? lorazepam
Ans. Antiepileptic drugs are the drugs used during epilepsy. H. Cyclic GABA analogue: Gabapentin
I. Newer drugs: Vigabatrin, topiramate, tiagabine, leveti-
Classification of antiepileptic drugs is as follows: racetam
PHENYTOIN SODIUM ii. Simple and complex partial seizures: First choice
drug—100 mg BD, maximum of 400 mg/day (children:
Phenytoin sodium or diphenylhydantoin sodium is a barbi-
5–8 mg/kg/day)
turate analogue and is a major antiepileptic drug.
iii. Status epilepticus: 25 mg/min slow IV, as alternate to
diazepam
Pharmacological Action (Mechanism of Action) iv. Trigeminal neuralgia and other neuralgia: Second
choice to carbamazepine
l Phenytoin prolongs the inactivated state of voltage sen-
v. Cardiac arrhythmias: Alternative in acute therapy of
sitive neuronal Na1 channel and governs the refractory
digitalis-induced ventricular extrasystole—100 mg IV
period of the neurons.
every 10 min (max 600 mg) or 100–200 mg orally
l As a result, high frequency discharges are inhibited with
2–6 hourly followed by 400 mg/day for maintenance
little effect on normal low frequency discharges.
l It has a stabilizing influence on the neuronal membrane
and thus prevents the spread of seizure discharges. MANAGEMENT OF CONVULSION

l This stabilizing influence consists of a synchronous and PRECIPITATED DURING TOOTH
unusually large depolarization over which action poten- EXTRACTION
tials are superimposed.
l At higher concentrations, phenytoin inhibits Ca
21
influx l Diazepam 10 mg IV bolus injection followed by frac-
into the neuron, reduces glutamate levels and causes tional doses every 10 min or slow infusion titrated to
facilitation of GABA responses. control the fits or phenobarbitone 100–200 mg IM/IV
or phenytoin 25 mg/min IV may be used alterna-
tively.
Therapeutic Uses l Maintenance of airway, oxygenation, fluid and electro-
Phenytoin is used for the treatment of the following: lyte balance, BP, normal cardiac rhythm, euglycaemia
i. Generalized tonic-clonic seizures (grand mal epilepsy) and care of unconsciousness.
SHORT ESSAYS
Q. 1. Diphenylhydantoin sodium 2. In status epilepticus 25 mg/min slow IV, used as alterna-
tive to diazepam
Ans.
3. It is second choice to carbamazepine in trigeminal neu-
Phenytoin sodium or diphenylhydantoin sodium is a barbi- ralgia and other neuralgias.
turate analogue and is a major antiepileptic drug. 4. As an antiarrhythmic in cardiac arrhythmias
Pharmacological Action (Mechanism Adverse Reactions

of Action) Phenytoin has dose-dependent toxicity. The adverse effects
l Phenytoin acts by stabilizing the neuronal membrane are as follows:
and thus prevents the spread of seizure discharges. 1. Hypertrophy and hyperplasia of gums
l Prolongs the inactivated state of voltage sensitive neuro- 2. It produces hypersensitivity reactions like urticaria, skin
nal Na1 channel and governs the refractory period of rashes, neutropenia and rarely hepatic necrosis.
the neurons. As a result, high frequency discharges are 3. It causes hirsutism, acne and coarsening of facial features.
inhibited with little effect on normal low frequency dis- 4. Phenytoin is a potent microsomal inducer and increases
charges. its own metabolism and also of other drugs.
l At higher concentrations, phenytoin inhibits Ca
21
influx a. It causes osteomalacia due to increased metabolism
into the neuron, reduces glutamate levels and causes of vitamin D.
facilitation of GABA responses b. Phenytoin decreases folate absorption and increases
its excretion causing megaloblastic anaemia.
c. If it is used during pregnancy it causes fetal hydantoin
Therapeutic Uses syndrome: cleft lip, cleft palate, digital hypoplasia, etc.
1. First choice drug in generalized tonic-clonic seizures, d. During higher doses zero order kinetics is ensued,
simple and complex partial seizures slight increase in dose causes marked toxicity.
Q. 2. Sodium valproate Therapeutic Uses

Ans. 1. It is highly effective and first drug of choice in absence
seizures. It is also effective against myoclonic and
l Sodium valproate or valproic acid is a broad-spectrum atonic seizures.
anticonvulsant. 2. Second choice drug in
l It is a branched chain aliphatic carboxylic acid and is
a. generalized tonic-clonic seizures and
more potent in blocking PTZ seizures than in modifying b. simple partial seizures with or without generalization.
maximal electroshock. 3. Alternative or add on drugs: In mania and bipolar illness
it is used as alternative to lithium.
Mechanism of Action
Q. 3. Phenytoin sodium in grand mal epilepsy
l Valproate delays the recovery of Na1 channels from
inactivation like phenytoin and carbamazepine. Ans.
21
l Attenuation of Ca -mediated T current in thalamic
l Phenytoin prolongs the inactivated state of voltage sen-
neurons like ethosuximide. sitive neuronal Na1 channel and it also governs the re-
l Augmentation of release of inhibitory transmitter GABA
fractory period of the neurons.
by inhibiting its degradation and increasing its synthesis. l As a result high frequency discharges are inhibited with
little effect on normal low frequency discharges.

Adverse Effects l It has a stabilizing influence on the neuronal membrane
and thus prevents repetitive detonation of normal brain

l Common side effects related to GIT tract are anorexia, cells during depolarization shift.
vomiting, drowsiness, ataxia and tremor—dose re- l This stabilizing influence consists of a synchronous and
lated unusually large depolarization over which action poten-
l CNS side effects include sedation, ataxia and tremor
tials are superimposed.
l The other adverse effects include skin rashes, alopecia
l At high doses it
and curling of hair. l reduces Ca
21
influx during depolarization.
l A symptomatic rise in serum transaminase is common.
l inhibits glutamate.
l Fulminate hepatitis: Rare but serious and occurs in chil-
l facilitates GABA responses.
dren below 3 years. l prevents intracellular accumulation of Na occurring
1
l Teratogenicity: Neural tube defects in the offspring if
during repetitive firing.
used during pregnancy l Therefore phenytoin sodium is used in grand mal epilepsy.
SHORT NOTES
Q. 1. Phenytoin is contraindicated during pregnancy. l Phenobarbitone raises the seizure threshold and thus
prevents epileptic attacks.
Ans.
l It is used in generalized tonic-clonic seizures and partial
l Phenytoin is a teratogenic drug. When taken during seizures.

pregnancy, phenytoin induces fetal hydantoin syndrome. l It is preferred due to its efficacy and low cost.
l This syndrome is characterized by
1. cleft lip and cleft palate, Q. 3. Carbamazepine

2. hypoplastic phalanges and Ans.
3. microcephaly.
Carbamazepine is an antiepileptic drug chemically related
Q. 2. Phenobarbitone to imipramine.
Ans.
Mechanism of Action
l Phenobarbitone is an important drug of choice in the
treatment of epilepsy. Carbamazepine modifies maximal electroshock seizures
l Phenobarbitone inhibits the neurotransmitory action by as well as raises threshold to PTZ and electroshock
enhancing the GABA receptors thus facilitating them to convulsions. It prolongs inactivated state of Na1
open the chloride ion channels. channel.
Adverse Effects Therapeutic Uses

l Dose-related neurotoxicity—sedation, dizziness, vertigo, l It is highly effective and first drug of choice in absence
diplopia and ataxia seizures.
l Higher doses cause vomiting, diarrhoea, worsening of l Second choice drug in generalized tonic-clonic seizures
seizures. and simple partial seizures.

l Hypersensitivity—rashes, photosensitivity, hepatitis, lupus- l Alternative or add-on drugs in mania and bipolar illness.
like syndrome, leukopenia and rarely agranulocytosis and

aplastic anaemia Q.5. Phenytoin sodium
l Minor fetal malformations
Or,
Therapeutic Uses Diphenylhydantoin sodium
l Epilepsy—generalized tonic-clonic and simple partial Ans.
seizures
l Trigeminal and related neuralgias Phenytoin sodium or diphenylhydantoin sodium is a barbi-
l Manic depressive illness and acute mania turate analogue and is a major antiepileptic drug.
Q. 4. Sodium valproate
Pharmacological Action (Mechanism of
Ans. Action)
Sodium valproate or valproic acid is a broad-spectrum Phenytoin acts by stabilizing the neuronal membrane and
anticonvulsant. thus prevents the spread of seizure discharges.
Mechanism of Action Therapeutic Uses

l Valproate delays the recovery of Na channels from
1
l First choice drug in generalized tonic-clonic seizures,
inactivation and causes attenuation of Ca21-mediated simple and complex partial seizures.
T current in thalamic neurons. l It is second choice to carbamazepine in trigeminal neu-
l Augmentation of release of inhibitory transmitter GABA. ralgia and other neuralgias.

l As an antiarrhythmic in cardiac arrhythmias
Adverse Effects
Adverse Reactions
l Common side effects are anorexia, vomiting, drowsi-
ness, ataxia and tremor—dose-related. l The adverse effects include hypertrophy and hyperpla-
l CNS side effects include sedation, ataxia and tremor. sia of gums, hypersensitivity reactions, osteomalacia.
l The other adverse effects include skin rashes, alopecia l If it is used during pregnancy it causes fetal hydantoin
and curling of hair and teratogenicity. syndrome.
Topic 26
Antiparkinsonian Drugs
LONG ESSAY
Q. 1. Classify the drugs used in parkinsonism and dis- Antiparkinsonian drugs are drugs that help to reduce the
cuss pharmacology and adverse effects of L-DOPA. symptoms of parkinsonism in two ways, either by enhanc-
Ans. ing the dopamine activity or by depressing cholinergic
overactivity.
Classification Pharmacological Actions

I. Drugs that increase dopamine levels i CNS: Hypokinesia, rigidity, tremors improve first, later
i. Dopamine precursor: Levodopa other symptoms like gait, speech, sialorrhoea, mood is
ii. Drugs that release dopamine agonists: Amantadine normalized.
iii. Dopamine agonists: Bromocriptine, pergolide, ii CVS: It causes tachycardia.
pramipexole, ropinirole iii. CTZ: It causes nausea and vomiting.
iv. Inhibit dopamine metabolism: MAO inhibitors, iv. Endocrine: It inhibits prolactin release.
deprenyl (selegiline)
II. Drugs influencing cholinergic receptors
Adverse Reactions
i. Centrally acting anticholinergics: Benztropine, ben-
zhexol, biperidine, trihexyphenidyl i. GIT: Gastrointestinal side effects like nausea, vomiting
ii. Antihistamines (H1 blockers) with anticholinergic ac- and anorexia are common early in the treatment with
tivity: Diphenhydramine, orphenadrine, promethazine l-DOPA. Tolerance to emetic effect develops slowly.
Antiemitics such as domperidone is preferred to control
l-DOPA induced vomiting.
LEVODOPA ii. CVS: Postural hypotension is the commonest side
Levodopa is a dopamine precursor that is converted to effect, which is usually asymptomatic. It can also
dopamine with the help of decarboxylase. cause tachycardia, palpitation, cardiac arrhythmia
and angina.
iii. Abnormal movements: Dyskinesias, tics, tremors and
Mechanism of Action choreoathetoid movements may occur.
l Levodopa crosses blood-brain barrier and is taken up by iv. Alteration in smell and taste sensation
presynaptic terminals of dopaminergic neurons and is v. Behavioural effects like insomnia, agitation, anxiety,
dehydroxylated to dopamine. nightmares, depression, confusion and mania may be
l Levodopa is converted to dopamine in peripheral tissue seen.
and dopamine thus formed acts on heart, blood vessels
and peripheral organs.
SHORT ESSAYS
Q. 1. What is dopamine? Mention one use and route of Mechanism of Action
administration.
l Levodopa crosses blood-brain barrier and is taken up by
Ans. presynaptic terminals of dopaminergic neurons and is
dehydroxylated to dopamine.
l Dopamine is an enzyme whose deficiency results from l Levodopa is converted to dopamine in peripheral tissue
degeneration of nigrostriatal neurons in the basal ganglia. and dopamine thus formed acts on heart, blood vessels
l This deficiency results in parkinsonism, which is char-
and peripheral organs.
acterized by rigidity, tremors, bradykinesia, seborrhoea
and mood changes.
l Though dopamine helps to reduce the symptoms of
parkinsonism, it is not administered directly as it is of
no therapeutical use since it does not cross the blood- l CNS: Hypokinesia, rigidity, tremors improve first, later
brain barrier (BBB). other symptoms like gait, speech, sialorrhoea, mood is
l It is administered as levodopa which crosses the BBB normalized.
and then gets converted to dopamine with the help of l CVS: It causes tachycardia.
decarboxylase. l CTZ: It causes nausea and vomiting.
l Uses: Dopamine in the form of levodopa is an effective l Endocrine: It inhibits prolactin release.
drug of choice in the treatment of idiopathic parkinsonism.

Q. 3. Explain why levodopa is given along with carbidopa.
Q. 2. Levodopa is used in parkinsonism. Ans.
Ans.
Decarboxylase inhibitor, i.e. carbidopa prevents conver-
Levodopa is a dopamine precursor that is converted to do- sion of levodopa to dopamine outside brain by inhibiting
pamine with the help of decarboxylase. DOPA decarboxylase enzyme peripherally. Thus, greater
concentration of levodopa can cross blood-brain barrier 2. Systemic concentration of dopamine is decreased due
and reach its site of action in brain. to which nausea, vomiting and cardiac effects are
Benefits obtained on combining levodopa with carbi- prevented.
dopa are as follows: 3. Pyridoxine cannot increase decarboxylase activity in
1. Doses of levodopa can be reduced up to three-fourth its presence of carbidopa. On–off effect is decreased.
original dose.
SHORT NOTES
Q. 1. Is pyridoxine given with levodopa? l Levodopa crosses blood-brain barrier and there it is
converted to dopamine which helps to treat parkin-
Ans.
sonism.
Pyridoxine enhances decarboxylation of levodopa and re- l Uses: Dopamine in the form of levodopa is an effective
duces the amount of drug available to convert to dopamine drug of choice in the treatment of idiopathic parkinsonism.
to act on CNS. This may result in the need for greater doses
of levodopa for the same desired result. Hence pyridoxine Adverse Reactions
is not given with levodopa.
l GIT: It causes nausea, vomiting and anorexia.
Q. 2. Levodopa l CVS: It causes postural hypotension, palpitation, car-
diac arrhythmia and angina.
Ans.
l Abnormal movements
l Levodopa is a dopamine precursor that is converted to l Behavioural effects: Agitation, anxiety, nightmares,
dopamine with the help of decarboxylase. depression, confusion and mania
Topic 27
Drugs Used in Mental Illness: Antipsychotic

and Antianxiety Drugs
SHORT ESSAYS
Q. 1. Chlorpromazine paucity of through psychomotor slowing, emotional qui-
Ans. Chlorpromazine is a phenothiazine with aliphatic etening, reduction in initiative, tendency to go off to easily
side chain and is the prototype drug. arousable sleep and minimized spontaneous movements.
2 . In a psychotic patient
l Irrational behaviour, agitation and aggressiveness is
reduced.
Mechanism of Action
l Psychotic symptomatology is controlled.
l Chlorpromazine has potent dopamine D2 receptor l Disturbed through and behaviour are gradually nor-
blocking action. malized and anxiety is relieved.
l Antipsychotic action of chlorpromazine is contributed l Hyperactivity, hallucinations and delusions are sup-
to the blockade of dopaminergic receptors in the meso- pressed.
limbic system. l The sedative effect is produced immediately while
antipsychotic effect takes weeks to develop as chlor-

promazine has low potency.
Pharmacological Actions of Chlorpromazine
l Vigilance is impaired while intelligence is not affected.
Central Nervous System l It lowers seizure threshold and can precipitate fits in
untreated epileptics. At higher doses, temperature

1. In normal individuals: Chlorpromazine produces neurolep-
control is knocked off thus body temperature can fall
tic syndrome characterized by indifference to surroundings,
if surroundings are cold.
Chlorpromazine has potent antiemetic action medi-

l l Restores cognitive, affective and motor disturbances.
ated through CTZ. b. Mania: Given IM for 1–3 weeks for rapid control
simultaneously with antimania drugs.
Autonomic Nervous System c. Organic brain syndromes: Used on short-term basis
to avoid mental confusion, hypotension and precipi-
Chlorpromazine has potent adrenergic blocking activity tation of seizures.
and weak anticholinergic property. 2 . Anxiety: Used only in cases with psychotic basis or
those not responding to antianxiety drugs.
Local Anaesthetic 3. Antiemetic: Useful in drug and disease-induced vomit-
ing at dose lower than antipsychotic dose
Chlorpromazine is a potent local anaesthetic. 4. Other uses
l To potentiate hypnotics, analgesics and anaesthetics
Cardiovascular System in anaesthetic practice

l Used parenterally in intractable hiccups.
l Chlorpromazine by its central and peripheral action on l In tetanus as secondary drug to achieve muscle relaxation
sympathetic tone produces postural hypotension accom- l Alcoholic hallucinations, Huntington’s disease and
panied by reflex tachycardia especially after parenteral Gilles de la Tourette’s syndrome are rare indications.
administration.
l In high doses it directly depresses the heart and shows Q. 2. Neuroleptanalgesia
ECG changes in form of QT prolongation and suppres-
sion of T-wave. Ans.
l Due to its membrane stabilizing action, it also produces
l Neuroleptanalgesia is a state of analgesia characterized
antiarrhythmic action. by quiescence, psychic indifference and intense analge-
sia without loss of consciousness.
Skeletal muscle l It is obtained when 0.05 mg fentanyl and 4–6 mL droperi-
dol (2.5 mg/mL) are combined infused over 10 minutes.

Chlorpromazine through its action on basal ganglia or me-
dulla oblongata reduces certain types of spasticity though Advantages: Patient cooperative though he or she is drowsy.
they do not have any direct effect on skeletal muscles or Disadvantages: Respiratory depression, fall in BP and
neuromuscular transmission. heart rate are seen.
Endocrine Indications
l Chlorpromazine increases the prolactin release by 1 . Endoscopies
blocking the inhibitory action of dopamine on pitu- 2. Burn dressings
itary lactotropes resulting in galactorrhoea and gynae- 3. Angiographies
comastia. 4. Minor surgeries
l Gonadotropin secretion is reduced but amenorrhoea and
infertility occur only occasionally. Q. 3. Classification of antipsychotic drugs

l ACTH release in response to stress is diminished; thus Ans.
corticosteroid level fails to increase in stress.
l Urinary volume may be increased due to decreased Antipsychotic drugs are the drugs having a salutary thera-
ADH release and direct action on kidney tubules. peutic effect in psychoses.
Therapeutic Uses Classification

1. Psychoses 1. Phenothiazines
a. Schizophrenia a. Aliphatic side chain: Chlorpromazine, triflupromazine
l Chlorpromazine has definite therapeutic effect in b. Piperidine side chain: Thioridazine
all forms of functional psychoses and used pri- c. Piperazine side chain: Trifluoperazine, fluphenazine
marily in them. Chlorpromazine is preferred in 2. Butyrophenones: Haloperidol, trifluperidol, droperidol,
agitated, combative and violent patients. penfluridol
l Produces wide range of symptomatic relief of 3. Thioxanthenes: Thiothixene, flupenthixol
positive symptoms, like hallucinations, delusions, 4. Other heterocyclics: Pimozide, loxapine, reserpine
restlessness, insomnia, anxiety, fighting, aggres- 5. Atypical neuroleptics: Clozapine, risperidone, olanzap-
sion than negative symptoms. ine, quetiapine, aripiprazole, ziprasidone
SHORT NOTES
Q. 1. Chlorpromazine l Alcoholic hallucinations, Huntington’s disease and
Gilles de la Tourette’s syndrome are rare indications.
Ans. Chlorpromazine is a phenothiazine with aliphatic
side chain. Q. 2. Mention two uses and two adverse effects of chlor-
promazine.
Mechanism of Action Ans.
Antipsychotic action of chlorpromazine is contributed to Chlorpromazine is a phenothiazine with aliphatic side chain.
potent dopamine D2 receptor blocking action in the limbic
system and in mesocortical area. Therapeutic Uses
1. Used in treating psychoses like schizophrenia, mania
Therapeutic Uses and various organic brain syndromes. Chlorpromazine
1. Psychoses has definite therapeutic effect in all forms of functional
a. Schizophrenia: Chlorpromazine has definite thera- psychoses.
peutic effect in all forms of functional psychoses and 2. Restores cognitive affective and motor disturbances.
used primarily in them. Restores cognitive affective 3. Used in anxiety cases with psychotic basis or those not
and motor disturbances. responding to antianxiety drugs.
b. Mania: Given IM for 1–3 weeks for rapid control 4. As an antiemetic in drug and disease-induced vomiting
simultaneously with antimania drugs. at dose lower than antipsychotic dose.
c. Organic brain syndromes: Used on short-term basis
to avoid mental confusion, hypotension and precipi- Adverse Effects
tation of seizures
2. Anxiety: Used only in cases with psychotic basis or l Central nervous system
those not responding to antianxiety drugs 1. Drowsiness, lethargy, mental confusion
3. Antiemetic: Useful in drug and disease induced vomit- 2. Increased appetite and weight gain
ing at dose lower than antipsychotic dose 3. Aggravation of epilepsy
4. Other uses 4. Development of tolerance
l To potentiate hypnotics, analgesics and anaesthetics l Adrenergic blockade: Produces postural hypotension,
l Intractable hiccups palpitation and inhibition of ejaculation

l In tetanus as secondary drug to achieve muscle l Anticholinergic action results in dry mouth, blurring of
relaxation vision constipation, urinary hesitancy.
Topic 28
Opioid Analgesics and Antagonists

LONG ESSAY
Q. 1. Classify narcotic analgesic group of drugs and Classify narcotic analgesics. Describe the actions, thera-
write about morphine. peutic uses and toxic effects of morphine.
Or, Or,
Classify narcotic analgesics. Discuss the uses and dan- What are narcotic analgesics? Describe the pharmaco-
gers of morphine. Name morphine antagonists available. logical actions, uses and toxicity of opium alkaloids.
Or, Ans.
Opioid analgesics are the analgesics which are either l Rate and tidal volume are both decreased and in poi-
derived from the opium or resemble opium in action. soning death occurs by respiratory failure. There is
indifference to breathing.
l Cough suppression by direct action on cough centre
CLASSIFICATION in the medulla.
a. Natural opium alkaloids: Morphine, codeine, thebaine, v. Temperature regulating centre: It is depressed. Hypo-
papaverine and noscapine thermia occurs in cold surroundings.
b. Semisynthetic opioids: Diacetylmorphine (heroin), vi. Vasomotor centre: It is depressed at higher doses and
pholcodine, hydromorphone and oxymorphone contributes to the fall in BP.
c. Synthetic opioids: Pethidine (meperidine), fentanyl,
methadone, dextropropoxyphene, tramadol, ethohepta- II. Stimulant Effects
zine, alfentanil, sufentanil and remifentanil
i. Nausea and vomiting
l Morphine appears to sensitize the CTZ to vestibular
MORPHINE and other impulses.
Morphine is a natural opioid and the principal alkaloid in l Nausea and vomiting occur as side effects specially if
opium. stomach is full and the patient stands or moves about.

However larger doses depress vomiting centre directly.
ii. Miosis: By central stimulating action on Edinger-West-
Pharmacology Actions phal nucleus of third nerve, morphine causes constriction
a. Central Nervous System of pupils (miosis) and also decreases intraocular tension.
iii. Vagal centre: It is stimulated and can cause bradycardia.
Morphine has site specific depressant and stimulant actions. iv. Certain cortical areas and hippocampal cells: Muscular
rigidity and immobility is consistently manifested at
I. Depressant Actions high doses. Excitation is seen in occasional individuals.
i. Analgesia: Morphine is a strong analgesic.

l Dull, poorly localized visceral pain is relieved better
b. Neuroendocrine
than sharply defined somatic pain. l Influence of hypothalamus on pituitary is reduced. As a
l Degree of analgesia increases with increasing dose. result FSH, LH, ACTH levels are reduced while prolac-
l Nociceptive pain arising from stimulation of pe- tine and GH levels are increased.
ripheral pain receptors is relieved better than neu- l Sex hormone and corticosteroid levels are lowered in
rotic pain due to inflammation or damage of neural the short term but tolerance develops in the long term.
structures. Few chronic abusers suffer from infertility.
l Intrathecal injection of morphine causes segmental l Morphine can release ADH and reduce urine volume.
analgesia without affecting other modalities.
l Release of substance P from primary pain afferents
in the spinal cord and its postsynaptic action on dor- c. Cardiovascular System
sal horn neurons is inhibited by morphine. l Morphine causes vasodilatation due to the following:
ii. Sedation: Drowsiness and indifference to surroundings i. Direct action on decreasing tone of blood vessels
as well as to own body occurs without motor incoordi- ii. Histamine release
nation, ataxia or apparent excitement. Higher doses iii. Depression of vasomotor centre (VMC)
progressively cause sleep and coma. l Postural hypertension and fainting occurs due to impair-
iii. Mood and subjective effects (euphoria) ment of vascular reflexes but therapeutic doses causes
l The mood and subjective effects are prominent and little change in BP.
are called euphoria. Morphine has a calming effect. l Intracranial tension tends to rise as a consequence of
l There is loss of apprehension, feeling of detachment, CO2 retention leading to cerebral vasodilatation.
lack of initiative; limbs feel heavy and body warm,
mental clouding and inability to concentrate.
l However patients in pain or anxiety and addicts spe-
d. Gastrointestinal Tract
cially perceive it as pleasure. Morphine causes constipation by
iv. Respiratory depression l acting directly on intestines and the CNS action in-
l Morphine depresses respiratory centre in a dose- creases tone and segmentation but decreases propulsive
dependent manner. movements.
l decrease in all gastrointestinal secretions, reduction in l Reducing preload on heart due to vasodilatation and
transfer of water and electrolytes from mucosa to lumen. peripheral pooling of blood
l Tending to shift blood from pulmonary to systemic
circuit, relieves pulmonary congestion and oedema.

e. Other Smooth Muscles
l Allays air hunger by depressing respiratory centre.
i. Biliary tract: Morphine causes spasm of sphincter. l Cuts down sympathetic stimulation by calming the
Intrabiliary pressure is increased. patient, reduces cardiac work.

ii. Urinary bladder: Morphine increases tone of both detrusor a. To relieve pulmonary oedema due to infarction of
and sphincter. Contractions of ureter are also increased. lung and other causes
iii. Uterus: It may prolong labour but it is clinically insig- b. In balanced anaesthesia and surgical analgesia
nificant. c. For relief of anxiety, apprehension in MI and in-
iv. Bronchi: Morphine releases histamine which causes ternal bleeding
bronchoconstriction.
Contraindications
f. Autonomic Nervous System
l Infants and the elderly are more susceptible to the respi-
Morphine causes mild hyperglycaemia due to central sym- ratory depression by morphine.
pathetic stimulation. l In patients with respiratory insufficiency like emphy-
sema, pulmonary fibrosis, cor pulmonale and bronchial

asthma, it can precipitate an attack by its histamine re-
Therapeutic Uses
leasing action.
a. As analgesic: Morphine is indicated in severe pain of l Head injury: By retaining CO2 it increases intracranial
any type. tension, which will add to that, caused by head injury
l It is specially indicated in traumatic, visceral, isch- itself.
aemic, postoperative, burn, cancer pain and like. l Even therapeutic doses can cause marked respiratory
l It should be promptly given in myocardial infarction to depression in these patients.
allay apprehension and reflex sympathetic stimulation. l Vomiting, miosis and altered mentation produced by
l It may prevent neurogenic shock and other auto- morphine interfere with assessment of progress in head
nomic effects of excruciating pain. injury cases.
l 10–50 mg orally, 10–15 mg IM or SC or 2–6 mg IV, l Hypotensive states and hypovolaemia exaggerate fall in
2–3 mg as epidural or intrathecal injection BP due to morphine.
b. Preanaesthetic medication: l0 mg of morphine IM to l In undiagnosed acute abdominal pain morphine can
allay anxiety and apprehension of the operation, produce aggravate diverticulitis, biliary colic, pancreatitis, etc.
pre- and postoperative analgesia, smoothen induction, l Elderly male: Chances of urinary retention are high.
reduce the dose of anaesthetic required and supplement l Hypothyroidism, liver and kidney diseases are more
poor analgesics or weak anaesthetics likely to develop.
c. In acute left ventricular failure (cardiac asthma) mor- l Unstable personalities are more liable to continue its
phine affords dramatic relief by the following: use and become addicted.
SHORT ESSAYS
Q. 1. Morphine is contraindicated in head injury. l Vomiting, miosis and altered mentation produced by
Explain. morphine interferes with assessment of progress in head
injury cases.
Ans. Morphine is contraindicated in head injury because
of the following:
Q. 2. Pentazocine
l By retaining CO2 it increases intracranial tension, which Ans.
will add to that tension caused by head injury itself.
l Even therapeutic doses can cause marked respiratory l Pentazocine is a kappa receptor agonist which has lesser
depression in these patients. addiction liability compared to morphine.
l Compared to morphine, the sedation, and respiratory Onset of action Low Rapid
depression are less marked while BP and heart rate are
Duration of action Longer (4–6 h) Shorter (3–4 h)
increased.
l Pentazocine can be given orally (50–100 mg) or intra- Suppression of Effective Not effective
cough
muscularly (30–60 mg).
Spasmodic action Marked miosis, Less marked mio-
on smooth muscle constipation and sis, constipation
Uses urinary retention and urinary reten-
tion
Pentazocine is the preferred analgesic for postoperative and
chronic pain. Local anaesthetic Absent Present
action
Heart rate Bradycardia Tachycardia
Adverse Effects
Status in Contraindicated Safer
1 . Dizziness, sedation, nausea, sweating and halluci- asthmatics
nations Oral absorption Unreliable Well absorbed
2. Sterile abscess at the site of the injection
Metabolism In liver by In liver by
glucuronide hydrolysis and
Q. 3. Dextropropoxyphene
conjugation demethylation
Ans. Tolerance and High and devel- Low and develops
physical depen- ops rapidly slowly
l Dextropropoxyphene is a congener of methadone and is dence
structurally similar to it.
Withdrawal Develop slowly Develop rapidly
l It binds to the opioid receptor and produces pharmaco-
symptoms and the auto-
logical effects similar to morphine, though it has less nomic distur-
constipating effect. bances are less
l Actions and side effects are similar to codeine, but less marked
potent than codeine when given orally. Route of IV, IM, SC Oral, IV
l The side effects are nausea, constipation, sedation, administration
abdominal pain, etc. Therapeutic uses 1. Analgesic in 1. Postoperative
l It is irritating when injected parenterally and has equal traumatic, vis- or chronic pain,
abuse potential as morphine. ceral, ischaemic labour pain
l It is used orally in mild to moderate dose usually in pain, postopera-
tive,
combination with aspirin as they have synergistic
burn and cancer
action: Dextropropoxyphene 32 mg 1 aspirin 600 mg pain
Q. 4. Morphine is used in acute left ventricular failure. 2. Preanaesthetic 2. Preanaesthetic

medication medication
Ans. Morphine is used in acute left ventricular failure (car- 3. Balanced an- 3. Balanced
diac asthma) as it affords dramatic relief by the following: aesthesia and anaesthesia
surgical analgesia and surgical
l Reducing preload on heart due to vasodilatation and analgesia
peripheral pooling of blood
4. Antianxiety
l Tending to shift blood from pulmonary to systemic
and antiappre-
circuit, relieves pulmonary congestion and oedema. hension
l Allays air hunger by depressing respiratory centre.
5. Acute left ven-
l Cuts down sympathetic stimulation by calming the
tricular failure
patient, reduces cardiac work.
6. Cough and
diarrhoea
Q. 5. Compare morphine and pethidine.
Ans. Both morphine and pethidine are opioid analgesics.
Q. 6. Rationale of using imipramine in mental depression
Parameters to
Be Compared Morphine Pethidine Ans.
Source Natural opium Synthetic
1. Imipramine is a tricyclic antidepressant used for the
alkaloid
treatment of mental depression.
2. The patient responds to the treatment 2–3 weeks after 3. They cause an elevation in the mood of the patient and
the initiation of dosage. It blocks the reuptake of nor- normalize the sleep patterns. The patient shows more
adrenaline or 5-hydroxytryptamine and prolongs their interest in the surroundings.
action on the CNS.
SHORT NOTES
Q. 1. Pentazocine l For relief of anxiety, apprehension in MI and internal
bleeding
Ans.
l Pentazocine is an opioid agonist-antagonist. Q. 4. Mention two contraindications of morphine.

l Pentazocine can be given orally in dose of 50–100 mg Ans.
or intramuscularly in dose of 30–60 mg.
l Uses: Pentazocine is preferred analgesic for postopera- Morphine is contraindicated in the following:
tive and chronic pain. 1. Infants and the elderly: As they are more susceptible to
l Adverse effects the respiratory depression by morphine.
1. Dizziness, sedation, nausea, sweating, hallucinations 2. Patients with respiratory insufficiency like emphysema,
2. Sterile abscess at the site of the injection pulmonary fibrosis, cor pulmonale
3. In bronchial asthma: It can precipitate an attack by its
Q. 2. Codeine histamine releasing action.
Ans. Q. 5. Write the depressant CNS pharmacological actions
l Codeine is a natural opium alkaloid that is less potent of morphine.
compared to morphine as an analgesic. Ans. Morphine has site specific depressant and stimulant ac-
l It produces lesser respiratory depression and constipat- tions. The CNS depressant actions of morphine are as follows:
ing effect compared to morphine. It is also has lesser
tendency for addiction liability. 1 . Analgesia: Morphine is a strong analgesic.
l Codeine is used as antitussive and is usually combined 2. Sedation: Drowsiness and indifference to surroundings,
with paracetamol for analgesic effect. higher doses progressively cause sleep and coma.
l It is well absorbed orally and has a duration of action of 3. Mood and subjective effects (euphoria): Morphine has a
4–6 h. calming effect.
4. Respiratory depression: Depression of temperature reg-
Q. 3. Therapeutic uses of morphine ulating centre and vasomotor centre which contributes
to the fall in BP.
Ans.
l As analgesic: Morphine is indicated in severe pain of Q. 6. Four drugs used in mental depression
any type. It is specially indicated in traumatic, visceral, Ans.
ischaemic, postoperative, burn, cancer pain, in myocar-
dial infarction. Drugs used for the treatment of mental depression are
l Preanaesthetic medication—10 mg IM to allay anxiety called antidepressants.
and apprehension of the operation, produce pre- and Various drugs used as antidepressants are classified as
postoperative analgesia, smoothen induction, reduce the follows:
dose of anaesthetic required and supplement poor anal- 1. Tricyclic antidepressants (TCAs): Imipramine, desip-
gesics or weak anaesthetics. ramine, amitriptyline, doxepin
l Acute left ventricular failure (cardiac asthma)— 2. Selective serotonin (5-HT) reuptake inhibitors (SSRIs):
morphine affords dramatic relief. Fluoxetine, fluvoxamine, paroxetine
l To relieve pulmonary oedema due to infarction of lung 3. Monoamine oxidase inhibitors (MAO) inhibitors: Phen-
and other causes elzine, tranylcypromine
l In balanced anaesthesia and surgical analgesia 4. Atypical antidepressants: Trazodone, bupropion, mianserin
Topic 29
CNS Stimulants and Cognition Enhancers

SHORT ESSAYS
Q. 1. Classify neuroleptic drugs. l Chlorpromazine is the first effective phenothiazine neu-
roleptic.
Ans. Neuroleptics are also known as antipsychotics or ata-
l They have very high therapeutic index.
ractics or major tranquilizers. These drugs have salutary
therapeutic effect in psychosis.
Actions
They are classified as follows:
1. Phenothiazines l Causes emotional quietening and psychomotor slowing
a. Aliphatic side chain: Chlorpromazine, triflu- in psychotics.
promazine l They have antiemetic effect, anticholinergic effect and
b. Piperidine side chain: Thioridazine weak antihistaminic and antiserotonin action.

c. Piperazine side chain: Trifluoperazine, fluphenazine, l They cause hypothermia, hypotension and failure of
thioproperazine ejaculation.
2. Butyrophenones: Haloperidol, trifluperidol, droperidol
3. Thioxanthenes: Chlorprothixene, thiothixene, flupen- Therapeutic Uses
thixol
4. Others: Pimozide, molindone, sulpiride, loxapine, re- l Schizophrenia and allied psychiatric disturbances
serpine l As a preanaesthetic medication
5. Atypical neuroleptics: Clozapine, risperidone l Neuroleptanalgesia
l To control a wide range of drug and disease-induced
Q. 2. Neuroleptics vomiting
l To treat intractable hiccoughs
Ans.
l Neuroleptics are antipsychotics or major tranquilizers Side Effects

used to treat patients of psychosis or schizophrenia.
l The pharmacological actions of these neuroleptics are l Parkinson-like syndrome
due to their ability to block dopamine receptors in spe- l Tardive dyskinesia
cific areas of brain. l Anticholinergic and adrenergic blocking effect
SHORT NOTES
Q. 1. Analeptic drugs l Postictal depression adds to existing depression which
may worsen the condition.
Ans.
Analeptics are the drugs which stimulate respiration and Therapeutic Uses
have resuscitative in fainting or coma.
The role of analeptics in therapeutics is very limited. They
are used in
Toxic Effects l hypnotic drug poisoning,
l The patients may get convulsions still in coma if he is l suffocation on drowning,
on analeptic therapy. l respiratory failure due to removal of hypoxic drive and
l apnoea in premature infants.

Part VIII
Cardiovascular Drugs
Topic 30
Drugs Affecting Renin-Angiotensin System

and Plasmakinins
SHORT NOTES
Q. 1. Enalapril l Hyperkalaemia
Ans. l Alteration in the taste
l Skin rashes, headache, nausea, abdominal pain
l Enalapril is an angiotensin converting enzyme inhibitor. l Hypotension
It is a prodrug and is long-acting (24 h).
l It prevents the formation of angiotensin II and raises Q. 2. Angiotensin antagonists
bradykinin levels which contributes to the fall in BP. Ans.
l It maintains adequate blood flow to the vital organs like
kidney, brain and heart. l Angiotensin antagonists are drugs that inhibit the action
l It is well absorbed in the body. of angiotensin receptors like AT1 and AT2. For example:
Losartan is the most widely used angiotensin inhibitor.
l They relax smooth muscles, promotes salt and water
Uses
excretion and reduces plasma volume.
l Hypertension l Compared to ACE inhibitors, angiotensin antagonists
l Congestive cardiac failure show no increase in bradykinin levels and so the adverse
l Myocardial infarction effects are lesser. They include hypotension and hyper-
kalaemia.
l Uses: They are used in the treatment of hypertension.
Adverse Effects
l Persistent dry cough
Topic 31
Cardiac Glycosides and Drugs for CHF

SHORT ESSAYS
Q. 1. Therapeutic uses and adverse effects of digoxin. l It is the most widely used cardiac glycoside.
Ans. l Mechanism of action: It acts by inhibiting the Na1/K1
ATPase present on the cardiac myocytes. This causes an
l Digoxin is a cardiac glycoside obtained from the seeds increase in the intracellular sodium and calcium. The extra
of Strophanthus gratus (digitalis or foxglove plant). calcium causes contraction with greater force and velocity.
Uses 3. CNS effects: These include headache, fatigue, confu-

sion, hallucinations, blurred vision and gynaecomastia.
1. Cardiac arrhythmias: Atrial fibrillation, atrial flutter,
paroxysmal supraventricular tachycardia. Q. 2. Digoxin is used in congestive cardiac failure.
2. Digoxin therapy is indicated in patients with severe left
ventricular systolic dysfunction after initiation of ACE Ans.
inhibitor and diuretic therapy.
l Congestive cardiac failure is a condition where the heart
3. Digoxin major indication is congestive cardiac failure
is not able to provide enough blood supply to meet the
with atrial fibrillation.
demand of the body.
l Digoxin is used in the treatment of congestive cardiac
Adverse Effects failure that cannot be controlled with diuretics or vaso-

dilators.
Digitalis toxicity is one of the most commonly encountered
l Digoxin improves cardiac performance: Administration of
adverse drug reactions. Types of adverse effects include the
digoxin shifts the ventricular function curve towards nor-
following:
mal. Increased contractility leads to increased cardiac out-
1. Cardiac effects: Arrhythmias like extrasystoles, brady-
put and decreased sympathetic reflexes and vascular tone
cardia, pulse bigeminy, AV block
cause a decrease in the ventricular end diastolic pressure.
2. GIT effects: Anorexia, nausea and vomiting are com-
l It restores the cardiac output and relieves congestion
monly encountered adverse effects.
and thereby reduces morbidity and mortality.
SHORT NOTES
Q. 1. Digitoxin down the AV node and bundle of hiss.
l It increases effective refractory period of AV node by
Ans.
direct vagomimetic and antiadrenergic action. Therefore,
Digitoxin is a cardiac glycoside obtained from the seeds of digoxin is the drug of choice for controlling ventricular
Strophanthus gratus and is the most widely used cardiac rate in atrial fibrillations.
glycoside.
Q. 3. Therapeutic uses of digoxin
Pharmacokinetics Ans.
1 . It has a plasma half-life of 5–7 days. Digoxin is the most widely used cardiac glycoside because
2. Its onset of action is in about 30–120 min. it has favourable pharmacokinetic properties.
Uses Therapeutic Uses

1. Cardiac arrhythmias: Atrial fibrillation, atrial flutter, 1. Cardiac arrhythmias: Atrial fibrillation, atrial flutter,
paroxysmal supraventricular tachycardia paroxysmal supraventricular tachycardia
2. Congestive cardiac failure 2. Congestive cardiac failure: Digoxin is used in the treat-
ment of congestive cardiac failure that cannot be con-
trolled with diuretics or vasodilators. Digoxin improves
Adverse Effects cardiac performance in the dilated failing patient. It
1. Cardiac effects: Arrhythmias like extrasystoles, brady- restores the cardiac output and relieves congestion.
cardia, pulse bigeminy, AV block
2. Extracardiac effects: Anorexia, nausea, vomiting, diar- Q. 4. Write the cardiac toxicity of digoxin.
rhoea, weakness, confusion, hallucinations, blurred vision Ans.
and gynaecomastia
l Digoxin has a low safety threshold and has high incidence
Q. 2. Rationale of using digoxin in atrial fibrillation of adverse effects.
l Digoxin produces cardiac toxicity characterized by ar-
Ans.
rhythmias like extrasystoles, bradycardia, pulse bigem-
l Digoxin reduces ventricular rate in atrial fibrillation by iny, AV block—ventricular tachycardia and fibrillation.
decreasing the number of impulses that are able to pass l Cardiac toxicity is enhanced by hypokalaemia.
Treatment 3 . Arrhythmias are treated with IV phenytoin.

4. Bradycardia is treated with atropine and supraventricu-
1 . Stop administration of digoxin.
lar arrhythmias with propranolol.
2. Oral or parenteral potassium supplements are administered.
Topic 32
Antiarrhythmic Drugs
SHORT NOTES
Q. 1. Why procainamide is preferred to procaine? Various uses of calcium channel blockers are as follows:
Ans. 1. Angina pectoris: It is useful in both types of angina, i.e.
classical and variant angina.
l Procainamide is a derivative of procaine. 2. Hypertension: They are first line drugs in hypertension.
l It is preferred to procaine as it has a weak anticholinergic Calcium channel blockers decrease total peripheral resis-
action. It has antiarrhythmic action while procaine has tance and hence decreases BP.
only local anaesthetic effect. 3. Arrhythmias: Calcium channel blockers are preferred in
l It is better tolerated compared to procaine. supraventricular tachycardia.
4. Calcium channel blockers are also used in hypertensive
Q. 2. Verapamil emergencies.
Ans.
Q. 4. Classification of antiarrhythmic drugs
Verapamil is a phenylalkylamine that acts as a calcium Ans.
channel blocker.
Antiarrhythmic drugs were classified by Vaughan Williams
based on the cardiac cycle as follows:
Mechanism of Action
1. Class I: Sodium channel blockers
l It blocks all type of calcium channels and decreases a. Prolong repolarization: Quinidine, procainamide,
availability of calcium ions; thus causing relaxation of disopyramide
smooth muscle cell or cardiac cell. Effect is more on b. Shorten repolarization: Lignocaine, mexiletine,
arterioles and less on veins. Negative, chronotropic, phenytoin
ionotropic and dromotropic action. c. Little or no effect on repolarization: Encainide,
l Calcium channel blockers inhibit calcium movement flecainide
inside cell in depolarization phase, thus inhibiting con- 2. Class II: b-adrenergic blockers
traction of cardiac muscle. Cardiac work and oxygen a. Reduce sympathetic tone: Propranolol, acebutolol,
consumption is decreased. esmolol
l Calcium channel blockers inhibit refractory period of 3. Class III: K1 channel blockers
AV node, decrease SA nodal discharge, suppress ecto- a. Prolong repolarization: Amiodarone, sotalol
pic foci, produce antiarrhythmic action. 4. Class IV: Ca21 channel blockers
a. Prolong conduction and refractoriness (especially in
Q. 3. Uses of calcium channel blockers SA and AV nodes): Verapamil, diltiazem
Ans.
Topic 33
Antianginal and Other Anti-ischaemic Drugs

LONG ESSAY
Q. 1. Classify antianginal drugs. Describe the pharma- l There is reduced availability of active phosphorylated
cological actions of nitrates, their clinical uses and side MLCK.
effects. l Hence myosin is not activated and it fails to interact
Ans. with actin, as a result contraction does not occur.

The mechanism of action of nitrates can be summarized as
The antianginal drugs are classified as follows:
follows:
a . Organic nitrates
l Short-acting: Glycerol trinitrate (nitroglycerin)
Nitrates
l Long-acting: Isosorbide dinitrate, isosorbide mononi- Denitrated in the smooth muscle
trate, erythrityl tetranitrate, pentaerythritol tetranitrate cell and release
b
. b-blockers: Propranolol, metoprolol, atenolol, acebutolol Nitric oxide
c. Calcium channel blockers: Amlodipine, verapamil, dil-
tiazem, nifedipine, felodipine, nitrendipine, nicardipine, stimulates
lacidipine Guanylyl cyclase
d
. Potassium channel openers: Nicorandil ↓
e. Others: Dipyridamole, trimetazidine, oxyfedrine Increased cGMP
↓
Dephosphorylation of myosin light chain
ORGANIC NITRATES (Reduced Ca+ concentration in the cytosol)
l Organic nitrates are prodrugs and they include short- ↓
acting drugs like glycerol trinitrate and long-acting drugs Relaxation of vascular smooth muscle fibres
like isosorbide dinitrate, isosorbide mononitrate, erythri-
tyl tetranitrate and pentaerythritol tetranitrate. Mainly venodilation Arterial dilation Dilatation of coronary vessels
l The only major action of nitrates is direct nonspecific
smooth muscle relaxation. They are mainly venodila-

tors, but also cause arteriolar dilatation and as a result Adverse Effects
reduce both preload and after load. Adverse affects are mostly due to vasodilatation and are as
l Since nitroglycerin tablet disintegrates in liver its bio- follows:
availability is decreased but when it is kept under l Fullness in head, throbbing headache, some degree of
tongue it is well absorbed from buccal mucosa. So, tolerance on continued use
when nitroglycerin tablet is given sublingually it is l Flushing, weakness, sweating, palpitation, dizziness and
more effective. fainting. These are mitigated by lying down and accentu-
ated by erect posture and alcohol.
l Methemoglobinemia and reduced O2 carrying capacity
Mechanism of Action
of blood in severe anaemia
l Nitrates decrease coronary vasoconstriction or spasm l Rashes are rare though relatively more common with
and increase perfusion of myocardium by relaxing coro- pentaerythritol tetranitrate.
nary arteries.
l Organic nitrates are rapidly denitrated enzymatically in
the smooth muscle cell. This causes relaxation of the Therapeutic Uses
muscle and there is release of reactive-free radical nitric a. Angina Pectoris
oxide (NO) that activates cytosolic guanylyl cyclase.
l There is increased intracellular cGMP and Ca
21
entry is l Nitrates are effective in exertional and Prinzmetal’s
reduced. angina, i.e. classical as well as variant angina.
l For aborting or terminating an anginal attack, sublin-
l This causes dephosphorylation of myosin light chain
kinase (MLCK) through a cGMP-dependent protein gual nitroglycerin tablet (0.5 mg) or spray (0.4–0.8 mg)
kinase. or isosorbide dinitrate (5–10 mg) is taken on as and
when required basis.
l Glycerol trinitrate (nitroglycerin) produces relief within of necrosis by favourably altering balance in the marginal
3 min in 75% of patients. The rest may require another partially ischaemic zone by reducing cardiac work.
dose or take longer time. l They do not alter the mortality but are used for relief of
l They increase exercise tolerance and postpone ECG angina.
changes of ischaemia.
l Longer acting formulations of glycerol trinitrate or
other nitrates are used orally on regular schedule for d. Interventional Cardiac Procedures
chronic prophylaxis. Glycerol trinitrate is used as adjuvant therapy to dilate
l Even transdermal patches of glycerol trinitrate contain- coronaries in percutaneous coronary angioplasty, thrombo-
ing 5–10 mg of the drug are available. One patch is lytic therapy of acute MI, etc.
applied for 14–16 h per day.
l The dosage of various drugs for chronic prophylaxis:
1. Glycerol trinitrate: 5–10 mg e. Biliary Colic

2. Isosorbide dinitrate: 20–40 mg Sublingual glycerol trinitrate or isosorbide dinitrate re-
3. Isosorbide 5 mononitrate: 20–40 mg lieves the biliary colic produced due to disease states or
4. Erythrityl tetranitrate: 15–60 mg morphine.
5. Pentaerythritol tetranitrate: 80 mg
Six to eight drug-free hours are advised to prevent develop-
ment of tolerance and dependence. f. Oesophageal Spasm
l Sublingual glycerol trinitrate promptly relieves pain.
b. Congestive Cardiac Failure and Acute Left l Nitrates taken before a meal facilitate feeding in
oesophageal achalasia by reducing oesophageal tone.
Ventricular Failure
l Nitrates afford relief by causing venous pooling of blood
that reduces venous return (preload). This in turn de-
g. Cyanide Poisoning
creases end diastolic volume. This causes an improvement l Nitrates generate methaemoglobin, which has high
in left ventricular function by Laplace’s law and regres- affinity for cyanide radical and forms cyanomethae-
sion of pulmonary congestion. moglobin.
l Preparation of choice is 5–10 mg/min IV infusion of l Then sodium thiosulphate is given to prevent dissocia-
glycerol trinitrate for emergency use. tion and release of cyanide by forming sodium thiocya-
nate which is poorly dissociable and is excreted in
urine.
c. Myocardial Infarction
l The antidote should be repeated as required. Thus cyto-
l IV infusion of glycerol trinitrate started soon after the chrome and other oxidative enzymes are protected from
atrial occlusion, prevents tachycardia and reduces the area cyanide.
SHORT NOTES
Q. 1. Classify drugs used in treatment of angina pectoris. b. Benzothiazepine: Diltiazem
c. Dihydropyridines: Nifedipine, felodipine, amlodipine,
Or,
nitrendipine, nimodipine, lacidipine
List three groups of drugs used in angina pectoris with 4 . Potassium channel openers: Nicorandil
one example for each group. 5. Others: Dipyridamole, trimetazidine, oxyfedrine
Ans. Q. 2. Nifedipine
Drugs used in the treatment of angina pectoris are classified Ans.
as follows:
1. Nitrates Nifedipine is dihydropyridine, a class of calcium channel
a. Short-acting: Glycerol trinitrate (GTN) or nitroglycerine blockers (CCBs) which blocks voltage sensitive calcium
b. Long-acting: Isosorbide dinitrate (short-acting by channels.
sublingual route), isosorbide mononitrate, erythrityl
tetranitrate, pentaerythritol tetranitrate Mechanism of Action
2. b-blockers: Propranolol, metoprolol, atenolol
3. Calcium channel blockers l CCBs cause relaxation of smooth muscle by decreasing
a. Phenylalkylamine: Verapamil intracellular availability of Ca21.
l Nifedipine releases NO from the vascular endothelium Other uses: Nifedipine is an alternative drug for pre-
and inhibit cAMP-phosphodiesterase resulting in raised mature labour.
smooth muscle cAMP.
Contraindications
Action on Heart
l Myocardial inadequacy CCF
l In the working atrial and ventricular fibres Ca21 l Conduction defects, sick sinus
moves in during plateau phase of action potential and l IHD, post-MI cases
it releases more Ca21 from sarcoplasmic retinaculum l Left ventricular hypertrophy
and causes contraction through binding to troponin l Males with prostate enlargement
and allowing interaction of myosin with actin. Thus, l Gastroesophageal reflux
nifedipine has negative inotropic action.
l The overriding action of nifedipine is arteriolar. The total Q. 3. Calcium channel blockers in cardiovascular
peripheral resistance decreases and BP falls. Reflex sym- disorders
pathetic stimulation of heart predominates and causes Ans.
tachycardia, increased cardiac contractility and cardiac
output. As a net result coronary flow is increased. Calcium channel blocking agents are the drugs which block
l It also has mild natriuretic action but does not produce voltage sensitive calcium channels.
significant diuresis. They have wide application in the diseases of cardiovas-
cular system. They are used as antiarrhythmic agents, anti-
Pharmacokinetics anginal drugs and antihypertensives.
l The bioavailability is 30–60%.

l All are highly plasma protein bound. Classification of Calcium Channel
l All are . 90% metabolized in liver and excreted in urine. Blockers (CCBs)
1 . Phenylalkylamine: Verapamil
Adverse Effects 2. Benzothiazepine: Diltiazem
3. Dihydropyridines: Nifedipine, felodipine, amlodipine,
l Palpitations, flushing, ankle oedema, hypotension, nitrendipine, nimodipine, lacidipine
headache, drowsiness and nausea are frequent. These
are related to peaks of drug level in blood and can be
minimized by low starting dose, fractionation of dose or Pharmacological Actions
use of retard formulations. The common property of all three subclasses of CCBs is to
l Paradoxically increases the frequency of angina in some
inhibit Ca21-mediated slow channel component of action
patients. potential in smooth and cardiac muscle cells.
l Increases the urine voiding difficulty in elderly males by
The two most important actions of CCBs are as follows:
its relaxant action on the bladder. 1. Smooth muscle relaxation
2. Negative chronotropic, inotropic and dromotropic action
Therapeutic Uses on heart
Angina Pectoris
Mechanism of Action
l Nifedipine is effective in reducing frequency and sever-
ity of classical as well as variant angina. Voltage sensitive Ca21 channels are of five subtypes. They are
l Benefit is primarily due to reduction in cardiac work as L, N, T, P and R subtypes. L type is predominantly present in
a result of reduced afterload in classical angina. cardiac and smooth muscle cells.
l They can increase coronary flow in normal individuals.
l Exercise tolerance is increased.

Smooth Muscle
l Capacity to prevent arterial spasm is beneficial in vari-
ant angina. l They markedly relax the arterioles but have mild
l Nifedipine is used as add-on therapy in patients unre- effect on veins. Extravascular smooth muscles like
sponsive to nitrates and b-blockers. bronchial, biliary, intestinal, vesical, uterine are also
Hypertension: Nifedipine lowers BP by decreasing relaxed.
peripheral resistance without compromising cardiac output l CCBs cause relaxation of smooth muscle by decreasing
and vasodilatation. intracellular availability of Ca21.

l Nitrendipine and some other dihydropyridines (DHPs) Hypertension

release NO from the vascular endothelium and inhibit
Calcium channel blockers lower BP by decreasing periph-
cAMP-phosphodiesterase resulting in raised smooth
eral resistance without compromising cardiac output and
muscle cAMP.
vasodilatation.
Heart
Other Uses
l In the working atrial and ventricular fibres Ca21 moves
They are alternative drugs for premature labour.
in during plateau phase of action potential. It releases
more Ca21 from sarcoplasmic retinaculum and causes Q. 4. List one cardioselective and one nonselective b re-
contraction through binding to troponin and allowing ceptor antagonist. Mention two therapeutic uses of them.
interaction of myosin with actin. Thus CCBs have nega-
tive inotropic action. Ans.
l CCBs have negative chronotropic and dromotropic
action except DHPs. Cardioselective b-blockers

Mechanism of action can be summarized as follows: l Cardioselective b-blockers selectively block b 1 recep-
tors and weakly b 2 receptors, e.g. atenolol, metoprolol
CCBs block voltage-sensitive L-type Ca+ channels by bind- and esmolol.
ing to specific site on the α1 subunit. l They are safe to use in diabetics as their inhibition of
glycogenolysis is low and incidence of bronchospasm is

Prevent entry of Ca2+ into the cell. less or negligible.
l There is reduced chances of peripheral vascular diseases.
l The exercise performance impaired to a lesser degree.

No excitation–contraction coupling in the heart and vascu-
l They are used in the treatment of cardiac arrhythmias,
lar smooth muscles.
angina pectoris and hypertension.
Therapeutic Uses Nonselective Beta Receptor Antagonists

Angina Pectoris l They include drugs like timolol, nadolol, sotalol, pro-
Calcium channel blockers are effective in reducing pranolol.
frequency and severity of classical as well as variant l They are used in the treatment of glaucoma, anxiety, pheo-
angina. chromocytoma, thyrotoxicosis and prophylaxis of migraine.
SHORT NOTES
Q. 1. Nifedipine 3. As an alternative drug for premature labour
Ans. Q. 2. Name of drugs causing gingival hyperplasia.
l Nifedipine is dihydropyridine, a class of calcium channel Ans.
blocker which blocks voltage sensitive calcium channels.
l It acts by causing relaxation of smooth muscle by de- l Noninflammatory type of gingivitis or drug induced gin-
creasing intracellular availability of Ca21. gival hyperplasia is caused by three groups of drugs: anti-
convulsants, antihypertensives and immunosuppressants.
a. Anticonvulsants: Phenytoin sodium, phenobarbitone,
Adverse Effects carbamazepine, sodium valproate, primidone
1. Palpitations, flushing, ankle oedema, hypotension, head- b. Antihypertensives: Nifedipine, amlodipine, nimodip-
ache, drowsiness and nausea are frequent. ine, nicardipine, diltiazem
2. Paradoxically increases the frequency of angina in some c. Immunosuppressants: Cyclosporine
patients.
3. Increases the urine voiding difficulty in elderly males by Q. 3. Nitroglycerine
its relaxant action on the bladder. Ans.
l Nitroglycerine or glycerol trinitrate is a short-acting

Therapeutic Uses antianginal drug that is converted to nitric oxide to
1 . Angina pectoris cause relaxation of vascular smooth muscles which
2. Hypertension leads to vasodilation, mainly that of veins.
l This venodilation reduces venous return and reduces the 2. Long-acting: Isosorbide dinitrate, isosorbide mononi-
preload on the heart. trate, erythrityl tetranitrate, pentaerythritol tetranitrate
l When nitroglycerine tablet is given sublingually it is
more effective as it is well absorbed from buccal mucosa. Q. 5. Cardioselective b-blockers

l Uses: Nitroglycerine is used in the treatment of
Ans.
angina, cardiac failure, myocardial infarction and
cyanide poisoning. l Cardioselective b–blockers selectively block b 1 recep-
tors and weakly b 2 receptors, e.g. atenolol, metoprolol
Q. 4. Name organic nitrates used in the treatment of and esmolol.
angina pectoris. l They are safe to use in diabetics as their inhibition of
Ans. glycogenolysis is low and incidence of bronchospasm is

less or negligible.
The organic nitrates used in the treatment of angina pectoris l They are used in the treatment of cardiac arrhythmias,
are as follows: angina pectoris and hypertension.

1. Short-acting: Glycerol trinitrate (nitroglycerine)
Topic 34
Antihypertensive Drugs
LONG ESSAY
Q. 1. Classify antihypertensive drugs. Describe the ii. Angiotensin (AT1) antagonists: Losartan, candesartan,
pharmacological actions of any two commonly used irbesartan, valsartan
drugs. iii. Calcium channel blockers: Verapamil, diltiazem, nifedip-
Or, ine SR, felodipine, amlodipine, nitrendipine, lacidipine
iv. Diuretics
Classify the drugs used on the treatment of hyperten- a. Thiazides: Hydrochlorothiazide, chlorthalidone,
sion. State the mechanism of action, indications and indapamide
adverse effects of any three of them. b. High ceiling (loop) diuretics: Frusemide, bumetanide,
Or, torsemide
c. Potassium sparing diuretics: Amiloride, triamterene,
Classify the drugs used in hypertension. Write the phar- spironolactone
macological actions and adverse effects of angiotensin v. b adrenergic blockers: Propranolol, metoprolol, atenolol
converting enzyme (ACE) inhibitors. vi. b 1 a adrenergic blockers: Labetalol, carvedilol
Ans. vii. a adrenergic blockers: Prazosin, terazosin, doxazosin,
phentolamine, phenoxybenzamine
l Hypertension is a very common disorder, particularly viii. Central sympatholytics: Clonidine, methyldopa
past middle age. Hypertension is not a disease in itself but ix. Vasodilators:
is an important risk factor for cardiovascular morbidity a. Arteriolar: Hydralazine, minoxidil, diazoxide
and mortality. b. Arteriolar 1 venous: Sodium nitroprusside
l Hypertension risk appears to increase progressively Detail description of few antihypertensive drugs is as follows:
with BP values over 120/80 mm Hg.
Hypertension has been defined by WHO-ISH guidelines
to be values above 140/90 mm Hg.
A. DIURETICS
Diuretics act as antihypertensives as follows:
ANTIHYPERTENSIVE DRUGS
These are the drugs used to lower BP in hypertension.
a. Thiazide Diuretics
Classification of antihypertensive drugs is as follows: l Thiazides are the first-line antihypertensives.
i. ACE inhibitors: Captopril, enalapril, lisinopril, perindo- l They are used in uncomplicated mild to moderate
pril, ramipril hypertension and have a long duration of action.
Mechanism of Action iv. Adrenergic Receptor Blockers

Diuretics enhance the excretion of sodium and water result- a. b-blockers: These are mild antihypertensives. They
ing in reduce the BP due to a fall in the cardiac output. They
i. gPlasma volume n g Cardiac output n g BP also lower plasma renin activity and have an additional
or central antihypertensive action.
ii. gBody sodium n Relaxation of vascular smooth mus- b. a -blockers: Prazosin is a selective a 1 blocker. It dilates
cles (due to Na1 depletion) both arterioles and venules. Peripherally vascular resis-
gPVR n BP. tance is decreased leading to a fall in BP with only mild
tachycardia.
Adverse Effects c. a - and b -blockers: Labetalol blocks both a 1 and
b receptors. It is used in treatment of hypertension in
Hypokalaemia, hyperglycaemia, hyperuricaemia, hyperlip- pheochromocytoma and in hypertensive emergencies.
idaemia, impotence and decreased libido
v. Vasodilators
Loop Diuretics
They reflex the vascular smooth muscles thus reducing BP
These have shorter duration of action. Therefore, they are due to decreased peripheral resistance.
not used in hypertension except in the presence of renal or a. Hydralazine is a directly acting arteriolar dilator. The
cardiac failure. fall in BP is associated with tachycardia, renin release
and fluid retention.
B. SYMPATHOLYTIC DRUGS b. Minoxidil is a directly acting arteriolar dilator used in
severe hypertension not responding to other drugs. It
i. Drugs Acting Centrally acts by opening the K1 channels.
a. Clonidine c. Diazoxide is a relative thiazide diuretic and is potent
l Clonidine, an imidazoline derivative, is a selective
arteriolar dilator. It is used in hypertensive emergencies.
a2 agonist. It is centrally-acting antihypertensive drug. d. Sodium nitroprusside is a rapidly acting vasodilator. It
l Major haemodynamic effects result from stimulation
dilates both arterioles and venules. Both peripheral resis-
of a 2 receptors in the CNS. They decrease central tance and cardiac output are reduced resulting in lower
sympathetic outflow, block the release of noradrena- myocardial oxygen consumption.
line from the nerve terminals leading to a fall in BP
and bradycardia. vi. Calcium Channel Blockers
b. a -methyldopa: It is a prodrug and is an analogue of
dopa. It is metabolized in the body to a -methyl norepi- These are important antihypertensive drugs that dilate the
nephrine which is an a 2 agonist and acts like clonidine. arterioles resulting in reduced peripheral vascular resis-
tance. Nifedipine produces reflex tachycardia.
ii. Ganglion Blockers

vii. Angiotensin Converting Enzyme
Trimethaphan: These drugs block both sympathetic and
(ACE) Inhibitors
parasympathetic ganglia resulting in decreased sympathetic
tone and a fall in BP. It has rapid and short duration of l Angiotensin II is powerful vasoconstrictor. Aldosterone
action (15 min). also rises the BP by increasing plasma volume.
l ACE inhibitors prevent the formation of angiotensin II
and aldosterone. ACE inhibitors also raise bradykinin

iii. Adrenergic Neuron Blockers levels all of which contribute to the fall in BP.
a. Guanethidine: This depletes the stores of noradrenaline l It maintains adequate blood flow to the vital organs like
in the adrenergic neurons and also blocks its release. kidney, brain and heart.
Because of the adverse effects like postural hyperten- l ACE inhibitors are well absorbed in the body. Except
sion diarrhoea and sexual dysfunction, it is not used. captopril and lisinopril all the other ACE inhibitors are
b. Reserpine: This is an alkaloid obtained from Rauvolfia prodrugs.
serpentina (sarpagandha) that grows in India. In the neu- l The duration of action varies for each drug, captopril
rons it binds to the vesicles that store monoamines like acts for about 6–12 h, lisinopril with a duration more
noradrenaline, dopamine and 5-HT and destroys these than 24 h, enalapril acts for 24 h and ramipril for about
vesicles. It thus depletes the stores of these monoamines. 8–48 h.
Uses c. Alteration in the taste

d. Skin rashes, headache, nausea, abdominal pain
a . Hypertension
e. Hypotension
b. Congestive cardiac failure
f. Blood disorders
c. Myocardial infarction
viii. Angiotensin II Receptor Antagonists

Adverse Effects
Losartan is an angiotensin II antagonist. It relaxes smooth
a . Persistent dry cough
muscles, promotes salt and water excretion and reduces
b. Hyperkalaemia
plasma volume. Thus there is a fall in BP.
SHORT ESSAYS
Q. 1. Captopril Q. 2. Calcium channel blocking drugs in treatment of
hypertension
Ans.
Ans.
l Captopril is an angiotensin converting enzyme (ACE)
inhibitor. l Calcium channel blockers are important antihyperten-
l Captopril prevents the generation of angiotensin II sive drugs that dilate the arterioles resulting in reduced
which is a powerful vasoconstrictor. There is vasodila- peripheral vascular resistance, e.g. verapamil, diltiazem
tion and decrease in PVR resulting in decrease in BP. and dihydropyridines.
l It also inhibits the degradation of bradykinin, which is a l Dihydropyridines like nifedipine, amlodipine, felodipine,
potent vasodilator and stimulates the synthesis of vaso- nicardipine, etc. are preferred among calcium channel
dilating PGs through bradykinin. blockers because of their more selective action on blood
l It reduces sympathetic nervous system activity, all of vessels. The long-acting DHPs are often used as first-line
which contribute to the fall in BP. antihypertensive drugs.
l Captopril is not a prodrug. Its daily dose in hypertension l The antihypertensive effect of DHPs is mainly due to
is about 12.5–50 mg BD and duration of action lasts the reduction of total peripheral resistance.
from about 6 to 12 h. l Nifedipine produces some reflex tachycardia, though it is
not seen with verapamil or diltiazem as they are cardiac

depressants.
Mechanism of Action l Fluid retention is negligible compared to other arteriolar
l ACE inhibitors also reduce aldosterone production, dilators. They are well tolerated, safe and effective.
hence sodium and water retention. l They have special value in people who also have angina.
l Captopril-induced hypotension is a result of decrease in l Calcium channel blockers are used in treatment of short
total peripheral resistance. periods to control hypertension.

l The arterioles dilate and compliance of larger arteries is l Nifedipine is administered sublingually and is used in
increased. Both systolic and diastolic BP fall. It has no patients for hypertensive emergencies. It effectively
effect on cardiac output. Cardiovascular reflexes are not lowers BP in 10 min.
interfered with and there is little dilatation of capaci-
tance vessels. As such, postural hypotension is not a Q. 3. List two centrally acting antihypertensive drugs.
problem. The renal blood flow is not compromised even Mention the adverse effects of anyone of them.
when BP falls substantially. Cerebral and coronary Ans.
blood flow also not compromised.
Drugs acting centrally to reduce BP are clonidine and
a-methyl dopa.
Adverse Effects
Persistent brassy dry cough
l
Clonidine
l Hypotension
l Hyperkalaemia Clonidine, an imidazoline derivative, is a selective a 2 ago-
l Alteration of taste sensation, urticaria, skin rashes and nist. Stimulation of a 2 receptors in the CNS (in the vasomo-
angioedema tor centre and hypothalamus), decreases central sympathetic
l Headache, dizziness, nausea, abdominal pain and bowel upset outflow, blocks the release of noradrenaline from the nerve
l Blood disorders like granulocytopenia and proteinurea terminals leading to a fall in BP and bradycardia.
Adverse Effects l b-blockers are the first- line of drugs used to treat
patients with mild hypertension, e.g. propranolol, ateno-
l Drowsiness
lol, metoprolol.
l Dryness of eyes (xerophthalmia), mouth, nose
l They reduce the cardiac output and lower the plasma
l Parotid gland swelling and pain
rennin activity. These two actions help in reducing the BP.
l Fluid retention
l They can also be used in patients with angina and
l Constipation
cardiac arrhythmias.
l Impotence
l They can be used in combination with other antihyper-
tensive drugs.
a -Methyl Dopa l They are well tolerated and do not have many adverse
effects.
This is an analogue of dopa prodrug. It is metabolized in the
l Due to these reasons b-blockers like propranolol and
body to a -methyl norepinephrine which is an a 2 agonist
atenolol are used in treatment of hypertension.
and acts like clonidine.
Q. 6. Prazosin
Adverse Effects Or,
l Sedation What is prazosin? Mention one therapeutic use of it.
l Dryness of eyes (xerophthalmia), mouth, nose
l Postural hypotension Ans.
l Impotence
l Prazosin is a selective a1 adrenergic blocker used in the
l Fluid retention
treatment of mild to moderate hypertension.
l Headache
l It is a vasodilator as it dilates both arterioles and venules
Q. 4. Rationale of using clonidine in hypertension thus decreasing the peripheral resistance that helps in
reducing the BP.
Ans. l Prazosin dosage is started with an initial dose of 0.5 mg
given at bed time.

l Clonidine, an imidazoline derivative, is a selective a 2
l The dosage is gradually increased.
agonist.
l Prazosin can be used in combination with diuretics and
l Stimulation of a 2 receptors in the CNS (in the vasomotor
b-blockers. It is usually combined with b-blockers in
centre and hypothalamus); decreases central sympathetic
cases of emergency and in pheochromocytoma.
outflow; blocks the release of noradrenaline from the
nerve terminals leading to a fall in BP and bradycardia. Q. 7. Propranolol
l Adverse effects are lesser compared to other antihy-
pertensives and include drowsiness, dryness of eyes Ans.

(xerophthalmia), mouth, nose, parotid gland swelling
l Propranolol is a b-blocker and is the first-line of drug
and pain, fluid retention, constipation and impotence.
used to treat patients with mild hypertension.
l In addition it has other benefits like it reduces with-
l It reduces the BP by decreasing the cardiac output and
drawal symptoms of opioid analgesics, may be used in
lowering the plasma rennin activity.
diabetic neuropathy, it stimulates the a 2 receptors in the
l It can also be used in patients with angina and cardiac
intestine to improve NaCl and water absorption thus
arrhythmias.
controlling diarrhoea.
l It is usually used in combination with other antihyper-
Q. 5. Rationale of using b-blockers in hypertension tensive drugs.

l It is well tolerated and does not have many adverse effects.
Ans. l Its dosage is usually tapered while withdrawing.
SHORT NOTES
Q. 1. Clonidine l Stimulation of a2 receptors in the CNS and decreases
central sympathetic outflow; blocks the release of nor-
Ans.
adrenaline from the nerve terminals leading to a fall in
l Clonidine, an imidazoline derivative, is a selective a2 BP and bradycardia.
agonist. l Adverse effects are lesser compared to other antihy-
pertensives and include drowsiness, dryness of eyes

(xerophthalmia), mouth, nose, parotid gland swelling Q. 5. Enalapril

and pain, fluid retention, constipation and impotence.
Ans.
l In addition it has other benefits like it reduces with-
drawal symptoms of opioid analgesics, may be used in l Enalapril is an angiotensin converting enzyme (ACE) in-
diabetic neuropathy. hibitor which prevents the formation of angiotensin II and
raises bradykinin levels which contributes to the fall in BP.
Q. 2. Reserpine l It maintains adequate blood flow to the vital organs like
Ans. kidney, brain and heart.

l It is well absorbed in the body.
l Reserpine is an alkaloid obtained from an Indian plant
called Rauvolfia serpentina.
l The monoamine stores which store noradrenaline,
Uses
dopamine and 5-hydroxytryptamine are depleted by l Hypertension
the destruction of the vesicles by reserpine. l Congestive cardiac failure
l It is not usually preferred due to high incidence of adverse l Myocardial infarction
effects like drowsiness, depression, oedema, parkinson-
ism, postural hypotension and impotence.
Adverse Effects
Q. 3. Mention two uses and two adverse effects of thiazide. l Persistent dry cough
Ans. l Hyperkalaemia
l Alteration in the taste
Chlorothiazide, hydrochlorothiazide and chlorthalidone are
the thiazides used in the treatment of hypertension. Q. 6. Captopril
Ans.
Uses
l Captopril is an angiotensin converting enzyme (ACE) in-
l Thiazide diuretics are used in the treatment of mild hibitor which prevents the formation of angiotensin II and
hypertension. raises bradykinin levels which contributes to the fall in BP.
l It takes about 2–4 weeks for the blood pressure to l It maintains adequate blood flow to the vital organs like
decrease by about 15–20 mm of Hg. kidney, brain and heart.
l They decrease the plasma volume that decreases the l It is well absorbed in the body. Unlike all the ACE
cardiac output and decrease the body sodium that inhibitors it is not a prodrug and acts for 6–12 h.
reduces the PVR, both processes causing excretion
of sodium and water from the body leading to fall
in BP. Uses
l Hypertension
Adverse Effects l Congestive cardiac failure
Hypokalaemia, hyperglycaemia, hyperuricaemia, hyperlip-
idaemia, impotence and decreased libido.
Adverse Effects
Q. 4. Name four drugs used in hypertension. l Persistent dry cough
Ans. l Hyperkalaemia
l Alteration in the taste
Drugs used in hypertension are as follows:
1. ACE inhibitors: Enalapril, lisinopril, perindopril, ramipril Q. 7. Chlorothiazide diuretics in hypertension
2. Calcium channel blockers: Verapamil, diltiazem, nife-
Or,
dipine, felodipine, amlodipine, nitrendipine, lacidipine
3. Diuretics Mention thiazides as an antihypertensive drug.
a. Thiazides: Hydrochlorothiazide, chlorthalidone, in-
Ans.
dapamide
b. High ceiling: Frusemide l Chlorothiazide, hydrochlorothiazide and chlorthalidone
4. b adrenergic blockers: Propranolol, metoprolol, atenolol are the thiazides used in the treatment of hypertension.
l Chlorothiazide is a thiazide diuretic that is used in the PVR, both processes causing excretion of sodium and
treatment of mild hypertension. water from the body leading to fall in BP.
l It decreases the plasma volume that decreases the cardiac l They may cause hypokalaemia and hence they are to be
output and it decreases the body sodium that reduces the used in combination with potassium sparing diuretics
like spironolactone, amiloride and triamterene.
Part IX
Diuretics and Antidiuretics
Topic 35
Diuretics and Antidiuretics

SHORT ESSAYS
Q. 1. Classify diuretics and write mechanism of action MECHANISM OF ACTION OF THIAZIDES
of thiazides.
Thiazides are medium efficacy diuretics that act in the early
The drugs that increase urine and solute excretion caus- parts of distal convoluted tubule and inhibit the Na1Cl2
ing loss of sodium and water from the body are called symport and increase sodium and chloride excretion.
diuretics. They act in two ways to prevent uptake and induce excre-
tion of sodium and chloride ions as follows:
1. By the organic acid secretory pathway: They are initially
CLASSIFICATION OF DIURETICS
secreted in the proximal convoluted tubule, from there they
Based on the efficacy of action diuretics are classified as are transported to the distal convoluted tubule via tubular
follows: fluid where they bind to the sodium and chloride symporter
1 . High efficacy (loop) diuretics situated on the membrane. This inhibits the uptake of sodium
a. Sulphamoyl derivatives: Frusemide, bumetanide and chloride ions by the cells and promotes their excretion.
b. Phenoxyacetic acid derivatives: Ethacrynic acid 2. They have weak carbonic anhydrase inhibitory action in
c. Organomercurials: Mersalyl the proximal convoluted tubule. This causes increased
2 . Medium efficacy diuretics amounts of sodium that is presented to the distal convo-
a. Benzothiadiazines (thiazides): Chlorothiazide, hydro- luted tubule. Here again the sodium chloride symporter
chlorothiazide, polythiazide, benzthiazide, hydroflu- is inhibited and they are excreted in the urine.
methiazide, clopamide The sodium presented to the distal convoluted tubule may also
b. Thiazide-like drugs (related heterocyclics): Chlortha- be exchanged for potassium ions which may be excreted in the
lidone, indapamide, metolazone, xipamide urine. This may lead to hypokalaemia. There is a net loss of
3. Low efficacy or weak or adjunctive diuretics Na1, K1Cl2, HCO32 in the urine. This is the reason for which
a. Potassium sparing diuretics: Triamterene, amiloride, thiazides are usually combined with potassium sparing diuretics.
spironolactone
b. Carbonic anhydrase inhibitors: Acetazolamide Q. 2. Compare frusemide and spironolactone.
c. Osmotic diuretics: Mannitol, urea, isosorbide, glycerol Ans. Frusemide and spironolactone are compared based on
d. Xanthines: Theophylline parameters which are given in Table 35.1.
TABLE 35.1 Comparison between Frusemide and

Parameters to Be
Spironolactone
Compared Spironolactone Chlorothiazide
Parameters Frusemide Spironolactone Mechanism of Antagonizes Inhibits Na1Cl2
Type High ceiling (loop) Weak or adjuvant action the action of symport
diuretic potassium sparing aldosterone
diuretic Site of action Late section of Early section of
Mechanism of 1– 1– Antagonizes distal convo- distal convoluted
Inhibits Na K 2Cl
action the action of luted tubule and tubule
cotransport
aldosterone collecting duct
Site of action Thick ascending limb Late section of Free water No effect on No effect on negative
of Henle’s loop distal convoluted clearance free water free water clearance
tubule and collect- clearance but decreases
ing duct cells positive free water
clearance
Free water Blockade of positive No effect on free
clearance and negative free water clearance Excretion of Excretes sodium Excretes sodium,
water clearance electrolytes and chloride but potassium and
retains potas- chloride ions
Excretion of Excretes sodium, Excretes sodium and sium ions
electrolytes potassium and chloride ions but re-
chloride ions tains potassium ions Carbonic anhydrase Present Absent
inhibitory action
Glomerular Unchanged Decreases
filtration rate Adverse effects Acute salt Acute salt depletion—
depletion— hypokalaemia, hypo-
Enterohepatic Absent Present hypokalaemia, calcaemia, hepatic
circulation hypocalcaemia coma in cirrhotics,
hepatic coma in photosensitivity,
Adverse Acute salt depletion— Hyperkalaemia,
cirrhotics, photo- headache, giddiness,
effects hypokalaemia, hypo- acidosis, peptic ul-
sensitivity, head- nausea, vomiting,
calcaemia, hepatic cer, stomach upset,
ache, giddiness, paraesthesia,
coma in cirrhotics, drowsiness, confu-
nausea, vomit- impotence
photosensitivity, sion, hirsutism,
ing, paraesthesia,
headache, giddiness, gynaecomastia, im-
impotence
nausea, vomiting, potence, menstrual
paraesthesia, irregularities Uses More useful in Oedema, hyperten-
impotence oedema— sion, diabetes insipi-
cirrhotic and ne- dus, hypercalcaemia
Uses Oedema—acute pul- More useful in
phrotic oedema, and renal stones
monary and cerebral oedema—
hypertension, to
oedema, hyperten- cirrhotic and
counteract potas-
sion, forced diuresis, nephrotic oedema,
sium loss due to
hypercalcaemia and hypertension, to
thiazide and
renal stones along counteract potas-
loop diuretics,
with blood transfu- sium loss due to
congestive
sion to prevent thiazide and loop
cardiac failure
vascular overload diuretics, congestive
cardiac failure
Q. 4. Chlorothiazide
Q. 3. Compare chlorothiazide and spironolactone.
Ans.
Ans. Chlorothiazide and spironolactone are compared
based on parameters which are given in Table 35.2. l Chlorothiazide is a drug of thiazide group of medium
efficacy diuretics.
l The primary site of action of these diuretics is cortical
TABLE 35.2 Comparison between Chlorothiazide and
Spironolactone diluting segment or the early DT.
l They inhibit the Na Cl symport at the luminal membrane.
1 2
Parameters to Be l It acts in two ways to increase sodium and chloride

Compared Spironolactone Chlorothiazide excretion from the body as follows:
Type and efficacy Weak or Medium efficacy— 1. It is secreted initially in the proximal convoluted tu-
adjuvant— thiazide diuretic bule by the organic acid secretory pathway. From here
potassium spar- it is transported to the distal convoluted tubule where it
ing diuretic
binds to the sodium and chloride symporter situated on
the membrane. This inhibits the uptake of sodium and TABLE 35.3 Comparison between Hydrochlorothiazide and
chloride ions by the cells and promotes its excretion. Frusemide
2. It has weak carbonic anhydrase inhibitory action in
Parameter to
the proximal convoluted tubule. This causes increased
Be Compared Frusemide Hydrochlorothiazide
amounts sodium that is presented to the distal convo-
Type High ceiling (loop) Medium efficacy
luted tubule. Here again the sodium chloride sym-
diuretic thiazide diuretic
porter is inhibited and they are excreted in the urine.
The sodium presented to the distal convoluted tubule may Mechanism of Inhibits Na1–K1– Inhibits Na1Cl2
action 2Cl cotransport symport
also be exchanged for potassium ions which may be ex-
creted in the urine. This may lead to hypokalaemia. For this Site of action Thick ascending Early section of distal
reason chlorothiazide is usually combined with potassium limb of Henle’s loop convoluted tubule
sparing diuretics like spironolactone, amiloride and triam- Free water Blockade of positive No effect on negative
terene. clearance and negative free free water clearance
water clearance but decreases positive
free water clearance
Uses of Chlorothiazide Excretion of Excretes sodium, Excretes sodium,
1. Oedema: Thiazides are the preferred drugs for treating electrolytes potassium and chlo- potassium and
ride ions chloride ions
mild to moderate cases of oedema. They are used to
reduce oedema caused by congestive cardiac failure Glomerular Unaltered Decreases
(CCF). filtration rate
2. Hypertension: It is one of the first-line drugs used in the Glucose levels Increases and causes No effect on glucose
treatment of mild hypertension. It takes about 2–4 weeks hyperglycaemia levels
for the blood pressure to decrease by about 15–20 mm of Adverse effects Acute salt depletion— Acute salt depletion—
Hg. It decreases the plasma volume that decreases the hypokalaemia, hypo- hypokalaemia, hypo-
cardiac output and it decreases the body sodium that re- calcaemia hepatic calcaemia hepatic
duces the peripheral vascular resistance (PVR), both coma in cirrhotics, coma in cirrhotics,
photosensitivity, photosensitivity,
processes causing excretion of sodium and water from headache, giddiness, headache, giddiness,
the body leading to fall in BP. nausea, vomiting, nausea, vomiting,
3. Hypercalciuria: It is used in treating hypercalciuria with paraesthesia, paraesthesia,
recurrent calcium stones in the kidney as it acts by impotence impotence
reducing calcium excretion. Uses Oedema—acute pul- Oedema, hyperten-
4. Diabetes insipidus: It is used in treatment of diabetes monary and cerebral sion, diabetes insipi-
insipidus as it reduces plasma volume and glomerular oedema, hyperten- dus, hypercalcaemia
filtration rate (GFR). sion, forced diuresis, and renal stones
hypercalcaemia and
renal stones, during
Adverse Effects blood transfusion
1. Thiazides cause electrolytic disturbances which include

hypokalaemia, hyponatraemia, i.e. acute salt depletion,
Q. 6. Compare frusemide and triamterene.
metabolic alkalosis, hypomagnesaemia and hypercal-
caemia. Ans. Comparison between frusemide and triamterene is
a. Hypokalaemia is more common with thiazides listed in Table 35.4.
because of its long duration of action.
b. Hypercalcaemia is due to decreased urinary excre-
TABLE 35.4 Comparison between Frusemide and
tion of Ca21.
Triamterene
2. The metabolic disturbances are also same as that of loop
diuretics—hyperglycaemia, hyperlipidaemia and hyper- Parameters to Be
uricaemia. Compared Frusemide Triamterene
3. They may cause photosensitivity, headache, giddiness, Type High ceiling (loop) Low ceiling potas-
nausea, vomiting, paraesthesia and impotence. diuretic sium sparing
diuretic
Q. 5. Compare hydrochlorothiazide and frusemide.
Mechanism of Inhibits Na1–K1– Inhibits sodium
Ans. Comparison between and hydrochlorothiazide and action 2Cl cotransport channels on the
renal epithelium
frusemide is listed in Table 35.3.
Parameters to Be Parameters to Be
Compared Frusemide Triamterene Compared Frusemide Triamterene
Site of action Thick ascending Early section of Adverse effects Acute salt Muscle cramps,
limb of Henle’s distal convoluting depletion— increased blood
loop tubule hypokalaemia, urea levels, photo-
hypocalcaemia, sensitivity, hyper-
Free water Blockade of No effect on
hepatic coma in cir- kalaemia, im-
clearance positive and nega- positive or nega-
rhotics, photosensi- paired glucose
tive free water tive free water
tivity, headache, tolerance
clearance clearance
giddiness, nausea,
Excretion of elec- Excretes sodium, Excretes sodium vomiting, paraesthe-
trolytes potassium and and chloride ions, sia, impotence
chloride ions but does not allow
Uses Oedema—acute It is used in the
potassium secretion
pulmonary and ce- treatment of hy-
Glomerular Unaltered Decreases rebral oedema, hypertension along
filtration rate pertension, forced with other diuret-
diuresis, hypercal- ics to reduce
Glucose levels Increases and No effect on caemia and renal potassium loss,
causes hypergly- glucose levels stones, during in renal oedema
caemia blood transfusion and cirrhosis
SHORT NOTES
Q. 1. Mention two therapeutic uses and two adverse l Chlorothiazide is a drug of thiazide group of medium
effects of frusemide. efficacy diuretics.
l The primary site of action of these diuretics is cortical
Ans.
diluting segment or the early DT.
l They inhibit the Na Cl symport at the luminal mem-
1 2
Frusemide is a high efficacy loop diuretic that acts in the
Henle’s loop to inhibit the sodium-potassium-chloride ion brane.
cotransport.
Uses
Therapeutic Uses
1. Oedema: Thiazides are the preferred drugs for treating
1. Oedema: During the initial stages of renal, hepatic and mild to moderate cases of oedema. They are used to re-
cardiac oedema loop diuretics are preferred. duce oedema caused by congestive cardiac failure (CCF).
2. May be used in cerebral oedema. 2. Hypertension: It is one of the first-line drugs used in the
3. Hypertension: Frusemide is used in the presence of renal treatment of mild hypertension.
failure, congestive cardiac failure (CCF) or hypertensive 3. Hypercalciuria: It is used in treating hypercalciuria with
emergency. recurrent calcium stones in the kidney as it acts by
4. Forced diuresis reducing calcium excretion.
5. Hypercalcaemia and renal stones 4. Diabetes insipidus: It is used in treatment of diabetes
insipidus as it reduces plasma volume and glomerular
Adverse Effects filtration rate (GFR).
1. Electrolyte disturbances like acute salt depletion, hypo-

kalaemia, hyponatraemia and hypocalcaemia Adverse Effects
2. Metabolic disturbances like hyperglycaemia, hyperuri- 1. Thiazides cause electrolytic disturbances which include
caemia and hyperlipidaemia hypokalaemia, hyponatraemia, metabolic alkalosis, hypo-
3. Ototoxicity and hypersensitivity magnesaemia and hypercalcaemia.
4. Headache, giddiness, nausea, vomiting, paraesthesia and
a. Hypokalaemia is more common with thiazides
impotence because of its long duration of action.
b. Hypercalcaemia is due to decreased urinary excre-
Q. 2. Chlorothiazide
tion of Ca21.
Ans.
2. The metabolic disturbances are also same as that of loop Uses

diuretics—hyperglycaemia, hyperlipidaemia and hyper-
1. They are used to maintain urine volume and prevent
uricaemia.
oliguria during haemolysis and shock.
3. It may cause impotence, hence is not preferred antihy-
2. They are used in the reduction of intracranial and intra-
pertensive in young males.
ocular pressure.
Q. 3. Potassium sparing diuretics
Ans.
Adverse Effects
Dehydration, ECF volume expansion, headache and hyper-
l Potassium sparing diuretics do not cause excretion of allergic reactions.
potassium from the body and hence are named so. They
include spironolactone, triamterene and amiloride. Q. 6. Mannitol
l Aldosterone facilitates reabsorption of sodium and se-
cretion of potassium. Spironolactone acts by inhibiting Ans.

the action of aldosterone. l Mannitol helps to retain water in the proximal convoluted
l Triamterene and amiloride act directly by enhancing
tubule and the descending limb of the Henle’s loop by
sodium excretion and reduce the loss potassium. osmosis. This causes water diuresis and loss of sodium.
l Uses: They are mostly used along with thiazides and
l They are ineffective when administered orally as they
loop diuretics to prevent potassium loss, oedema, hyper- cannot be absorbed and hence are given IV.
tension and aldosteronism.
Q. 4. Spironolactone Uses
Ans. 1. They are used to maintain urine volume and prevent
oliguria during haemolysis and shock.
l Spironolactone is an aldosterone antagonist which com- 2. They are used in the reduction of intracranial and intra-
petes with aldosterone by binding to the receptors in the ocular pressure.
distal convoluting tubule and collecting duct.
l It inhibits the action of aldosterone and hence stops the
reabsorption of sodium and potassium secretion.

Adverse Effects
l It is a low efficacy diuretic. It is generally used along Dehydration, ECF volume expansion, headache and hyper-
with other diuretics to reduce the loss of potassium allergic reactions
caused by them.
Q. 7. Loop diuretics. Name two loop diuretics. Mention
two uses of them.
Uses
Ans.
1. It can be used in treatment of hypercalcaemia and renal
stones. l Loop diuretics are high efficacy diuretics that act by
2. It can be used along with other diuretics in the treatment inhibiting sodium chloride reabsorption in the ascend-
of hypertension, to reduce hypokalaemia. ing limb of Henle’s loop and stop the sodium potassium
3. It is used in the treatment of aldosteronism. chloride ion cotransport.
l They include frusemide, bumetanide, piretanide, ethacrynic
acid and mersalyl.

Adverse Effects
l They block positive and negative free water clearance
Drowsiness, hyperkalaemia in patients with renal insuffi- and promote excretion of sodium potassium and chlo-
ciency, gynaecomastia, skin rashes ride ions. In addition they cause loss of water and salts
like calcium and magnesium.
Q. 5. Osmotic diuretics l Given IV they are rapid acting taking about 2–5 min to
Ans. act, while when given orally they are slow acting as it
takes long time to be absorbed and to reach the site of
l Osmotic diuretics help to retain water in the proximal action it takes about 3–6 h.
convoluted tubule and the descending limb of the Henle’s
loop by osmosis. This causes water diuresis and loss of Uses
sodium.
l They include inert drugs like mannitol, urea and glycerol. 1. They are used in the treatment of cardiac, cerebral, he-
l They are ineffective when administered orally as they patic and renal oedema. It reduces pulmonary oedema
cannot be absorbed and hence are given IV. by vasodilator and diuretic effect.
2. It is used in the treatment of hypertension along with 3. Low efficacy diuretics

potassium sparing diuretics. a. Potassium sparing diuretics: Triamterene, amiloride,
3. It is used in cases of hypercalcaemia, renal stones and spironolactone
hyperkalaemia. Use: They are used along with other diuretics in hy-
4. They are used in cases of poisoning with barbiturates to pertension to reduce loss of potassium and in treat-
induce forced diuresis. ment of aldosteronism.
b. Carbonic anhydrase inhibitors: Acetazolamide
Q. 8. Name four diuretics. Enlist three diuretic drugs Use: They are used to inhibit formation of aqueous
and one different use for each. humour and cerebrospinal fluid (CSF) and reduce intra-
Ans. ocular pressure and intracranial pressure respectively.
c. Osmotic diuretics: Mannitol, urea, glycerol
Diuretics are drugs that increase urine and solute excretion Use: They are used in the treatment of cranial and
causing loss of sodium and water from the body. intraocular pressure.
d. Methylxanthines: Theophylline
Classification Q. 9. Rationale of combining thiazides with spironolactone
Diuretics are classified based on the efficacy of action as Or,
follows:
1. High efficacy (loop) diuretics: Frusemide, bumetanide, Spironolactone with frusemide
piretanide, ethacrynic acid, mersalyl Ans.
Use: They are used in treatment of pulmonary, cardiac,
renal and hepatic oedema, in poisoning with barbitu- l Thiazides and frusemide cause excess excretion of po-
rates to enhance forced diuresis, in treatment of hyper- tassium from the body. The sodium presented to the
tension. distal convoluted tubule may also be exchanged for po-
2. Moderate efficacy diuretics tassium ions which may be excreted in the urine. This
a. Thiazides: Benzothiadiazines like chlorothiazide, may lead to hypokalaemia.
hydrochlorothiazide, polythiazide, bendroflumethia- l Spironolactone reduces potassium loss by inhibiting the
zide action of aldosterone that is responsible for potassium
b. Thiazide-related drugs: Chlorthalidone, clopamide, secretion.
indapamide, metolazone, xipamide This is why thiazides are usually combined with potassium
Use: Used in the treatment of mild hypertension, oe- sparing diuretics like spironolactone, amiloride and triamterene.
dema due to congestive cardiac failure, renal stones due
to hypercalciuria, diabetes insipidus.
Part X
Drugs Affecting Blood and Blood Formation
Topic 36
Haematinics and Erythropoietin

LONG ESSAY
Q. 1. Explain the mechanism of iron absorption and l Iron is essential component of haemoglobin, myoglo-
storage in the body. Add a note on different iron prepa- bin and a number of enzymes necessary for oxygen
rations. transfer.
l Total amount of iron in the body is 2.5–5 g, two-thirds
Ans.
of which is present in haemoglobin.
l Iron, vitamin B12 and folic acid are essential for normal l Each molecule of haemoglobin has four iron-containing
erythropoiesis. residues.
DIETERY SOURCES OF IRON l This transferrin is taken up by various tissues like

reticulocytes in the bone marrow for haemoglobin
Liver, egg yolk, meat, fish, chicken, spinach, dry fruits, synthesis, reticuloendothelial cells in liver, spleen,
wheat and apple etc. and stored.
l Small amount of iron is excreted from the body mainly
PHARMACOKINETICS by shedding of GI mucosal cells, desquamated skin,

very little in the bile, sweat and least in urine.
Absorption and Storage (Fig 36.1)
l Only 10% of iron is absorbed as haeme or as inorganic Factors that Influence Iron Absorption
iron.
l Increase absorption: Ascorbic acid, amino acids, meat,
l Dietary iron exists in the ferric form, which is reduced
gastric acidity
to ferrous iron with the help of HCl in the stomach.
l Decrease absorption: Presence of food in the stomach,
l Absorption of most of the iron takes place in the duode-
antacids, phosphates, phytates, tetracyclines
num and upper jejunum.
l Transportation and distribution: Iron is transported with
l Iron absorption is regulated by a protein apoferritin in
the help of glycoprotein called transferrin.
the intestinal mucosal cells. Ferrous iron is oxidized in
l Stored as ferritin and haemosiderin in liver, spleen and
the mucosal cells to ferric iron and it combines with
bone marrow
apoferritin to form ferritin.
l Excretion: 0.5–1 mg of iron is excreted daily
l Iron will be in the mucosal cells for a long time and is
very slowly released in to plasma. The released iron in

the plasma is oxidized again to ferric iron which gets PREPARATION OF IRON
incorporated into transferring, a transport protein.
Iron is generally given orally or parenterally.
3+
Dietary iron (mostly Fe )
In the stomach Fe3+ Fe2+

1. Oral Iron
a. Preparations
i. Ferrous sulphate contains 20% hydrated salt and 32%
2+
In the mucosal cell Fe Fe 3+ dried salt or elemental iron—200 mg tab. It is the oldest
Apoferritin and cheapest iron preparation.
ii. Ferrous fumarate contains 33% elemental iron—
200 mg tab.
iii. Ferrous gluconate contains 12% elemental iron in a
Ferritin (stored) 300 mg tab. It causes less gastric irritation.
iv. Ferrous succinate: 100 mg
v. Iron calcium complex: 5% iron
l Ferrous salts are better absorbed than ferric salts.
iron is slowly released l Last three preparations are better tolerated.
In the plasma Fe2+ Fe3+ b. Indications

Transferrin l Iron deficiency anaemia, prophylactic treatment. For
3–6 months to replenish iron stores.
l Dose: Ferrous sulphate 3–4 tablets daily
Iron-bound transferrin
c. Adverse Effects
Transfers iron to i. Epigastric pain
ii. Nausea, vomiting, gastritis
Bone marrow, liver, spleen (stored) iii. Metallic taste
FIGURE 36.1 Schematic representation of absorption and iv. Constipation (due to astringent effect) or diarrhoea
storage of iron. v. Liquid preparations stain the teeth
2. Parenteral Iron iv. Iron requirement (mg) 5 4.4 3 body weight (kg) 3 Hb
deficit (g/dL)
l Intramuscular injection is given deep IM in the gluteal
region using ‘Z’ technique to avoid skin staining.
l Intravenous iron is given slowly 5–10 min or as infusion. c. Adverse Effects
Local: Pain at the site of injection
a. Indications Systemic: Fever, headache, joint pain, palpitation, difficulty
in breathing, lymph node enlargement and rarely anaphy-
1 . Parenteral iron is indicated when
laxis
i. oral iron is not tolerated,
Acute iron poisoning
ii. failure of absorption,
l Intake of 10 tablets or more can be lethal.
iii. noncompliance and
l Results in vomiting, abdominal pain, haematemesis, bloody
iv. deficiency with bleeding.
diarrhoea, shock, drowsiness, cyanosis, acidosis, dehydra-
tion, cardiovascular collapse and coma.
b. Preparations l Death may occur in 6–12 h.
i. Iron dextran (Imferon) has 50 mg (2 mL ampoule) can

be given IM/IV. TREATMENT
ii. Iron–sorbitol–citric acid complex (Jectofer)—50 mg/mL
l Gastric lavage with sodium bicarbonate
given IM but never IV.
l Desferrioxamine is injected IV/IM.
iii. The total dose of parenteral iron is calculated using the
l Correction of acidosis and shock
formula:
SHORT ESSAYS
Q. 1. Parental iron preparations Adverse Effects
Ans. Parenteral iron preparations are as follows: 1 . Local: Pain at the site of injection
2. Systemic: Fever, headache, joint pain, palpitation,
1. Iron dextran (Imferon) has 50 mg (2 mL ampoule) can difficulty in breathing, lymph node enlargement and
be given IM/IV. It is most commonly used parenteral rarely anaphylaxis
iron preparation.
2. Iron–sorbitol–citric acid complex (Jectofer): 50 mg/mL. Q. 2. Cyanocobalamin
It is given IM but never IV.
3. Sodium ferric gluconate: Recently approved prepara- Ans.
tion for IV use has much low risk of anaphylactic reac- 1. Cyanocobalamin and hydroxocobalamin are complex
tion than iron dextran. cobalt containing compounds present in diet and re-
The total dose of parenteral iron is calculated using the ferred to as vitamin B12.
formula: 2. Synthesized by microorganisms
Iron requirement (mg) 5 4.4 3 body weight (kg) 3 Hb 3. Sources: Liver, fish, egg yolk, meat, cheese, pulses
deficit (g/dL)
4. Intramuscular injection is given deep IM in the gluteal
region using ‘Z’ technique to avoid skin staining. Physiological Functions
5. Intravenous iron is given slowly 5–10 min or as infu- 1 . Acts as coenzyme for several vital metabolic reactions.
sion. 2. Essential for DNA synthesis
Indications Causes of Vitamin B12 Deficiency

Parenteral iron is indicated when 1. Addisonian pernicious anaemia due to deficiency of
1. oral iron is not tolerated, intrinsic factor, due to destruction of parietal cells, re-
2. failure of absorption, sulting in failure of B12 absorption.
3. noncompliance and 2. Other causes are gastrectomy, chronic gastritis, malab-
4. deficiency with bleeding. sorption and fish tape worm infestation (consumes
vitamin B12), nutritional deficiency and increased de- 2. Results in vomiting, abdominal pain, haematemesis,
mand during pregnancy and lactation. bloody diarrhoea, shock, drowsiness, cyanosis, acidosis,
dehydration, cardiovascular collapse and coma.
3. Death may occur in 6–12 h.
Manifestations of Deficiency
1 . Megaloblastic anaemia
Treatment
2. Glossitis
3. Neurological symptoms 1 . Gastric lavage with sodium bicarbonate
2. Desferrioxamine is injected IV/IM
3. Correction of acidosis and shock
Preparations, Dose and Administration
1. Cyanocobalamin: Redisol, Macrabin 35 µg/5 mL liq.; Q. 4. Iron–sorbitol–citric acid
100, 500, 1000 µg inj. daily Ans.
2. Hydroxocobalamin: Redisol-H, Macrabin-H 500, 1000 µg
inj. daily 1. Iron–sorbitol–citric acid complex (Jectofer) is a type of
3. Methylcobalamin: Biocobal, Diacobal 0.5 mg tab parenteral iron preparation.
2. Citric acid improves iron absorption.
Q. 3. Oral preparations of iron 3. It is low molecular weight compound, used only intra-
Ans. Iron is generally given orally or parenterally. muscularly. Absorbed directly into circulation and about
30% is excreted in urine.
4. It is indicated when
Oral Iron Preparations a. oral iron is not tolerated,
1. Ferrous sulphate contains 20% hydrated salt and 32% b. failure of absorption,
dried salt or elemental iron—200 mg tab. It is the oldest c. noncompliance and
and cheapest iron preparation. d. deficiency with bleeding.
2. Ferrous fumarate contains 33% elemental iron— 5. Iron–sorbitol–citric acid complex: 50 mg iron/mL;
200 mg tab. Jectofer 1.5 mL ampoule
3. Ferrous gluconate contains 12% elemental iron— 6. Intramuscular injection is given deep IM in the gluteal
300 mg tab. It cause less gastric irritation. region using ‘Z’ technique to avoid skin staining.
4. Ferrous succinate—100 mg 7. Intravenous iron is given slowly 5–10 min or as infu-
5. Iron calcium complex—5% iron sion.
a. Ferrous salts are better absorbed than ferric salts.
b. Last three preparations are better tolerated. Adverse Effects
1 . Local: Pain at the site of injection.
Indications of Oral Iron 2. Systemic: Fever, headache, joint pain, palpitation,
1. Iron deficiency anaemia, prophylactic treatment. difficulty in breathing, lymph node enlargement and
For 3–6 months to replenish iron stores. rarely anaphylaxis
2. Dose: Ferrous sulphate 3–4 tablets daily
Q. 5. Acute iron poisoning and role of desferrioxamine
in iron poisoning
Adverse Effects of Oral Iron
Ans.
1 . Epigastric pain
2. Nausea, vomiting, gastritis
3. Metallic taste ACUTE IRON POISONING
4. Constipation (due to astringent effect) or diarrhoea
5. Liquid preparations stain the teeth. 1 . Occurs on intake of 10 tablets or more can be lethal.
2. Results in vomiting, abdominal pain, haematemesis,
bloody diarrhoea, shock, drowsiness, cyanosis, acidosis,
Acute Iron Poisoning dehydration, cardiovascular collapse and coma.
1. Intake of 10 tablets or more can be lethal. 3. Death may occur in 6–12 h.
Treatment as that from haemosiderin and ferritin but not from

haemoglobin and cytochromes. One gram desferriox-
1 . Gastric lavage with sodium bicarbonate
amine is capable of chelating 85 mg of elemental iron.
2. Desferrioxamine is injected IV/IM.
3 . The straight chain desferrioxamine molecule winds
3. Correction of acidosis and shock
round ferric iron and forms a stable nontoxic compound
which is excreted in urine.
Role of Desferrioxamine
The role of desferrioxamine is as follows: Uses
1. Desferrioxamine is isolated from Streptomyces pilosus.
1 . Acute iron poisoning
2. It chelates iron and has a high affinity for iron, forms
2. Chronic iron poisoning—as in thalassaemia patients
stable complex and removes loosely bound iron as well
who receive repeated blood transfusions.
SHORT NOTES
Q. 1. Aetiology and drugs for anaemia 2. Ferrous salts are better absorbed than ferric salts.
Ans.
Adverse Effects of Oral Iron
ANAEMIA 1 . Epigastric pain
2. Nausea, vomiting, gastritis
Aetiology 3. Metallic taste
It occurs when the balance between production and destruc- 4. Constipation (due to astringent effect) or diarrhoea
tion of RBC is disturbed by the following: 5. Liquid preparations stain the teeth.
1. Blood loss
2. Impaired red cell formation due to deficiency of essen- Q. 3. Folic acid
tial factors like iron, vitamin B12, folic acid Ans. Folic acid is pteroylglutamic acid from spinach and
3. Bone marrow depression and increased destruction of RBC named as folic acid (from leaf).
1. Dietary source: Green vegetables, liver, yeast, egg, milk

Treatment and some fruits
Haematinics are drugs used for the formation of blood and 2. Absorption: It takes place in the duodenum and is trans-
treatment of anaemia. ported by active and passive transport.
Different drugs used for the treatment of anaemia are as 3. Widely distributed in the body and is stored in the liver.
follows:
1. Iron Functions
a. Oral ferrous gluconate, ferrous sulphate, ferrous
fumarate, colloidal ferric hydroxide Folic acid is converted to dihydrofolic acid and then to tet-
b. Parenteral iron dextran, iron–sorbitol–citric acid rahydrofolic acid which serves as a coenzyme for many
complex vital (one-carbon transfer) reactions necessary for DNA
2. Vitamin B12 synthesis.
3. Folic acid
Deficiency
Q. 2. Ferrous sulphate
1. Foliate deficiency may be due to dietary foliate defi-
Ans.
ciency.
Ferrous sulphate is a type of oral iron preparation. 2. Malabsorption and other diseases of the small intes-
Dose: Ferrous sulphate 3–4 tablets daily, 200 mg tab. tine or drug-induced phenytoin phenobarbitone, oral
contraceptives, methotrexate, increased requirements
like growing, pregnancy, etc. can cause folic acid
Indications deficiency.
1. Iron deficiency anaemia, prophylactic treatment. For 3. Manifestations include megaloblastic anaemia, glossi-
3–6 months to replenish iron stores tis, diarrhoea and weakness.
4. Dosage: Folic acid 2–5 mg/day orally Oral Iron Preparations

1. Ferrous sulphate contains 20% hydrated salt and 32%
Uses dried salt or elemental iron—200 mg tab. It is the oldest
and cheapest iron preparation.
1. In folic acid deficiency due to malabsorption syn-
2. Ferrous fumarate contains 33% elemental iron—
dromes, folic acid is given IM.
200 mg tab.
2. Prophylactically in pregnancy, lactation, infancy require
3. Ferrous gluconate contains 12% elemental iron—300 mg
500 µg daily orally.
tab. It causes less gastric irritation.
Q. 4. Indications for parenteral use of iron 4. Ferrous salts are better absorbed than ferric salts.
Ans.
Parenteral Iron Preparations
Iron is generally given parenterally as follows:
1. Iron dextran (Imferon) has 50 mg (2 mL ampoule) can
1. Intramuscular injection deep IM in the gluteal region
be given IM/IV.
using ‘Z’ technique to avoid skin staining.
2. Iron–sorbitol–citric acid complex (Jectofer)—50 mg/mL
2. Intravenous iron is given slowly 5–10 min or as in-
given IM but never IV.
fusion.
Q. 6. Vitamin C is given with iron in the treatment of
Indications anaemia of scurvy.
Parenteral iron is indicated when Ans.
1. oral iron is not tolerated,
1. Vitamin C and citric acid improve the absorption of iron
2. failure of absorption,
in the intestines.
3. noncompliance and
2. Ascorbic acid enhances iron absorption and is frequently
4. deficiency with bleeding.
combined with ferrous salts as it maintains them in re-
duced state. Anaemia of scurvy is corrected by ascorbic
Q. 5. Mention two oral and parenteral preparations.
acid, but no adjuvant value in other anaemias. Hence
Ans. vitamin C is used in the treatment of anaemia of scurvy.
Topic 37
Drugs Affecting Coagulation, Bleeding and Thrombosis

LONG ESSAYS
Q. 1. Enumerate the agents used to control bleeding. Thrombin Fibrinogen
Discuss the actions and uses of systemic coagulants.
Fibrin glue Antihaemophilic factor
Ans.
Gelatin Adrenochrome
l The agents that help in controlling bleeding and are Calcium alginate Adrenochrome monosemi-
used in preventing or treating haemorrhagic conditions carbazone
are known as coagulants. Oxidized cellulose Ethamsylate
l The coagulants are classified as follows:
Russell’s viper venom Desmopressin
Local Agents (Styptics) Systemic Agents

Astringents Fresh whole blood
Pharmacological actions and uses of various coagulants are
Adrenalin Vitamin K as follows:
SYSTEMIC AGENTS D. Antihaemophilic Factor

A. Whole Blood or Plasma l It is short-acting agent and is concentrated in human
antihaemophilic globulin (AHG) prepared from pooled
l Fresh blood or plasma provides all the factors needed human plasma.
for coagulation. l It contains coagulation factor VIII with von Willebrand’s
l It is the best treatment for deficiency of any clotting factor.
factor.
It acts immediately. l Uses: Used in patients with haemophilia, antihaemo-
l Uses: Emergency conditions to stop blood flow to prevent
philic globulin deficiency.
excess loss of blood.
E. Ethamsylate
B. Vitamin K
l It is a haemostatic, available for oral, IM and IV admin-
It is available as follows: istration.
i. K1 (from plants): Phytonadione (phylloquinone) l It reduces capillary bleeding when platelets are ade-
ii. K2 (produced by bacteria): Menaquinones quate, exerts antihyaluronidase action improves capillary
iii. K3 (synthetic) wall stability.
a. Fat-soluble: Menadione, acetomenaphthone l It inhibits PGI2 production and corrects abnormal plate-
b. Water-soluble: Menadione sodium bisulphate, mena- let function.
dione sodium diphosphate l Uses: In prevention and treatment of capillary bleeding
It is a dietary supplement required for the synthesis of in menorrhagia, after abortion, epistaxis, melena, hae-
the clotting factors. maturia and after tooth extraction.
Actions F. Desmopressin

l Vitamin K acts as a cofactor at a late stage in the liver It is synthetic analogue of vasopressin. It is used to control
for the synthesis of coagulation proteins: Prothrombin, mild to moderate bleeding in haemophilia A and von
factors VII, IX, and X. Willebrand’s disease. It is administered intravenously slowly.
l Vitamin K is also required for the carboxylation of glu-
tamic acid residues of osteocalcin, which is important Q. 2. Classify anticoagulants. Discuss the mechanism of
for bone development. action, uses and adverse effects of the coumarin deriva-
l It participates in coagulation cascade. tives.
l Fat-soluble forms of vitamin K are absorbed from intes-
Ans.
tine via lymph and require bile for absorption, while
water-soluble forms are directly absorbed into the portal Anticoagulants are drugs used to reduce the coagulability
blood. of blood. They may be classified according to their use as
follows:
Uses I. Used in vivo
a. Parenteral anticoagulants
i. Vitamin K is used in the prophylaxis and treatment of i. Heparin
bleeding due to deficiency of clotting factors. ii. Low molecular weight heparins (LMWHs):
ii. All newborns are recommended 1 mg IM of vitamin K Enoxaparin, dalteparin, tinzaparin and ardeparin
soon after birth as they have low levels of prothrombin iii. Heparinoids: Heparan sulphate, lepirudin and
and other clotting factors. danaparoid
iii. To reverse the overdose of oral anticoagulants b. Oral anticoagulants
iv. Water-soluble derivatives like menadione are used in i. Coumarin derivatives: Bishydroxycoumarin, war-
G-6-PD deficient patients. farin sodium, acenocoumarol, ethylbiscoumacetate
ii. Indanedione derivative: Phenindione
C. Fibrinogen (Human) II. Used in vitro
a. Heparin
l It is obtained from human plasma. b. Calcium complexing agents
l Fibrinogen initiates formation of fibrin clot and helps in i. Sodium citrate (used in blood banks to store the
coagulation. blood)
Uses: Used in patients with haemophilia, antihaemo- ii. Sodium oxalate
philic globulin deficiency and acute afibrinogenic states. iii. Sodium edetate
Coumarin Derivatives l They are to be applied topically and are not to be injected.
l Commonly used styptics or local haemostatic agents are
l Coumarin derivatives like bishydroxycoumarin, warfa-
as follows:
rin sodium, acenocoumarol, ethylbiscoumacetate act as
i. Thrombin
anticoagulants only in vivo and not in vitro.
ii. Fibrin
l This is because they act indirectly by interfering with
iii. Gelatin foam
the synthesis of vitamin K-dependent clotting factors
iv. Russell’s viper snake venom
(II, VII, IX and X) in the liver.
v. Adrenaline
l They behave as competitive antagonists of vitamin K
vi. Astringents
and reduce the plasma levels of functional clotting
factors in a dose dependent manner.
l They interfere with the regeneration of active hydroqui- a. Thrombin
none form of vitamin K which carries out the final step
l It is a freeze-dried powder obtained from bovine plasma
of gamma carboxylating glutamate residues of pro-
and applied topically as a dry powder or freshly pre-
thrombin and factors VII, IX and X.
pared solution on bleeding surfaces.
l Used in haemophilia, neurosurgery, skin grafting.
Uses l It can cause hypersensitivity reactions.
i. Deep vein thrombosis and pulmonary embolism

ii. Myocardial infarction b. Fibrin
iii. Unstable angina
It is prepared from the human plasma and used topically
iv. Rheumatic heart disease, atrial fibrillation
as sheets or foam for covering or packing the bleeding
v. Vascular surgery, prosthetic heart valves, retinal vessel
surfaces and left in the site as it is absorbed.
thrombosis, extracorporeal circulation, haemodialysis
Adverse Effects c. Gelatin Foam

l It is a protein and is used as a haemostatic in surgical
i. Bleeding: Bleeding is most important and common side
procedures. Spongy gelatin that is moistened with saline
effect of warfarin. It can occur anywhere like skin, GIT,
or thrombin solution and used for packing wounds.
urinary tract, cerebral, hepatic, uterine, etc.
l It also gets absorbed in 1–2 months.
ii. Teratogenic effect: Warfarin is contraindicated during
Russell’s viper snake venom
pregnancy as it may cause CNS abnormalities, fetal
l It contains proteolytic enzymes. It acts as thromboplas-
haemorrhage, abortion or intrauterine death.
tin when applied locally and is used to stop external
iii. Skin necrosis: It is a rare complication that occurs
bleeding in haemophilics.
within the first week of therapy. Skin lesions are com-
monly seen on breast, buttocks, abdomen and thighs.
iv. Other rare side effects: They include diarrhoea, alope- d. Vasoconstrictors
cia, urticaria, abdominal cramps and anorexia.
l One percent adrenaline soaked in sterile cotton gauze
Commonly seen adverse effects associated with individual may stop epistaxis or some other similar bleeding.
drugs are as follows: l Two percent adrenaline is used in local anaesthetics to
a. Bishydroxycoumarin: Frequent GIT disturbances control bleeding during tooth extraction.
b. Warfarin sodium: Alopecia, dermatitis, diarrhoea
c. Acenocoumarol: Oral ulceration, GIT disturbances,
dermatitis, urticaria, alopecia
e. Astringents
d. Ethylbiscoumacetate: Alopecia, bad taste They precipitate proteins locally in the bleeding site and
control capillary oozing, e.g. 20% tannic acid mixed in
Q. 3. Enumerate styptics. Describe the role of vitamin K glycerine is used for bleeding gums, bleeding piles.
when bleeding is due to oral anticoagulation therapy.
Ans. Role of Vitamin K
l Styptics are local haemostatic substances used to stop Role of vitamin K in bleeding due to oral anticoagulation
bleeding from a local approachable site. therapy is as follows:
l They are particularly effective on oozing surfaces like l Oral anticoagulants act by interfering with the synthesis
tooth sockets. of vitamin K-dependent clotting factors in the liver.
l They behave as competitive antagonist of vitamin K and Adverse Effects

reduce the plasma levels of functional clotting factors in
i. Bleeding due to overdose
a dose-dependent manner.
ii. Thrombocytopenia
l It interferes with regeneration of the active hydroqui-
iii. Osteoporosis and alopecia
none form of vitamin K which carries out the final step
of g-carboxylating residues of prothrombin and factors
VII, IX and X. Heparin Antagonist
l This carboxylation is essential for the ability of the
Protamine sulphate is a highly basic, low molecular weight
clotting factors to bind Ca21 and to get bound phospho- protein obtained from the sperm of fish. It neutralizes
lipid surface necessary for the coagulation sequence to heparin weight. One milligram is required for every 100 U
proceed. of heparin. It is used when heparin action needs to be ter-
l Vitamin K acts as an antidote for warfarin.
minated rapidly as in after cardiac or vascular surgery and
l Administration of vitamin K by competitive antagonism
for heparin-induced bleeding.
with oral anticoagulants reduces the anticoagulant
action and brings about carboxylation of glumate resi-
dues of prothrombin and factor VII, IX and X necessary Warfarin Sodium
for coagulation sequence to proceed. l Warfarin sodium is an oral anticoagulant derived from
l Hence vitamin K is used for bleeding due to oral antico- coumarin.
agulant therapy. l They are used in vivo and not vitro. This is because they
act indirectly by interfering with the synthesis of vita-

Q. 4. Describe how heparin and dicumarol act as anti- min K-dependent clotting factors in the liver.
coagulants. Indicate their route of administration, l Mechanism of action: They behave as competitive an-
duration of action and name their antagonists. tagonists of vitamin K and reduce the plasma levels of
functional clotting factors in a dose-dependent manner.
l They interfere with the regeneration of active hydroqui-
Heparin none form of vitamin K which carries out the final step
l Heparin is named so because of its high concentration of gamma carboxylating glutamate residues of pro-
in the liver. It is a fast-acting anticoagulant used in vitro thrombin and factors VII, IX, X.
and vivo.
l It is a mucopolysaccharide, found in the mast cells of Uses
liver, lung and intestinal mucosa. It is the strongest or-
ganic acid in the body. i. Deep vein thrombosis and pulmonary embolism
l Heparin acts as an anticoagulant, clears lipaemia and
ii. Myocardial infarction
also has antiplatelet activity. iii. Unstable angina
l Mechanism of action: Heparin acts by activating plasma
iv. Rheumatic heart disease, atrial fibrillation
antithrombin III which binds to and inactivates clotting v. Vascular surgery, prosthetic heart valves, retinal vessel
factors Xa and thrombin-mediated conversion of fi- thrombosis, extracorporeal circulation, haemodialysis
brinogen to fibrin.
l Heparin–antithrombin complex binds to the clotting Adverse Effects
factors of intrinsic as well as extrinsic pathways. Thus
i. Bishydroxycoumarin: Frequent GIT disturbances
heparin inactivates the clotting factors halting the pro-
ii. Warfarin sodium: Alopecia, dermatitis, diarrhoea
gression of coagulation pathway and increases the clot-
iii. Acenocoumarol: Oral ulceration, GIT disturbances,
ting time.
dermatitis, urticaria, alopecia
iv. Ethyl biscoumacetate: Alopecia, bad taste
Uses
Role of vitamin K in bleeding due to oral anticoagulation
i. Prophylaxis of deep vein thrombosis in high risk pa- therapy as follows:
tients undergoing surgery l Oral anticoagulants act by interfering with the synthesis
ii. Treatment of established deep vein thrombosis of vitamin K-dependent clotting factors in the liver.
iii. Unstable angina l They behave as competitive antagonist of vitamin K and
iv. To maintain patency of the canula and shunts in dialysis reduce the plasma levels of functional clotting factors in
patients and in extracorporeal circulation a dose-dependent manner.
l Vitamin K acts as an antidote for warfarin. l Heparin acts as an anticoagulant, clears lipaemia and
l Administration of vitamin K by competitive antagonism also has antiplatelet activity.
with oral anticoagulants, reduces the anticoagulant ac- l Mechanism of action: Heparin acts by activating plasma
tion and brings about carboxylation of glumate residues antithrombin III which binds to and inactivates clotting
of prothrombin and factor VII, IX and X necessary for factors Xa and thrombin-mediated conversion of fi-
coagulation sequence to proceed. brinogen to fibrin.
l Hence vitamin K is used for bleeding due to oral antico- l Heparin–antithrombin complex binds to the clotting
agulant therapy. factors of intrinsic as well as extrinsic pathways. Thus

heparin inactivates the clotting factors halting the pro-
Q. 5. Classify anticoagulants and explain in detail about gression of coagulation pathway and increases the clot-
pharmacological action, pharmacodynamics, therapeu- ting time.
tic uses and toxicity of heparin.
Ans. Uses
Anticoagulants are drugs used to reduce the coagulability of i. Prophylaxis of deep vein thrombosis in high risk pa-
blood. They may be classified according to their use as follows: tients undergoing surgery
1. Used in vivo ii. Treatment of established deep vein thrombosis
a. Parenteral anticoagulant—heparin, low molecular iii. Unstable angina
weight heparin iv. To maintain patency of the canula and shunts in dialysis
b. Oral anticoagulants patients and in extracorporeal circulation
i. Coumarin derivatives—bishydroxycoumarin, war-
farin sodium, acenocoumarol, ethylbiscoumacetate
Adverse Effects
ii. Indanedione derivative—phenindione
2. Used in vitro i. Bleeding due to overdose
a. Heparin ii. Thrombocytopenia
b. Calcium complexing agent iii. Osteoporosis and alopecia
i. Sodium citrate
ii. Sodium oxalate
Heparin Antagonist
iii. Sodium edentate
Protamine sulphate is a highly basic, low molecular weight
protein obtained from the sperm of fish. It neutralizes
Heparin heparin weight. One milligram is required for every 100 U
l Heparin is a fast-acting anticoagulant used in vitro and vivo. of heparin. It is used when heparin action needs to be ter-
l It is a mucopolysaccharide, found in the mast cells of minated rapidly as in after cardiac or vascular surgery and
liver, lung and intestinal mucosa. It is the strongest acid for heparin-induced bleeding.
in the body.
SHORT ESSAYS
Q. 1. Styptics 5. Adrenaline
6. Astringents
Ans.
l Styptics are local haemostatic substances used to stop Thrombin

bleeding from a local approachable site.
l They are particularly effective on oozing surfaces like l It is obtained from bovine plasma and applied as a dry
tooth sockets. powder or freshly prepared solution on bleeding surface.
l They are to be applied topically and are not to be injected. l Used in haemophilia, neurosurgery, skin grafting.
l Commonly used styptics or local haemostatic agents are
as follows: Fibrin
1. Thrombin
2. Fibrin It is prepared from the human plasma and used as sheets or
3. Gelatin foam foam for covering or packing the bleeding surface and left
4. Russell’s viper snake venom in the site as it is absorbed.
Gelatin Foam TABLE 37.1 Comparison between Heparin and Dicumarol
l It is spongy gelatin and used for packing wounds. Parameters to Be Warfarin (Oral
l It also gets absorbed in 1–2 months. Compared Heparin Anticoagulant)
Chemistry Mucopolysaccha- Coumarin deriva-
ride tive
Russell’s Viper Snake Venom
Source Beef lung, pig in- Synthetic
l It acts as thromboplastin when applied locally and is testine
used to stop external bleeding in haemophilics. Route of adminis- Parenteral (IV infu- Oral
tration sion or IV intermit-
tent injection)
Vasoconstrictors
Onset of action Immediate Delayed (3–4
l One percent adrenaline soaked in sterile cotton gauze days)
may stop epistaxis or some other similar bleeding.
Duration of action 4–6 h 3–6 h
Activity In vivo and vitro In vivo only
Astringents
Mechanism Blocks action of Inhibits synthesis
One percent tannic acid mixed in glycerine is used for factor X and of clotting factors
bleeding gums, bleeding piles. thrombin
Antagonist Prothrombin sul- Vitamin K
Q. 2. Anticoagulants phate
Ans. Variability in re- Little Marked

sponse
Anticoagulants are drugs used to reduce the coagulability Drug interaction Few and insignifi- Many and signifi-
of blood. They may be classified according to their use as cant cant
follows: Use To initiate antico- For maintenance
1. Used in vivo agulant therapy
a. Parenteral anticoagulant—heparin, low molecular
weight heparin
b. Oral anticoagulants Q. 4. Name two oral anticoagulants. Mention one drug
i. Coumarin derivatives—bishydroxycoumarin, war- treating toxicity of oral anticoagulants.
farin sodium, acenocoumarol Or,
ii. Indanedione derivative—phenindione
2. Used in vitro Dicumarol poisoning
a. Heparin Ans.
b. Calcium complexing agent
i. Sodium citrate l Oral anticoagulants are drugs given orally used to re-
ii. Sodium oxalate duce the coagulability of blood.
iii. Sodium edentate l They may be classified as follows:
3. Uses of anticoagulants 1. Coumarin derivatives—bishydroxycoumarin, warfa-

a. Deep vein thrombosis and pulmonary embolism rin sodium, acenocoumarol, ethylbiscoumacetate
b. Myocardial infarction 2. Indanedione derivative—phenindione
c. Unstable angina
Role of vitamin K in bleeding due to oral anticoagulation
d. Rheumatic heart disease, atrial fibrillation
therapy:
e. Vascular surgery, prosthetic heart valves, retinal ves-
l Oral anticoagulants act by interfering with the synthesis
sel thrombosis, extracorporeal circulation, haemodi-
of vitamin K-dependent clotting factors in the liver.
alysis
l They behave as competitive antagonist of vitamin K and
Q. 3. Compare heparin and oral anticoagulants reduce the plasma levels of functional clotting factors in
Or, l It interferes with regeneration of the active hydroqui-
Compare heparin and dicumarol none form of vitamin K.

l Vitamin K acts as an antidote for warfarin.
Ans. Comparison between heparin and dicumarol is listed l Administration of vitamin K by competitive antagonism
in Table 37.1. with oral anticoagulants, reduces the anticoagulant
action and brings about carboxylation of glumate resi- Ans.

dues of prothrombin and factor VII, IX and X necessary
for coagulation sequence to proceed. l It is a fibrinolytic obtained from b haemolytic strepto-
l Hence vitamin K is used for bleeding due to oral antico-
cocci group C.
l It is inactive till it combines with circulating plasmino-
agulant therapy.
gen to form an activator complex, which then causes
Q. 5. Adverse effects of cyanocobalamin or vitamin B12 limited proteolysis of other plasminogen molecules to
plasmin.
Ans. l If antistreptococcal antibodies are present in the
l Vitamin B12 also known as cyanacobalamin, antiperni- body, they inactivate a considerable amount of initial
cious vitamin or extrinsic factor of Castle, is a water- dose.
soluble vitamin, synthesized by microorganisms.
l Sources: Liver, fish, egg yolk, meat, cheese, pulses Mechanism of Action
l Physiological functions: Acts as coenzyme for several
vital metabolic reactions, essential for DNA synthesis. Streptokinase combines with plasminogen to form plasmin,
l Daily requirement
which helps in the conversion of insoluble fibrin to soluble
l Adults: 1–3 µg
fibrin fragments.
l Pregnancy and lactation: 3–4 µg Streptokinase 1 PlasminogennPlasmin
l Causes of deficiency: Addisonian anaemia due to defi- g
ciency of intrinsic factor or due to destruction of parietal Insoluble fibrinnSoluble fibrin fragments
cells resulting in failure of B12 absorption.
l Other causes: Gastrectomy, chronic gastritis, malab-
sorption and fish tape worm infestation (consumes
vitamin B12) l Venous thrombi are lysed more easily than arterial
thrombi.
l Recent thrombi respond better.
Uses l Effect on thrombi more than 3 days old is less.
1. Treatment of vitamin B12 deficiency

a. Cyanocobalamin: 100 mL inj. daily Disadvantages
b. Hydroxocobalamin: 100–500, 1000 mg daily.
2. Multivitamins for oral use l It is antigenic and can cause hypersensitivity reactions
a. B12 deficiency: Prophylaxis 3–10 mg daily and anaphylaxis.
b. Treatment of megaloblastic anaemia l Can be neutralized by antibodies.
3. B12 neuropathies, psychiatric disorders, cutaneous sar- l Fever, hypotension and arrhythmias can occur.
coid and as general tonic to allay fatigue and improve

growth Uses
1 . Myocardial infarction: 7.5 lakh IU infused over 1 h
Adverse Effects 2. DVT and pulmonary embolism: 2.5 lakh IU loading
Anaphyloid reaction on IV injection due to sulphite con- dose over ½–1 h followed by 1 lakh IU/h for 24 h
tained in the formulation.
Advantage
Q. 6. Explain the mechanism of action of streptokinase
and mention one use of it. 1. Cheap to use among all fibrinolytics
SHORT NOTES
Q. 1. Vitamin K deficiency l Deficiency causes bleeding tendencies which manifests
itself first as haematuria and then in the GIT, nose and
Ans.
under skin such as ecchymoses.
l Vitamin K acts as a cofactor in the synthesis of coagula-
tion proteins—prothrombin, factors VII, IX and X in the Q. 2. Styptics
liver. Ans.
l Deficiency of vitamin K occurs due to liver diseases,
obstructive jaundice, malabsorption and long-term anti- l Styptics are local haemostatic substances used to stop
microbial therapy which alters intestinal flora. bleeding from a local approachable site.
l They are particularly effective on oozing surfaces like Adverse Effects

tooth sockets. They are to be applied topically and are
Bleeding due to overdose, thrombocytopenia, osteoporosis
not to be injected.
and alopecia
l Commonly used styptics are as follows:
1. Thrombin
Q. 5. Vitamin K
2. Fibrin
3. Gelatin foam Ans.
4. Russell’s viper snake venom
5. Vasoconstrictors l Vitamin K is a fat-soluble dietary principle required for
6. Astringents the synthesis of clotting factors.
l Vitamin K acts as a cofactor in the synthesis of coagulation
Q. 3. Streptokinase proteins—prothrombin, factors VII, IX and X in the liver.

Ans.
Uses
l It is a fibrinolytic obtained from b haemolytic strepto-
cocci of group C. 1 . In vitamin K deficiency
l It is inactive till it combines with circulating plasmino-
2. Newborn babies lack intestinal flora and have low levels
gen to form an activator complex, which then causes of prothrombin and other clotting factors. Routine ad-
limited proteolysis of other plasminogen molecules to ministration of vitamin K—1 mg IM prevents haemor-
plasmin. rhagic diesease of the newborn.
l Deficiency of vitamin K occurs due to liver diseases,
obstructive jaundice, malabsorption, and long-term

Mechanism of Action antimicrobial therapy which alters intestinal flora.
l Streptokinase combines with plasminogen to form plas-
min, which helps in the conversion of insoluble fibrin to Q. 6. Fibrinolytic agents
soluble fibrin fragments. Ans.
l Fibrinolytics or thrombolytics are drugs that lyse the

Disadvantages clot or thrombus by activating the natural fibrinolytic
l It is antigenic and can cause hypersensitivity reactions system. The fibrinolytic agents are streptokinase, uroki-
and anaphylaxis. nase and alteplase.
l Can be neutralized by antibodies. l Mechanism of action: Fibrinolytics combine with circu-
l Fever, hypotension and arrhythmias can occur. lating plasminogen to form plasmin, which helps in the
conversion of insoluble fibrin to soluble fibrin fragments.
Uses
Uses
l DVT and pulmonary embolism 1 . Acute myocardial infarction
2. Deep vein thrombosis, pulmonary emboli
Q. 4. Heparin l Adverse effects: Bleeding, hypotension, fever. Ana-
phylactic reactions are common with streptokinase.

Ans.
l They are contraindicated in recent surgeries, injury,
l Heparin is named so because of its high concentration gastrointestinal bleeding, stroke, severe hypertension
in the liver. and bleeding disorders.
l It is found in the mast cells of liver, lung and intestinal
mucosa. Q. 7. Haemostasis
l Heparin acts as an anticoagulant and is used in vitro and
Ans.
vivo.
l Haemostasis is the process of stopping bleeding post-
surgically or from a site of injury.
Uses l Haemostasis may be achieved by applying pressure at
1 . Treatment of established deep vein thrombosis the bleeding site or by suturing it. Uncontrolled bleed-
2. Unstable angina ing may be stopped using styptics.
3. To maintain patency of the cannula and shunts in dialysis l Styptics are local haemostatic substances, which are
patients and in extracorporeal circulation applied topically, used to stop bleeding from a local
approachable site. Commonly used styptics are throm- Ans.

bin, fibrin, gelatin foam, etc.
l Heparin acts by activating plasma antithrombin III
Q. 8. Warfarin sodium which binds to and inactivates clotting factors Xa and
thrombin-mediated conversion of fibrinogen to fibrin.
Ans. l Heparin–antithrombin complex binds to the clotting
l Warfarin sodium is an oral anticoagulant derived from factors of intrinsic as well as extrinsic pathways.
l Thus heparin inactivates the clotting factors halting the
coumarin.
l They are used in vivo and not vitro. This is because they
progression of coagulation pathway and increasing the
act indirectly by interfering with the synthesis of vita- clotting time.
min K-dependent clotting factors in the liver.
Q. 11. Drugs used in pernicious anaemia
l They behave as competitive antagonists of vitamin K and
reduce the plasma levels of functional clotting factors in Ans.

l Deficiency of vitamin B12 occurs due to absence of in-
trinsic factor and manifests itself as pernicious anaemia
Used in in which there is autoimmune gastric mucosal damage
1. Deep vein thrombosis and pulmonary embolism, myo- or chronic gastritis, gastric carcinoma.
l It can be treated with vitamin B12 supplements along with
cardial infarction
2. Unstable angina, vascular surgery, prosthetic heart 1–5 mg of folic acid and an iron preparation. The folic acid
valves, retinal vessel thrombosis, extracorporeal circu- and iron preparations are added because reconstitution of
lation, haemodialysis, etc. brisk haemopoiesis may unmask deficiency of these factors.
Q. 9. Oral anticoagulants Q. 12. Classification of anticoagulants
Ans. Ans.
l Oral anticoagulants are drugs given orally used to re- Anticoagulants are drugs used to reduce the coagulability
duce the coagulability of blood. of blood.
l They may be classified as follows:
They may be classified according to their use as follows:
1. Coumarin derivatives—bishydroxycoumarin, warfa- 1. Used in vivo
rin sodium, acenocoumarol, ethylbiscoumacetate a. Parenteral anticoagulant: Heparin, low molecular
2. Indanedione derivative—phenindione weight heparin
l They are used in vivo and not vitro. This is because they
b. Oral anticoagulants
act indirectly by interfering with the synthesis of vita- i. Coumarin derivatives: Bishydroxycoumarin, war-
min K-dependent clotting factors in the liver. farin sodium, acenocoumarol, ethylbiscoumacetate
l They behave as competitive antagonists of vitamin K
ii. Indanedione derivative: Phenindione
and reduce the plasma levels of functional clotting fac- 2. Used in vitro
tors in a dose-dependent manner. a. Heparin
b. Calcium complexing agents: Sodium citrate, sodium
Q. 10. Mechanism of action of heparin oxalate and sodium edentate
Topic 38
Hypolipoproteinaemic Drugs and Plasma Expanders

SHORT ESSAYS
Q. 1. What is plasma expander? Give two examples and when infused intravenously they retain fluid in the vascular
briefly describe them. compartment. For example: Human albumin, dextran, de-
graded gelatinpolymer (polygeline), hydroxyethyl starch
Ans. The plasma expanders are high molecular weight
(HES, hetastarch), polyvinyl pyrrolidone (PVP).
substances which exert colloidal osmotic pressure and
Human Albumin l It is a polysaccharide obtained from sugar beat.

l Dextran 70 is most commonly used preparation. It expands
l Available as Albudac, Albupan 50, 100 mL inj, Albumed
plasma volume for nearly 24 h. It is slowly excreted by
5%, 20% infusion (100 mL).
glomerular filtration and as well oxidized in the body over
l It is obtained from pooled human plasma; 100 mL of 20%
a period of weeks.
human albumin solution is osmotically equivalent to 400 mL
l Dextran 40 acts more rapidly than Dextran 70
of fresh frozen plasma or 800 mL of whole blood.
and it reduces blood viscosity and prevents RBC
sludging.
Advantages l Advantage of dextran: Dextran can be stored for
1 . It can be used irrespective of patient's blood group. 10 years and is economical.

2. It does not interfere with coagulation.
Q. 2. Classify the hypolipidemic drugs.
3. As the preparation is heat treated it is free from risk of
transmitting serum hepatitis. Ans.
4. No risk of sensitization on repeated infusions
Hypolipidemic drugs are classified as follows:
1. HMG–CoA reductase inhibitors (statins): Lovastatin,
Disadvantages simvastatin, atorvastatin
1 . Occasionally febrile reaction occurs to human albumin. 2. Bile acid sequestrants (resins): Cholestyramine, cole
2. It is expensive. stipol
3. Active lipoprotein lipase (fibric acid derivatives): Clofi-
brate, gemfibrozil, fenofibrate
Dextran
4. Inhibit triglyceride synthesis and lipolysis: Nicotinic
l Most commonly used plasma expander. Available in acid
two forms Dextran 70 and Dextran 40. 5. Others include: Ezetimibe, gugulipid
SHORT NOTES
Q. 1. Plasma expanders Q. 2. Atorvastatin
Ans. Ans.
l The plasma expanders are high molecular weight sub- l It is the latest statin and is more potent and has highest
stances which exert colloidal osmotic pressure and LDL-CH lowering efficacy and also has additional anti-
when infused intravenously they retain fluid in the vas- oxidant property.
cular compartment, e.g. human albumin, dextran, hy- l Available as Aztor, Atorva, Atorlip 10, 20 mg tablets.
droxyethyl starch (HES, hetastarch), etc. l Should be given in the doses of 10–40 mg/day with
l They are primarily used as substitutes for plasma in maximum limit of 80 mg.
conditions like burns, severe trauma, etc. l Uses: It is the first choice of drug in primary hyperlipid-
l Contraindications to plasma expanders are severe anae- emias and secondary hypercholesterolemia.
mia, cardiac failure, pulmonary oedema renal insuffi- l Adverse effects: Headache, nausea, sleep disturbances,
ciency. muscle tenderness, etc.

Part XI
Gastrointestinal Drugs
Topic 39
Drugs for Peptic Ulcer

SHORT ESSAYS
Q. 1. What is antacid? Describe the properties and l Most of the antacids have either magnesium hydroxide
mechanism of action. Classify them with suitable ex- or aluminium hydroxide or calcium carbonate alone or
amples. Mention the merits and demerits of NaHCO3 as in combination with their main components.
an antacid. l They are effective in relieving pain of peptic ulcer.
l Antacids are potent drugs in gastroesophageal reflux

Ans.
disease.
l Antacids are basic substances, which chemically react
with gastric acid to form salts and water and increase
the pH of the gastric contents above 4, thereby reducing
Classification
gastric acidity immediately. The antacids are classified into following two types:
l Antacids do not decrease acid production and hence the A. Systemic antacids, e.g. sodium bicarbonate and sodium
potency of an antacid is generally expressed in terms of citrate
its acid neutralizing capacity (ANC). B. Nonsystemic antacids, e.g. magnesium hydroxide,
aluminium hydroxide gel, calcium carbonate
Mechanism of Action
Systemic Antacids
l Antacids do not reduce the acid production but raise the
antral pH, which causes reflex gastrin release. This l They are water soluble.
causes more secretion of gastric acid. Then acid rebound l They act instantaneously but duration of action is short.
occurs and the gastric motility is increased causing rapid l They are potent neutralizers as they may rise the pH up
gastric emptying. to above 7.
l Mechanism of action of antacids is depicted as follows:
Nonsystemic Antacids
Administration of antacid l They are insoluble and poorly absorbed basic com-
pounds and react in stomach to form corresponding
Increase in antral pH above 4 chloride salt.
l When this reaches the intestine, the chloride salt reacts
with bicarbonate, so HCO3 is not available for absorp-

Reflux gastrin release
tion hence there is no systemic alkalosis.
Increased gastric acid production

Sodium Bicarbonate NAHCO3
Increased gastric motility It is water soluble, acts instantaneously. It is very effective
and rapidly neutralizes gastric acid, but the duration of
Rapid gastric emptying action is short.
The demerits of NaHCO3 are as follows:
l It is absorbed systemically, large doses will induce
Gastric acidity reduced metabolic alkalosis.
l It produces carbon dioxide in the stomach which may . Ulcer healing drugs: Carbenoxolone sodium
d
cause distension, discomfort, belching and risk of ulcer e. Anti-H. pylori drugs: Amoxicillin, clarithromycin,
formation. metronidazole, tinidazole and tetracycline
l Increased sodium retention causes oedema and conges-
tive heart failure (CHF). Q. 3. Antihistaminic drugs in peptic ulcer

l It should be avoided in the patients with hypertension and
Or,
congestive cardiac failure as it causes sodium retention.
l It produces rebound acidity. H2 blockers
Ans.
Uses
l The antihistamines used in the treatment of peptic ulcer
Sodium bicarbonate is used to alkalinize the urine and to are H2 receptor antagonists or H2 blockers.
treat acidosis. l They include cimetidine, ranitidine, famotidine, loxati-
Combination of antacids produces various benefits which dine and roxatidine.

are as follows: l They competitively block the effects of histamine and
l A combination of two or more antacids is frequently inhibit its action on H2 receptors on parietal cells and
used, e.g. acidin, digene, gelusil and mucaine. this in turn inhibits gastric acid secretion.
l Aluminium hydroxide gel and magnesium trisilicate are l They suppress the secretion of acid in all the phases
combined and used as antacids to maximize the wanted (basal, cephalic and gastric). They mainly suppress
effects and minimize the adverse effects. nocturnal gastric acid secretion. They also reduce acid
l Magnesium containing antacids can cause diarrhoea secretion stimulated by acetylcholine (ACh), food,
while aluminium and calcium containing antacids cause gastrin, etc.
constipation. l They heal about 90% of the ulcerations in one dose.
l Magnesium trisilicate is a fast-acting drug and hastens These help in effectively promoting healing of peptic
gastric emptying, while aluminium hydroxide is slow ulcer and preventing its recurrence.
acting and delays gastric emptying. Combining the l They play important role in Zollinger-Ellison syndrome
drugs prolong the action of the drug to a required level and in gastroesophageal reflex.
and makes it intermediate acting. l They are highly selective and have no effect on H1
l Combining the drugs neutralizes the laxating effect of mediated responses.

magnesium trisilicate and constipating effect of alu-
minium hydroxide. Q. 4. Cimetidine
Ans.
Q. 2. Classify drugs used in treatment of peptic ulcer.
Ans. l Cimetidine was first H2 blocker to be introduced. It is a
competitive inhibitor.
The gastric mucosa is protected due to its ability to secrete l It is well absorbed orally but due to first-pass metabo-
mucous, bicarbonate and prostaglandins. lism, the bioavailability of the drug reduces to about
Classification of drugs used in the treatment of peptic ulcer 60–80%.
is as follows: l It has shorter duration of action. It acts for about 6–8 h.
1. Drugs that inhibit gastric acid secretion l Though it has poor ability to penetrate the CNS, it
a. Proton pump inhibitors: Omeprazole, lansoprazole, crosses the placental barrier easily and is also secreted
pantoprazole, rabeprazole in milk.
b. H2 receptor antagonists: Cimetidine, ranitidine,
famotidine, nizatidine and roxatidine
Adverse Effects
c. Antimuscarinic agents (anticholinergic agents):
Pirenzepine, telenzepine 1. It has antiandrogenic action and inhibits oestrogen to be
d. Prostaglandin analogues: Misoprostol, enprostil metabolized in the liver. Gynaecomastia, loss of libido
2. Drugs that neutralize gastric acid secretion (antacids) and impotence are caused due to prolonged use.
a. Systemic antacids: Sodium bicarbonate, sodium citrate 2. Headache, dizziness, xerostomia, rashes and diar-
b. Nonsystemic antacids: Aluminium hydroxide, mag- rhoea are some common effects seen with the use of
nesium hydroxide, magnesium trisilicate, calcium cimetidine.
carbonate 3. It crosses blood-brain barrier (BBB) and produces
c. Ulcer protectives: Sucralfate, colloidal bismuth sub- confusion, hallucination and delirium in some people
citrate (CBS) especially geriatric patients.
Q. 5. Ranitidine l Most of the antacids have either magnesium hydroxide

or aluminium hydroxide or calcium carbonate alone or
Ans.
in combination with their main components.
l It is well absorbed orally but due to first-pass metabolism, l They are effective in relieving pain of peptic ulcer.
the bioavailability of the drug reduces to about 60–80%. l Antacids are potent drugs in gastroesophageal reflux
l It is a competitive inhibitor, and is five times more po- disease.

tent than cimetidine.
l It has longer duration of action. It acts for about 12–24 h.
Classification
l It has lesser ability to penetrate the CNS than cimetidine.
The antacids are classified into following two types:
1. Systemic antacids, e.g. sodium bicarbonate and sodium
Adverse effects citrate
1. Headache, dizziness, xerostomia, rashes and diarrhoea 2. Nonsystemic antacids, e.g. magnesium hydroxide,
are some common effects seen with the use of cimetidine. aluminium hydroxide gel, calcium carbonate
2. It may also cause confusion, hallucination and delirium
in some people especially geriatric patients. Systemic Antacids
Q. 6. Antacids l They are water soluble.
l They act instantaneously but duration of action is short.
Ans.
l They are potent neutralizers as they may rise the pH up
l Antacids are basic substances, which chemically react to above 7.

with gastric acid to form salts and water and increase
the pH of the gastric contents above 4, thereby reducing Nonsystemic Antacids
gastric acidity immediately.
l Antacids do not decrease acid production and hence the l They are insoluble and poorly absorbed basic com-
potency of an antacid is generally expressed in terms of pounds and react in stomach to form corresponding
its acid neutralizing capacity (ANC). chloride salt.
l When this reaches the intestine, the chloride salt reacts
with bicarbonate, so HCO3 is not available for absorp-

Mechanism of Action tion, hence there is no systemic alkalosis.
l Antacids do not reduce the acid production but raise the
antral pH, which causes reflex gastrin release. This Q. 7. Aluminium hydroxide
causes more secretion of gastric acid. Then acid rebound Ans.
occurs and the gastric motility is increased causing rapid
gastric emptying. l Aluminium hydroxide gel is a weak base, which chemi-
l Mechanism of action of antacids is depicted as follows: cally reacts with gastric acid to form salt and water and
increase the pH of the gastric contents above 4, thereby
Administration of antacid reducing gastric acidity immediately.
l It is a weak antacid which polymerises on storing, to
Increase in antral pH above 4

further form lesser reactive products. Thus the acid neu-
tralizing capacity of the drug decreases on prolonged
storage.
Reflux gastrin release
Increased gastric acid production

Mechanism of Action
l It does not reduce the acid production but raises the an-
Increased gastric motility tral pH, which causes reflex gastrin release. This causes
more secretion of gastric acid. Then acid rebound occurs
and the gastric motility is increased causing rapid gastric
Rapid gastric emptying
emptying.
l It is effective in relieving pain of peptic ulcer.
Gastric acidity reduced l It is a potent drug in gastroesophageal reflux disease.
Combining Antacids l Magnesium trisilicate is a fast-acting drug and hastens

gastric emptying, while aluminium hydroxide is slow
l Aluminium hydroxide gel and magnesium trisilicate are acting and delays gastric emptying. Combining the
combined and used as antacids to maximize the wanted drugs neutralizes the laxating effect of magnesium tri-
effects and minimize the adverse effects. silicate and constipating effect of aluminium hydroxide.
SHORT NOTES
Q. 1. Cimetidine l Omeprazole reduces pain rapidly. Faster healing has
been demonstrated with 40 mg/day.
Ans.
l Cimetidine was first H2 blocker and is a competitive Uses

inhibitor.
l It is well absorbed orally but due to first-pass metabo-
l Omeprazole is more effective than H2 blockers on ulcers
lism, the bioavailability of the drug reduces to about and in healing of oesophageal lesions.
l It controls hyperacidity in Zollinger-Ellison syndrome.
60–80%.
l Continued treatment can prevent relapse. It also con-
l Has shorter duration of action. It acts for about 6–8 h.
trols bleeding from peptic ulcer.
l Omeprazole is an integral component of anti-H. pylori
Adverse Effects therapy.
l It has antiandrogenic action.
l Headache, dizziness, xerostomia, rashes and diarrhoea Q. 4. Ranitidine
are some common effects seen with the use of cimetidine. Ans.
Q. 2. Antacids l It is a H2 receptor antagonist, a competitive inhibitor,

and is five times more potent than cimetidine.
Ans.
l It is well absorbed orally but due to first-pass metabolism,
l Antacids are weak bases, which chemically react with the bioavailability of the drug reduces to about 60–80%.
gastric acid to form salts and water and increase the pH l Has longer duration of action, acts for about 12–24 h.
of the gastric contents above 4, thereby reducing gastric

acidity immediately. Adverse Effects
l Most of the antacids have either magnesium hydroxide
or aluminium hydroxide or calcium carbonate alone or l Headache, dizziness, xerostomia, rashes and diarrhoea
in combination with their main components. are some common effects seen with the use of ranitidine.
l It may also cause confusion, hallucination and delirium
l Antacids do not decrease acid production and hence
potency of antacid is expressed in terms of its acid in some people especially geriatric patients.
neutralizing capacity.
Q. 5. Aluminium hydroxide
l The antacids are classified into two types as follows:
a. Systemic antacids, e.g. sodium bicarbonate and Ans.

sodium citrate
b. Nonsystemic antacids, e.g. magnesium hydroxide, l Aluminium hydroxide gel is a weak base, which chemi-
aluminium hydroxide gel, calcium carbonate. cally reacts with gastric acid to form salt and water and
increase the pH of the gastric contents above 4, thereby
Q. 3. Omeprazole reducing gastric acidity immediately.
l It does not reduce the acid production but raises the an-
Or, tral pH, which causes reflex gastrin release. This causes
What is omeprazole? Mention its two uses. more secretion of gastric acid. Then acid rebound occurs
and the gastric motility is increased causing rapid gastric
Ans. emptying.
l It is effective in relieving pain of peptic ulcer.
l Omeprazole is a proton pump inhibitor which inhibits
l It is a potent drug in gastroesophageal reflux disease.
final common step in gastric acid secretion.
l The significant pharmacological action of omeprazole is
Q. 6. Cimetidine and ranitidine
dose-dependent suppression of gastric acid secretion. It
is powerful inhibitor of gastric acid and totally abolishes Ans. Comparison between cimetidine and ranitidine is
HCl secretion. listed in Table 39.1.
TABLE 39.1 Comparison between Cimetidine and Q. 9. Sucralfate

Ranitidine
Ans.
Cimetidine Ranitidine
l Sucralfate is an ulcer protecting drug.
Potent competitive H2 Competitive H2 receptor
receptor blocker blocker—5 times more l At the gastric pH it forms a sticky viscid gel that gets at-
potent than cimetidine tached to the base of the ulcer and acts as a physical barrier
protecting the ulcer from contact from acid and pepsin.
Intermediate acting Long acting
l It stimulates synthesis of prostaglandins in the gastric
Poor CNS penetration No CNS penetration—does mucosa which helps in inhibition of gastric acid secre-
not cross blood-brain barrier
tion, increases mucosa production and protects the cells
Has antiadrenergic effects— Has no antiadrenergic effects in the mucosa.
causes loss of libido, impo- l These actions help in the healing of the ulcer.
tence, gynaecomastia
l Dose: Each tablet is given 1 h before food and at bed
time for 4–8 weeks. Then 1 g tablets BD are given for

6 months as a maintenance course.
Q.7. Ranitidine is preferred to cimetidine. Q. 10. Proton pump inhibitors

Or, Ans.
Give two reasons for prescribing ranitidine over l The clinically used proton pump inhibitors are omeprazole,
cimetidine. lansoprazole, pantoprazole, rabeprazole, esomeprazole.
l Proton pump inhibitors act by blocking the final step in
Ans.
gastric acid secretion and are most powerful inhibitors
Because of the following advantages, ranitidine is preferred of gastric acid secretion.
over cimetidine: l The proton pump inhibitors are inactive at neutral pH
1. Ranitidine is five times more potent compared to and only get activated at a pH less than 5.
cimetidine. l They get rearranged to two cationic forms—a sulphenic
2. It is longer acting compared to cimetidine. acid and a sulphonamide configuration. These cations
3. Cimetidine has antiadrenergic effects while ranitidine inactivate the H1K1ATPase from the -SH by reacting
has no antiadrenergic effects, no CNS effects as it does with it.
not cross blood-brain barrier.
4. It does not inhibit microsomal enzymes. Q. 11. Aspirin is contraindicated in peptic ulcers.
Q. 8. Rationale of combining aluminium hydroxide gel Ans.

and magnesium trisilicate as antacids. The aspirin is contraindicated in peptic ulcers because of
Ans. following reasons:
1. Aspirin irritates the gastric mucosa and leads to epigas-
l Aluminium hydroxide gel and magnesium trisilicate are tric distress, nausea and vomiting.
combined and used as antacids to maximize the wanted 2. In acidic pH of the stomach, aspirin remains in an
effects and minimize the adverse effects. unionized form. The drug particles get attached to the
l Magnesium trisilicate is a fast-acting drug and hastens gastric mucosa and irritate it. They also promote back
gastric emptying, while aluminium hydroxide is slow diffusion of the acid in the stomach.
acting and delays gastric emptying. Combining the 3. Apart from this they also inhibit prostaglandin synthesis
drugs prolongs the action of the drug to a required level which is responsible for inhibiting gastric acid secretion
and makes it intermediate acting. and increase production of mucosa. This leads to occur-
l Combining the drugs neutralizes the laxating effect rence of ulcers.
of magnesium trisilicate and constipating effect of 4. Aspirin also leads to reduced platelet aggregation and
aluminium hydroxide. promotes bleeding in ulcers.
Topic 40
Emetics, Antiemetics and Other Gastrointestinal Drugs

SHORT ESSAYS
Q. 1. Compare promethazine and ranitidine. l Most commonly used emetics are one spoon of mustard
powder with water or hypertonic salt solution. They act
Ans. Comparison between promethazine and ranitidine is
peripherally by irritating the stomach and are used as
household emetics.
l Morphine and apomorphine are centrally acting emetics;
TABLE 40.1 Comparison between Promethazine and
they induce vomiting by stimulating CTZ.
Ranitidine
l Syrup ipecac is a safe emetic. It has both peripheral and
Points of central actions.

Comparison Promethazine Ranitidine l Emetics are indicated in certain cases of poisoning.
l Some drugs used as emetics are as follows:

Type H1 antihistamine H2 antihistamine
1. Apomorphine: It is derived from morphine. When
Action on hista- Block H1 receptors Block H2
given SC or IM induces vomiting within 5–10 min
mine receptors receptors
by stimulating the CTZ centre.
Effects They induce effects They act on hista- 2. Ipecacuanha is an alkaloid emetine that induces
on smooth muscles mine-induced gas-
vomiting in 15 min. It is available as a syrup ipecac
of gut, blood tric secretion, car-
vessels and triple diac stimulation, and is given even to children.
response uterine and bron- l All emetics are contraindicated in the following:
chial relaxation 1. Corrosive (acid, alkali) poisoning due to risk of
Uses Used in blocking Used in treatment perforation to oesophageal mucosa.
histamine-induced of peptic ulcer 2. CNS stimulant drug poisoning: Convulsions may be
allergic reactions, precipitated.
antimotion sick- 3. Kerosene (petroleum) poisoning: Chances of aspira-
ness, sedation, par-
kinsonism, local
tion of the liquid and chemical pneumonia are high.
anaesthetic in 4. Unconscious patients, because they may aspirate the
higher doses vomitus.
Adverse effects Sedation, dizziness, Headache,
motor incoordina- dizziness, bowel
Q. 3. Metoclopramide
tion, inability to upset, dry mouth, Ans.
concentrate, hepatic injury,
dryness of mouth, haematological Metoclopramide is a prokinetic agent and an antiemetic that
blurred vision, con- changes in elder
stipation, urinary re- patients
is chemically related to procainamide.
tention, teratogenic
Actions
l It acts by blocking the D2 receptors and antagonizes the
Q. 2. Emetics dopamine thus hastening gastric emptying by increasing
gastric peristalsis.
Ans.
l It acts on the CTZ area in the brain by acting against the
l Drugs that produce vomiting are called emetics. dopaminergic receptors and inhibits vomiting reflex.
l They help to produce vomiting by stimulating the l It increases lower oesophageal tone.
vomiting centre in the medulla oblongata. l It opposes gastroesophageal reflux.
l The vomiting centre has two zones of stimulation as
follows: Therapeutic Uses

1. Chemoreceptor trigger zone (CTZ) located in the
postrema 1. As antiemetic: It is popular and effective drug for many
2. Nucleus tractus solitarius types of vomiting like postoperative, drug-induced,
radiation sickness, etc. It is less effective in motion Q. 5. Rationale of using domperidone as antiemetics
sickness.
Or,
2 . Gastrokinetics: To accelerate gastric emptying
l When emergency general anaesthesia has to be given Domperidone is preferred over metoclopramide in
and patient had taken food less than 4 h before vomiting.
l To relieve gastric stasis associated with diabetes or
Ans.
postvagotomy
l To facilitate duodenal intubation l Dopamine is a prokinetic and antiemetic that acts by
3. In functional gastrointestinal disorders like persistent hic- blocking D2 dopamine receptor.
cups, dyspepsia, gastroesophageal reflux disease (GERD) l It is less potent and less efficacious than metoclo-
and during cancer therapy pramide. It acts on the chemoreceptor trigger zone
(CTZ) to inhibit vomiting reflux.
l As it does not cross blood-brain barrier, the extrapyra-
Adverse Effects
midal adverse effects are rare and few. It is the preferred
Sedation, dystonia, diarrhoea, gynecomastia, galactorrhoea antiemetic in children.
and parkinsonism, increased sodium retention l Domperidone is usually administered orally, but its oral
bioavailability is low because of extensive first-pass

Q. 4. Prokinetic agents effect; metabolized in the liver and metabolites are
Ans. excreted in urine.
l Side effects are much less than that of metoclopramide.
l Prokinetic drugs are those that enhance gastroduodenal It may cause headache, dryness of mouth, diarrhoea and
motility and gastric emptying by enhancing acetylcho- rashes.
line release from the cholinergic neurons in the gut.
l They act by blocking the D2 receptors and antagonize Q. 6. Name antiemetic drugs and mention their adverse
the dopamine thus hastening gastric emptying by in- effects.
creasing gastric peristalsis.
Ans.
l By blocking dopamine receptors in the CTZ. They act
as antiemetics. Antiemetics are drugs that inhibit the vomiting reflex by

l Commonly used prokinetic agents are as follows: acting on the chemoreceptor trigger zone (CTZ) located in
1. Metoclopramide the postrema and nucleus tractus solitaries both of which
2. Domperidone are located in the medulla oblongata.
3. Cisapride
4. Mosapride
Classification
Uses 1. Dopamine antagonists (prokinetics): Domperidone,
metoclopramide
Prokinetic agents are used to hasten gastric emptying in 2. Antimuscarinic drugs: Hyoscine, H1-antihistamines like
conditions like the following: cyclizine, promethazine, diphenhydramine
1. Major surgeries in emergency situations where the time 3. 5HT3 antagonists: Ondansetron, granisetron and dola-
gap between food intake and the surgery is less than 4 h setron
2. To relieve gastric stasis caused due to postvagotomy or 4. Neuroleptics: Chlorpromazine, prochlorperazine and
diabetes haloperidol
3. To facilitate duodenal intubation 5. Other agents: Cisapride, corticosteroids
Adverse Effects Adverse Effects

1. Metoclopramide: Sedation, drowsiness, dizziness and 1. Metoclopramide: Sedation, dystonia, diarrhoea, gyneco-
diarrhoea, gynecomastia, galactorrhoea and parkinson- mastia, galactorrhoea and parkinsonism
ism while dystonia is rarely seen. 2. Domperidone: Headache, dryness of mouth, diarrhoea,
2. Domperidone: Headache, dryness of mouth, diarrhoea, rashes
rashes 3. Cisapride: Diarrhoea
3. Cisapride: Diarrhoea
SHORT NOTES
Q. 1. Metronidazole Metoclopramide is a prokinetic agent and an antiemetic that
is chemically related to procainamide.
Ans.
Rationale of using metoclopramide in vomiting is that
l Metronidazole is a nitroimidazole that inhibits various l it acts on the CTZ area in the brain by acting against the
microorganisms like Entamoeba histolytica, Tricho- dopaminergic receptors and inhibits vomiting reflex.
monas vaginalis, Giardia lamblia and Balantidium coli. l it acts by blocking the D2 receptors and antagonizes the
l Metronidazole is toxic to the microbial DNA and kills dopamine thus hastening gastric emptying by increasing
the organism. gastric peristalsis.
Q. 5. Rationale of using domperidone as antiemetics

Uses
Ans.
1 . Intestinal and extraintestinal amoebiasis
2. Trichomonas vaginitis l Dopamine is a prokinetic and antiemetic that acts by
3. Giardiasis blocking D2 dopamine receptor.
4. Helicobacter pylori infections l It acts on the chemoreceptor trigger zone (CTZ) located
in the postrema to inhibit vomiting reflux.

Q. 2. Name two drugs used to suppress vomiting. l As it does not cross blood brain barrier, the extrapyra-
midal adverse effects are rare and few.

Ans.
l It may cause headache, dryness of mouth, diarrhoea and
The drugs that suppress the vomiting reflex by acting on the rashes.
chemoreceptor trigger zone (CTZ) are called antiemetics.
Various drugs that are used to suppress the vomiting are as Q. 6. Promethazine
follows: Ans.
1. Dopamine antagonists (prokinetics): Domperidone,
metoclopramide l Promethazine is a H1 antihistamine that acts on the
2. Antimuscarinic drugs: Hyoscine, H1-antihistamines like histamine receptors and induces effects on smooth
cyclizine, promethazine, diphenhydramine muscles of gut, blood vessels and triple response.
3. 5HT3 antagonists: Ondansetron, granisetron l Uses: Used in blocking histamine-induced allergic reac-
4. Neuroleptics: Chlorpromazine, prochlorperazine tions, antimotion sickness, sedation, parkinsonism, local

5. Other agents: Cisapride, corticosteroids anaesthetic in higher doses
l Adverse effects: Sedation, dizziness, motor incoordina-
Q. 3. Metoclopramide tion, inability to concentrate, dryness of mouth, blurred

vision, constipation, urinary retention, teratogenic
Ans.
l Metoclopramide is a prokinetic agent and an antiemetic Q. 7. Prokinetic drugs. Mention two prokinetic drugs
that is chemically related to procainamide. and their two adverse effects.
l It increases gastric peristalsis and helps in gastric Ans.
emptying.
l It acts on the CTZ area in the brain and inhibits vomit- l Prokinetic drugs are those that enhance gastroduodenal
ing reflex. motility and gastric emptying by enhancing acetylcho-
l Therapeutic uses: As antiemetic, gastrokinetics, in gas- line release from the cholinergic neurons in the gut.
trointestinal disorders like persistent hiccups, dyspep- l They act as antiemetics by blocking dopamine receptors
sia, gastroesophageal reflux disease (GERD) and during in the CTZ.

cancer therapy l Various prokinetic drugs and their adverse effects are as
l Adverse effects: Sedation, dystonia, diarrhoea, gyneco- follows:

mastia, galactorrhoea and parkinsonism 1. Metoclopramide: Sedation, dystonia, diarrhoea,
gynecomastia, galactorrhoea and parkinsonism
Q. 4. Rationale of using metoclopramide in vomiting 2. Domperidone: Headache, dryness of mouth, diarrhoea,
rashes
Ans.
3. Cisapride: Diarrhoea
Topic 41
Drugs for Constipation and Diarrhoea

SHORT ESSAYS
Q. 1. Drugs used as purgatives Q. 2. ORS
Ans. Ans.
Purgatives are drugs that are used to promote defaecation l Oral rehydration solution (ORS) is used in patients with
and they are used in treatment of constipation. diarrhoea to replenish the lost water and maintain the
electrolyte balance.
l The principle behind an ideal ORS is that it should be
Classification of Purgatives
isotonic or a little hypotonic. The osmolarity should be
1. Bulk forming purgatives: Dietary fibres like bran, ispa- around 200–310 mOsm/L.
ghula (isabgol), methyl cellulose, psyllium l The molar ratio of glucose should be equal to or higher
2. Fecal softeners (stool wetting agents): Docusate sodium than that of sodium, but it should not exceed 110 mM.
(DOSS), liquid paraffin l The amount of potassium and salts like bicarbonate and
3. Osmotic purgatives: Magnesium sulphate, magnesium citrate lost due to diarrhoea should be replaced with
hydroxide, sodium salts, lactulose the ORS.
4. Stimulant or irritant purgatives: Bisacodyl, phenol-
phthalein, senna, caster oil Composition (WHO recommended standard formula)
5. Prokinetic agents: 5-HT4 agonist, tegaserod 1. Sodium chloride (NaCl)—3.5 g
2. Potassium chloride (KCl)—1.5 g
3. Trisodium citrate—2.9 g
Uses of Purgatives 4. Glucose—20 g
1. Bulk forming purgatives are used in simple constipation All the above components should be dissolved in 1 L of
and when straining at stools has to be avoided. water.
2. Fecal softeners such as docusates increase absorption of
nonabsorbable drugs. Uses
3. Liquid paraffin lubricates hard stool by coating it.
4. Osmotic purgatives are used to prepare bowel before sur- 1. ORS is used to replace the fluids and salts lost from the
gery, food poisoning, after purge in tapeworm infestation. body during diarrhoea.
5. Purgatives are used in flushing out antihelminthic drugs 2. They are used to maintain hydration in patients post
and helminthes. surgically, after burns and trauma, and in cases of heat
6. Saline purgatives are used in food or drug poisoning. stroke.
SHORT NOTES
Q. 1. Rationale of using loperamide in diarrhoea Q. 2. Bulk purgatives
Ans. Ans.
l Loperamide is an opiate drug used in the treatment of l Bulk forming purgatives are hydrophilic substances
diarrhoea. like bran, methylcellulose, agar, plantago, ovata, etc.
l It has selective action on the gastrointestinal tract and which absorb water, swell up and increase in bulk of
has antisecretory action. the stools.
l It is slowly soluble in water and does not have desired l They cause mechanical distension, so stimulate peristal-
effect when given parenterally. sis and promote defaecation.

l It has very few adverse effects like nausea, vomiting and l They are used in simple constipation and when straining
abdominal cramps. at stools has to be avoided.

l Bulk forming purgatives commonly used are as follows: Ans.

1. Dietary fibres like bran
2. Ispaghula l Liquid paraffin is a type of fecal softener. It lubricates
3. Methyl cellulose hard stool by coating it and softens it.
l Chemically it is an inert mineral oil which cannot be
4. Psyllium
digested.
Q. 3. Name two osmotic purgatives.
Ans. Adverse Effects
l Osmotic or saline purgatives are the most powerful and 1 . Causes discomfort as it may leak out of the anus.
rapid-acting agents. 2. May cause paraffinomas when absorbed in the intestine.
l They are the salts of magnesium, sodium or potassium.
3. May cause lipoid pneumonia when aspirated.
l Osmotic purgatives are used to prepare bowel before
Q. 7. Anthraquinone preparations
surgery, after food or drug poisoning, after purge in
tapeworm infestation. Ans.
l Osmotic purgatives commonly used are as follows:
1. Magnesium sulphate l The senna and cascara are the popular anthracene
2. Magnesium hydroxide purgatives.
l They are usually administered at bed time to produce
3. Sodium salts
4. Lactulose their effect in the morning as they take 6–7 h to act.
l They are contraindicated in lactating mothers, they are
Q. 4. Magnesium sulphate secreted in the milk.

l The side effects are skin rashes, black pigmentation of
Ans. the colonic mucosa and discolouration of urine.
l Magnesium sulphate is an osmotic purgative, which has
Q. 8. Hazards of using purgatives
strong action and results in more fluid evacuation than
laxative. l Regular use of purgatives may cause various gastroin-
l Mechanism of action: It acts by increasing the water testinal disturbances like irritable bowel syndrome, loss
content of the faeces by increasing colonic content and of electrolytes, loss of salts like calcium, dehydration.
makes it easily propelled. It decreases the absorption of l Excessive dehydration may lead to death.
water and electrolytes from the intestines.

l It produces 1–2 fluid evacuation within 1–3 h. It can Q. 9. ORS
nearly empty the bowels. Ans.
l It may cause slight cramping of the stomach, and are not
used in regular constipation therapy. Oral rehydration solution (ORS) is used in patients with
l They are used in evacuation before surgeries like colo- diarrhoea to replenish the lost water and maintain the
noscopy, in cases of food poisoning or drug overdosage electrolyte balance.
and after antihelminthic (hookworm) treatment to evac-
uate the dead worms.
Composition
Q. 5. Loperamide 1 . Sodium chloride (NaCl)—3.5 g
Ans. 2. Potassium chloride (KCl)—1.5 g
3. Trisodium citrate—2.9 g
l Loperamide is an opiate drug used in the treatment of 4. Glucose—20 g
diarrhoea. 5. Water—1 L
l It has selective action on the gastrointestinal tract and
has antisecretory action.

Uses
l It is slowly soluble in water and does not have desired
effect when given parenterally. 1. ORS is used to replace the fluids and salts lost from the
l It has very few adverse effects like nausea, vomiting and body during diarrhoea.
abdominal cramps. 2. They are used to maintain hydration in patients post sur-
gically, after burns, and trauma, and in cases of heat
Q. 6. Liquid paraffin stroke.
Part XII
Antimicrobial Drugs
Topic 42
General Considerations
LONG ESSAYS
Q. 1. Mention classification of antibiotics and describe g. Drugs that interfere with DNA synthesis: Idoxuridine,
the mechanism of action and uses of two commonly used acyclovir, zidovudine
antibiotics. h. Drugs that interfere with intermediary metabolism: Sul-
Ans. Antimicrobial agents are the substances which sup- phonamides, sulfones, dapsone, PAS, trimethoprim, py-
press the growth of or kills other microorganisms. rimethamine, ethambutol
The mechanism of action and side effects of two com-
monly used antibiotics are as follows:
CLASSIFICATION OF ANTIMICROBIAL
AGENTS A. PENICILLIN
I. Based on Type of Action Penicillin is most important of the antibiotics and belongs
to a group of antibiotics called as b-lactam antibiotics.
a . Bactericidal agents: Penicillin, cephalosporins, amino-
glycosides, fluoroquinolones, rifampin, metronidazole
b
. Bacteriostatic agents: Tetracyclines, chloramphenicol, Mechanism of Action
sulphonamides, erythromycin, clindamycin
l Penicillin and all b-lactam antibiotics interfere with
the bacterial cell wall synthesis by inhibiting trans-
II. Based on Their Spectrum of Activity peptidase so that synthesis and crosslinking of pepti-
a . Narrow-spectrum antibiotics: Penicillin G, erythromy- doglycan chain does not take place. This weakens the
cin, streptomycin bacterial cell wall and makes the organisms vulnera-
b
. Broad-spectrum antibiotics: Tetracyclines, chloram- ble to damage by solutes in the surrounding medium,
phenicol i.e. plasma.
l Penicillin is a bactericidal drug. As cell wall synthesis
occurs during growth phase, antibiotic is most effective

III. Based on Their Mechanism of Action against actively multiplying organisms.
a . Drugs that inhibit cell wall synthesis: Penicillins, cepha- l In addition penicillins activate the bacterial, endoge-
losporins, cycloserine, vancomycin, bacitracin nous, autolytic system and initiate cell lysis and death.
b
. Drugs that cause leakage from cell membranes: Poly-
peptides, polymyxins, colistin, bacitracin, polyenes, Uses
amphotericin B, nystatin, hamycin
c. Drugs that inhibit protein synthesis: Tetracyclines, The penicillin is a drug of choice for infections caused by
chloramphenicol, erythromycin, clindamycin, linezolid organisms susceptible to it.
d
. Drugs that cause misreading of m-RNA code and affect I. Dental infections
permeability: Aminoglycosides, streptomycin, gentami- l Penicillin G is effective in most of the common in-
cin, etc. fections in dentistry.

e. Drugs that inhibit DNA gyrase: Fluoroquinolones, l It is also used for periodontal abscess, periapical
ciprofloxacin abscess, pericoronitis, ulcerative gingivitis, etc.

f. Drugs that interfere with DNA function: Rifampin, l It can also be used prophylactically to cover dental
metronidazole procedures.
II. Medical conditions It is active against Gram-negative bacilli especially entero-

a. Streptococcal infections: Pharyngitis, tonsillitis, oti- bacteriaceae and neisseria. Ciprofloxacin has rapid bacteri-
tis media, rheumatic fever, etc. cidal activity by digesting DNA.
b. Pneumococcal infections
c. Gonorrhoea
Therapeutic Uses
d. Syphilis: Benzathine penicillin is drug of choice.
e. Diphtheria, tetanus, anthrax, actinomycosis infec- i. It is used in
tions a. urinary tract infections,
f. Prophylactic use: To prevent recurrence of rheumatic b. bacterial gastroenteritis,
fever, surgical fever c. typhoid fever,
d. gonorrhoea and
e. skin, soft tissue, gynaecological infections, skeletal
B. FLUOROQUINOLONES infections etc.
Fluoroquinolones are the synthetic fluorinated analogues of ii. It is used in combination with other antibiotics for seri-
nalidixic acid. They are quinolone antimicrobials having ous infections like Gram-negative septicaemias, menin-
one or more fluorine substitutions. gitis, etc.
iii. It is used as component chemotherapy against multi-
drug resistance TB.
Classification iv. During conjunctivitis topical therapy is effective of
a. First generation fluoroquinolones: Norfloxacin, cipro- ciprofloxacin.
floxacin, ofloxacin, pefloxacin
b. Second generation fluoroquinolones: Lomefloxacin, Q. 2. Classify antimicrobial agents based on the
sparfloxacin, levofloxacin, gatifloxacin, moxifloxacin mechanism of action with examples. Explain four
advantages of combined use of antimicrobial with
examples.
Mechanism of Action
Ans.
l The fluoroquinolones are bactericidal and act by inhibit-
ing the enzyme bacterial DNA gyrase, and hence pre- Antimicrobial agents are the substances which suppress the
vent the supercoiling of DNA resulting in the inhibition growth of or kills other microorganisms.
of DNA synthesis which is responsible mainly for their
activity against Gram-negative bacteria.
CLASSIFICATION
l They also inhibit topoisomerase IV which contributes
towards their activity against Gram-positive bacteria. Based on their mechanism of action antimicrobial agents
l In Gram-positive bacteria, their major target is topoi- are classified as follows:
somerase IV that has similar function as that of a sub- a. Drugs that inhibit cell wall synthesis: Penicillins, cepha-
unit of DNA gyrase. losporins, cycloserine, vancomycin, bacitracin
l The bactericidal action probably is due to digestion of b. Drugs that cause leakage from cell membranes: Poly-
DNA by exonucleases produced on signals from dam- peptides, polymyxins, colistin, bacitracin, polyenes,
aged DNA. amphotericin B, nystatin, hamycin
c. Drugs that inhibit protein synthesis: Tetracyclines,
Fluoroquinolones inhibit bacterial DNA gyrase enzyme chloramphenicol, erythromycin, clindamycin, linezolid
d. Drugs that cause misreading of m-RNA code and affect
Fluoroquinolones damage bacterial DNA permeability: Aminoglycosides, streptomycin, genta
micin
e. Drugs that inhibit DNA gyrase: Fluoroquinolones,
Exonucleases
ciprofloxacin
f. Drugs that interfere with DNA function: Rifampin,
Digest DNA metronidazole
g. Drugs that interfere with DNA synthesis: Idoxuridine,
acyclovir, zidovudine
Uses h. Drugs that interfere with intermediary metabolism:
They are generally used in bacterial infections. Ciprofloxa- Sulphonamides, sulfones, dapsone, PAS, trimethoprim,
cin is a first generation fluoroquinolone antimicrobial drug. pyrimethamine, ethambutol
ADVANTAGES OF COMBINED USE OF effects especially if the drugs have low safety margin. For
ANTIMICROBIAL DRUGS example:
l Streptomycin with penicillin G for SABE due to Strep-
a. Synergism tococcus faecalis
l Amphotericin B with rifampicin or minocycline (lat-
l A combination of two or more antibacterials has either
synergism, additive actions, indifference or antagonism ter though not antifungal enhance action of the for-
depending on the drugs and microorganism. mer)
l Amphotericin B with flucytosine for cryptococcal
l If minimum inhibitory concentration of each antibacte-
rial is reduced to meningitis

l 25% or less, then the combination is synergistic.
l 25–50% then it is additive.

c. Prevention of Emergence of Resistance
l more than 50% then it is antagonism.
l A synergistic drug sensitizes the organism to action of the l Resistance to one antibacterial substance due to muta-
other members of combination manifesting as more rapid tion is independent of resistance to another. If incidence
lethal action of combination than individual members alone. of resistance to one drug is 1024 and of another is 1026
i. Two bacteriostatic agents are often additive, some- then chances of resistance to the other drugs is one ba-
times synergistic. For example: cilli out of 1010 bacilli.
l Sulphonamide and trimethoprim have supra-addi- l Thus the chances of bacilli surviving the host defence
tive effects exerting bactericidal effect. and to cause relapse are minimal. This approach is
l b-lactamase inhibitor clavulanic acid or sulbactam valid primarily for chemotherapy of chronic infections
with amoxicillin or ampicillin for b-lactamase needing prolonged therapy like tuberculosis, leprosy,
producing Haemophilus influenzae, Neisseria H. pylori, HIV.
gonorrhoeae and others. l It is of less value in most acute and short-lived infec-
ii. Two bactericidal drugs are frequently additive if the tions, however used in
organism is sensitive to both producing faster cure l Haemophilus influenzae: Sulphonamides with strep-
and reducing chances of relapse. For example: tomycin

l Penicillin or ampicillin with streptomycin or gen- l Staphylococcus aureus: Ciprofloxacin with rifampicin
tamicin for enterococcal SABE

l Carbenicillin or ticarcillin with gentamicin for
d. Broadened Spectrum of Antimicrobial
pseudomonas infection
l Ceftazidime with ciprofloxacin for pseudomonas
Action
infected orthopaedic prostheses i. Treatment of mixed infections: In mixed infections, two
l Rifampicin with isoniazid in tuberculosis or more antibacterial agents are used to cover the patho-
iii. Combination of a bactericidal with a bacteriostatic gen. Drugs are chosen on the basis of bacteriological
drug may be synergistic or antagonistic depending diagnosis, sensitivity pattern and are employed in full
on the organism. doses.
l If organism is highly sensitive to the cidal drug then re- l To cover anaerobes, clindamycin or metronidazole
sponse is equal to static drug given alone because cidal are commonly used.
drug primarily acts on the rapidly multiplying bacteria l However, it may sometimes be possible to find a
while the static drug retards multiplication. For example: single drug effective against all the infecting organ-
l Penicillin with erythromycin for group A streptococci isms. Bronchiectasis, peritonitis, certain UTIs, brain
l Nalidixic acid with nitrofurantoin of E. coli abscesses, diabetic foot infections, bedsores, gynae-
l If the organism has low sensitivity to the cidal drug then cological infections, etc.
synergism may be seen. ii. Initial treatment of severe infections: In cases where the
l Penicillin with sulphonamides for actinomycosis bacteriological diagnosis is unknown, the combination
l Streptomycin with tetracyclines for brucellosis of drugs covering Gram-positive and Gram-negative
l Streptomycin with chloramphenicol for Klebsiella organisms and sometimes even anaerobes is given till
pneumoniae infection the causative organism is identified.
l Rifampicin with dapsone in leprosy l Penicillin with streptomycin
l Cephalosporins or erythromycin with an aminogly-
b. Reduction in Severity or Incidence coside with metronidazole or clindamycin

iii. Topically: Antibacterial agents covering a broad range
of Adverse Effects of Gram-positive and Gram-negative bacteria are com-
If the combination of drugs is synergistic, then dose can be bined for topical applications. For example: Bacitracin,
reduced, reducing the severity or incidence of adverse neomycin, polymyxin B
SHORT NOTES
Q. 1. What is superinfection? Give two examples. destroyed by the antibacterials, there can be dangerous
infections due to various organisms especially the nor-
Ans.
mal commensals.
1 . Superinfection is the appearance of a new infection re- 2 . The broader the antibacterial spectrum of a drug, the
sulting from the use of antimicrobials. Antibacterials more are the chances of superinfection, as the alteration
alter the normal microbial flora of the intestinal, respira- of normal flora is greater.
tory and genitourinary tracts. The normal flora contrib- 3. Common microorganisms causing superinfection are
ute to the host defence mechanism by inhibiting the a. Candida albicans manifests as oral thrush, diar-
colonization of pathogenic organisms, by producing rhoea, vaginitis,
antibacterial substances called bacteriocins and by b. Staphylococci manifest as enteritis and
competing for nutrients. When the normal flora are c. E. coli manifests as UTI.
Topic 43
Sulphonamides, Co-trimoxazole and Quinolones

LONG ESSAYS
Q. 1. Enumerate fluoroquinolones. Mention their Klebsiella pneumoniae, Salmonella, Shigella, Hae-
antimicrobial spectrum, therapeutic uses and adverse mophilus ducreyi, Haemophilus influenzae, Neisseria
effects. gonorrhoeae, Neisseria meningitidis, etc.
l Moderate-to-low activity against Staphylococcus aureus,
Or,
Pseudomonas aeruginosa, Chlamydia, Mycoplasma and
Discuss the mechanism of action, uses and adverse Mycobacterium.
effects of fluoroquinolones. l Most of the anaerobes Bacteroides fragilis, Clostridium
Ans. Fluoroquinolones are the synthetic fluorinated ana- difficile, etc. are resistant to ciprofloxacin.
l Newer fluoroquinolones like levofloxacin, sparfloxacin,
logues of nalidixic acid. They are quinolone antimicrobials
having one or more fluorine substitutions. gatifloxacin, moxifloxacin, etc. have greater activity
against streptococci and some activity against anaerobes.
Classification Mechanism of Action

a . First generation fluoroquinolones: Norfloxacin, cipro- 1. The fluoroquinolones are bactericidal and act by inhibit-
floxacin, ofloxacin, pefloxacin ing the enzyme bacterial DNA gyrase, and hence pre-
b
. Second generation fluoroquinolones: Lomefloxacin, vent the supercoiling of DNA resulting in the inhibition
sparfloxacin, levofloxacin, gatifloxacin, moxifloxacin of DNA synthesis which is responsible mainly for their
activity against Gram-negative bacteria.
The first generation fluoroquinolones (FQs) that were intro-
2. DNA gyrase consists of two subunits A and B. The A
duced in 1980s have one fluoro substitution.
subunit nicks the DNA and reveals it. The B subunit
The second generation fluoroquinolones (FQs) that were
introduces negative supercoils. The action of DNA gy-
introduced in 1990s have additional fluoro and other
rase is important in bacterial replication as it prevents
substitutions with further extending antimicrobial activity
excessive positive supercoiling of the strands when they
to Gram-positive cocci and anaerobes and conferring
separate to permit transcription.
metabolic stability (longer t1/2).
3. The fluoroquinolones have high affinity towards A
subunit of DNA gyrase and thus prevent nicking and
Antibacterial Spectrum resealing of DNA thus interfere with DNA replication
producing damaged DNAs.
l Ciprofloxacin is highly effective against Gram-negative
4. They also inhibit topoisomerase IV which contributes
organisms like Escherichia coli, Enterobacter, Proteus,
towards their activity against Gram-positive bacteria.
5. In Gram-positive bacteria, their major target is topoi- iv. Typhoid Fever

somerase IV that has similar function as that of A sub- l Ciprofloxacin (500–700 mg BD for 10 days) is the drug
unit of DNA gyrase. of choice used to treat acute stage as well as carriers.
6. The bactericidal action probably is due to digestion of DNA Course of treatment varies between 10 and 14 days.
by exonucleases produced on signals from damaged DNA. l Pefloxacin or ofloxacin can also be used. They are also
effective in eliminating the chronic carrier state of Sal-

Pharmacokinetics monella typhi when therapy is continued for 6 weeks.
1. Ciprofloxacin is rapidly absorbed orally but its absorp- v. Bone, Soft Tissue, Gynaecological and Wound
tion is delayed by food. Infections
2. The oral bioavailability is 60–80% and plasma protein l High cure rates in infections caused by S. aureus and
binding is less (20–35%). Gram-negative bacteria.
3. It has high tissue permeability thus achieving higher l High dose prolonged treatment is required for osteomy-
concentration of the drug in lung, sputum, muscle, elitis and joint infection.
bone, prostate and phagocytes than plasma. l For diabetic foot infections fluoroquinolones are used
4. It is excreted primarily in the urine by both glomerular along with antianaerobic agents like clindamycin or
filtration and tubular secretion. metronidazole.
Uses vi. Respiratory Infections

l Used for Mycoplasma, Legionella, H. influenzae, Bran-
1. Because of wide-spectrum bactericidal activity, oral ef-
hamella catarrhalis and some Gram-negative bacilli.
ficacy and good tolerability ciprofloxacin is used exten-
l Ciprofloxacin has been used to eradicate meningococci
sively in broad range of infections even as blind therapy.
from nasopharynx thus eliminating carrier state, but the
2. The usual dose is 250–750 mg BD orally and
preferred drug is rifampicin.
100–200 mg IV.
i. Urinary Tract Infections vii. Mycobacterial Infections

l Fluoroquinolones are one of the most commonly used
Fluoroquinolones are used in combination with other anti-
antimicrobial agents for UTI. microbial agents as a part of therapy of multidrug resistant
l They are superior to co-trimoxazole for the treatment
tuberculosis, MAC infections in AIDS patients and leprosy.
of UTI.
viii. Gram-negative Septicaemia
l They are also effective for the treatment of bacterial
l Used parenterally along with a third generation cepha-
prostatitis as they are concentrated in the prostatic tissue.
l High cure rates even in complicated cases or those with
losporins or an aminoglycoside.
l Ciprofloxacin is used topically for conjunctivitis due to
indwelling catheters and prostatitis
Gram-negative organisms.
ii. Gonococcal Infections (Gonorrhoea)
ix. Prophylaxis of Infections in Neutropenic, Cancer
l Single dose of 500 mg ciprofloxacin or 400 mg of
or Susceptible Patients
ofloxacin is nearly 100% curative in cervicitis, urethritis
and pelvic inflammatory disease due to N. gonorrhoeae. Fluoroquinolones are often used in combination with an
l Now ceftriaxone is the first drug of choice due to in- aminoglycoside.
creased prevalence of quinolone resistant gonococci.
l Fluoroquinolones are also effective for chlamydial in-
Adverse Effects
fections and chancroid. Three-day treatment is excellent
alternative to co-trimoxazole in chancroid. i. Common adverse effects are related to GI tract like
nausea, vomiting, bad taste, anorexia and abdominal
iii. Bacterial Gastroenteritis or Diarrhoeas discomfort.
l Fluoroquinolones are very effective in severe cases due to ii. CNS effects like dizziness, headache, restlessness, anx-
E. coli, Shigella, Salmonella and Campylobacter jejuni iety, insomnia, impairment of concentration, dexterity
respond quickly. They reduce stool volume in cholera. tremors and seizures at high doses or in presence of
l For travellers’ diarrhoea due to E. coli, fluoroquinolones precipitating factors.
are as effective as co-trimoxazole. iii. Hypersensitivity reactions include skin rashes, pruritus,
l Norfloxacin, ciprofloxacin or ofloxacin therapy for photosensitivity, urticaria, swelling of lips, etc.
3–5 days is adequate. iv. Tenosynovitis and tendon rupture can occur rarely.
Q. 2. Classify sulphonamides. Discuss the mechanism of Antibacterial Spectrum

action, adverse effects and uses of co-trimoxazole.
Antibacterial spectra of trimethoprim and sulphonamides
Ans. overlap considerably. Additional organisms covered by the
combination are as follows:
l Salmonella typhi, Serratia, Klebsiella, Enterobacter,
SULPHONAMIDES Yersinia enterocolitica, Pneumocystis jiroveci

l Sulphonamide-resistant strains of Staphylococcus
l Sulphonamides are derivatives of p-amino-benzene sul- aureus, Streptococcus pyogenes, Shigella, Entero-
phonamides (sulphanilamide). pathogenic Escherichia coli, Haemophilus influenzae,
l Classification of sulphonamides based on duration of
Gonococci and Meningococci
action is as follows:
a. Short-acting (4–8 h): Sulphadiazine
b. Intermediate-acting (8–12 h): Sulphamethoxazole Adverse Effects
c. Long-acting (,7 days): Sulphadoxine, sulphame- l Nausea, vomiting, stomatitis, headache and rashes: usu-
thoxypyrazine ally occurring side effects
d. Special purpose sulphonamides: Sulphacetamide so- l Folate deficiency (megaloblastic anaemia): infrequent
dium, sulphasalazine (topical), silver sulphadiazine l Blood dyscrasias: rarely seen
(topical), mafenide (topical) l Neonatal haemolysis and methamoglobinemia: if given
near term in pregnancy

CO-TRIMOXAZOLE l Uraemia: in patients with renal disease
l Fever, rash and bone marrow hypoplasia: in AIDS pa-

Co-trimoxazole is the fixed dose combination of trime- tients with Pneumocystis carinii infection
thoprim 80 mg and sulphamethoxazole 400 mg. l Bone marrow toxicity: in elderly
Mechanism of Action Therapeutic Uses

l Co-trimoxazole acts by sequential blockade of folate i. Urinary Tract Infections
metabolism.
l Most acute uncomplicated infections respond rapidly.
l Trimethoprim selectively inhibits bacterial dihydrofo-
l Single dose therapy with four tablets of co-trimoxazole
late reductase whereas the sulphamethoxazole inhibits
conversion of PABA to dihydrofolate. is recommended for acute cystitis. Three to ten days
l Individually both the drugs are bacteriostatic but their
course for lower and upper urinary tract infections.
l It is especially valuable in chronic and recurrent cases and
combination renders co-trimoxazole bacteriocidal.
l Maximum synergism is seen when the organism is sen-
in prostatitis as the trimethoprim is concentrated in prostate.
sitive to both the components. ii. Respiratory Tract Infections
l Both upper and lower respiratory tract infections in-
Preparation cluding chronic bronchitis and faciomaxillary infec-
l Optimal synergy of co-trimoxazole is seen at a con- tions, otitis media caused by Gram-positive cocci and
centration ratio of sulphamethoxazole:trimethoprim H. influenzae respond well.
l It is drug of choice in nocardia infection. It is also used
(20:1).
l This ratio is obtained in plasma when both these drugs are
in whooping cough.
given in dose ratio of 5:1 because trimethoprim enters many iii. Typhoid
tissues and has a larger volume of distribution than sulpha-
l Co-trimoxazole is used as an alternative in patients not
methoxazole and attains lower plasma concentration.
tolerating fluoroquinolones.
l Sensitive strains respond to one double strength tab BD
Pharmacokinetics for 2 weeks.
l Twelve-week course eradicates carrier state provided
l Trimethoprim adequately crosses blood-brain barrier and
placenta while sulphamethoxazole has a poorer entry. gallbladder is not involved.
l Trimethoprim is more rapidly absorbed than sulpha-
iv. Bacterial Diarrhoeas and Dysentery
methoxazole.
l Co-trimoxazole is used for many severe and invasive
l Trimethoprim is 40% plasma protein bound while sul-
phamethoxazole is 65% bound. infections by Campylobacter, E. coli, Shigella and Yer-

l Trimethoprim is partly metabolized in liver and ex-
sinia enterocolitica.
l It is effective in ampicillin-resistant cases.
creted in urine.
v. Chancroid and other infections in them. Intensive parenteral

l Cotrimoxazole (trimethoprim 800 1 sulphamethoxazole co-trimoxazole therapy is used successfully in septi-
160 mg) BD for a week days is the third drug of choice caemiae.
and inexpensive alternative to ceftriaxone, erythromycin
or ciprofloxacin. vii. Pneumocystis Jirovecii
vi. Granuloma Inguinale 1. Cotrimoxazole is of therapeutic as well as prophylactic
l It is an alternative to doxycycline or erythromycin. value. One double strength (DS) tablet 4–6 times/day
l It is an effective alternative to penicillin for protect- for 2–3 weeks is curative and one DS tab daily is used
ing agranulocytosis patients and treating respiratory prophylactically.
SHORT ESSAYS
Q. 1. Classify sulphonamides. Write important adverse Ans.
effects.
1. Sulphonamides inhibit the conversion of PABA to dihy-
Ans. drofolic acid (DHF) and trimethoprim inhibits dihydro-
folate reductase (DHFR). It thus prevents the reduction
Classification of Sulphonamides of DHF to tetrahydrofolic acid (THF).
Classification of sulphonamides based on duration of action 2. Co-trimoxazole is the combination of sulphamethoxa-
is as follows: zole and trimethoprim. Trimethoprim selectively in-
1. Short-acting (4–8 h): Sulphadiazine hibits bacterial dihydrofolate reductase whereas the
2. Intermediate-acting (8–12 h): Sulphamethoxazole sulphamethoxazole inhibits conversion of PABA to
3. Long-acting (,7 days): Sulphadoxine, sulphamethoxy- dihydrofolate.
pyrazine 3. Individually both the drugs are bacteriostatic but their
4. Special purpose sulphonamides: Sulphacetamide so- combination renders co-trimoxazole bacteriocidal.
dium, sulphasalazine (topical), silver sulphadiazine 4. Maximum synergism is seen when the organism is sen-
(topical), mafenide (topical) sitive to both the components. Presence of pus, blood
and tissue breakdown products make sulphonamides
ineffective as these are rich in PABA.
Important Adverse Effects
Q. 3. Explain the mechanism of action of co-trimoxazole.
1. Usually occurring side effects are nausea, vomiting,
stomatitis, headache and rashes. Ans.
2. Folate deficiency (megaloblastic anaemia) is infrequent.
3. Dose-related crystalluria, renal irritation, haematuria 1. Co-trimoxazole produces sequential blockade of folate
and anuria metabolism, i.e. two drugs interfere with two successive
4. Hypersensitivity reactions in form of rashes, urticaria steps in the same metabolic pathway and produce supra-
and drug fever, arthritis, serum sickness like syndrome additive effect.
and polyarteritis nodosa are infrequent. 2. Sulphamethoxazole inhibits folate synthetase and hence
5. Stevens-Johnson syndrome and exfoliative dermatitis it inhibits the conversion of PABA to dihydrofolic acid
with long-acting agents. (DHF) and trimethoprim inhibits dihydrofolate reduc-
6. Rarely causes hepatitis and suppression of bone marrow. tase (DHFR). It thus prevents the reduction of DHF to
7. Contact sensitization with topical use. tetrahydrofolic acid (THF) as shown:
8. Haemolytic anaemia may occur in a dose-dependent
PABA
manner in individuals with G-6-PD deficiency.
9. Causes kernicterus in premature newborns by displace-
Folate synthetase ← (-)sulphamethoxazole
ment of bilirubin from plasma protein binding sites and
deposition in basal ganglion due to more permeable
Dihydrofolic acid (DHF)
blood-brain barrier.
Q. 2. Sulphonamides are not very effective in the Folate reductase ← (-)Trimethoprim

presence of pus. Explain.
Tetrahydrofolic acid (THF)
3. Co-trimoxazole is the combination of sulphamethoxazole 4. Individually both the drugs are bacteriostatic but their
and trimethoprim. Trimethoprim selectively inhibits bac- combination renders co-trimoxazole bactericidal. Maxi-
terial dihydrofolate reductase whereas the sulphamethox- mum synergism is seen when the organism is sensitive
azole inhibits conversion of PABA to dihydrofolate. to both the components.
SHORT NOTES
Q. 1. Co-trimoxazole Ans.
Ans. 1. Trimethoprim selectively inhibits bacterial dihydrofo-
late reductase whereas the sulphamethoxazole inhibits
1. Co-trimoxazole is the fixed dose combination of trime-
conversion of PABA to dihydrofolate.
thoprim and sulphamethoxazole.
2. Individually both the drugs are bacteriostatic but their
2. Co-trimoxazole acts by sequential blockade of folate
combination renders co-trimoxazole bactericidal.
metabolism.
3. Maximum synergism is seen when the organism is sen-
3. Therapeutic uses
sitive to both the components.
a. Urinary tract infections: Valuable in chronic and re-
current cases and as well as in prostatitis Q. 3. Long-acting sulphonamides
b. Respiratory tract infections: Both upper and lower
respiratory tract infections Ans.
c. Typhoid: Co-trimoxazole is used as an alternative in
1. Sulphonamides that are long acting are
patients not tolerating fluoroquinolones.
a. sulphadoxine and
d. Bacterial diarrhoea and dysentery
b. sulphamethoxypyrazine.
e. Chancroid
2. They act for about 7 days.
f. Intensive parenteral co-trimoxazole therapy is used
3. They are generally used in chloroquine-resistant ma-
successfully in septicaemiae.
laria along with pyrimethamine.
Q. 2. Rationale of combination of sulphamethoxazole
with trimethoprim
Topic 44
Beta-Lactam Antibiotics
LONG ESSAYS
Q. 1. Define the term antibiotics and chemotherapy. Ans.
Classify penicillins. Explain their mechanism of action,
uses and adverse effects. CHEMOTHERAPY
Or, Chemotherapy means the treatment of infectious diseases
or malignancy with drugs to destroy microorganisms or
Classify penicillins. Write in brief the therapeutic uses
cancer cells preferentially with minimal damage to the host
of penicillin G. Add a note on treatment of acute ana-
tissues. The infection may be due to bacteria, virus, fungi,
phylactic shock due to intramuscular injection of pro-
protozoa or helminthes.
caine penicillin.
Or, ANTIBIOTICS
Define antibiotics. Classify penicillins. Explain their These are substances produced by microorganisms, which
mechanism of actions, toxicity and important uses of suppress the growth of or kill other microorganism at very
penicillins. low concentrations.
PENICILLIN pneumococci, Bacillus anthracis, Corynebacterium diphthe-

riae, Clostridia, Listeria, Spirochaetes and Neisseria species.
It is the most important and the first antibiotic to be used,
a. Streptococcal infections
obtained from a fungus of Penicillium notatum, but the
i. Pharyngitis, otitis media, scarlet fever, rheumatic
yield was very low. The present source of pencillin is the
fever. 0.525 MU IV 8 hourly for 7–10 days.
high-yielding Penicillium chrysogenum.
ii. Subacute bacterial endocarditis caused by Streptro-
coccus viridians or faecalis. 10–20 MU IV. daily
Classification with streptomycin 0.5 g IM BD for 2–6 weeks.
b. Pneumococcal infections: Though not recommended
a . Natural penicillins: Benzyl penicillin (penicillin G)
but can be given if organism is sensitive. 3–6 MU IV
b. Semisynthetic penicillins
every 6 hourly.
i. Acid-resistant penicillins: Phenoxymethyl penicil-
c. Meningococcal infections: Respond well to high dose
lin (penicillin V)
of penicillins.
ii. Penicillinase-resistant penicillins: Methicillin, oxa-
d. Gonorrhoea
cillin, cloxacillin, dicloxacillin
i. Penicillins have been taken over by fluoroquino-
iii. Extended-spectrum penicillins: Aminopenicillins,
lones or ceftriaxones as the first-line drugs. How-
ampicillin, bacampicillin, amoxicillin
ever it can be used in NPPG infection as 4.8 MU IM
c. Carboxypenicillins: Carbenicillin, carbenicillin indanyl,
single dose divided and given in both buttocks or
carbenicillin phenyl (carfecillin), ticarcillin
procaine penicillin with 1g probenecid orally.
d. Ureidopenicillins: Piperacillin, mezlocillin, mecillinam
ii. For ophthalmia neonatorum due to sensitive Neis-
(amdinocillin)
seria gonorrhoeae.
e. b-lactamase inhibitors: Clavulanic acid, sulbactam
l Saline irrigation 1 1 drop containing 10,000–
20,000 U/mL of sodium penicillin G in each eye

Mechanism of Action every 1–2 h for 1 week.
l In severe cases give 50,000 U IM BD in addition.
l b-lactam antibiotics produce bactericidal effect by in-
e. Syphilis: Penicillin G is the drug of choice for syphilis
hibiting cell wall synthesis.
i. Early and latent syphilis: 1.2 MU of procaine peni-
l Bacterial cell wall is composed of peptidoglycan, a
cillin daily for 10 days or 2.4 MU of benzathine
highly crosslinked structure.
penicillin weekly for 1–3 weeks.
l It makes the cell wall rigid and also gives it stability.
ii. Late syphilis: 2.4 MU of benzathine penicillin
l b-lactam antibiotics inhibit the biosynthesis of peptido-
weekly for 4 weeks or 5 MU IM of sodium penicil-
glycans.
lin G 6 hourly for 2 weeks.
Mechanism of action of penicillins can be summarized as
f. Diphtheria: Penicillin treatment is of adjuvant value to
follows:
antitoxin therapy and prevents carrier state. 1–2 MU of
procaine penicillin daily for 10 days.
Penicillins
g. Tetanus and gas gangrene: Penicillin is used to kill the
organism and has adjuvant value to antitoxin. 6–12 MU
Bind and inactivate penicillin binding proteins (PBPS) of penicillin G daily.
on the cell wall of susceptible bacteria h. Anthrax: 4 MU of penicillin G 6 hourly for 2 weeks
i. Actinomycosis: 2–4 MU IV of penicillin G 6 hourly for
Inhibit transpeptidase 4 weeks
j. Trench mouth: Along with metronidazole, low doses of
penicillin G for 7 days is effective.
Prevent peptidoglycan synthesis
k. Penicillin G is the drug of choice for rare infections like
anthrax, actinomycosis, rat-bite fever and those caused
Cell wall deficient forms develop (spheroplasts and filamen- by Listeria monocytogenes, Pasteurella multocida.
tous forms)
Autolysis Prophylactic Use

i. Rheumatic fever: Low concentration of penicillin pre-
Cell death (bactericidal effect) vents colonization by streptococci responsible for
rheumatic fever. The most convenient regimen of ben-
zathine penicillin is 1.2 MU every 4 weeks till 18 years
Therapeutic Uses of age or 5 years after an attack which ever is more.
Penicillin G or benzyl penicillin is the drug of choice for in- ii. Gonorrhoea and syphilis: 2.4 MU single dose of pro-
fection caused by bacteria susceptible to it, i.e. streptococci, caine penicillin or benzathine penicillin before or
within 12 h of contact provides protection for both Q. 2. Classify cephalosporins. Describe the antibacterial
these sexually transmitted diseases. spectrum, therapeutic uses and adverse effects of third
iii. Bacterial endocarditis: Penicillin is used before dental generation cephalosporins.
extraction, endoscopies, catheterization and other sur-
Ans.
gical procedures to prevent bacteremia in patients with
valvular heart disease. Cephalosporins are a group of semisynthetic antibiotics
iv. Agranulocytosis: Penicillin alone or in combination derived from cephalosporin C, obtained from a fungus
with an aminoglycoside. Cephalosporium. They are chemically related to penicillins.
v. Surgical infections: 1 MU of procaine penicillin with
an aminoglycoside injected 1 M 1 h before and 8–12 h
after surgery can reduce wound infection. Classification
Cephalosporins Parental Oral
Adverse Effects a. First generation Cephalothin Cephalexin
Cephapirin Cephradine
Penicillin causes the following: Cefazolin Cefadroxil
i. Hypersensitive reactions such as skin rashes, urticaria, Cephaloridine
fever, dermatitis, joint pain, serum sickness or even
b. Second Cefoxitin Cefaclor
acute anaphylactic reactions. generation Cefuroxime Cefuroxime
ii. Other effects: Pain and sterile abscess at the site of IM axetil
injection c. Third Cefotaxime Cefixime
iii. Prolonged use of IV may cause thrombophlebitis. generation Ceftizoxime Cefpodoxime
iv. Acute anaphylactic reactions: The symptoms of ana- Ceftriaxone proxetil
phylactic shock are severe hypotension, bronchospasm Ceftazidime Cefdinir
and laryngeal oedema. Cefoperazone Ceftibuten
v. Crossreactivity can occur among penicillins and also d. Fourth Cefepime
among b-lactams. generation Cefpirome
Jarisch-Herxheimer Reaction Third Generation Cephalosporins

l It is an acute exacerbation of signs and symptoms of Antibacterial spectrum, therapeutic uses and adverse effects
syphilis during penicillin therapy. of third generation cephalosporins are as follows:
l It is due to release of endotoxins from the dead organisms. l These compounds were introduced in 1980. Third genera-
l The manifestations are fever, chills, myalgia, hypoten- tion cephalosporins have potent action against aerobic
sion, circulatory collapse, etc. Gram-negative as well as some Gram-positive bacteria but
l It is treated with aspirin and corticosteroids. it is not so active on aerobes, particularly Bacteriodes fragi-
lis, Staphylococcus aureus and Pseudomonas aeruginosa.
l They have highly augmented activity against Gram-
Treatment of Anaphylactic Shock
negative enterobacteriaceae. All are highly resistant to
l The patient is kept in reclining position, administered b-lactamases from Gram-negative bacteria.
oxygen at high flow rate and performed cardiopulmo- l Drugs like ceftazidime and cefoperazone are active
nary resuscitation if required. against pseudomonas.
l Inject adrenaline 0.3–0.5 mg (0.3–0.5 mL of 1 in 1000
solution) IM and repeat every 5–10 min if patient does

Therapeutic Uses
not improve. It is the only life-saving measure.
l Administer (H1 antihistaminic) diphenhydramine Third generation cephalosporins are used alone or with
50–100 mg IM or slow IV. aminoglycosides in severe Gram-negative infections.
l Inj. hydrocortisone sodium succinate 100–200 mg IV a. Meningitis
Bacterial meningitis caused by Gram-negative bacilli especially
in children caused by Haemophilus influenzae, enterobacteria-
Limitations or Drawbacks of Penicillins ceas. Inj. Cefotaxime or Ceftriaxone are the preferred drugs.
l Orally not very effective (acid labile) Dose:
l Short duration of action l Cefotaxime 1–2 g (50–100 mg/kg/day in children)
l Narrow spectrum of antibacterial activity IM or IV 6–12 hourly.

l Destroyed by penicillinase enzymes l Ceftriaxone 4 g followed by 2 g IV (children 75–100
l Possibility of anaphylaxis mg/kg) once daily for 7–10 days.

b. Penicillinase producing N. gonorrhoeae (PPNG) infec- in patients with cancer, intra-abdominal infection or re-
tions: Single dose treatment with third generation ceph- nal failure. Moreover, moxalactam has a carboxyl sub-
alosporins is used in infection. stitution in the side chain at position 7. This causes per-
l Cefotaxime 19 IM 1 19 probenecid orally turbation of platelet surface receptors prolonging the
l Ceftriaxone 250 mg IM single dose is the drug of bleeding time.
choice. vi. Neutropenia and thrombocytopenia are reported with
c. Typhoid fever: Ceftriaxone 4 g IV daily for 2 days fol- ceftazidime but are rare.
lowed by 2 g/day till 2 days after fever subsides (chil- vii. A disulfiram-like interaction with alcohol has been
dren 75 mg/day) and cefoperazone are very effective for reported with moxalactam and cefoperazone.
treatment of multidrug resistant salmonella infections. viii. Rise in plasma transaminases and blood urea is seen
d. Mixed aerobic-anaerobic infection in cancer or immu- with ceftazidime.
nocompromised patients and those undergoing colorec-
tal surgery, obstetric complications. Q. 3. Classify semisynthetic penicillins. Discuss the
l Cefotaxime 1–2 g IM or IV 6–12 hourly (children mechanism of action, adverse effects and therapeutic
50–100 mg/kg/day) uses of amoxicillin.
e. Infection by odd organisms or hospital infections or Ans.
nosocomial infection: Infection by the organisms resis-
tant to common antibiotics may respond to third genera- Extended spectrum penicillins are semisynthetic penicil-
tion cephalosporins. lins, which are active against a variety of Gram-negative
bacilli in addition to Gram-positive cocci.
Cefotaxime 1–2 g IM or IV 6–12 hourly (children
50–100 mg/kg/day)
CLASSIFICATION OF SEMISYNTHETIC
Ceftizoxime 0.5–1 g IM or IV 8–12 hourly PENICILLINS
Ceftriaxone 1–2 g IM or IV/day
i. Acid-resistant alternative to penicillin G: Phenoxy-
Ceftazidime 0.5–2 g IM or IV 8 hourly methylpenicillin (penicillin V)
ii. Penicillinase-resistant penicillins: Methicillin, oxacil-
f. Septicaemia caused by Gram-negative organisms: A lin, cloxacillin
cephalosporin may be combined with an aminoglycoside. iii. Extended-spectrum penicillins
g. Prophylaxis and treatment of infections in neutropenic a. Aminopenicillins: Ampicillin, bacampicillin, amox-
patients: Third generation cephalosporins may be used icillin
alone or in combination with an aminoglycoside. b. Carboxypenicillins: Carbenicillin, carbenicillin in-
h. Respiratory infections like pneumonia, acute exacerba- danyl, carbenicillin phenyl (carfecillin), ticarcillin
tions of chronic bronchitis c. Ureidopenicillins: Piperacillin, mezlocillin
l Cefpodoxime proxetil 200 mg BD d. Mecillinam (amdinocillin)
l Cefdinir 300 mg BD iv. b-lactamase inhibitors: Clavulanic acid, sulbactam
l Ceftibuten 200 mg BD
l Ceferamet pivoxil 500 mg BD-TDS ACTION OF PENICILLINS

i. Urinary infections, skin and soft tissue and gastrointes-
tinal infections: Produced by Gram-negative organisms Penicillins
respond well to third generation cephalosporins.
Bind and inactivate penicillin-binding proteins (PBPs)

Adverse Effects on the cell wall of susceptible bacteria
i. Cephalosporins are more toxic than penicillin but are
generally well tolerated. Inhibit transpeptidase
ii. Pain after IM injection mainly with cephalothin and
thrombophlebitis after IV injection. Prevent peptidoglycan synthesis
iii. GI disturbances like diarrhoea due to alteration of gut
ecology or irritative effect is common with parenteral
cefoperazone and cefixime. Cell wall deficient form (spheroplasts and filamen-
tous forms)
iv. Hypersensitivity reactions may manifest as rashes,
anaphylaxis, angioedema, asthma and urticaria. A
10% may show crossreaction with penicillin. Autolysis
v. Severe bleeding is seen in cefoperazone and ceftriaxone.
It is produced due to hypoprothrombinemia commonly Cell death (bactericidal effect)
ANTIBACTERIAL SPECTRUM ii. Carboxypenicillins: Carbenicillin, carbenicillin in-

danyl, carbenicillin phenyl (carfecillin), ticarcillin
l Gram-positive: Streptococci (including enterococci),
iii. Ureidopenicillins: Piperacillin, mezlocillin, mecil-
pneumococci, Staphylococcus aureus, Bacillus anthra-
linam (amdinocillin)
cis, Corynebacterium diphtheriae, Clostridia, Listeria,
d. b-lactamase inhibitors: Clavulanic acid, sulbactam
Spirochaetes
l Gram-negative: Neisseria gonorrhoeae, Neisseria men-
ingitidis, Haemophilus influenzae, Escherichia coli, Pro- MECHANISM OF ACTION OF AMPICILLIN

tease, Salmonella and Shigella
Penicillins
ADVANTAGES OVER AMPICILLIN
l Oral absorption is better and food does not interfere Bind and inactivate penicillin binding proteins (PBPs)
with its absorption. Thus higher and more sustained on the cell wall of susceptible bacteria
blood levels are produced.
l Incidence of diarrhoea and skin rash is less. Inhibit transpeptidase
l It is less active against Shigella and Haemophilus influenzae.
l It is preferred over ampicillin in typhoid, bronchitis,
Prevent peptidoglycan synthesis
urinary tract infections, SABE and gonorrhoea in a dose
of 0.25–1 g TDS oral.
Cell wall deficient form
(spheroplasts and filamentous forms)
ADVERSE EFFECTS
l Diarrhoea due to irritation to the lower intestine by the Autolysis
unabsorbed drug and alteration of bacterial flora but is
less compared to ampicillin. Cell death (bactericidal effect)
l Maculopapular skin rashes in patients with AIDS, EB
virus infections or leukaemia and concurrent adminis-

tration of allopurinol ANTIBACTERIAL SPECTRUM
Ampicillin is active against all organisms sensitive to penicillin
THERAPEUTIC USES G, e.g. Gram-positive streptococci (including enterococci),
pneumococci, Staphylococcus aureus, Bacillus anthracis, Co-
i. Urinary tract infections: It is the drug of choice in UTI rynebacterium diphtheriae, Clostridia, Listeria, Spirochaetes.
caused by Escherichia coli, Proteus mirabilis, nonhae- In addition it is active against many Gram-negative bacilli
molytic streptococci and enterococci. In a dose of like Neisseria gonorrhoeae, Neisseria meningitidis, Hae-
250–1000 mg TDS. mophilus influenzae, Escherichia coli, Protease, Salmonella
ii. Upper respiratory tract infections: It is effective for phar- and Shigella.
yngitis, sinusitis, otitis media, acute exacerbation of
chronic bronchitis caused by Streptococcus pyogenes,
Streptococcus pneumoniae and Haemophilus influenzae. ADVERSE EFFECTS
l Diarrhoea due to irritation to the lower intestine by the
Q. 4. Classify penicillins. Describe the mechanism of ac-
unabsorbed drug and alteration of bacterial flora.
tion, antibacterial spectrum and the therapeutic uses of
l Maculopapular skin rashes in patients with AIDS, EB
ampicillin.
Ans. tration of allopurinol.
The penicillins are classified as follows:

a. Natural penicillins: Benzyl penicillin (penicillin G) THERAPEUTIC USES
b. Semisynthetic penicillins: i. Urinary tract infections: It is the drug of choice in UTI
i. Acid-resistant penicillins: Phenoxymethyl penicil- caused by Escherichia coli, Proteus mirabilis, non-
lin (penicillin V) heamolytic streptococci and enterococci. Dose: 500 mg
ii. Penicillinase-resistant penicillins: Methicillin, oxa- 6 hourly for 7–10 days. But now incidence of resistance
cillin, cloxacillin, dicloxacillin has increased and fluoroquinolones or cotrimoxazole
c. Extended-spectrum penicillins are now commonly used for empirical therapy.
i. Aminopenicillins: Ampicillin, bacampicillin, amoxi- ii. Respiratory tract infections: Particularly mixed infec-
cillin tions with Haemophilus influenzae and Diplococcus
pneumoniae, e.g. bronchitis, sinusitis, otitis media, v. Bacillary dysentery: It is used in bacillary dysentery as
etc. are best treated with ampicillin. Shigella often responds to ampicillin but now as many
iii. Meningitis: Ampicillin is the first-line drug for oral strains are resistant to it, quinolones are preferred.
treatment of NPPG infections. Single dose 3.5 g am- vi. Subacute bacterial endocarditis: Ampicillin 2 g IV
picillin with 1 g probenecid is adequate. But now as a 6 hourly with concurrent administration of gentamicin
significant number of meningococci are resistant, it is is advocated.
usually combined with third generation cephalosporin vii. Septicaemiae and mixed infections: Injectable ampi-
or chloramphenicol for initial therapy. cillins are used in combination with gentamicin or
iv. Typhoid fever: Ampicillin is used to treat typhoid carrier newer cephalosporins.
states but ciprofloxacin is superior to it. It is infrequently viii. Miscellaneous: Ampicillin is preferred to tetracycline in
used when ciprofloxacin and other drugs cannot be pregnant women and infants in management of intesti-
given. nal malabsorption and treatment of whooping cough.
SHORT ESSAYS
Q. 1. Adverse effects of penicillin THERAPEUTIC USES OF BENZYL PENICILLIN
Ans. Penicillin G or benzyl penicillin is the drug of choice for in-
fection caused by bacteria susceptible to it, i.e. Streptococci,
Adverse effects of penicillin are as follows: Pneumococci, Bacillus anthracis, Corynebacterium diphthe-
l Hypersensitive reactions such as skin rashes, urticaria,
riae, Clostridia, Listeria, Spirochaetes and Neisseria species.
fever, dermatitis, joint pain, serum sickness or even
acute anaphylactic reactions. 1. Streptococcal infections
l Other effects: Pain and sterile abscess at the site of IM l Pharyngitis, otitis media, scarlet fever, rheumatic
injection. fever. 0.5–5 MU IV 8 hourly for 7–10 days.

l Prolonged use of IV may cause thrombophlebitis. l Subacute bacterial endocarditis caused by Strepto-
l Acute anaphylactic reactions: The symptoms of ana- coccus viridians or faecalis. 10–20 MU IV daily
phylactic shock are severe hypotension, bronchospasm with streptomycin 0.5 g IM BD for 2–6 weeks.
and laryngeal oedema. 2. Pneumococcal infections: Though not recommended
l Cross-reactivity can occur among penicillins and also but can be given if organism is sensitive. 3–6 MU IV
among b-lactams. every 6 hourly.
3. Meningococcal infections: Respond well to high dose
of penicillins.
Jarisch-Herxheimer Reaction 4. Gonorrhoea
l It is an acute exacerbation of signs and symptoms of a. Penicillins have been taken over by fluoroquinolones
syphilis during penicillin therapy. or ceftriaxones as the first-line drugs. However, it
l It is due to release of endotoxins from the dead organisms. can be used in NPPG infection as 4.8 MU IM single
l The manifestations are fever, chills, myalgia, hypoten- dose divided and given in both buttocks or procaine
sion, circulatory collapse, etc. penicillin with Ig probenecid orally.
l It is treated with aspirin and corticosteroids. b. For ophthalmia neonatorum due to sensitive Neisse-
ria gonorrhoeae.
i. Saline irrigation with 1 drop containing 10,000–
Treatment of Anaphylactic Shock 20,000 U/mL of sodium penicillin G in each eye
l The patient is kept in reclining position, administered every 1–2 h for 1 week.
oxygen at high flow rate and performed cardiopulmo- ii. In severe cases give 50,000 U IM BD in addition
nary resuscitation if required. 5. Syphilis: Penicillin G is the drug of choice for syphilis.
l Inject adrenaline 0.3–0.5 mg (0.3–0.5 mL of 1 in 1000 a. Early and latent syphilis: 1.2 MU of procaine peni-
solution) IM and repeat every 5–10 min if patient does cillin daily for 10 days or 2.4 MU of benzathine
not improve. It is the only life-saving measure. penicillin weekly for 1–3 weeks.
l Administer (H1 antihistaminic) diphenhydramine 50– b. Late syphilis: 2.4 MU of benzathine penicillin
100 mg IM or slow IV. weekly for 4 weeks or 5 MU IM of sodium penicillin
l Inj. hydrocortisone sodium succinate 100–200 mg IV G 6 hourly for 2 weeks.
6. Diphtheria: Penicillin treatment is of adjuvant value to
Q. 2. Uses of benzyl penicillin antitoxin therapy and prevents carrier state. 1–2 MU of
procaine penicillin daily for 10 days.
Ans.
7. Tetanus and gas gangrene: Penicillin is used to kill the 4. b-Lactamase inhibitors: Clavulanic acid, sulbactam
organism and has adjuvant value to antitoxin. 6–12
MU of penicillin G daily
THERAPEUTIC USES
8. Anthrax: 4 MU of penicillin G 6 hourly for 2 weeks.
9. Actinomycosis: 2–4 MU IV of penicillin G 6 hourly 1. Urinary tract infections: It is the drug of choice in UTI
for 4 weeks caused by Escherichia coli, Proteus mirabilis, nonhae-
10. Trench mouth: Along with metronidazole, low doses molytic streptococci and enterococci. Dose: 500 mg
of penicillin G for 7 days is effective 6 hourly for 7–10 days. But now incidence of resistance
11. Penicillin G is the drug of choice for rare infections like has increased and fluoroquinolones or co-trimoxazole
anthrax, actinomycosis, rat-bite fever and those caused are now commonly used for empirical therapy.
by Listeria monocytogenes, Pasteurella multocida. 2. Respiratory tract infections: Particularly mixed infec-
tions with Haemophilus influenzae and Diplococcus
pneumoniae, e.g. bronchitis, sinusitis, otitis media, etc.
PROPHYLACTIC USE are best treated with ampicillin.
Penicillin G or benzyl penicillin is used as prophylactic in 3. Meningitis: Ampicillin is the first-line drug for oral
following conditions: treatment of NPPG infections. But now as a significant
1. Rheumatic fever number of meningococci are resistant it is usually com-
2. Gonorrhoea and syphilis bined with third generation cephalosporin or chloram-
3. Bacterial endocarditis phenicol for initial therapy.
4. Agranulocytosis 4. Typhoid fever: It is infrequently used when ciprofloxa-
5. Surgical infections cin and other drugs cannot be given.
5. Bacillary dysentery: It is used in bacillary dysentery as
Q. 3. Classification of cephalosporins Shigella often responds to ampicillin but now as many
Ans. strains are resistant to it, quinolones are preferred.
6. Subacute bacterial endocarditis: Ampicillin 2 g IV 6 hourly
Cephalosporins are a group of semisynthetic antibiotics with concurrent administration of gentamicin is advocated.
derived from cephalosporin C obtained from a fungus 7. Septicaemiae and mixed infections: Injectable ampicil-
Cephalosporium. They are chemically related to penicillins. lins are used in combination with gentamicin or newer
cephalosporins.
8. Miscellaneous: Ampicillin is preferred to tetracycline in
Classification pregnant women and infants in management of intesti-
Cephalosporins Parenteral Oral nal malabsorption and treatment of whooping cough.
1. First generation Cephalothin Cephalexin Q. 5. Penicillins act as bactericidal agent.
Cephapirin Cephradine
Cefazolin Cefadroxil Ans.
Cephaloridine
2. Second generation Cefoxitin Cefaclor
Penicillins act as bactericidal agent by inhibiting the syn-
Cefuroxime Cefuroxime thesis of the bacterial cell wall.
axetil Mechanism of action is given as follows:
3. Third generation Cefotaxime Cefixime
Ceftizoxime Cefpodoxime Penicillins
Ceftriaxone proxetil
Ceftazidime Cefdinir
Cefoperazone Ceftibuten Bind and inactivate penicillin binding proteins (PBPs)
on the cell wall of susceptible bacteria
4. Fourth generation Cefepime
Cefpirome
Inhibit transpeptidase
Q. 4. Classification and therapeutic uses of extended-
spectrum penicillins Prevent peptidoglycan synthesis
Ans.
Extended-spectrum penicillins include the following: Cell wall deficient form
1. Aminopenicillins: Ampicillin, bacampicillin, amoxicillin (spheroplasts and filamentous forms)
2. Carboxypenicillins: Carbenicillin, carbenicillin indanyl,
carbenicillin phenyl (carfecillin), ticarcillin Autolysis
3. Ureidopenicillins: Piperacillin, mezlocillin, mecillinam
(amdinocillin) Cell death (bactericidal effect)
l Penicillins act on bacterial cell wall and inhibit the en- 2. Penicillinase-resistant penicillins: Methicillin, oxacil-
zyme transpeptidase and carboxypeptidase. Thus the lin, cloxacillin
crosslinking between the N-acetyl muramic acid and 3. Extended-spectrum penicillins:
N-acetyl glucosamine which is necessary for mainte- a. Aminopenicillins: Ampicillin, bacampicillin, amoxi-
nance of structure of the cell wall does not take place. cillin
l When bacteria divide in presence of penicillin, the resultant b. Carboxypenicillins: Carbenicillin, carbenicillin in-
bacteria are cell wall deficient or are the L forms. As the indanyl, carbenicillin phenyl (carfecillin), ticarcillin
terior of the bacterium is hyperosmotic, these L forms swell c. Ureidopenicillins: Piperacillin, mezlocillin
and burst ultimately causing bacterial lysis or cell death. 4. Mecillinam (amdinocillin)
l They are also said to act by depressing some of the bac- 5. b-lactamase inhibitors: Clavulanic acid, sulbactam
terial autolysins, which usually function during bacte-
rial cell division.
l As the cell wall of a Gram-positive bacterium is almost
ADVANTAGES OVER AMPICILLIN
entirely made up of peptidoglycans, the penicillins are l Oral absorption is better and food does not interfere
highly effective in Gram-positive bacterial infections. with its absorption. Thus higher and more sustained
They are more lethal in the phase of rapid multiplication blood levels are produced.
when the cell wall synthesis takes place. l Incidence of diarrhoea and skin rash is less.
l It is less active against Shigella and Haemophilus influ-

Q. 6. Cloxacillin and the staphylococcal infections enzae.
Ans. l It is preferred over ampicillin in typhoid, bronchitis,
urinary tract infections, SABE and gonorrhoea in a dose

l Cloxacillin is a penicillinase-resistant pencillin. Cloxa- of 0.25–1 g TDS oral.
cillin has an isoxazolyl side chain and is resistant to acid
and penicillinase.
l It is less active against penicillin G sensitive organisms and ADVERSE EFFECTS
should not be used as a substitute. It is more active against l Diarrhoea due to irritation to the lower intestine by the
methicillin against penicillinase producing staphylococci, but unabsorbed drug and alteration of bacterial flora but is
not against MRSA. Because staphylococcal infections are less compared to ampicillin
rare in the oral cavity, cloxacillin is rarely used in dentistry. l Maculopapular skin rashes in patients with AIDS, EB
l It is incompletely but dependably absorbed from oral
route, especially if taken in empty stomach. tration of allopurinol
l It is more than 90% plasma protein bound.
l Elimination occurs primarily by kidney and partly by
liver. Plasma half-life is about 1 h. THERAPEUTIC USES

l Dose: 0.25–0.5 g orally every 6 h and for severe infections
1. Urinary tract infections: It is the drug of choice in UTI
0.25–1 g IM or IV for higher blood concentration levels.
caused by Escherichia coli, Proteus mirabilis, nonhaemo-
Q. 7. Name four semisynthetic penicillin preparations, lytic streptococci and enterococci. In a dose of 250–1000 mg
their advantages and therapeutic uses. TDS.
2. Upper respiratory tract infections: It is effective for
Ans. pharyngitis, sinusitis, otitis media and acute exacerba-
tion of chronic bronchitis caused by Streptococcus
Extended-spectrum penicillins are semisynthetic penicil-
pyogenes, Streptococcus pneumoniae and Haemophilus
lins, which are active against a variety of Gram-negative
influenzae.
bacilli in addition to Gram-positive cocci.
Q. 8. Amoxicillin and gentamicin
CLASSIFICATION OF SEMISYNTHETIC
PENICILLINS Ans.
1. Acid-resistant alternative to penicillin G: Phenoxymeth- The comparison between amoxicillin and gentamicin is as
ylpenicillin (penicillin V) given in Table 44.1.
TABLE 44-1 Comparison between Amoxicillin and Q. 9. Ampicillin and amoxicillin

Gentamicin
Ans.
Parameters to
Be Compared Amoxicillin Gentamicin Ampicillin and amoxicillin both are semisynthetic extended-
spectrum penicillins (amino penicillins).
Type Extended-spectrum Aminoglycoside
penicillin (amino Both of them are bactericidal drugs and act by interfering
penicillin) with synthesis of bacterial cell wall.
Comparison between ampicillin and amoxicillin is
Source Synthetic Natural (obtained
from Micromonos- given in Table 44.2.
pora purpurea)
Mechanism of Interference with Inhibition of pro- TABLE 44-2 Comparison between Ampicillin and
action synthesis of bacterial tein synthesis Amoxicillin
cell wall
Ampicillin Amoxicillin
Antibacterial Most Gram-positive Some Gram-positive
spectrum and few Gram- (staphylococci and Route of administration: Oral Route of administration:
negative bacilli Streptococcus or parenteral Oral or parenteral
(streptococci, fecalis) and many Acid stable, incompletely Acid stable, completely ab-
enterococci, pneu- Gram-negative ba- absorbed from GIT, hence sorbed from GIT, hence inci-
mococci, meningo- cilli (pseudomona, diarrhoea is more common dence of diarrhoea is less
cocci) and some protem, Escherichia
Gram-negative ba- coli, Klebsiella, Food interferes with Food does not interfere with
cilli (Escherichia coli, Enterobacter, absorption absorption
Proteus, Salmonella) Serratia) Superinfections are more Superinfections are less
Route of Oral or parenteral Parenteral only (not common common
administration effective orally) Uses: UTI, RTI, meningitis, Uses: Typhoid, bronchitis
Adverse effects Not serious (diar- Serious ototoxicity, gonorrhoea, typhoid, bacil- UTI, SABE and gonorrhoea
rhoea and rashes nephrotoxicity lary dysentery, cholecystitis,
may develop) neuromuscular SABE, septicaemia and
blockade mixed infections
Uses Typhoid, bronchitis Respiratory tract Effective against Shigella and Less effective against Shigella
UTI, SABE and gon- infections, burns, Haemophilus influenzae and H. influenzae
orrhoea UTI, lung abscess, Ampicillin reduces the Amoxicillin does not reduce
osteomyelitis, otitis effectiveness of oral the effectiveness of oral
media, septicae- contraceptives contraceptives
mia, meningitis
and SABE Dose: 250–500 mg QID Dose: 250–500 mg TID
SHORT NOTES
Q. 1. Probenecid and penicillin in chemotherapy l D-penicillamine is a copper chelating agent with a
gold-like action in rheumatoid arthritis, but less effi-
Ans.
cacious.
l Probenecid competes with b-lactams (penicillins l It is not favoured now because it does not offer any ad-
and cephalosporins) for active tubular secretion and vantage over gold in terms of toxicity.
retards their excretion, thereby increasing the plasma l Loss of taste, systemic lupus erythematosus, myasthe-
concentration as well as the duration of action of nia gravis are some major disadvantages.
b-lactams.
l Hence simultaneous administration of probenecid and
Q. 3. Rationale of combining amoxicillin and clavulanic
penicillin is useful in the treatment of bacterial endocar- acid. Write one indication of this combination.
ditis and gonococcal infections to enhance therapeutic Ans.
efficacy.
l Clavulanic acid is added along with amoxicillin to re-
establish the activity of the latter against b-lactamase
Q. 2. What is D-penicillamine? Mention its two uses.
producing resistant Staphylococcus aureus, Haemophi-
Ans. lus influenzae, Neisseria gonorrhoeae, Escherichia coli,
Proteus, Klebsiella, Salmonella, Shigella and Bacteroides Cephalosporins are a group of semisynthetic antibiotics
fragilis. derived from cephalosporin C obtained from a fungus
l After binding to the enzyme, clavulanic acid itself gets Cephalosporium. They are chemically related to penicillins.
inactivated, hence called a suicide inhibitor. Third generation cephalosporins are as follows:
l The combination of clavulanic acid and amoxicillin
(augmentin) is available for oral administration.

l Augmentin is used for the treatment of skin and soft Parenteral Oral
tissue, ear, respiratory and urinary tract infections Cefotaxime Cefixime
caused by b-lactamase producing strains. Ceftizoxime Cefpodoxime proxetil
Ceftriaxone Cefdinir
Ceftazidime Ceftibuten
Q. 4. Name few semisynthetic penicillins.
Cefoperazone
Ans.
A few examples of semisynthetic penicillins are as follows: Q. 7. Why penicillin (bactericidal drugs) is not com-
1. Acid-resistant penicillin: Phenoxymethylpenicillin bined with sulphonamides (bacteriostatic drugs)?
(penicillin V)
2. Penicillinase-resistant penicillins: Methicillin, oxacillin, Ans.
cloxacillin
3. Extended-spectrum penicillins: Aminopenicillins, am- l Penicillins (bactericidal drugs) are highly lethal in the
picillin, amoxicillin phase of active multiplication because rapid cell wall
synthesis occurs when the organism are actively multi-
Q. 5. Ampicillin plying.
l Administration of sulphonamides (bacteriostatic drugs)
Ans.
simultaneously retards the active multiplication of the
l Ampicillin belongs to semisynthetic extended-spectrum organisms.
penicillins (amino penicillins). l Thus when a bactericidal drug like penicillin is com-
l It is a bactericidal drug and acts by interfering with bined with bacteriostatic drug like sulphonamides, there
synthesis of bacterial cell wall. is antagonism instead of synergism of both the drugs;
l Antibacterial spectrum: Ampicillin is active against all hence penicillin is not combined with sulphonamides.
organisms sensitive to penicillin G, e.g. Gram-positive
and in addition it is active against many Gram-negative Q. 8. Amoxicillin
bacilli also. Ans.
l Therapeutic uses
1. Urinary tract infections l Amoxicillin is semisynthetic extended spectrum peni-

2. Respiratory tract infections cillin (amino penicillin).
3. Meningitis l It is a bactericidal drug and acts by interfering with
4. Typhoid fever synthesis of bacterial cell wall.

5. Bacillary dysentery l Less effective against Shigella and Haemophilus
6. Subacute bacterial endocarditis influenzae.

7. Septicaemiae and mixed infections l Normal dose: 250–500 mg TID
8. Miscellaneous: Ampicillin is preferred to tetracycline l Advantages over ampicillin are as follows:
in pregnant women and infants in management of intes- 1. Oral absorption is better and food does not interfere
tinal malabsorption and treatment of whooping cough. with its absorption. Thus higher and more sustained
blood levels are produced.
Adverse Effects 2. Incidence of diarrhoea and skin rash is less.
3. It is preferred over the ampicillin in typhoid, bron-
1 . Diarrhoea chitis, urinary tract infections, SABE and gonor-
2. Maculopapular skin rashes in patients with AIDS, EB rhoea in a dose of 0.25–1 g TDS.
virus infections or leukaemia l Therapeutic uses: It is a drug of choice in urinary tract
infections caused by Escherichia coli, Proteus mirabilis,

Q. 6. Name third generation cephalosporins.
nonhaemolytic streptococci and enterococci and upper
Ans. respiratory infections.
Q. 9. b-lactamase inhibitors 7. Tetanus and gas gangrene

8. Anthrax
Ans.
9. Actinomycosis
l b-lactamase inhibitors are the drugs which inhibit the 10. Trench mouth: Along with metronidazole, low doses
enzyme b-lactamase produced by many Gram-positive of penicillin G for 7 days is effective.
and Gram-negative bacteria. Penicillin G is the drug of choice for rare infections like
l Clinically available b-lactamase inhibitors are clavu- anthrax, actinomycosis, rat-bite fever and those caused by
lanic acid, sulbactam and tazobactam. Listeria monocytogenes, Pasteurella multocida.
l Clavulanic acid competitively and irreversibly inhibits
b-lactamases produced by a wide range of gram- PROPHYLACTIC USE

positive and Gram-negative bacteria.
l After binding to the enzyme, clavulanic acid itself gets Penicillin G or benzyl penicillin is used as prophylactic in
inactivated hence called a suicide inhibitor. following conditions:
l The combination of clavulanic acid and amoxicillin 1. Rheumatic fever
(augmentin) and with ticarcillin (timentin) is available 2. Gonorrhoea and syphilis
for IV administration. For example, augumentin is used 3. Bacterial endocarditis
for the treatment of skin and soft tissue, ear, respiratory 4. Agranulocytosis
and urinary tract infections caused by b-lactamase 5. Surgical infections
producing strains.
l Sulbactam is a semisynthetic b-lactamase inhibitor,
Q. 11. Cloxacillin in staphylococcal infection
available in combination with ampicillin. Used in the Ans.
treatment of skin soft tissue, intra-abdominal and pelvic
infections by b-lactamase producing strains l Cloxacillin has an isoxazolyl side chain and is highly
l Tazobactam is more potent than sulbactam and is avail- penicillinase as well as acid resistant.
able in combination with piperacillin. l It is more active than methicillin against penicillinase
l Tazobactam–piperacillin combination is used for infec- producing Staphylococcus.

tions caused by b-lactamase producing strains of Esch- l With rampant use of penicillin to treat infections, many
erichia coli and Bacteroides. staphylococcal strains have started producing penicillin
rendering penicillin G ineffective. Therefore, now clox-
Q. 10. Uses of benzyl penicillin acillin is preferred in penicillinase producing staphylo-
coccal infection.
Ans.
Q. 12. Explain the rationale for the combination of
ampicillin and probenecid in chemotherapy.
THERAPEUTIC USES OF BENZYL
Ans.
PENICILLIN
Penicillin G or benzyl penicillin is the drug of choice for l Probenecid blocks the tubular secretions of ampicillin,
infections caused by bacteria susceptible to it, i.e. strepto- thus achieving higher and longer lasting plasma concen-
cocci, pneumococci, Bacillus anthracis, Corynebacterium tration of ampicillin.
l It also decreases the volume of distribution of ampi-
diphtheriae, Clostridia, Listeria, Spirochaetes and Neisseria
species. cillin.
l For these reasons probenecid is combined with ampicillin
1. Streptococcal infections
2. Pneumococcal infections in chemotherapy of infections.
l It is used to prolong penicillin or ampicillin action by
3. Meningococcal infections
4. Gonorrhoea increasing and sustaining their blood levels, e.g. in
5. Syphilis gonorrhoea, SABE available as Benemid or Bencid
6. Diphtheria 0.5 g tab.
Topic 45
Tetracyclines and Chloramphenicol

LONG ESSAY
Q. 1. Enumerate tetracyclines. Write their antimicro- Prevents
bial spectrum and therapeutic uses. Addition of amino acid to growing peptide chain
Or,
Peptide chain fails to grow
Explain broad-spectrum antibiotics. Describe the mech-
anism of action, therapeutic uses and toxic effects of
tetracyclines. Inhibits protein synthesis (bacteriostatic)
Or,
Describe the clinical uses and toxicity of tetracyclines.
Uses
How will you treat a case of superinfection due to tetra- A. Medicinal Uses
cycline therapy?
i. Rickettsial infections: It is a drug of first choice in rick-
Ans. Tetracyclines are antibiotics obtained from soil acti- ettsial infections like epidemic typhus, Rocky Mountain
nomycetes. They are broad-spectrum antibiotics as they are spotted fever, scrub fever, rickettsial pox and Q fever.
effective against a large number of microorganisms except ii. Chlamydial infections
fungi and viruses. They are bacteriostatic and bacteriocidal. l Lymphogranuloma venereum: It is caused by Chla-
mydia trachomatis and is a sexually transmitted dis-

ease, where doxycycline is the drug of choice.
Classification l Trachoma
l Psittacosis
Tetracyclines are classified into three groups as follows:
iii. In atypical pneumonia due to Mycoplasma pneumoniae
l Group I (short-acting): Tetracyclines, oxytetracycline,
tetracyclines are used to shorten the duration of illness.
chlortetracycline
iv. Cholera: Single dose of tetracycline 2 g or doxycycline
l Group II (intermediate-acting): Demeclocycline, meth-
300 mg is effective in adults. It reduces stool volume
acycline
and eradicates the Vibrio cholerae from the stool.
l Group III (long-acting): Doxycycline, minocycline
v. Lyme disease is successfully treated with tetracyclines.
vi. It is a drug of second choice in the following:
Mechanism of Action l To penicillin or ampicillin for tetanus, anthrax, acti-
nomycosis
l They inhibit protein synthesis by binding with 30S ribo-
l To penicillin or ciprofloxacin in gonorrhoea
somes and block t-RNA attachment to m-RNA ribo-
l To penicillin or ceftriaxone in syphilis
some complex and thus peptide chain fails to grow and
results in inhibition of protein synthesis.
l In the Gram-negative bacteria tetracyclines diffuse
B. Orodental Conditions
through porin channels. Lipid-soluble members enter l It is specially useful in chronic periodontitis or juvenile
through positive diffusion. periodontitis.
Mechanism of action of tetracyclines can be depicted as l They benefit some periodontal diseases by their antimi-
follows: crobial activity and also suppress activity of collagenase
by chelating calcium and inhibition of free radicals.
Tetracyclines
Adverse Effects
Bind reversibly to 30S ribosomes in susceptible organism A. Gastrointestinal: On oral administration, they cause GI
interferes with irritation manifested as
l epigastric pain, nausea, vomiting and diarrhoea.
Attachment of aminoacyl tRNA to the mRNA
l oesophageal ulceration specially with doxycycline
ribosome complex
due to release of drug from capsule in the oesophagus.
B. Dose-related toxicity v. Antianabolic effect

i. Hepatotoxicity l Reduced protein synthesis and overall catabolic
l Fatty infiltration of liver and jaundice effect

l Precipitation of acute hepatic necrosis in pregnancy l Induce negative nitrogen balance and increase
ii. Renal toxicity blood urea.

l Prominent only in presence of existing kidney vi. Increased intracranial pressure: Noted in some
disease infants
l All except doxycycline accumulate and enhance vii. Diabetes insipidus: Demeclocyclines antagonize
renal failure. ADH action and reduces urine concentrating ability
l Outdated tetracyclines produce a reversible of kidney.
Fanconi’s syndrome due to damage to PCT by viii. Vestibular toxicity: Minocyclines produce ataxia,
degraded products like epitetracyclines, anhy- vertigo and nystagmus which subsides on discon-
drotetracycline, epianhydrotetracyclines. tinuation of drug.
iii. Phototoxicity ix. Hypersensitivity
l Sunburn-like or other severe skin reactions on l Skin rashes, urticaria, glossitis, pruritus ani and
exposed body parts especially with demeclocy- vulvae and even exfoliative dermatitis but not
clines and doxycyclines. common.
l Occasionally they may also produce pigmenta- l Angioedema and anaphylaxis are extremely
tion and distortion of nails. rare.

iv. Teeth and bones: Tetracyclines have chelating prop- x. Superinfections
erty and calcium tetracycline chelate gets deposited l Tetracyclines are most common antibiotic re-
in developing bone and teeth. sponsible for superinfections causing marked

a. If given from mid pregnancy to 5 months of ex- suppression of the resident flora.
trauterine life, following conditions occur: l Involves mouth, skin or vaginal flora.
l Deciduous teeth are affected. l Intestinal superinfection like pseudomembra-
l Brown discolouration of ill-formed teeth nous enterocolitis is most prominent.

l Teeth becomes susceptible to caries. l Higher the dose, complete suppression flora re-
b. If given at 3 months to 6 years of age, following sults with greater risk of superinfection.
conditions occur:
l Permanent anterior dentition affected
Contraindications
l Repeated course more damaging
c. Given during late pregnancy or childhood, fol- i. Renal impairment

lowing conditions occur: ii. Hepatic insufficiency
l Temporary suppression of bone growth occurs. iii. Pregnant and lactating mothers
l With prolonged uses possibility of deformities iv. Children below 10 years of age
and height reduction v. Patients on diuretics
SHORT ESSAYS
Q. 1. Adverse effects of broad-spectrum antibiotics 2. Dose-related toxicity
a. Liver damage: Fatty infiltration of liver and jaundice
Ans.
b. Kidney damage: Prominent only in presence of
The broad-spectrum antibiotics are tetracyclines and chlor- existing kidney disease
amphenicol. They are so termed as they are used against a c. Phototoxicity: Sunburn-like or other severe skin
number of Gram-negative and Gram-positive infections. reactions on exposed body parts especially with
demeclocyclines and doxycyclines
d. Teeth and bones
ADVERSE EFFECTS OF BROAD-SPECTRUM
i. Tetracyclines have chelating property and cal-
ANTIBIOTICS cium tetracycline chelate gets deposited in devel-
1. Irritative effects oping bone and teeth.
a. Epigastric pain, nausea, vomiting and diarrhoea ii. Brown discolouration of ill-formed teeth
b. Pain at IM injected site, thrombophlebitis of injected 5. Antianabolic effect: Reduced protein synthesis and
vein on repeated use overall catabolic effect
6. Increased intracranial pressure: Noted in some infants are effective against a large number of microorganisms
7. Diabetes insipidus: Demeclocyclines antagonize ADH except fungi and viruses.
action and reduce urine concentrating ability of kidney
8. Vestibular toxicity: Minocyclines produce ataxia, ver-
Classification
tigo and nystagmus which subsides on discontinuation
of drug. Tetracyclines are classified into three groups as follows:
9. Hypersensitivity reactions: Skin rashes, urticaria, glos- a. Group I (short-acting): Tetracyclines, oxytetracycline,
sitis, pruritus and even exfoliative dermatitis occur but chlortetracycline
not common. b. Group II (intermediate-acting): Demeclocycline, meth-
10. Superinfections: Tetracyclines are most common antibi- acycline
otics responsible for superinfections by causing marked c. Group III (long-acting): Doxycycline, minocycline
suppression of the resident flora.
11. Adverse effects especially associated with chloram- Mechanism of Action
phenicol are bone marrow depression, agranulocytosis,
grey baby syndrome, aplastic anaemia and hypersensi- 1. They inhibit protein synthesis by binding with 30S ribo-
tivity reactions. somes and block t-RNA attachment to m-RNA ribo-
some complex and thus peptide chain fails to grow and
Q. 2. Differences between oxytetracycline and doxycy- results in inhibition of protein synthesis.
cline.
Ans. Differences between oxytetracycline and doxycycline Uses
are given in Table 45.1. a. Orodental Conditions
TABLE 45-1 Differences between Oxytetracycline and It is specially useful in chronic periodontitis or juvenile
Doxycycline periodontitis and also suppress activity of collagenase by
chelating calcium and inhibition of free radicals.
Parameters Oxytetracycline Doxycycline
Source Streptomyces Semisynthetic . Medicinal Uses
b
rimosus derivative
1. It is a drug of first choice in the following diseases:
Potency Low High a. Veneral diseases like lymphogranuloma venereum
Intestinal Moderate Complete, no b. Atypical pneumonia due to Mycoplasma pneumoniae
absorption interference by c. Cholera
food d. Plague
Plasma protein Low High e. Rickettsial infections
binding 2. It is a drug of second choice in tetanus, anthrax, actino-
Elimination By rapid renal Primarily excreted mycosis, gonorrhoea and syphilis.
excretion in faeces
Plasma half-life 6–10 h 18–24 h Adverse Effects
Dosage 250–500 mg TDS 200 mg initially, 1. GI irritation manifested as epigastric pain, nausea,
or QID followed by vomiting, and diarrhoea
100–200 mg OD 2. Hepatotoxicity
Alteration of Marked Least 3. Renal toxicity
intestinal flora 4. Phototoxicity
Incidence of High Low 5. Teeth and bones: Tetracyclines have chelating property
diarrhoea and calcium tetracycline chelate gets deposited in
Phototoxicity Low High developing bone and teeth.
6. Antianabolic effect
Specific toxicity Less tooth Low renal toxicity
7. Diabetes insipidus
discolouration
8. Vestibular toxicity
9. Hypersensitivity reactions like skin rashes, urticaria, etc
Q. 3. Tetracyclines 10. Superinfections
Ans. Q. 4. Give reasons for not prescribing tetracyclines to a

child of 5 years.
1. Tetracyclines are antibiotics obtained from soil actino-
mycetes. They are broad-spectrum antibiotics as they Or,
Tetracyclines are contraindicated during pregnancy b. With prolonged uses possibility of deformities and
and infancy. Explain. height reduction
Ans. Tetracyclines have chelating property and calcium Q. 5. Adverse effects of chloramphenicol
tetracycline chelate gets deposited in developing bone and
teeth. Ans.
1. Chloramphenicol is a broad-spectrum antibiotic obtained

1. If given from mid pregnancy to 5 months of extrauterine from Streptomyces venezuelae.
life, following conditions occur: 2. It is bacteriostatic and not bactericidal.
a. Deciduous teeth are affected 3. It is effective against Gram-positive and Gram-negative
b. Brown discolouration of ill-formed teeth organisms, Rickettsiae, Chlamydiae and Mycoplasma.
c. Teeth become susceptible to caries Adverse effects of chloramphenicol are as follows:
2. If given at 3 months to 6 years of age, following condi- 1. Bone marrow depression
tions occur: 2. Leukopenia
a. Permanent anterior dentition affected 3. Thrombocytopenia
b. Repeated course more damaging 4. Agranulocytosis
3. If given during late pregnancy or childhood, following 5. Aplastic anaemia
conditions occur: 6. Grey baby syndrome
a. Temporary suppression of bone growth occurs 7. Hypersensitivity reactions
SHORT NOTES
Q. 1. Enlist four tetracyclines. Q. 4. Doxycycline
Ans. Ans.
Tetracyclines are antibiotics obtained from soil actinomy- 1 . Doxycycline is semisynthetic derivative of tetracycline.
cetes. They are broad-spectrum antibiotics as they are ef- 2. It is a highly potent drug with a broad-spectrum of ac-
fective against a large number of microorganisms except tivity against Gram-positive, Gram-negative organisms,
fungi and viruses. Rickettsiae, Chlamydiae.
Various tetracyclines are as follows: 3. Its absorption is complete in the intestine and is not in-
a. Group I: Tetracylcine, oxytetracycline terfered by the presence of food.
b. Group II: Demeclocycline 4. Its plasma protein binding is high and duration of action
c. Group III: Doxycycline, minocycline is long.
5. Its plasma half-life is about 18–24 h.
Q. 2. Tetracycline should not be given with antacids. 6. Dosage: 200 mg initially, then 100–200 mg OD.
Explain. 7. It does not cause any alteration in the intestinal flora and
Ans. Tetracyclines are not given along with calcium salts, hence occurrence of diarrhoea is low.
milk, antacids or iron preparations as they have chelating prop- 8. It is primarily excreted in faeces as conjugate.
erty, so when calcium is taken along with tetracycline will form 9. It has low renal toxicity but high phototoxicity.
insoluble complexes and reduces absorption of tetracyclines.
Q. 5. Chloramphenicol
Ans.
Q. 3. Mention the uses of tetracyclines.
Ans. 1. Chloramphenicol is a broad-spectrum antibiotic ob-
tained from Streptomyces venezuelae.
Uses of tetracyclines are as follows: 2. It is bacteriostatic and is effective against Gram-positive
1. Orodental conditions: It is especially useful in chronic and Gram-negative organisms, Rickettsiae, Chlamydiae
periodontitis or juvenile periodontitis. and Mycoplasma.
2. It is a drug of first choice in veneral diseases like Lym- 3. Uses
phogranuloma venereum, atypical pneumonia, cholera, a. Typhoid fever
plague and rickettsial infections. b. Bacterial meningitis
3. It is a drug of second choice in tetanus, anthrax, actino- c. Anaerobic infections
mycosis, gonorrhoea and syphilis. d. Rickettsial infections
e. Eye infections Parameters Tetracycline Doxycycline

4. Adverse effects
Potency Low High
a. Bone marrow depression
b. Leukopenia Intestinal Moderate Complete, no
c. Thrombocytopenia absorption interference by food
d. Agranulocytosis Plasma protein Intermediate High
e. Aplastic anaemia binding
f. Grey baby syndrome Plasma half-life 6–10 h 18–24 h
g. Hypersensitivity reactions Alteration of Marked Least
intestinal flora
Q. 6. Enumerate two differences between tetracyclines
and doxycycline. Incidence of High Low
diarrhoea
Ans. Elimination By rapid renal Primarily excreted
excretion in faeces
Tetracyclines and doxycycline exhibit following differences:
Topic 46
Aminoglycoside Antibiotics
LONG ESSAY
Q. 1. Enumerate aminoglycoside antibiotics, their c. Kanamycin
mechanism of action and their adverse effects. Write d. Amikacin
about the antimicrobial spectrum and therapeutic uses e. Tobramycin
of gentamycin. f. Netilmicin
g. Sisomycin
Or,
II. For GI infections and gut sterilization
Enumerate aminoglycoside antibiotics. Write the anti- a. Neomycin
microbial spectrum, therapeutic uses and adverse effects b. Paromomycin
of any one of them. III. For topical use in the eye and on the skin
a. Neomycin
Or,
b. Framycetin
What are aminoglycoside antibiotics? Briefly state the c. Gentamicin
pharmacological actions, adverse effects and uses of any
one of them.
Mechanism of Action
Ans.
The aminoglycosides are bactericidal antibiotics, acting in
AMINOGLYCOSIDE two main steps:
a. Transport of aminoglycosides through the bacterial cell
l Aminoglycoside antibiotics are a group of natural and wall and cytoplasmic membrane
semisynthetic antibiotics having polybasic amino groups b. Binding to ribosomes and resulting in inhibition of pro-
linked glycosidically to two or more aminosugar resi- tein synthesis
dues. They are mainly used to treat Gram-negative infec- Transport across the bacterial cell wall
tions. l The antibiotics diffuse through the outer coat of the
l Aminoglycosides in current therapeutic use are as Gram-negative bacteria through porin channels.
follows: l Thus penetration is dependent upon maintenance of a
I. For systemic use polarized membrane and on oxygen-dependent active
a. Streptomycin processes.
b. Gentamicin
l These are inactivated under anaerobic conditions. IV. Hypersensitivity Reactions: They are rare, occasionally
Therefore, anaerobes and facultative anaerobes under skin rashes, drug fever and eosinophilia may occur.
deficient O2 supply are resistant to aminoglycosides.
l Penetration is also favoured by high pH. Aminoglyco-
sides are 20 times more active in alkaline pH than in GENTAMICIN

acidic medium. Gentamicin is the most commonly used aminoglycoside
Ribosomal binding and inhibition of protein synthesis: antibiotic obtained from micromonospora purpurea.
l Once inside the bacterium, the antibiotic binds to 30S
and 50S subunits as well as 30S and 50S interface. They

freeze initiation of protein synthesis. Antibacterial Spectrum
l The cidal action of the antibiotic is due to leaking of
l Gentamicin has a broad antibacterial spectrum.
ions, amino acids and even proteins through highly per- l It is the most commonly used aminoglycoside antibiotic
meable cell membrane leading to cell death. for aerobic Gram-negative infections due to E. coli,
Both these mechanisms are attributed to the incorpora- Klebsiella, Proteus and Pseudomonas aeruginosa. It is
tion of the defective proteins into the cell membrane. also effective against Gram-positive infections like en-
terococci, streptococci and staphylococci.
Adverse Effects l It inhibits many Streptococcus faecalis and some Staph-
ylococcus aureus.
The adverse effects common to aminoglycosides are as follows:
I. Ototoxicity
Therapeutic Uses
l It is the most important adverse effect but is dependent
on dose and duration of the treatment. Ototoxicity is Gentamicin is the first-line aminoglycoside but its use is
greater when plasma concentration of the drug is persis- restricted to serious Gram-negative bacillary infections.
tently high and above threshold level. Dose: 3–5 mg/kg/day IM either as a single dose or divided
l Vestibular and cochlear dysfunctions can occur due to
in three 8 hourly doses.
8th cranial nerve damage and vestibular dysfunction is a. Gentamicin may be used alone or in combination with
manifested as headache appearing first followed by nau- penicillin or cephalosporins or any other antibiotic
sea, vomiting, dizziness, nystagmus, vertigo and ataxia. (mixed infections) or with another aminoglycoside (nos-
Important risk factors for ototoxicity are as follows: ocomial infection) depending on the sensitivity pattern
a. Elderly patients in following situations:
l Preventing and treating respiratory infections in crit-
b. Repeated use of aminoglycosides
c. Persistently increased concentration of drug in plasma ically ill patients
l Patients on respirators with tracheostomy.
d. Concurrent use of other ototoxic drugs like vancomy-
l Postoperative pneumonia
cin, minocycline, loop diuretics, etc.
l Patients with implants and in ICU
II. Nephrotoxicity l Gentamicin however should be used to treat commu-
l Aminoglycoside concentrate in the renal cortex depend- nity acquired pneumonias caused by Gram-positive
ing on the dose. cocci and anaerobes.
l They cause renal damage by interfering with the prosta- b. Gentamicin’s important use alone or in combination
glandin production by the kidney. with piperacillin or any third generation cephalosporins
l This renal damage is totally reversible if the drug is (serious infections) is in Pseudomonas, Proteus or
promptly discontinued. Klebsiella infections presenting as
l The risk factors for nephrotoxicity are as follows: l burns,
a. Elderly patients l urinary tract infection,
b. Pre-existing renal disease l pneumonia,
c. Concurrent use of other nephrotoxic drugs like l lung abscess,
AMB, vancomycin, cisplatin, cyclosporine, etc. l osteomyelitis,
l middle ear infections and

III. Neuromuscular Blockage l septicaemia, etc.
l Apnoea and muscular paralysis have been reported. c. Meningitis caused by Gram-negative bacilli is best
l All aminoglycosides reduce release of ACh from the treated with gentamicin as follows:
motor nerve endings. Myasthenic patients are more l 3–5 mg/kg/day IM in 3–8 hourly doses with 4 mg
susceptible to this effect. Hence should be avoided. intrathecal injection daily

l Combination with third generation cephalosporins e. Topical use: Gentamicin is used topically as an ointment
d. Subacute bacterial endocarditis: Gentamicin is used in (0.1%) for various skin lesions and burns and as an eye
combination with penicillin drop (0.3%) in conjunctivitis.
SHORT ESSAYS
Q. 1. Mention therapeutic uses and two adverse effects Q. 2. Mention two therapeutic uses and two adverse
of neomycin. effects of gentamicin.
Ans. Ans.
1. Neomycin is obtained from Streptomyces fradiae, and is Therapeutic Uses

wide-spectrum aminoglycoside active against most
Gram-negative bacilli and some Gram-positive cocci. 1. Gentamicin is the most economical and first-line amino-
2. It is highly nephrotoxic and ototoxic (mainly auditory). glycoside antibiotic, but its use is restricted to serious
It is therefore not used systemically. Gram-negative bacillary infections.
2. Gentamicin’s important use alone or in combination
Therapeutic uses of neomycin are as follows: with piperacillin or any third generation cephalosporins
1. Used topically for infections of skin and mucous mem- (serious infections) is in Pseudomonas, Proteus or Kleb-
brane like ulcers, wounds and burns. siella infections presenting as
2. Used in combination with bacitracin or polymyxin B for a. burns,
infections of eye and external ear. b. urinary tract infection,
3. Used orally for the followings: c. pneumonia,
a. Preparation of bowel before abdominal surgery in d. lung abscess,
order to reduce postoperative infections. e. osteomyelitis,
b. Hepatic coma or encephalopathy: Neomycin on oral f. middle ear infections and
administration reduces ammonia levels in blood g. septicaemia, etc.
by destroying colonic bacteria. However because 3. Meningitis caused by Gram-negative bacilli is best
of toxic potential it is infrequently used for this treated with gentamicin.
purpose. 4. Subacute bacterial endocarditis: Gentamicin is used in
Adverse effects of neomycin are as follows: combination with penicillin.
1. Topically applied neomycin has low sensitizing potential. 5. Topical use: Gentamicin is used topically as an ointment
2. Neomycin on oral administration has damaging effect (0.1 %) for various skin lesions and burns and as an eye
on intestinal villi. drop (0.3%) in conjunctivitis.
3. Prolonged treatment can result in malabsorption syn-
drome with diarrhoea and steatorrhoea. Adverse Effects
4. Due to marked suppression of gut, flora superinfection
by Candida can occur. Adverse effects of gentamicin are as follows:
5. This may accumulate in patients with renal insuffi- 1. Ototoxicity
ciency causing kidney damage, hence is contraindicated 2. Nephrotoxicity
if renal function is impaired. 3. Neuromuscular blockade
6. When applied to peritoneum it can cause apnoea due to The aminoglycosides produce toxic effects common to
muscle paralyzing action. all the members whereas relative propensity differs.
SHORT NOTES
Q. 1. Aminoglycoside antibiotics 3. The aminoglycosides are bactericidal antibiotics acting
by inhibition of protein synthesis.
Ans.
4. Aminoglycosides in current therapeutic use are as follows:
1. Aminoglycoside antibiotics are a group of natural and a. For systemic use: Streptomycin, gentamicin
semisynthetic antibiotics having polybasic amino groups b. For GI infections and gut sterilization: Neomycin,
linked glycosidically to two or more aminosugar residues. paromomycin
2. They are widely used in treatment in medical, gynaeco- c. For topical use in the eye and on the skin: Neomycin,
logical and other systemic infections but rarely in dentistry. framycetin
Q. 2. Streptomycin Q. 3. Gentamicin
Ans. Ans.
1. Obtained from Streptomyces griseus and is mainly ef- 1. Gentamicin is the most commonly used aminoglycoside
fective against aerobic Gram-negative bacilli. antibiotic obtained from Micromonospora purpurea.
2. When used alone, bacteria, especially tubercle bacillus 2. Gentamicin has a broad antibacterial spectrum.
rapidly develops resistance to it. 3. Therapeutic uses of gentamicin are as follows:
3. It is the least nephrotoxic of all the aminoglycosides. a. Serious Gram-negative aerobic bacillary infections
4. Uses b. Subacute bacterial endocarditis
a. Tuberculosis c. Tuberculosis
b. Subacute bacterial endocarditis d. Meningitis caused by Gram-negative bacilli is best
c. Plague treated with gentamicin.
d. Tularaemia e. Topical use: It is used topically as an ointment
e. Brucellosis (0.1 %) for various skin lesions and burns and as an
eye drop (0.3%) in conjunctivitis.
Topic 47
Macrolide and Other Antibacterial Drugs in Treatment

of Urinary Tract Infections
LONG ESSAY
Q. 1. Enumerate macrolide antibiotics. Describe the Pharmacokinetics
antimicrobial spectrum and therapeutic uses of erythro-
mycin. l Erythromycin is adequately absorbed from the upper GI
tract. It is destroyed by gastric acid (acid labile) and
Ans. hence must be administered as enteric-coated tablets to
l Macrolide antibiotics contain a many membered lactone protect it from gastric acid.
l Food may delay the absorption of erythromycin. It is
ring with attached sugars, e.g. erythromycin, clarithro-
mycin and azithromycin which are bacteriostatic in low widely distributed in the body and reaches therapeutic
concentration and bactericidal in the large concentration. concentration in prostatic secretions but does not cross
l Erythromycin is obtained from Streptomyces erythreus.
the blood-brain barrier (BBB).
l It is partly metabolized in the liver, excreted in bile and
Roxithromycin, clarithromycin and azithromycin are
semisynthetic macrolides. undergoes enterohepatic cycling.
ERYTHROMYCIN Antibacterial Spectrum and Therapeutic

Uses
Mechanism of Action
Erythromycin is narrow spectrum, includes mostly Gram-
l Erythromycin and other macrolides bind to bacterial positive and few Gram-negative organisms and overlaps
50S ribosomal subunit and inhibit protein synthesis. considerably with that of pencillin G.
They are bacteriostatic, but at high concentrations, they Enterobacteriaceae, other Gram-negative bacilli and Bacte-
can act as bactericidal agents. They are more active in roides fragilis are not inhibited.
alkaline pH. I. Erythromycin is used as a drug of first choice in the fol-
l These antibiotics are used against Gram-positive organisms. lowing conditions:
a. Mycoplasma pneumoniae infections: Erythromycin infections in children and pregnant women. Eryth-
hastens the rate of recovery. romycin 500 mg 6 hourly for 7 days is effective,
b. Diphtheria: Erythromycin is very effective for elimi- alternative to single dose of azithromycin.
nating the carrier state and for the treatment of acute d. Penicillin-resistant staphylococcal infections: Its
infection. value has reduced due to emergence of erythromy-
c. Pertussis (whooping cough): Erythromycin is most cin resistance as well.
effective for the treatment as well as for prophylaxis III. Erythromycin is used as an alternative drug in patients
of close contacts. who are allergic to penicillin.
d. Chancroid: Erythromycin 2 g/day for 7 days is one a. Tetanus: Administration of human tetanus antitoxin,
of the drugs of choice. tetanus toxoid, anticonvulsant (e.g. diazepam) and
II. Erythromycin is used as a second drug of choice in the debridement of wound are the important therapeutic
following conditions: measures. A course of oral erythromycin for 10 days
a. Campylobacter enteritis: Here duration of diarrhoea may be given to eradicate Clostridium tetani.
and presence of organisms in stools is reduced. b. Streptococcal infections: Tonsillitis, pharyngitis,
However fluoroquinolones are superior. cellulitis, pneumonia, etc. respond to erythromycin.
b. Legionnaire’s pneumonia: Though 3 week erythro- c. Staphylococcal infections in mild cases.
mycin treatment is effective. Especially azithromy- d. Prophylactic uses
cin is preferred as the drug of choice. l For prophylaxis of recurrences of rheumatic fever
c. Chlamydia trachomatis infections of urinogenital l Before surgery to prevent bacterial endocarditis
tract: Erythromycin base is preferred for chlamydial in patients with valvular lesion.
SHORT ESSAYS
Q. 1. Erythromycin a. Mycoplasma pneumoniae infection
b. Diphtheria
Ans.
c. Pertussis (whooping cough)
l Erythromycin is a macrolide antibiotic obtained from d. Chancroid
Streptomyces erythreus. 2 . Erythromycin is used as a second drug of choice in the
l It is bacteriostatic in low concentration and bactericidal following conditions:
in the large concentration. a. Campylobacter enteritis
l Mechanism of action: Erythromycin binds to bacterial b. Legionnaire’s pneumonia
50S ribosomal subunit and inhibits protein synthesis. c. Chlamydia trachomatis infections of urinogenital
l Erythromycin is adequately absorbed from the upper GI tract
tract. It is destroyed by gastric acid (acid labile) and d. Penicillin-resistant staphylococcal infections
hence must be administered as enteric-coated tablets to 3. Erythromycin is used as an alternative drug in patients
protect it from gastric acid. who are allergic to penicillin.
l It is partly metabolized in the liver, excreted in bile and a. Tetanus
undergoes enterohepatic cycling. b. Streptococcal infections
c. Staphylococcal infections in mild cases
Antibacterial Spectrum d. For prophylaxis of recurrences of rheumatic fever
and before surgery to prevent bacterial endocarditis
Erythromycin is narrow spectrum, includes mostly Gram-
in patients with valvular lesion.
positive and few Gram-negative organisms and overlaps consid-
erably with that of pencillin G. While Enterobacteriaceae, other
Gram-negative bacilli and Bacteroides fragilis are not inhibited. Q. 2. Compare and contrast penicillin and erythromycin.
Ans.
Therapeutic Uses
Comparison between contrast penicillin and erythromycin
1. Erythromycin is used as a drug of first choice in the fol- is given in Table 47.1.
lowing conditions:
TABLE 47-1 Comparison between Contrast Penicillin and

Penicillin Erythromycin
Erythromycin
Penicillin interferes with bacterial Erythromycin inhibits
Penicillin Erythromycin cell wall synthesis by inhibiting bacterial protein synthesis
transpeptidase so that cell wall by binding with the 50S
The penicillin has a b-lactam ring The erythromycin has a
deficient species are produced ribosomes
in their chemical structure macrocyclic lactone ring.
which swell and burst
attached with sugars
Penicillin is rapidly excreted in Renal excretion of erythro-
The penicillin is a bactericidal Erythromycin is a bacterio-
urine by active tubular mycin is minimal. It is usu-
drug static at low but bacteri-
secretion ally excreted in bile
cidal at high concentration
Penicillins exhibit adverse Erythromycin is remark-
effects like hypersensitivity reac- ably a safe drug
tion, pain at IM site, etc.
SHORT NOTES
Q. 1. Four therapeutic uses of erythromycin Q. 2. Macrolide antibiotics
Ans. The therapeutic uses of erythromycin are as follows: Ans.
l Mycoplasma pneumoniae infections l Macrolide antibiotics contain a many-membered lactone

l Diphtheria and sepsis ring with attached sugars, e.g. erythromycin, clarithro-
l Whooping cough mycin and azithromycin.
l Genital and respiratory tract infections l They are bacteriostatic in low concentration and bacte-
l Community acquired pneumonia ricidal in the large concentration.

l For prophylaxis of bacterial endocarditis during dental l Erythromycin is obtained from Streptomyces erythreus.
procedures in patients with valvular heart disease Roxithromycin, clarithromycin and azithromycin are
semisynthetic macrolides.
Topic 48
Antitubercular Drugs
LONG ESSAY
Q. 1. Classify drugs used in tuberculosis. Write the l Classification of antitubercular drugs is as follows
pharmacology of any two commonly used drugs. (Table 48.1):
i. First-line antitubercular drugs (standard drugs):
Or,
These drugs have high antitubercular efficacy as
Enumerate the drugs used in the treatment of tubercu- well as low toxicity and are used routinely.
losis. Write the mechanism of action and adverse effects ii. Second-line antitubercular drugs (reserve drugs):
of any one of them? These drugs have low antitubercular efficacy or high
toxicity or both and are used in special circumstances.
Or,
Discuss chemotherapy of pulmonary tuberculosis. Men- TABLE 48-1 Classification of Antitubercular Drugs
tion mechanism of action adverse effects of three com- First-Line Drugs Second-Line Drugs Newer Drugs
monly used drugs? Isoniazid (H) Thiacetazone Ciprofloxacin
Ans. Rifampicin (R) Paraaminosalicylic acid Moxifloxacin
The drugs which are given against tuberculosis are known Pyrazinamide (Z) Ethionamide Gatifloxacin
as antitubercular drugs. Ethambutol (E) Cycloserine Clarithromycin
l It acts best on slowly or intermittently dividing bacilli.

First-Line Drugs Second-Line Drugs Newer Drugs
l It is bactericidal to Mycobacterium tuberculosis and
Streptomycin (S) Kanamycin Azithromycin covers all subpopulations of TB bacilli and also atypical
Amikacin Rifabutin mycobacteria.
l It acts by inhibiting bacterial DNA-dependent RNA poly-
Capreomycin Rifapentine
merase and thereby suppressing chain initiation in RNA
synthesis thus stopping expression of bacterial genes.
l Two of the standard drugs commonly used in treatment
of tuberculosis are Adverse Effects
a. isoniazid and l Hepatitis: It is the major adverse effect and is dose de-
b. rifampicin. pendent. It usually occurs in patients with pre-existing
liver diseases. The drug should be discontinued on the
A. ISONIAZID (INH) development of jaundice.
l Respiratory syndrome: It presents as breathlessness as-
Isoniazid is a highly effective and the most widely used
antitubercular drug and is an essential component of all sociated with shock and collapse.
antitubercular regimens. Other minor reactions common with intermittent therapy
are as follows:
Mechanism of Action i. Cutaneous syndrome: Flushing, pruritus and rash on
face and scalp, redness and watering of eyes
l Isoniazid acts by inhibition of synthesis of mycolic
ii. Flu-like syndrome: Chills, fever, headache, malaise
acids, which are unique fatty acid components of the
and bone pain
mycobacterium cell wall.
iii. Abdominal syndrome: Nausea, vomiting, abdominal
l It targets INH-A gene which encodes fatty acid synthase
cramps with or without diarrhoea
enzyme.
l The sensitive mycobacterium concentrates INH and con-
verts it to an active metabolite by a catalase-peroxidase C. STREPTOMYCIN

enzyme which interacts with the INH-A gene. Streptomycin is an aminoglycoside antibiotic. It was the
l Isoniazid acts on extracellular as well as intracellular first effective drug developed for the treatment of tubercu-
bacilli. Fast multiplying organisms are rapidly killed but losis. It is a bactericidal drug and acts only against extracel-
quiescent ones are only inhibited. lular organisms due to poor penetrating power.
Adverse Effects Mechanism of Action

l Peripheral neuritis, paraesthesia, numbness, mental dis- It binds to the 30S ribosomes and inhibits bacterial protein
turbances and rarely convulsions are the most important synthesis. They are bactericidal.
dose-dependent toxic effects of INH.
l Peripheral neuritis: It is produced due to interference with Toxic Manifestations of Streptomycin
utilization of pyridoxine and its increased excretion in
i. Streptomycin is avoided during pregnancy because if
urine. The risk of peripheral neuritis is prevented by rou-
used in infants it causes fetal ototoxicity.
tinely giving 10 mg/day of pyridoxine along with INH.
l It is avoided using with other ototoxic drugs like
l Hepatitis: It is another major adverse effect common in
minocycline and diuretics.
older people and in alcoholics. It is due to dose-related dam-
l It is avoided using with nephrotoxic drugs like am-
age to hepatocytes and is reversible on stopping the drug.
photericin-B and cyclosporine.
l Rashes, fever, acne and arthralgia are other side effects.
ii. It should not be mixed with any other drug in same
syringe.
B. RIFAMPICIN iii. Resistance develops when used alone.
It is a semisynthetic antibiotic obtained from Streptomyces
mediterranei. It is a first-line antitubercular drug. It is Therapeutic Uses
called sterilizing agent, as it is the only agent that can act It is used in tuberculosis, plague, tularemia, brucellosis,
on all types of bacillary subpopulations. urinary tract infections and septicaemia.
Mechanism of Action
Treatment of Tuberculosis
l Rifampicin affects both extracellular and intracellular
organisms. It is the only drug active against persisters l Tuberculosis is one of the most difficult infections to
present in central caseous lesion. cure.
l The properties of mycobacteria like slow division, de- TABLE 48-2 Category-wise Alternative Treatment Regimens
velopment of resistance, ability to remain as persisters for Tuberculosis (WHO 1997)
for years and intracellular location of the bacilli have
enhanced the problem. Cate- Initial Phase
l The aim of treatment is to kill the dividing bacilli thus mak-
gory (Daily/3 3 Continua- Total
ing the patient sputum negative and to destroy the persisters of TB Type of Patient Per Week) tion Phase Duration
in order to prevent relapse and ensure complete cure. I New sputum 2HRZE (S) 4HR/4H3R3 6 months
l A combination of drugs is used in treatment of tubercu-
positive or
Seriously ill 6HE 8 months
losis to sputum negative
a. delay the development of resistance, Seriously ill
b. reduce toxicity and extrapulmonary
c. shorten the course of treatment. II Sputum positive 2HRZES 1 5HRE or 8 months
l Majority of cases are sensitive to first-line drugs. Initial relapse 1HRZE 5H3R3E3 8 months
treatment should be intensive and include drugs that Sputum positive
have maximum effect. failure
l Good patient compliance and cost of therapy should
Sputum positive
treatment after
also be considered. default
III Sputum 2HRZ 4HR/4H3R3 6 months
Treatment Regimens for Tuberculosis negative not or 6HE 8 months
seriously ill
Depending upon the duration of treatment, the regimens are Extrapulmonary
divided into the following: not seriously ill
Long-course regimens (conventional regimens): These IV Chronic or For H resistance RZE for 12
consist of INH along with one or two bacteriostatic drugs suspected For H 1 R months
for 18 months. This is usually not recommended now be- MDR-TB cases resistance
ZE 1 S/Etm
cause of poor patient compliance and high failure rate. 1 Cipro/ofl
Short-course chemotherapy: There are several short-
course regimens of 6–9 months duration, which are conve-
nient, highly effective and less toxic. TABLE 48-3 Treatment Regimes Followed in India Under
All regimens will have two phases as follows: the Revised National Tuberculosis Control Programme
i. Initial intensive phase: The patient receives intensive (RNTCP 1997)
treatment with 3–4 tuberculocidal drugs daily or thrice
Category Continuation Total
weekly for a period of 2–3 months. The main objective
of TB Initial Phase Phase Duration
of this phase is to render the patient noncontagious.
ii. Continuation phase: The patient receives 2–3 drugs, I 2H3R3Z3E3 4H3R3 6 months
usually INH and rifampicin daily or thrice weekly for a II 2H3R3Z3E3S3 5H3R3E3 8 months
period of 4–6 months. This phase helps to eliminate 1 1H3R3Z3E3
persisters and prevents relapse. III 2H3R3Z3 4H3R3 6 months
WHO Guidelines for Treatment

of Tuberculosis l Each antitubercular drug is given standard abbreviations:
l Isoniazid (H)
There are two treatment regimens sharing the common cri- l Rifampicin (R)
teria of classification as follows: l Pyrazinamide (Z)
l Category-wise alternative treatment regimens recom- l Ethambutol(E)
mended by WHO in 1997 l Streptomycin (S)
l Revised National Tuberculosis Control Programme (RN- l Ethionamide (Etm)
TCP) 1997 of India, recommended and followed in India. l The number before a phase is the duration of that phase
Under Revised National Tuberculosis Control Programme in months.
DOTS (directly observed treatment short-course) is being l The number in the subscript is the number of doses of
implemented (Tables 48.2 and 48.3). that drug per week. If there is no subscript number the
The standard code is explained below: drug is given daily.
SHORT ESSAYS
Q. 1. Mention four adverse effects of rifampicin. Mechanism of Action
Or, l Isoniazid acts by inhibition of synthesis of mycolic
acids, which are unique fatty acid components of the
Mention two important uses of rifampicin and its two
mycobacterium cell wall.
adverse effects.
l It targets INH-A gene which encodes fatty acid synthase
Ans. enzyme.
l The sensitive mycobacterium concentrates INH and con-
Rifampicin is a semisynthetic antibiotic obtained from verts it to an active metabolite by a catalase-peroxidase
Streptomyces mediterranei. It is a first-line antitubercular enzyme which interacts with the INH-A gene.
drug. It is called sterilizing agent, as it is the only agent that l Isoniazid acts on extracellular as well as intracellular
can act on all types of bacillary subpopulations. bacilli. Fast multiplying organisms are rapidly killed but
quiescent ones are only inhibited.
Mechanism of Action
l Rifampicin affects both extracellular and intracellular Adverse Effects
organisms. It is the only drug active against persisters l Peripheral neuritis, paresthesia, numbness, mental dis-
present in central caseous lesion. turbances, and rarely convulsions are the most impor-
l It acts best on slowly or intermittently dividing bacilli.
tant dose-dependent toxic effects of isoniazid (INH).
l It is bactericidal to Mycobacterium tuberculosis and
l Peripheral neuritis
covers all subpopulations of TB bacilli and also atypical l It is produced due to interference with utilization of
mycobacteria. pyridoxine and its increased excretion in urine.
l It acts by inhibiting bacterial DNA-dependent RNA
l The risk of peripheral neuritis is prevented by routinely
polymerase and thereby suppressing chain initiation in giving 10 mg/day of pyridoxine along with INH.
RNA synthesis thus stopping expression of bacterial l Hepatitis
genes. l It is another major adverse effect common in older
people and in alcoholics.

Adverse Effects l It is due to dose-related damage to hepatocytes and is
reversible on stopping the drug.

l Hepatitis: It is the major adverse effect and is dose de- l Rashes, fever, acne and arthralgia are other side effects.
pendent. It usually occurs in patients with pre-existing
liver diseases. The drug should be discontinued on the Q. 3. DOTS in chemotherapy of TB
development of jaundice.
l Direct observed treatment short-course (DOTS) therapy
sociated with shock and collapse. is a community-based tuberculosis treatment and care
Other minor reactions common with intermittent therapy strategy under the revised National Tuberculosis Con-
are as follows: trol Programme.
l Under this strategy, the antitubercular drugs during the
l Cutaneous syndrome: Flushing, pruritus and rash on
face and scalp, redness and watering of eyes intensive phase are administered under direct supervi-
l Flu-like syndrome: Chills, fever, headache, malaise and
sion of peripheral health staff such as MPWs or through
bone pain voluntary workers such as teachers, anganwadi workers,
l Abdominal syndrome: Nausea, vomiting, abdominal
dias, ex-patients and social workers.
l This strategy has ensured high cure rate through its
cramps with or without diarrhoea
three components as follows:
Q. 2. One use and mechanism of action of isonicotinic l Appropriate medical treatment
acid hydrazide (INH) l Supervision and motivation by health and nonhealth
workers
Ans. l Monitoring of disease status by health services
Isoniazid (INH) is a highly effective and the most widely

Q. 4. Mention the six drugs used in tuberculosis.
used antitubercular drug and is an essential component of
all antitubercular regimens. Ans.
The drugs which are given against tuberculosis are known Q. 5. Explain why multidrug therapy is used in the
as antitubercular drugs. treatment of tuberculosis?
Classification of antitubercular drugs is as follows (Table 48.4):
Ans.
1. First-line antitubercular drugs (standard drugs): These
drugs have high antitubercular efficacy as well as low l Tuberculosis is one of the most difficult infections to cure.
toxicity and are used routinely. l The properties of mycobacteria like slow division, de-
2. Second-line antitubercular drugs (reserve drugs): These velopment of resistance, ability to remain as persisters
drugs have low antitubercular efficacy or high toxicity for years and intracellular location of the bacilli have
or both and are used in special circumstances. enhanced the problem.
l The aim of treatment is to kill the dividing bacilli
TABLE 48.4 Classification of Antitubercular Drugs
thus making the patient sputum negative and to destroy
First-Line Drugs Second-Line Drugs Newer Drugs the persisters in order to prevent relapse and ensure
Isoniazid (H) Thiacetazone Ciprofloxacin complete cure.
l A combination of drugs is used in tuberculosis to
Rifampicin (R) Paraaminosalicylic Moxifloxacin
l delay the development of resistance,
acid
l reduce toxicity and
Pyrazinamide (Z) Ethionamide Gatifloxacin
l shorten the course of treatment.
Ethambutol (E) Cycloserine Clarithromycin l Majority of cases are sensitive to first-line drugs. Initial
Streptomycin (S) Kanamycin Azithromycin treatment should be intensive and include drugs that
have maximum effect.
Amikacin Rifabutin
l Good patient compliance and cost of therapy should
Capreomycin Rifapentine also be considered.
SHORT NOTES
Q. 1. Pyridoxine should be administered with INH. l Adverse effects
l Peripheral neuritis, paraesthesia, numbness, mental
Or,
disturbances, and rarely convulsions are the most
Rationale of combining INH (isonicotinic acid and hy- important dose-dependent toxic effects of isoniazid
drazide) with pyridoxine in the treatment of tuberculosis. (INH).
l Hepatitis is another major adverse effect common in
Ans.
older people and in alcoholics.
l INH causes peripheral neuritis and neurological mani- l Rashes, fever, acne and arthralgia are other side
festations due to interference with utilization of pyri- effects.

doxine and its rapid excretion through urine.
l This can be prevented by adding 10 mg/day of pyridox-
Q. 3. Rifampicin
ine or is treated by 100 mg/day of pyridoxine. Ans.
l Therefore, INH is combined with pyridoxine in the treat-
ment of tuberculosis to reduce the risk of peripheral neuritis. l Rifampicin is a semisynthetic derivative of rifamycin B
obtained from Streptomyces mediterranei.
Q. 2. Isonicotinic acid (INH) l Rifampicin affects both extracellular and intracellular
organisms. It acts best on slowly or intermittently divid-

Ans.
ing bacilli.
l Isoniazid (INH) is a highly effective and the most l It is bactericidal to Mycobacterium tuberculosis and
widely used antitubercular drug and is an essential com- covers all subpopulations of TB bacilli and also atypical
ponent of all antitubercular regimens. mycobacteria.
l Mechanism of action: Isoniazid acts by inhibition of l It acts by inhibiting DNA-dependent RNA synthesis,
synthesis of mycolic acids, which are unique fatty acid thus stopping expression of bacterial genes.
components of the mycobacterium cell wall. l Adverse effects: Hepatitis, other minor reactions com-
l Isoniazid acts on extracellular as well as intracellular mon with intermittent therapy include cutaneous syn-
bacilli. drome, flu-like syndrome and abdominal syndrome.
Q. 4. DOTS in chemotherapy of tuberculosis l Hyperuricaemia due to decreased excretion of uric

acid
Ans.
l Arthralgia
l Direct observed treatment short-course (DOTS) is a com- l Anorexia, vomiting and rashes
munity-based tuberculosis treatment and care strategy un-

der the revised National Tuberculosis Control Programme. Q. 6. Four adverse effects of rifampicin
l Under this strategy, the antitubercular drugs during the Ans.
intensive phase are administered under direct supervi-
sion of peripheral health staff such as MPWs or through Rifampicin is a semisynthetic derivative of rifamycin B
voluntary workers such as teachers, anganwadi workers, obtained from Streptomyces mediterranei.
dias, ex-patients and social workers. Adverse effects of rifampicin are as follows:
l Through its three components this strategy has ensured l Hepatitis is the major adverse effect and is dose
high cure rate. dependent.

l Appropriate medical treatment l It usually occurs in patients with pre-existing liver
l Supervision and motivation by health and nonhealth diseases.

workers l The drug should be discontinued on the development
l Monitoring of disease status by health services of jaundice.

Q. 5. Pyrazinamide sociated with shock and collapse.

l Purpura, haemolysis, shock and renal failure
Ans.
l Other minor reactions common with intermittent ther-
l Pyrazinamide is a tuberculocidal drug that is more apy are as follows:

active in acidic pH. l Cutaneous syndrome: Flushing, pruritus with rash on
l It is effective against intracellular bacteria. face and scalp, redness and watering of eyes
l It is well-absorbed and achieves good concentration in CSF. l Flu syndrome: Chills, fever, headache, malaise and
l Adverse effects bone pain

l Cannot be used alone as resistance develops. l Abdominal syndrome: Nausea, vomiting, abdominal
l Hepatotoxicity is the most common adverse effect. cramps with or without diarrhoea
Topic 49
Antileprotic Drugs
SHORT ESSAYS
Q. 1. Dapsone 2. Dapsone is structural analogue of PABA and hence
competitively inhibits bacterial folate synthetase which
Ans.
is involved in the conversion of PABA to folic acid. This
1. Dapsone or diaminodiphenyl sulfone is the oldest, causes folic acid deficiency resulting in injury to the
cheapest, most active and most commonly used agent bacterial cell.
for treatment of leprosy even today. 3. It also competitively inhibits the union of PABA with
pteridine residue to form dihydropteroic acid which
conjugates with the glutamic acid to produce dihydrofo-
Mechanism of Action lic acid.
1. Dapsone is chemically related to sulphonamide and has 4. It also gets incorporated to form an altered folate which
the same mechanism of action. is metabolically injurious.
5. Thus dapsone produces leprostatic effect as shown:
PABA skin smear negativity is attained or not and 6 months for

paucibacillary leprosy.
(-) Folate synthetase
4 . Treatment schedules of leprosy are listed in Table 49.1.
Dapsone →↓
DHFA TABLE 49.1 Treatment Schedule of Leprosy
Dihydrofolate reductase Multibacillary Paucibacillary

Drugs Used Leprosy (24 months) Leprosy (6 Months)
THFA Rifampicin 600 mg once a 600 mg once a month
month supervised supervised
Pharmacokinetics Dapsone 100 mg daily self- 100 mg daily self-

administered administered
1. Dapsone is given orally and is almost completely
Clofazimine 300 mg once a
absorbed from the gut. 70% is plasma protein bound. month supervised or
2. Widely distributed in the body and mainly concentrated 50 mg daily self-
in the infected skin, muscle, liver and kidney. administered
3. It is partly secreted in bile and undergoes enterohepatic
cycling.
4. Metabolized by acetylation and excreted in urine. Alternative regimens are as follows:
1. Clofazimine 50 mg with any two newer drugs (ofloxa-
cin, minocycline, clarithromycin, etc) daily for 6 months
Adverse Effects
followed by clofazimine 50 mg with any one new drug
1. The common adverse effects are dose-related haemo- daily for another 18 months.
lytic anaemia and methaemoglobinaemia, particularly 2. In case of single lesion paucibacillary leprosy: (ROM
in patients with G6PD deficiency. regimen)
2. Gastric intolerance like anorexia, nausea, vomiting, head-
ache, drug fever, paraesthesia and mental symptoms. Rifampicin 600 mg 
3. Cutaneous reactions include allergic rashes, fixed drug Ofloxacin 400 mg  as a single dose
Minoccycline 100 mg 
reaction, hypermelanosis, phototoxicity and rarely exfo-
liative dermatitis.
4. Hepatitis and agranulocytosis rarely occur. Q. 3. Explain briefly about lepra reactions.
5. Lepra reaction Ans.
1. Lepra reactions are immunologically-mediated reactions

Therapeutic Uses
that occur during the course of the disease. Aetiology is
1. Leprosy unknown and precipitated by infection, trauma, mental
a. Main indication: 100 mg daily self-administered for stress, etc. There are two types of reactions:
6 months in paucibacillary and 24 months in multi- a. Lepra reaction (erythema nodosum leprosum)
bacillary leprosy. b. Reversal reaction
b. Used in chloroquine-resistant malaria combined
with pyrimethamine.
Lepra Reaction
Q. 2. Schedule for treatment of leprosy or multidrug 1. Occurs in lepromatous leprosy (LL) usually with insti-
therapy in leprosy tution of chemotherapy or intercurrent infection.
Ans. 2. It is arthus type or type III hypersensitivity reaction due
to release of antigens from the killed bacilli.
1. Leprosy is treated by multidrug therapy (MDT) regime 3. It may be mild, severe or life threatening (erythema
introduced by WHO in 1981 and implemented under nodosum leprosum).
National Leprosy Eradication Programme. 4. Lepra reaction is of abrupt onset, existing lesions en-
2. The drugs used are dapsone, rifampicin and clofazi- large, become red, swollen and painful. Several new
mine. All these drugs are administered orally. lesions may appear.
3. The WHO recommended the following standard MDT 5. It is characterized by tender, inflamed subcutaneous
regimen in 1994 as fixed duration therapy of 2 years for nodules with fever, lymphadenopathy, arthritis, nerve
multibacillary leprosy, whether disease inactivity or pain, orchitis, etc.
6. Treatment Reversal Reaction

a. Temporary discontinuation of dapsone is recommended
1. It is delayed type of hypersensitivity seen in borderline
only in severe cases. The severe forms are treated with
categories of leprosy and is common in tuberculoid type
thalidomide but pregnancy is absolute contraindication.
of leprosy (TT).
b. Other drugs used are analgesics, antipyretics, antibi-
2. Even after completion of therapy, cutaneous ulcerations,
otics, etc.
multiple nerve involvement with pain and tenderness
c. Clofazimine 200 mg daily is highly effective in con-
occur suddenly.
trolling the reaction except the most severe ones.
3. It is treated with clofazimine or corticosteroids.
d. Corticosteroids should be used only in severe cases.
SHORT NOTES
Q. 1. Mention the drugs used in lepra reactions. b. Gastric intolerance like anorexia, nausea, vomiting,
Or, headache, fever, paraesthesia and mental symptoms
c. Cutaneous reactions include allergic rashes, fixed drug
Treatment of lepra reactions reaction, hypermelanosis, phototoxicity and rarely ex-
Ans. The drugs used in lepra reactions are as follows: foliative dermatitis
d. Lepra reaction
1. Type 1 lepra reactions or reversal reactions are treated
with oral prednisolone, i.e. corticosteroids or clofazi- Q. 3. Enlist three drugs for leprosy.
mine. Ans. The drugs used in treatment of leprosy are called as
2. Type 2 lepra reactions: The severe forms are treated antileprotic drugs. The treatment of leprosy is done by
with thalidomide but pregnancy is absolute contraindi- multidrug therapy.
cation. Other drugs used are aspirin, clofazimine, chlo-
roquine and prednisolone. Various drugs used for leprosy treatment are as follows:
1. Sulfone
Q. 2. DDS a. Dapsone
Ans. b. DADDS
2. Phenazine derivatives
1. Dapsone or diaminodiphenyl sulfone (DDS) is the old- a. Clofazimine
est, cheapest, most active and most commonly used 3. Antitubercular drugs
agent for treatment of leprosy even today. a. Rifampicin
2. Dapsone produces leprostatic effect by causing folic b. Ethionamide
acid deficiency resulting in injury to the bacterial c. Prothionamide
cell. 4. Other antibiotics
3. Therapeutic uses of dapsone are as follows: a. Ofloxacin
a. Main indication is treatment of leprosy. b. Minocycline
b. Used in chloroquine-resistant malaria combined c. Clarithromycin
with pyrimethamine
To deal with dapsone-resistant strains of Mycobacterium
4. Adverse effects
leprae, MDT with rifampicin, dapsone and clofazimine was
a. Dose-related haemolytic anaemia and methaemoglo-
introduced by WHO.
binaemia
Topic 50
Antifungal Drugs
SHORT ESSAYS
Q. 1. Amphotericin B 2. Amphotericin B (AMB) is active against a wide range
of fungi and yeast like Candida albicans, Histoplasma
Ans.
capsulatum, Cryptococcus neoformans, Blastomyces der-
1. Amphotericin B is a broad-spectrum antifungal agent matitidis, Coccidiodes rhodotorula, Aspergillus, Sporo-
obtained from Streptomyces nodosus. thrix and fungi causing mucormycosis.
Mechanism of Action Ans. Fungal infections may be systemic or superficial. An-

tifungal drugs are used in the treatment of fungal infections.
Amphotericin binds to ergosterol present
in fungal cell membrane
Antifungal drugs are classified as follows:
1. Antifungal antibiotics
Forms pores and channels in the cell membrane a. Polyenes: Amphotericin-B, nystatin, hamycin and
natamycin (pimaricin)
Permeability of the membrane increases b. Heterocyclic benzofuran: Griseofulvin
2. Antimetabolites: Flucytosine (5-FC)
Leakage of intracellular contents occurs leading to 3. Azoles
a. Imidazoles (topical): Ketoconazole, miconazole,
clotrimazole and econazole
Death of fungi (fungicidal)
b. Triazoles (systemic): Fluconazole and itraconazole
4. Allylamine: Terbinafine
Pharmacokinetics 5. Other topical agents: Tolnaftate, undecylenic acid, ben-
Amphotericin B is poorly absorbed from gut hence is not zoic acid, salicylic acid, selenium sulphide, ciclopirox
suitable orally and so it is given IV. olamine, sodium thiosulphate
Formulations Uses
1. AMB is poorly water soluble, hence IV and intrathecal Antifungal drugs are used against a large variety of fungi and
preparation are made with deoxycholate—AMB col- yeasts like Candida albicans, Histoplasma capsulatum, Cryp-
loidal deoxycholate complex (AMB—DOC). tococcus neoformans, Blastomyces dermatitidis, Coccidiodes
2. ABCD (AMB colloidal dispersion), ABLC (AMB lipid immitis, Torulopsis, Rhodotorula, Aspergillus, Sporothrix,
complex) and liposomal AMB are the lipid based new deep mycoses, Epidermophyton, Trichophyton, Microsporum.
formulations of AMB. They are developed mainly to
reduce its toxicity, improve tolerability and produce site Q. 3. Griseofulvin
specific delivery of the drug. Ans. Griseofulvin is a heterocyclic benzofuran, derived
from Penicillium griseofulvum. It is an antibiotic antifungal
Uses agent. It is a fungistatic and not a fungicidal agent.
1. It is used intravenously for all life-threatening deep
mycotic infections.
2. AMB is the drug of choice for severe deep mycosis in Spectrum of Activity
immunocompromized individuals. Griseofulvin is active against most of the dermatophytic
3. Topical AMB is used for cutaneous candidiasis. species of fungi like Epidermophyton, Trichophyton, Mi-
4. It is used as an alternative in the treatment of kala-azar crosporum. It is not active against species like Candida.
and mucocutaneous leishmaniasis.
Mechanism of Action
Adverse Effects
Griseofulvin gets deposited in the keratin forming cells in
1 . AMB is the most toxic of all the antifungal agents. the skin, nails and hair.
2. IV infusion of amphotericin B causes fever, chills, muscle
spasms, vomiting, headache, and hypotension.
3. Anaemia and electrolyte disturbances are commonly Griseofulvin
seen.
4. It also causes bone marrow depression which leads to Interacts with polymerized microtubules
anaemia and renal impairment.
Disrupts the mitotic spindles
Q. 2. Antifungal drugs
Or, Spindle poison
Name four drugs used in fungal infections. Thus griseofulvin inhibits fungal mitosis (fungistatic).
Adverse Effects Uses

1. Though toxicity due to griseofulvin is low, GI distur- 1. Griseofulvin is used in treatment of dermatophytic in-
bances, peripheral neuritis, CNS symptoms, headache fections. The duration of treatment depends on the site
are common complaints. of lesion and thickness of infected keratin layer.
2. Discontinuation of the drug is advised in case of rashes 2. It is reserved for cases involving nail, hair, or large body
and photoallergy. surface involvement.
3. It is used in cases of Athlete’s foot.
SHORT NOTES
Q. 1. Name two broad-spectrum antifungal antibiotics. 3. Nystatin can be used topically for oral, pharyngeal, cor-
neal, conjunctivitis, and cutaneous candidiasis.
Ans. Broad-spectrum antifungal drugs are used against a
4. It can also be combined with tetracycline to prevent
large variety of fungi and yeasts like Candida albicans,
superinfection.
Histoplasma capsulatum, Cryptococcus neoformans, Blas-
tomyces dermatitidis, Coccidiodes immitis, Torulopsis,
Rhodotorula, Aspergillus, Sporothrix, deep mycoses, Epi- Side Effects
dermophyton, Trichophyton, Microsporum.
Gastrointestinal disturbances, nausea and bad taste can oc-
cur on oral administration.
Antifungal Antibiotics Q. 3. Ketoconazole

1. Polyenes: Amphotericin-B, nystatin, hamycin and nata- Ans.
mycin (pimaricin)
2. Heterocyclic benzofuran: Griseofulvin 1. Ketoconazole is a broad-spectrum antifungal that is
used in superficial candidal infections, dermatophytosis,
Q. 2. Nystatin and deep mycosis.
2. It is effective orally as well as topically for various fun-
Ans.
gal infections.
1. Nystatin is a polyene antibiotic obtained from Strepto- 3. It is the most toxic among azoles, hence used commonly
myces noursei. by topical route for candida and dermatophytic infections.
2. It is used only topically in candida infections as it is 4. Adverse effects: Ketoconazole is less toxic than ampho-
poorly absorbed from the skin and mucous membranes tericin B, but it causes gastric irritation, headache, allergic
and has high systemic toxicity. reactions, gynaecomastia and sometimes hepatotoxicity.
5. Uses
a. Used in the treatment of dandruff with ketoconazole
Therapeutic Uses shampoo.
1. Nystatin can be used orally in case of monilial diarrhoea b. It is used in the treatment of dermatophytosis of
due to superinfection or otherwise in dose of 5 lakh large body surface, tinea of nails, dermal leishmani-
units TDS. asis and kala-azar.
2. It is effective in monilial vaginitis: As vaginal supposi- c. As it reduces the levels of corticosteroid production,
tories 1 lakh units tablet inserted twice daily. it is used in the treatment of Cushing’s syndrome.
Topic 51
Antiviral Drugs
SHORT ESSAY
Q. 1. Classify antiviral drugs. 1. Viruses are intracellular parasites and depend on host
cells for food, growth and multiplication.
Ans.
2. Antiviral drugs interfere with the steps of viral repro-
duction cycle within host cell.
CLASSIFICATION OF ANTIVIRAL AGENTS b. Nonnucleoside reverse transcriptase inhibitors:

Nevirapine, delaviridine and efavirenz
1. Drugs used against herpetic infection (antiherpes agents):
c. Protease inhibitors: Saquinavir, indinavir, ritonavir
Acyclovir, valacyclovir, ganciclovir, idoxuridine, vidara-
and lopinavir
bine, foscarnet
d. Fusion inhibitor: Enfuvirtide
2. Drugs used against HIV infection (antiretroviral agents)
3 . Anti-influenza virus agents: Amantadine, rimantadine,
a. Nucleoside reverse transcriptase inhibitors: Zidovudine,
and oseltamivir
didanosine, zalcitabine, stavudine, and lamivudine
4. Other antiviral agents: Ribavirin and interferons
SHORT NOTES
Q. 1. Acyclovir 2 . Herpes zoster infections
3. Chicken pox
Ans.
1 . Acyclovir is an antiherpes virus agent. Adverse Effects

2. It is effective against the following viruses:
a. Herpes simplex virus type I and type II 1. Common ill effects include nausea, diarrhoea, head-
b. Varicella zoster virus ache, rashes. Topical application can cause burning,
c. Epstein Barr virus irritation.
2. Given IV it can cause renal and neurotoxicity.
Mechanism of Action
Q. 2. Zidovudine
Acyclovir
Ans.
HSV thymidine kinase
Zidovudine is a thymidine analogue, active against HIV
Acyclovir monophosphate infections and other retroviruses. It is the first antiretrovi-
cellular enzymes ral drug approved for treatment of HIV infection.
Acyclovir diphosphate
Mechanism of Action
cellular enzymes
1. Zidovudine is converted to its triphosphate derivative
Acyclovir triphosphate which inhibits reverse transcriptase.
Inhibits DNA synthesis and viral replication. Adverse Effects

1. Bone marrow depression, headache, nausea, vomiting,
1. Acyclovir acts by inhibiting viral DNA synthesis by and insomnia can occur.
causing DNA chain termination. Acyclovir is a well- 2. High doses can cause myopathy and neurotoxicity.
tolerated drug available for oral, topical and intravenous
administration.
Uses
Uses 1 . Zidovudine is the drug of choice in HIV infections.
2. Given during pregnancy and continued in newborns
1. HSV type-I infections of face, mouth, skin, oesophagus
for up to 6 weeks, it reduces the risk of transmission to
or brain and type-II infections of genitals, rectum, skin,
the baby.
hands or meninges
Topic 52
Antimalarial Drugs
LONG ESSAY
Q. 1. Classify the drugs used in malaria and briefly out- CHLOROQUINE
line mechanism of action, clinical uses and toxicity of
l It is a synthetic 4-aminoquinoline. It is a rapidly acting
chloroquine.
erythrocytic schizontocide with activity against all the
Ans. four species of plasmodia.
l It also destroys gametocytes of P. vivax, P. ovale, P. malaria
Malaria is a major public health problem in most of the and completely cures falciparum malaria. Patients become
developing countries like India. It is caused by four species afebrile in 1–2 days.
of protozoan parasite Plasmodium. l Chloroquine is safe in pregnancy. It also has anti-
inflammatory properties.
CLASSIFICATION OF ANTIMALARIAL
DRUGS Mechanism of Action of Chloroquine
i. 4-Aminoquinolones: Chloroquine, amodiaquine l Mechanism of action of chloroquine is not completely
ii. Quinolone–methanol: Mefloquine known.
iii. Acridine: Quinacrine (Mepacrine, Atabrine) l It is actively concentrated by sensitive intraerythrocytic
iv. Cinchona alkaloid: Quinine plasmodia, higher concentration is found in infected RBCs.
v. Biguanides: Proguanil (Chloroguanide) l Chloroquine is a base. It concentrates in acidic food
vi. Diaminopyrimidines: Pyrimethamine vacuoles of the parasite and interferes with the degrada-
vii. 8-Aminoquinoline: Primaquine, bulaquine tion of haemoglobin by parasitic lysosomes.
viii. Sulphonamides and sulphone: Sulphadoxine, sulpha- l Polymerization of toxic haeme to nontoxic parasite pig-
methopyrazine, dapsone ment haemozoin is inhibited by formation of chloro-

ix. Tetracyclines: Tetracycline, doxycycline quine–haeme complex. Haeme itself or its complex with
x. Sesquiterpine lactones: Artesunate, artemether, ar- chloroquine then damages the plasmodial membranes.
teether l Clumping of pigment and changes in parasite mem-
xi. Phenanthrene methanol: Halofantrine branes follow.

xii. Naphthoquinone: Atovaquone
Antimalarial drugs can be classified according to stage of Adverse Effects
use as follows: l Toxicity of chloroquine is low but side effects are frequent
1. Casual prophylactics (primaquine, pyrimethamine): and unpleasant: Nausea, vomiting, pruritus, headache, vi-
These destroy the tissue forms of the parasite in liver sual disturbances, insomnia and skin rashes may occur.
cells and prevent invasion of the erythrocytes. They are l Parenteral administration can cause hypotension, car-
also called primary tissue schizontocides. diac depression, arrhythmias and CNS toxicity includ-
2. Blood schizontocides (suppressives like chloroquine, qui- ing convulsions.
nine, mefloquine, halofantrine, pyrimethamine, chlorogua- l Prolonged treatment with high doses can cause irrevers-
nide and artemisinin): Suppressives destroy erythrocytic ible retinopathy.
forms and terminate clinical attacks of malaria. l High doses can also cause cardiomyopathy and psychi-
3. Tissue schizontocides used to prevent relapse (prima- atric problems.
quine): They act on hepatic forms of P. vivax, P. ovale,
that produce relapses. Given with a blood schizonto- Uses
cide, they bring about radical cure and eradicate the
parasite from the body in these relapsing malarial i. Chloroquine is the drug of choice for clinical cure and
infections. suppressive prophylaxis of all types of malaria.
4. Gametocidal drugs (primaquine, chloroquine, quinine): ii. Chloroquine is highly effective in the treatment of
These destroy gametocytes and prevent the transmission malaria due to sensitive strains of all four species
of malaria. (600 mg base stat, 300 mg after 6 h and 300 mg
for the next 2 days). It is also used for prophy- v. Photogenic reactions
laxis—300 mg/week. vi. Lepra reactions
iii. Extraintestinal amoebiasis vii. Discoid lupus erythematosus—very effective.
iv. Rheumatoid arthritis viii. Infectious mononucleosis—affords symptomatic relief.
SHORT NOTES
Q. 1. Emetine 2. It also destroys gametocytes of P. vivax, P. ovale,
P. malaria and completely cures falciparum malaria.
Ans.
Patients become afebrile in 1–2 days.
1. Emetine is derived from Ipecac (Brazil root). Directly 3. Chloroquine is safe in pregnancy. It also has anti-
affects the trophozoites but not the cysts. inflammatory properties.
2. As oral absorption is improper, they are given parenterally. 4. Chloroquine attains high concentration in the liver, is
3. They can be used only in severe amoebiasis but not directly toxic against trophozoites and is therefore
preferred due to toxicity. useful in hepatic amoebiasis.
4. Adverse effects:
a. Pain at the injection site
b. Thrombophlebitis Uses
c. Nausea, vomiting, diarrhoea
1. Chloroquine is the drug of choice for clinical
d. Cardiotoxicity
cure and suppressive prophylaxis of all types of
Q. 2. Chloroquine malaria.
2. Extraintestinal amoebiasis
Ans. 3. Rheumatoid arthritis
4. Photogenic reactions and lepra reactions.
1. It is a synthetic 4-aminoquinoline. It is a rapidly acting
5. Infectious mononucleosis—affords symptomatic re-
erythrocytic schizontocide with activity against all the
lief.
four species of plasmodia.
Topic 53
Antiamoebic and Other Antiprotozoal Drugs

LONG ESSAY
Q. 1. Define chemotherapy. Classify the drugs used in It spreads through fecal contamination of food and
treatment of amoebiasis and malaria. water.
Antiamoebic drugs can be classified as follows:
Ans.
I. Tissue amoebicides
l Chemotherapy can be defined as the use of chemicals in A. Drugs effective in both intestinal and extraintestinal
infectious diseases to destroy microorganisms with amoebiasis. For example:
damaging the host tissues. i. Nitroimidazoles: Metronidazole, tinidazole, sec-
l Paul Ehrlich, the father of modern chemotherapy, coined nidazole, ornidazole, satranidazole
the term chemotherapy. He showed that certain dyes can ii. Alkaloids: Emetine, dehydroemetine
destroy microbes and demonstrated methylene blue can be B. Drugs effective only in extraintestinal amoebiasis:
used in malaria. He also synthesized some arsenical com- Chloroquine
pounds for treatment of syphilis and sleeping sickness. II. Luminal amoebicides: Drugs effective only in intestinal
amoebiasis. For example:
a. Amide: Diloxanide furoate
ANTIAMOEBIC DRUGS b. 8-Hydroxyquinolones: Quiniodochlor, diiodohy-
Amoebiasis caused by the protozoan Entamoeba histo- droxyquin (iodoquinol)
lytica is a tropical disease common in developing countries. c. Antibiotics: Tetracyclines
CLASSIFICATION OF ANTIMALARIAL These destroy the tissue forms of the parasite in liver
DRUGS cells and prevent invasion of the erythrocytes. They are
also called primary tissue schizontocides.
i. 4-Aminoquinolones: Chloroquine, amodiaquine ii. Blood schizontocides—Suppressives like chloroquine,
ii. Quinolone–methanol: Mefloquine quinine, mefloquine, halofantrine, pyrimethamine, chlo-
iii. Acridine: Quinacrine (Mepacrine, Atabrine) roguanide and artemisinin
iv. Cinchona alkaloid: Quinine Suppressives destroy erythrocytic forms and terminate
v. Biguanides: Proguanil (Chloroguanide) clinical attacks of malaria.
vi. Diaminopyrimidines: Pyrimethamine iii. Tissue schizontocides used to prevent relapse—Prima-
vii. 8-Aminoquinoline: Primaquine, Bulaquine quine
viii. Sulphonamides and sulphone: Sulphadoxine, sulpha- They act on hepatic forms of P. vivax, P. ovale
metopyrazine, dapsone that produce relapses. Given with a blood schizonto-
ix. Tetracyclines: Tetracycline, doxycycline cide, they bring about radical cure and eradicate the
x. Sesquiterpine lactones: Artesunate, artemether, arteether parasite from the body in these relapsing malarial
xi. Phenanthrene methanol: Halofantrine infections.
xii. Naphthoquinone: Atovaquone iv. Gametocidal drugs—Primaquine, chloroquine, quinine
Antimalarial drugs can be classified as follows: These destroy gametocytes and prevent the transmis-
i. Casual prophylactics—Primaquine, pyrimethamine sion of malaria.
SHORT ESSAYS
Q. 1. Therapeutic uses of metronidazole in dentistry Ans.
Ans. Uses
Metronidazole is a powerful amoebicide. Apart from this it Metronidazole is a powerful amoebicide.
also inhibits Trichomonas vaginalis and Balantidium coli.
Anaerobic bacteria are also sensitive. The uses of metronidazole are as follows:
The uses of metronidazole are as follows: 1. Amoebiasis: Metronidazole is the drug of choice in all
1. Amoebiasis—Metronidazole is the drug of choice in all forms of amoebiasis in the dose of 400–800 mg TDS for
forms of amoebiasis in the dose of 400–800 mg TDS for 3 days.
3 days. 2. It is highly effective in giardiasis.
2. It is highly effective in a dose of 200 mg TDS for 7 days 3. Trichomonas vaginitis: Metronidazole 400 mg TDS for
in giardiasis. A shorter course of 3 days with 2 g/day is 7 days is the drug of choice.
equally effective. 4. H. pylori infections in peptic ulcer patients can be
3. Trichomonas vaginitis: Metronidazole 400 mg TDS for treated with a combination of metronidazole, clarithro-
7 days is the drug of choice, achieves 100% cure. mycin and omeprazole/ranitidine.
4. H. pylori infections in peptic ulcer patients can be 5. Uses in dentistry
treated with a combination of metronidazole, clarithro- a. Metronidazole is used in anaerobic infections like
mycin and omeprazole/ranitidine. pericoronal abscess or periodontal abscess in combi-
5. Metronidazole is effective drug in anaerobic bacterial nation with ampicillin/ciprofloxacin.
infections which occur mostly after colorectal or pelvic b. Metronidazole is used in treatment of acute ulcer-
surgery, appendectomy, etc. ative gingivitis as an alternative to penicillin G.
6. Oral metronidazole 800 mg TDS is more effective,
more convenient, less toxic and is preferred over vanco- Adverse Effects
mycin.
7. Uses in dentistry Side effects to metronidazole are relatively frequent but
a. Metronidazole is used in anaerobic infections like mostly nonserious.
pericoronal abscess or periodontal abscess in combi- 1. Gastrointestinal effects like anorexia, nausea, abdomi-
nation with ampicillin/ciprofloxacin. nal pain, metallic taste in the mouth are the most com-
b. Metronidazole is used in treatment of acute ulcer- mon. Looseness of stool is occasional.
ative gingivitis as an alternative to penicillin G. 2. Less frequent side effects are headache, glossitis, sto-
matitis, dryness of mouth and transient neutropenia.
Q. 2. Mention three uses and three adverse effects of 3. CNS effects like dizziness, peripheral neuropathy, in-
metronidazole. somnia, high doses can cause convulsions.
SHORT NOTES
Q. 1. Metronidazole 3. Metronidazole is the drug of choice in all forms
of amoebiasis in the dose of 400–800 mg TDS for
Ans.
3 days.
1. Metronidazole is a powerful amoebicide. Apart from 4. Uses in dentistry
this it also inhibits Trichomonas vaginalis and Balan- a. Metronidazole is used in anaerobic infections like
tidium coli. Anaerobic bacteria are also sensitive. pericoronal abscess or periodontal abscess in combi-
2. Mechanism of action: In the microorganisms, metronidazole nation with ampicillin/ciprofloxacin.
is reduced to a derivative which is toxic to the DNA. It is well b. Metronidazole is used in treatment of acute ulcer-
absorbed and reaches adequate concentrations in the CSF. ative gingivitis as an alternative to penicillin G.
Topic 54
Anthelmintics
SHORT ESSAY
Q. 1. Treatment of hookworm infestation 6. It may rarely provoke abnormal migration of the
roundworms which may come out through the mouth
Ans.
or nose.
1. Hookworm infections are more common in the develop-
ing countries. It is seen in people with poor hygiene. Uses
2. Ancylostoma duodenale and Necator americanus are
some common hookworms that infest. Mebendazole is used in the treatment of roundworm,
3. Anthelmintics are deworming agents. A vermicide kills hookworm, pinworm, tapeworm, trichuriasis and hydatid
while a vermifuge promotes expulsion of worms. disease. It is of special value in multiple worm infestations.
Hook worm infections can be treated with mebendazole
and albendazole.
ALBENDAZOLE
1. It is a congener of mebendazole, has actions similar
MEBENDAZOLE to mebendazole but is better tolerated and it has the
1. It is a benzimidazole introduced in 1972. It is a broad- advantage of a single dose administration in many
spectrum antihelmintic cures roundworm, hookworm, cases.
pinworm and strongyloides infestations. 2. Adverse effects are similar to mebendazole but milder.
2. Mechanism of action
a. It blocks the glucose uptake in the parasite and
Uses
causes depletion of its glucose stores. The eggs and
larvae are also destroyed along with the worms. 1. Albendazole is the drug of choice in roundworm, hook-
b. The site of action of mebendazole appears to be micro- worm, pinworm, trichuriasis infestations in a single
tubular protein b-tubulin of the parasite. It binds to 400 mg dose. Dose to be repeated after 2 weeks in pin-
b-tubulin of susceptible worms with high affinity and worm infestation to prevent reinfection from ova that
inhibits its polymerization. Hatching of nematode eggs have matured later.
and their larvae are also inhibited. Ascaris ova are killed. 2. Trichinosis, tapeworms and strongyloidiasis require
3. It is given orally 100 mg twice a day for 3 days. 3 days treatment.
4. It is well tolerated. 3. Neurocysticercosis: Albendazole is the drug of choice.
5. Large doses may cause headache, dizziness, loss of hair 4. Hydatid disease: Albendazole is the drug of choice
and granulocytopenia. given for 4 weeks.
SHORT NOTES
Q. 1. Piperazine citrate 3 . Flaccid paralysis results and the worms are expelled.
4. Adverse effects are mild, gastrointestinal symptoms,
Ans.
headache and dizziness are seen occasionally. Pipera-
1. Piperazine citrate is effective in roundworm and pin- zine citrate for roundworm and pinworm infestations. It
worm infestations. is also safe in pregnancy.
2. It competitively blocks the action of acetylcholine there
by contractions in the worms.
Part XIII
Chemotherapy of Neoplastic Diseases
Topic 55
General Considerations
SHORT ESSAYS
Q. 1. List toxic effects of alkylating agents. GI bleeding and ulcers are due to necrosis of rapidly
dividing epithelial cells of gut mucosa.
Ans.
5. Gonads: Reduced spermatogenesis in men and amenor-
Alkylating agents are cell cycle nonspecific or phase non- rhoea and infertility in women.
specific anticancer drugs. They exert cytotoxic, immuno- 6. Fetus: Teratogenicity is common with administration of
suppressant and radiomimetic action. cytotoxic drugs during pregnancy. They cause multiple
defects in the fetus and may also cause fetal death.
Alkylating agents used in cancer therapy are as follows: 7. Hyperuricaemia: Gout and urate stones in urinary tract
1 . Nitrogen mustards: Mechlorethamine, cyclophospha- are due to excessive cell destruction.
mide, melphalan, chlorambucil 8. Carcinogenicity (secondary malignancy) and mutagen-
2 . Alkyl sulfonate: Busulfan icity.
3 . Nitrosureas: Carmustine, lomustine, streptozocin
4 . Platinum containing compounds: Cisplatin, carboplatin
Specific Toxicity
General toxic effects of alkylating agents include the following:
1 . Bone marrow suppression: It manifests as leukopenia, 1. Haemorrhagic cystitis especially caused by cyclophos-
agranulocytosis, thrombocytopenia, and in higher doses— phamide
aplastic anaemia. In such persons infections and bleeding 2. Pulmonary fibrosis caused by busulfan
are common. 3. Nephrotoxicity with cisplatin
2 . Immunosuppression: Decreased lymphocytes result in
immunosuppression. Such patients are prone to oppor- Q. 2. Vinca alkaloids
tunistic infections with fungi, bacteria and viruses. Ans.
3 . Skin and hair: Alopecia (loss of hair) occurs due to
damage to hair follicles. Dermatitis and skin rashes also 1. Vinca alkaloids are the antineoplastic drugs. They are
can occur. isolated from periwinkle plant (Vinca rosea, Catharan-
4 . GIT: Nausea and vomiting occur with most of the cyto- thus roseus). They are cell cycle specific (CCS) agents
toxic drugs due to central action. Stomatitis, diarrhoea, and act during M phase of cell cycle.
2. The clinically used vinca alkaloids are Q. 3. Name two antimetabolites used in cancer therapy.
a. vincristine (oncovin) and
Ans.
b. vinblastine.
1. Antimetabolites are analogues related to normal com-
Mechanism of Action ponents of DNA or of coenzyme involved in nucleic
acid synthesis. They are used in treatment of malig-
They act by inhibiting mitosis as follows: nancies.
2. They competitively inhibit utilization of normal sub-
Vincristine and vinblastine strate or get themselves incorporated forming dysfunc-
tional macromolecules.
Binds to microtubular protein, β-tubulin 3. The antimetabolites used in therapy are as follows:
a. Folate antagonist: Methotrexate
Prevents the formation of mitotic spindle b. Purine antagonists: 6-MP, 6-thioguanine (6-TG)
and polymerization and assembly of microtubules c. Pyramidine antagonists: 5-FU, cytarabine
The chromosomes fail to move apart during mitosis

Therapeutic Uses
Metaphase arrest occurs a. Folate Antagonists
i. Methotrexate (Mtx)
Cell division is inhibited
1. It is one of the most commonly used anticancer
drugs.
Pharmacokinetics 2. Methotrexate is curative in choriocarcinoma. It is also
Vinca alkaloids are not well absorbed orally. They are admin- used for maintaining remission in children with acute
istered through freely running IV infusion because they are leukaemiae.
irritants. They are primarily excreted by the liver through bile. 3. It is used to manage difficult neoplasms in higher doses.
250–1000 mg/m2 body surface area of methotrexate in-
Vincristine fused IV over 6 h followed by 3–15 mg IV calcium
leucovorin within 3 h repeated as required. It is also
It is a rapidly acting drug. useful in other malignancies, rheumatoid arthritis, pso-
riasis and as immunosuppressant.
Therapeutic uses
1. Vincristine is very useful for inducing remission in b. Purine Antagonists
childhood acute leukaemia. 1. 6-Mercaptopurine (6-MP): 2.5 mg/kg/day and 1.2 mg/kg/
2. Other indications are childhood tumours like neuroblas- day for maintenance.
toma, Hodgkin’s disease, Wilms tumour, Ewing’s sarcoma. 2. 6-Thioguanine (6-TG): It is also used for maintenance.
Toxicity c. Pyrimidine Antagonists

Neurotoxicity manifesting as cranial nerve palsies, periph- 1. 5-Fluorouracil (5-FU): Solid tumours of breast, colon,
eral neuritis with paraesthesia and constipation. It has mar- urinary bladder, liver, etc. (1 g orally on alternate days
row sparing effect. (6 doses) then 1 g weekly or 12 mg/kg/day IV for 4 days
followed by 6 mg/kg IV on alternate days) 1% topical
Vinblastine solution for cutaneous basal cell carcinoma.
2. Cytarabine (cytosine arabinoside): To induce remission
It is the most commonly employed drug. in acute leukaemia in children and adults. 1.5–3 mg/kg
IV BD for 5–10 days. Used in Hodgkin’s disease and
Therapeutic Uses non-Hodgkin’s lymphoma also.
It is primarily used in Hodgkin’s disease and testicular
Q. 4. Methods to ameliorate the toxicity of anticancer
tumours and carcinoma of breast.
drugs.
Toxic effects Ans.
Bone marrow suppression, nausea, anorexia, vomiting and Various methods to ameliorate the general and specific
diarrhoea toxic effects of anticancer drugs are as follows:
1. Bone marrow suppression can be ameliorated or re- 3. Haemorrhagic cystitis especially caused by cyclophos-
duced by the following: phamide is ameliorated by administering mesna sys-
a. Platelet transfusion temically and acetylcysteine locally.
b. Granulocyte colony stimulating factor (G-CSF) 4. Megaloblastic anaemia with methotrexate can be ame-
c. Erythropoietin liorated by folinic acid or leucovorin or citrovorum
d. Bone marrow transplantation factor.
e. Using bone marrow sparing drugs 5. Saline infusion and mannitol reduces the incidence of
2. Hyperuricaemia can be prevented by good hydration, nephrotoxicity.
allopurinol and corticosteroids.
SHORT NOTE
Q. 1. Nitrogen mustard c. Pyrimidine antagonist
i. 5-Fluorouracil (5-FU)
Ans.
ii. Cytarabine (cytosine arabinoside)
1. The nitrogen mustards are alkylating agents which in- 2 . Antimetabolites are analogues related to normal compo-
clude the following: nents of DNA or of coenzyme involved in nucleic acid
a. Mechlorethamin synthesis.
b. Cyclophosphamide 3. They competitively inhibit utilization of normal sub-
c. Melphalan strate or get themselves incorporated forming dysfunc-
d. Chlorambucil tional macromolecules.
2. Cyclophosphamide is the most commonly used alkylat- 4. They are used in treatment of malignancies.
ing agent used in combination with other anticancer
Q. 4. Methotrexate
agents in the treatment of Hodgkin’s disease, Burkitt’s
lymphoma, lymphatic leukaemia, etc. Ans.
3. It also has powerful immunosuppressant effect, hence is
useful in rheumatoid arthritis, nephritic syndrome and 1. Methotrexate (Mtx) is one of the most commonly used
to prevent as well as to treat graft rejection during organ anticancer drugs.
transplantation. 2. Methotrexate is curative in choriocarcinoma. It is also
4. Chlorambucil (leukeran) is a slow-acting and least toxic used for maintaining remission in children with acute
nitrogen mustard. It was the standard treatment for leukaemiae.
chronic lymphatic leukaemia (CLL). 3. It is used to manage difficult neoplasms in higher doses.
5. Melphalan is highly effective in multiple myeloma. 4. It is also useful in other malignancies, rheumatoid ar-
thritis, psoriasis and as immunosuppressant.
Q. 2. Name two antibiotics used in cancer therapy.
Q.5. Name vinca alkaloids.
Ans. The commonly used antibiotics used in cancer ther-
Ans.
apy are as follows:
1. Vinca alkaloids are the antineoplastic drugs. They are
1 . Actinomycin D (dactinomycin)
isolated from periwinkle plant (Vinca rosea, Catharan-
2. Doxorubicin
thus roseus).
3. Daunorubicin (rubidomycin)
2. The clinically used vinca alkaloids are (a) vincristine
4. Bleomycin
(oncovin) and (b) vinblastine.
5. Mitomycin C
3. Vincristine is very useful for inducing remission in child-
6. Mithramycin (plicamycin)
hood acute leukaemia but is not good for maintenance
Q. 3. Antimetabolites therapy. Other indications are lymphosarcoma, Hodgkin’s
disease, Wilms tumour, Ewing’s sarcoma and carcinoma
Ans. lung.
4. Vinblastine is primarily used in Hodgkin’s disease and
1. Commonly used antimetabolites are as follows:
testicular carcinoma with other antineoplastic drugs.
a. Folate antagonists
i. Methotrexate (Mtx) Q. 6. Cyclophosphamide
b. Purine antagonists
i. 6-Mercaptopurine (6-MP) Ans.
ii. 6-Thioguanine (6-TG) 1. Cyclophosphamide is most commonly used alkylating
iii. Azathioprine agent.
2. It is a prodrug and is active in liver by CYP450 system. 4. Cyclophosphamides are used in the treatment of Hodg-
The final active metabolites derived are phosphoramide kin’s lymphoma, leukaemiae in children and as an im-
mustard and acrolein. munosuppressant.
3. It is usually administered orally and also through IM 5. Common adverse effects include haemorrhagic cystitis,
or IV routes and metabolites are excreted mainly in alopecia, bone marrow depression, stomatitis, vomiting,
urine. amenorrhoea and teratogenicity.
Part XIV
Miscellaneous
Topic 56
Immunosuppressants, Gene Therapy and Drugs Acting

on Skin and Mucous Membranes
SHORT ESSAYS
Q. 1. Uses of astringents in dental practice Q. 2. Counter irritants
Ans. Ans.
1. Astringents are the substances which precipitate superfi- 1. Certain irritants produce remote effect which tends to
cial proteins without penetrating the cells when applied relieve pain and inflammation in deeper organs are
to skin or mucous membrane. They form a protective called counter irritants.
coating and harden the surface. 2. The mechanism of counterirritation is that when the
2. Astringents check minor haemorrhages, arrest capillary counterirritant is applied to the area of skin supplied by
oozing as they promote clotting and precipitate proteins nerves from the same segment as the deeper organs
on the bleeding surface. from which pain impulses are coming, the cutaneous
3. Astringents are mainly used as obtundents, styptics and impulses obscure the deeper sensations.
mummifying agents. 3. They are generally massaged to relieve headache,
4. Types of astringents muscular pain, joint pain, pleural or peritoneal pain,
a. Vegetable astringents: Tanic acid and tannins colics, etc.
b. Metallic or mineral astringents: Alum, salts of zinc, 4. Drugs commonly used are volatile oils like turpentine
copper, iron, aluminium and silver oil, clove oil, eucalyptus oil, mustard seeds, capsicum,
c. Miscellaneous: Alcohol methyl salicylate and alcohol.
For example:
Uses a. Vicks VapoRub: Contains menthol 2.8%, camphor
5.25%, thymol 0.1%, turpentine oil 5.5% ointment
Astringents are used as follows: b. Amruthanjan: Contains eucalyptus oil 17%, cam-
1. Mouthwashes phor 10%, thymol 1%, menthol 4.5%, methyl salicy-
2. Paints late 7% ointment
3. Lotions and dentifrices in aphthous ulcers, stomatitis c. Iodex: Contains methyl salicylate 5%, iodine 4%
and gingivitis nonstaining ointment
4. Local haemostatics
SHORT NOTES
Q. 1. Tannic acid and tannins 1. Clove oil is a type of obtundent. It is an agent that dimin-
ishes sensitivity. It is used to make the excavation painless.
Ans.
2. Its mechanism of action is that it paralyses the sensory
1 . Astringents are agents which precipitate superficial pro- nerves where it causes initial irritation followed by
teins when applied to skin or mucous membrane. They numbness.
form a protective coating and harden the surface. 3. The disadvantage of clove oil is that it may stain the
2 . Tannic acid is a vegetable astringent obtained from dentine yellow.
many plants but is generally obtained from the nutgalls
of oak. Q. 3. Astringents
3 . Tannins are found in tea, catechu, nutmeg, areca nut Ans.
(betel nut), etc. They denature the proteins forming pro-
tein tannate. 1. Astringents are agents which precipitate superficial pro-
4 . The uses are as follows: teins when applied to skin or mucous membrane.
a. Bleeding gums—as glycerine of tannic acid 2. They form a protective coating and harden the surface.
b. Bleeding piles—as tannic acid suppository 3. Astringents check minor haemorrhages—arrest capil-
c. Alkaloidal poisoning—precipitates ingested alka- lary oozing as they promote clotting and precipitate
loids as tannates proteins on the bleeding surface.
4. Astringents are used as obtundents, styptics and mummi-
Q. 2. Clove oil fying agents. For example: Tannic acid, galls of oak, alco-
Ans. hol, alum, salts of zinc, copper, iron, aluminium and silver
Topic 57
Antiseptics, Disinfectants and Ectoparasiticides

LONG ESSAY
Q. 1. Define and classify antiseptics. Mention about v. Phenol derivatives: Phenol, cresol, resorcinol,
mechanism of action and properties of antiseptics, dif- chlorhexidine, chloroxylenol, hexachlorophene
ferent preparations and uses of phenol. vi. Halogens: Iodine, iodophores, chlorine, chloramines
vii. Oxidizing agents: Hydrogen peroxide, potassium per-
Ans.
manganate, benzoyl peroxide
1. Antiseptic is an agent that destroys microorganisms on viii. Dyes: Gentian violet, methylene blue, brilliant green,
contact and can be used on living tissues. acriflavine, proflavin
2. The term germicide covers both antiseptics and ix. Metallic salts: Mercurial compounds, silver nitrate,
disinfectants. Germicides are widely used in domes- zinc compounds
tic products like soaps, toothpastes and aftershave
lotions. Mechanism of Action
Mechanism of action of germicides may be grouped into
Classification the following:
i. Acids: Boric acid, benzoic acid a. Oxidation of bacterial protoplasm
ii. Alcohols: Ethanol, isopropyl alcohol b. Denaturation of bacterial proteins
iii. Aldehydes: Formaldehyde, glutaraldehyde c. Detergent-like action
iv. Surfactants: Soaps, benzalkonium, cetrimide, cetyl- d. Competition with essential substrates for the important
pyridinium chloride, dequalinium chloride enzymes in the bacterial cell
Properties l It is used as a disinfectant for utensils and excreta

and for washing hands. For example: Lysol is 50%
An ideal germicide should have following properties:
soapy emulsion of cresol. It has higher antiseptic ac-
a. A wide antibacterial spectrum
tivity and is a useful disinfectant for hospital and
b. Should be chemically stable.
domestic use.
c. Should have rapid action.
d. Nonirritating to the tissues
e. Do not interfere with the wound healing activity even in Chloroxylenol (Dettol)
the presence of pus, exudates and the tissue degradation
l It is a less toxic-chlorinated phenol, effective against
products.
Gram-positive and Gram-negative organisms.
f. It should not be absorbed into systemic circulation.
l It has phenol coefficient of 70 and is noncorrosive and
nonirritating to intact skin.

Phenol Derivatives l Surgical dettol contains 1.4% of chloroxylenol for
skin, 6.25% for instruments and 1–3% in antiseptic

Phenol cream.
l It is one of the earliest antiseptics introduced by Lord
Lister in 1867. It is bactericidal and fungicidal but has Hexachlorophene
poor action against viruses and spores. It acts by dena-
turing the bacterial proteins. l This is chlorinated phenol acts by inhibiting bacterial
l It also has a mild local anaesthetic action. Phenol rap- enzymes and causing lysis.
idly penetrates even intact skin and mucous membrane. l It is effective mainly against Gram-positive organisms
It is a protoplasmic poison. and has weak action against Gram-negative organisms.

l Phenol is extremely irritant to exposed tissues (corrosive)— l It is odourless and nonirritating to use on skin. It is
when swallowed, it burns buccal, oesophageal and gastric used in soaps for surgical scrubbing, for cleaning
mucous membrane. the skin in obstetrics, carbuncles and seborrhoeic
dermatitis.
l It may cause allergic reactions. It also reduces body
Uses odour by preventing bacterial decomposition of organic
Phenol is used to disinfect urine, faeces, sputum of patients material and thus used as deodorant.
and is sometimes used as antipruritic because of its local
anaesthetic action. Chlorhexidine (Hibitane)
l Effective against Gram-positive and Gram-negative or-
Cresol ganisms and fungi.
l It is a methylphenol, which is as toxic as phenol but is l It is rapid acting and nonirritating, e.g. Savlon (chlorhex-
more active. idine 1 cetrimide).
SHORT ESSAY
Q. 1. Potassium permanganate a. 1:4000–1:10 000 solution of potassium permanganate is
used for gargling, irrigating cavities, urethra and wounds.
Ans.
b. For stomach washing in alkaloidal poisoning (except
1. Potassium permanganate is an oxidizing agent and an atropine and cocaine as they are not efficiently oxi-
astringent. The purple crystals are water soluble. dized).
2. It acts by liberating oxygen which oxidizes bacterial c. 1% solution in mycotic infections like athlete’s foot.
protoplasm. d. 5% solution as styptic.
3. Organic matter reduces its activity and the solution gets e. Topically to oxidize venom in case of snake and
decolourized. scorpion bite
4. It promotes rusting; concentrated solution is caustic and f. To purify well water
causes burns and blistering. g. To disinfect vegetables and fruits
5. Uses
SHORT NOTES
Q. 1. Acriflavine 1. Thymol is used as an antiseptic and a deodorant in
mouthwashes and gargles.
Ans.
2. Eugenol has the odour of clove and is also a local anaes-
1. Acriflavine is an orange-yellow acridine dye active thetic commonly used for dental filling.
against Gram-positive bacteria and gonococci.
2. It is nonirritant, efficacy is unaffected by organic matter Q. 4. Bleaching agents
but it is enhanced in alkaline medium. Ans.
3. 1:1000 solution is used in infected wounds and burns,
2% pessary in vaginitis and cervicitis. Bleaching agents are used to remove pigmentation of the teeth.
4. Solutions lose efficacy on exposure to light and hence Oxidizing agents like sodium peroxide and perhydrol, reduc-
are stored in amber bottles. For example: Acrinol 0.1% ing agents like sodium thiosulphate and other agents like
acriflavine cream. chlorides, hydrogen peroxide and ultraviolet rays have been
used as bleaching agents. Hypochlorites remove silver and
Q. 2. Chlorhexidine iron stains; sodium thiosulphate removes iodine stains while
chlorinated lime is used to remove stains by aniline dyes.
Ans.
Q. 5. Commonly used antiseptics in dentistry
1. Chlorhexidine (Hibitane) is a powerful nonirritating
antiseptic that disrupts bacterial cell membrane. Ans.
2. It is relatively more active against Gram-positive bacte-
ria though Gram-negative organisms and fungi. 1. Antiseptics commonly used in dentistry are thymol,
3. It is rapid acting and nonirritating, e.g. Savlon (chlorhex- menthol, eugenol, benzoic acid, boric acid, calcium and
idine 1 cetrimide). manganese peroxide.
2. Thymol is a powerful antiseptic and a deodorant in
Q. 3. Uses of antiseptics in dentistry mouthwashes and gargles.
3. Eugenol has the odour of cloves and is also a local an-
Ans. aesthetic commonly used for dental filling.
Topic 58
Chelating Agents
SHORT ESSAY
Q. 1. Name four chelating agents. many divalent and trivalent metallic ions and owe their
therapeutic application to this chelating property.
Ans.
2 . It chelates many divalent and trivalent metals like zinc,
The clinically useful chelating agents are manganese, iron, lead deposits in the bone and are
1. calcium disodium edetate (CaNa2EDTA), mobilized, chelated and excreted through kidneys.
2. dimercaprol, 3. Adverse effects include nephrotoxicity, fatigue, fever,
3. D-penicillamine and myalgia and dermatitis.
4. desferrioxamine. 4. CaNa2EDTA is mainly used in lead poisoning. It can
be also used in zinc, manganese and iron poisoning.
Sodium edetate is used in severe hypercalcaemia.
a. Calcium Disodium Edetate
(CaNa2EDTA) b. Dimercaprol
1. The calcium sodium and the disodium salts of EDTA 1. Dimercaprol or British anti-Lewisite (BAL) is a colour-
form stable and highly water-soluble complexes with less oily liquid synthesized by Stocken and Thompson
during World War II as an antidote to Lewisite—an ar- 2. It forms water-soluble complexes with copper, mercury
senical war gas. Hence it is also called British lewisite and lead ions thus facilitating their excretion in urine.
gas or BAL. 3. Therapeutic uses: Hepatolenticular degeneration (Wilson’s
2 . Dimercaprol chelates arsenic, mercury, lead and other disease), rheumatoid arthritis and is of some value in treat-
heavy metals. It is given IM; appropriate plasma con- ing acute lead and mercury poisoning.
centrations should be maintained.
3. Adverse effects are dose related and include hyperten-
d. Desferrioxamine
sion, tachycardia, vomiting, sweating, burning sensation
in the lips and the mouth and headache. 1. It is obtained from Streptomyces pilosus; is a potent and
specific chelator of iron.
2. Therapeutic uses: Acute iron intoxication, haemochro-
c. D-penicillamine matosis
1. This is a monothiol compound prepared by alkaline 3. The drug is contraindicated in patients with severe renal
hydrolysis of benzene penicillin. disease or anuria and in pregnant women.
SHORT NOTES
Q. 1. Dimercaprol Q. 3. EDTA
Ans. Ans.
1 . Dimercaprol is a colourless oily liquid developed by the 1. The calcium sodium and the disodium salts of EDTA
British during World War II as an antidote to lewisite— form stable and highly water-soluble complexes
an arsenical war gas. Hence it is also called British with many divalent and trivalent metallic ions and
lewisite gas (BAL). owe their therapeutic application to this chelating
2 . Dimercaprol chelates arsenic, mercury, lead and other property.
heavy metals. It is given IM; appropriate plasma con- 2. It chelates many divalent and trivalent metals like zinc,
centrations should be maintained. manganese, iron, lead deposits in the bone and are mo-
3 . Adverse effects are dose related and include hyperten- bilized, chelated and excreted through kidneys.
sion, tachycardia, vomiting, sweating, burning sensation 3. Adverse effects include nephrotoxicity, fatigue, fever,
in the lips and the mouth and headache. myalgia and dermatitis.
4. CaNa2 EDTA is mainly used in lead poisoning. It can
Q. 2. Chelating agents be also used in zinc, manganese and iron poisoning.
Ans. Sodium edetate is used in severe hypercalcaemia.
1 . Chelating agents or heavy metal antagonists bind the Q. 4. Dimercaprol used in arsenic poisoning
heavy metal ions and make them nontoxic, the chemical Ans.
complex formed is called a chelate. The process of com-
plex formation is known as chelation. 1. Dimercaprol or British anti-Lewisite (BAL) is a colour-
2 . The complex so-formed is water-soluble and is elimi- less oily liquid synthesized by Stocken and Thompson
nated by the kidneys. during World War II.
3 . The clinically useful chelating agents are CaNa2EDTA, 2. Dimercaprol chelates arsenic, mercury, lead and other
dimercaprol, d-penicillamine and desferrioxamine. heavy metals.
4 . Chelating agents are more effective in preventing the 3. Adverse effects are dose related and include hyperten-
utilization of ligands than in reactivating them; hence, sion, tachycardia, vomiting, sweating, burning sensation
the earlier they are given, the better. in the lips and the mouth and headache.
Topic 59
Vitamins
SHORT ESSAYS
Q. 1. Pyridoxine a. scurvy characterized by connective tissue defects re-
sulting in haemorrhages in subcutaneous tissue pete-
Ans.
chiae, ecchymoses, impaired wound healing, tender
1 . Vitamin B6 is also known as pyridoxine. bleeding gums,
2. Sources: Liver, meat, eggs, soya bean, cereals, legumes b. deformed teeth,
and milk c. brittle bones,
3. Physiological functions of pyridoxine: Pyridoxal phosphate d. anaemia and
is a coenzyme involved in the synthesis of several amino e. growth retardation.
acids, biogenic amines and other compounds like GABA. 5 . Therapeutic uses:
4. Symptoms of deficiency a. Prevention of ascorbic acid or vitamin C deficiency
a. Seborrhoeic dermatitis in individuals at risk: 50–100 mg/day.
b. Glossitis b. In treatment of scurvy: 500–1000 mg/day
c. Peripheral neuritis c. Large doses (0.5–1.5 g) of vitamin C has been tried
d. Anaemia as prophylactic against common cold with contro-
e. Mental confusion versial benefits.
f. Lowered seizure threshold due to decreased GABA d. To acidify urine: 1 g TDS in urinary tract infections
levels in the brain e. Anaemia of scurvy is corrected by ascorbic acid, but
5. Uses no adjuvant value in other anaemias.
a. Prophylaxis and treatment of pyridoxine deficiency.
Q. 3. Thiamine deficiency
b. INH-induced peripheral neuritis: Pyridoxine is used
both for prophylaxis and treatment. Ans.
c. Convulsions in infants and children due to pyridox-
ine deficiency 1. Vitamin B1 is essential for as a coenzyme in carbohy-
d. ‘Morning sickness’ in pregnancy: Pyridoxine may drate metabolism: Decarboxylation of keto acids, hex-
reduce vomiting by unknown mechanism. ose monophosphate shunt
e. To treat mental symptoms in women on oral contra- 2. Daily requirement: 1–2 mg
ceptives (50 mg daily) 3. Deficiency symptoms of vitamin B1 are as follows:
a. The syndrome of thiamine deficiency produces beri-
beri seen in dry and wet forms.
Q. 2. Vitamin C
i. Dry beriberi: Neurological symptoms are promi-
Or, nent. Polyneuritis with numbness, tingling, hyper-
aesthesia, muscular weakness and atrophy resulting
Ascorbic acid
in wrist drop, foot drop, paralysis of whole limb,
Ans. mental changes, sluggishness, poor memory, loss
of appetite, and constipation.
1 . Vitamin C is also known as ascorbic acid. ii. Wet beriberi: Cardiovascular system is primarily af-
2. Sources: Citrus fruits, tomatoes, gooseberry, vegetables, fected. The characteristic features are dependent oe-
and potatoes are rich in vitamin C. dema and high output cardiac failure. Protein defi-
3. Physiological role and actions of vitamin C are as follows: ciency is commonly associated and adds to the
a. Ascorbic acid is involved in several metabolic reac- generally anasarca due to chronic heart failure (CHF).
tions including oxidation and reduction reactions Wernicke encephalopathy and Korsakoff psychosis
and in cellular respiration. are also thought to be due to thiamine deficiency.
b. It is essential for the integrity of connective tissue,
for the development of cartilage, bone, and teeth and Q. 4. Name two fat-soluble vitamins and mention two
for wound healing. uses of them.
c. Essential for biosynthesis of adrenal steroids, cate-
Ans.
cholamines, oxytocin, and ADH, and metabolism of
cyclic nucleotides and prostaglandins. Fat-soluble vitamins are those that are soluble in lipids or fats
4. Symptoms of deficiency: Vitamin C deficiency results in and get excreted out of the body through them. There are four
fat-soluble vitamins. They are vitamin A, vitamin D, Vitamin K

vitamin E and vitamin K.
Uses
Vitamin A 1. Prophylaxis and treatment of bleeding due to deficiency

of clotting factors in the following:
Uses a. Dietary deficiency of vitamin K: 5–10 mg/day orally
b. Prolonged antimicrobial therapy: 5–10 mg/day
1. In the prophylaxis and treatment of vitamin A deficiency
orally
(prophylaxis of vitamin A deficiency during infancy, preg-
c. Obstructive jaundice or malabsorption syndrome:
nancy, lactation, hepatobiliary diseases, steatorrhoea):
10 mg/day IM or orally
3000–5000 IU/day in presence of increased requirement.
d. Liver diseases: 10 mg/day IM or orally
2. Treatment of established vitamin A deficiency: 50,000–
e. Newborns: 1 mg IM soon after birth or 5–10 mg IM
100,000 IU IM or orally for 1–3 days followed by inter-
to mother 4–12 h before delivery
mittent oral supplemental doses.
f. To reverse the effects of overdose of oral anticoagu-
3. In skin diseases like acne, psoriasis, ichthyosis retinoic
lants: 10 mg IM followed by 5 mg 4 hourly
acid or synthetic analogues of vitamin A like tretinoin or
isotretinoin are used.
SHORT NOTES
Q. 1. Ascorbic acid 3. Physiological functions: Pyridoxal phosphate is a coen-
zyme involved in the synthesis of several amino acids,
Or,
biogenic amines and other compounds like GABA
Vitamin C 4. Symptoms of deficiency: Glossitis, peripheral neuritis,
anaemia, dermatitis, and low seizure threshold
Ans.
6. Uses: Prophylaxis in the treatment of pyridoxine defi-
1 . Vitamin C is also known as ascorbic acid. ciency, INH-induced peripheral neuritis and convul-
2 . Sources: Citrus fruits, tomatoes, gooseberry, vegetables, sions in infants due to pyridoxine deficiency.
and potatoes are rich in vitamin C.
3. Physiological role and actions of vitamin C are as follows: Q. 3. Vitamin B12
a. Ascorbic acid is involved in several metabolic Or,
reactions.
b. It is essential for the integrity of connective tissue, Cyanocobalamin
for the development of cartilage, bone and teeth and Ans.
for wound healing.
4 . Symptoms of deficiency: Vitamin C deficiency results 1 . Synthesized by microorganisms.
in scurvy, impaired wound healing, tender bleeding 2. Sources: Liver, fish, egg yolk, meat, cheese and pulses.
gums, deformed teeth, brittle bones, anaemia and growth 3. Physiological functions: Acts as coenzyme for several
retardation. vital metabolic reactions, essential for DNA synthesis.
5 . Therapeutic uses 4. Symptoms of deficiency: Addisonian anaemia due to
a. Prevention of ascorbic acid or vitamin C deficiency deficiency of intrinsic factor, due to destruction of pari-
in individuals at risk: 50–100 mg daily etal cells, and resulting in failure of B12 absorption.
b. In treatment of scurvy: 500–1000 mg/day 5. Other causes: Gastrectomy, chronic gastritis, malab-
c. To acidify urine: 1 gm TDS in urinary tract infections sorption, and fish tapeworm infestation (consumes
vitamin B12).
Q. 2. Vitamin B6 6. Uses
a. Multivitamins for oral use
Ans.
b. B12 deficiency: Prophylaxis and treatment of mega-
1 . Vitamin B6 is also known as pyridoxine. loblastic anaemia (3–10 mg daily)
2 . Sources: Cereals, legumes, liver, milk, meat and eggs. B12 neuropathies
Topic 60
Vaccines and Sera

SHORT ESSAY
Q. 1. What procedure will be adapted so that tetanus 2. Wound care includes drainage of pus, excision of
does not result from your treatment? How will you treat necrosed tissue, removal of foreign body and proper
a case of tetanus? dressing.
3. Inj. tetanus toxoid 0.5 mL IM
Ans.
a. Antitetanus serum (ATS) 50,000 units intrave-
1 . Tetanus is a wound infection. It is caused by the bacte- nous, given after a test dose in the subcutaneous
rium Clostridium tetani, an anaerobic spore forming tissue.
bacterium that enters the wound, multiplies and pro- b. Instead of ATS, human antitetanus globulin 3000–
duces powerful toxins which produce the disease. It 4000 units can be administered to prevent anaphy-
produces two toxins tetanospasmin (neurotoxin) and laxis.
tetanolysin (haemolysin). 4. Inj. crystalline penicillin 10 lakh units every 6 hourly
2 . Tetanus may occur due to wounds caused due to pierc- for a period of 7–10 days.
ing of earlobes, injury with rusted nails, as a complica-
2. Specific Management
tion to road traffic accident, as infection acquired in
operation theatre, in neonates when the umbilical cord 1. Mild cases: There is only tonic rigidity without spasms
is treated with cow dung. or dysphagia. Patient can be managed by heavy sedation
3 . Prophylaxis during treatment: using a combination of chlorpromazine, phenobarbitone
a. Pregnant women can be administered two tetanus toxoid and diazepam.
injections, 1 mL IM in the third trimester of pregnancy. 2. Seriously ill cases: They have dysphagia and reflex
b. Immunized individuals can be given booster dose to spasms. A nasogastric tube is introduced for feeding
achieve active immunity. purpose and to administer drugs. Tracheostomy if breath-
c. Tetanus antitoxin can be used for penetrating wounds ing is difficult.
of head and face, and wounds of devitalized and 3. Dangerously ill cases: Patient have major cyanotic
contused tissues. convulsion. In addition to continuing sedatives, pa-
tients are paralysed with muscle relaxants (neuro-
Treatment of Established Cases muscular blocking agents) and positive pressure ven-
tilation is given till they recover. Adequate nutrition,
1. General Management care of urinary bladder, care of bowel, frequent
1 . Admission and isolation in a quiet room, to avoid minor change of position to avoid bedsores have to be taken
stimuli which precipitate spasms. care of.
SHORT NOTE
Q. 1. Posterior pituitary extract given by IV drip before 3. It is used before delivery to induce labour in case of
delivery only. postmaturity or to augment it in case of uterine inertia.
4. It is also used to control postpartum haemorrhage as an
Ans.
alternative to ergometrine.
1. Oxytocin is an octapeptide secreted by the posterior 5. Improper administration or overdosage causes too
pituitary gland. strong contractions forcing the presenting part through
2. It increases the force and the frequency of uterine con- incompletely dilated birth canal, causing maternal and
tractions. With low doses full relaxation occurs between fetal soft tissue injury, rupture of uterus, fetus asphyxia
contractions. and death.
Topic 61
Dental Pharmacology
LONG ESSAYS
Q. 1. Discuss fluoride pharmacology in relation to its b. Mouth rinses: 0.2% solution of sodium fluoride con-
utility as an anticaries agent. What are the different taining 900 ppm of fluoride is to be retained in mouth
formulations in which fluoride is used for this purpose? for a minute and this procedure should be done twice
Give a short account of fluoride toxicology. a week.
Ans. Fluoride is a halogen and is a highly reactive and
most electronegative of all elements. Fluoride Toxicity
Usually results from
Mechanism of Action l consumption of water with fluoride content above
2 ppm and
l The composition of apatite is affected by the ionic com-
l accidental or suicidal consumption of fluoride contain-
position of the fluid with which it is in contact and there
ing rat poisons.
is exchange of ions between the apatite crystals and the
oral fluid by the surface reaction.
l There is heteroionic substitution of OH by F ions as
2 2 Manifestations
F2 enters the hydration shell surrounding the apatite
crystals and gets incorporated into the crystal surface. Acute Toxicity
l Initially a friable layer of calcium fluoride is formed on l Nausea, vomiting, diarrhoea
the surface leaving underlying enamel intact. l Hypotension
l This fluoride rich surface layer then undergoes slow l Hypocalcaemia, hypomagnesaemia
exchange with F2 getting incorporated in the crystal l Cardiac arrhythmias
lattice forming fluoroapatite. l Acidosis
l Fluoroapatite makes tooth resistant to bacterial enzymes
and acids.
Chronic Toxicity
Mottling of enamel
Pharmacological Actions l
l Brownish-black discolouration of teeth

Fluorides alter the physiochemical properties of the teeth as l Joint pain and stiffness
follows: l Osteosclerosis of the spine and pelvis
l Fluorides inhibit the bacterial enzymes which pro- l Thickening of cortex of long bones and bony exostoses
duce acids and therefore, prevent decalcification of (crippling fluorosis)
the teeth.
Treatment of fluoride toxicity
l Fluorides convert the hydroxyapatite of enamel and
l Induce vomiting or gastric lavage with calcium contain-
dentine to fluoroapatite which is more resistant to de-
ing fluid
struction by acids thus making the outer layers of
l Treat cardiac arrhythmias
enamel harder and more resistant to demineralization.
l Correct the acid base imbalance
l Fluorides also stimulate remineralization of the enamel.
l Alkaline diuresis to enhance fluoride excretion
Therefore fluorides are used in caries.
Q. 2. Classify disinfectants and antiseptics used in den-

Fluoride Formulations tal practice with suitable examples. Describe their gen-
a. Dentifrices: Several commercial dentifrices contain fol- eral uses in dentistry. What are the specific uses of clove
lowing fluoride salts: oil and eugenol?
a. Sodium fluoride Ans.
b. Sodium monofluorophosphate
c. Stannous fluoride l Disinfectants are chemical agents which are used on
These dentifrices should be used twice a day regularly. inanimate objects to inhibit or kill microbes on contact.
l Antiseptics are chemical disinfectants which can be l Phenyl mercuric nitrate

safely applied to skin or mucous membrane and are l Merbromin
used to prevent infection by inhibiting the growth of l Sliver nitrate
bacteria. l Silver sulphadiazine
l Mild silver protein

Classification of disinfectants and antiseptics used in dental
l Zinc sulphate
practice:
l Calamine
a. Phenol derivatives
l Zinc oxide
l Phenol
j. Dyes
l Cresol
l Gentian violet
l Resorcinol
l Brilliant green
l Hexylresorcinol
l Acriflavine
l Chloroxylenol
l Proflavine
l Hexachlorophene
k. Furan derivatives
b. Oxidizing agents
l Nitrofurazone
l Potassium permanganate
l Hydrogen peroxide
l Benzoyl peroxide Uses in Dentistry

c. Halogens
l As a component of mouthwashes (chloroxylenol, chlorhex-
l Iodine
idine, cetylpyridinium chloride)
l Iodophores
l For gargling (potassium permanganate)
l Chlorine
l For root canal therapy (sodium hypochlorite solution)
l Chlorophores
l As gum paints (dequalinium chloride)
l Biguanides
l Chlorhexidine Specific uses of clove oil and eugenol are as follows:

d. Quaternary ammonium compounds l Clove oil and eugenol are useful for its disinfecting prop-
l Cetrimide erties, relieving of pain, especially toothache, arthritis

l Cetylpyridinium chloride and rheumatism.
l Benzalkonium chloride (Zephiran) l Clove oil is effective when used for complaints of the
l Dequalinium chloride digestion system. It is also of use for skin problems es-
e. Soaps of sodium and potassium pecially for skin sores and leg ulcers.
f. Alcohols l Clove oil can be useful for bronchitis and dizziness and
l Ethanol to help lift depression, while strengthening memory and

l Isopropanol fighting weakness and lethargy.
g. Aldehydes l Clove oil can be used in a blended massage oil to assist
l Formaldehyde with diarrhoea, bronchitis, chills, colds, muscular

l Glutaraldehyde numbness, spasms, rheumatism and arthritis.
h. Acids l For toothache the outer jaw can be massaged with this oil.
l Boric acid l When used in a cream or lotion, it helps to sort out leg
l Acetic acid ulcers and skin sores.

i. Metallic salts l Clove oil can be included at a low rate as part of a
l Ammoniated mercury mouthwash for toothache.
SHORT ESSAYS
Q. 1. Describe briefly obtundents. 2. Commonly used obtundents are phenol, thymol, menthol,
clove oil, camphor, silver nitrate, zinc chloride, parafor-
Ans.
maldehyde, absolute alcohol, benzyl alcohol, etc.
1. Obtundents are the agents which diminish dentine sen- 3. The mechanism of action, advantages and disadvan-
sitivity. tages of few of them are listed in Table 61.1.
TABLE 61.1 Obtundents b. Detergents

Mechanism Detergents are the cleaning agents which act by lowering
Obtundents of Action Advantage Disadvantage the surface tension, dissolving fatty substances and mucous
Phenol Protoplasmic Rapid in action. Infected plaques, foaming on scrubbing the teeth and acting as lubri-
poison which Does not stain dentine is cants, loosening the debris adhering to the teeth and few act
paralyses healthy dentine. darkened by liberating oxygen and acting as antiseptic. For example:
nerves Penetrability can Poor
followed by be increased by penetrability
Sodium lauryl sulphate—a pale yellow powder effective in
numbness combining with both acid and alkaline medium and in hard water.
KOH and glyc-
erin
c. Antiseptics
Menthol, Paralyses Rapid action Yellow
clove oil, sensory nerves staining of They are used to keep the commensal bacterial flora of the
camphor followed by dentine by oral cavity in check. For example: Thymol, menthol, eugenol,
numbness clove oil benzoic acid, boric acid, calcium and magnesium peroxide.
Silver nitrate Precipitates Rapid action Black staining
superficial of dentine
protein by as- Poor d. Sweetening Agents
tringent action penetrability
These are used to enhance palatability of the toothpaste.
Paraformal Precipitation Painless, Slow action The preferred sweetening agent is saccharine.
dehyde of protein by nonstaining Inflammation
formaldehyde of pulp by
released formaldehyde e. Colouring Agents
Absolute Destruction of
These do not serve any pharmacological purpose but are
alcohol, nervous tissue
benzyl Paralyses used only for commercial reasons making the toothpaste
alcohol sensory nerves attractive. For example: Commonly used colouring agents
followed by are liquor rubri (red) and methylene blue (blue).
numbness
f. Other Agents

Therapeutic Uses
(a) Binding agents like mucilage of tragacanth, gum acacia,
Previously they were used to make the excavation painless and bentonite, (b) humectants like glycerine and sorbitol
but now uses of local anaesthetics have made them outdated. and (c) antacids like sodium bicarbonate.
Q. 2. Dentifrices Q. 3. Disclosing agents

Ans. Ans.
1. Dentifrices are the agents which are used for cleaning Disclosing agents are certain dyes which are used to make
the teeth with the help of a toothbrush. They are avail- the relatively invisible supragingival plaques visible.
able as powders, liquids or pastes.
2. They are used to clean the teeth but in addition they also
have other benefits due to their contents. Methods of Application
3. An ideal dentifrice is one pleasant in taste, odour and Painting the teeth with cotton swab, rinsing the mouth and
consistency and does not damage the gums or the teeth. as a tablet or wafer to be chewed dissolving it in saliva fol-
Ingredients of a dentifrice are as follows: lowed by rinsing with water.
For example:
1. Erythrosin is most widely used disclosing agent. Eryth-
a. Abrasives rosin tablets are dissolved into a solution or chewed to
1. Dental abrasives are fine powdered substances which be dissolved in mouth. Stains the plaque area red.
assist the scouring action of toothbrush. 2. Fluorescein dye: Stains the plaque yellow and it does
2. They are inorganic salts of low solubility and are avail- not stain gingival tissues. Its disadvantage is that special
able in the form of powder or paste but the powdered light is required to see stained plaque and is expensive.
form is more powerful. For example: Prepared chalk, 3. Iodine-containing solutions: Matured plaques are
calcium phosphate, calcium and magnesium carbonates, stained blue while new plaques are stained red. Its dis-
magnesium oxide, ferric oxide, charcoal, silicates pow- advantage is that it causes high incidence of allergic
der pumice and kaolin. reactions and it has unacceptable taste.
Q. 4. Bleaching agents 3. Others: Chlorides, hydrogen peroxide, ultraviolet rays

Ans. Bleaching agents are the chemical substances used to
remove the pigmentation of the teeth. Therapeutic Uses
They are used to remove stains from the teeth like hypo-
Classification chlorites remove silver and iron stains, sodium thiosulphate
1 . Oxidizing agents: Sodium peroxide, perhydrol removes iodine stains while chlorinated lime is used to re-
2. Reducing agents: Sodium thiosulphate move stains by aniline dyes.
SHORT NOTES
Q. 1. Fluorides in dentistry gents and antiseptics in form of paste.
Q. 4. Mouthwashes
Ans. Fluorides are multipurpose substances used in den-
tistry. Fluoride is a halogen and is highly reactive and most Ans.
electronegative of all elements.
1. Mouthwashes are solutions containing active ingredi-
ents meant for cleansing and deodorizing the oral cavity
Therapeutic Uses like astringents, antiseptics and obtundents, flavouring
1. Caries and sweetening agents.
a. Fluoride is used topically for prophylaxis of caries. 2. Various types of mouth washes are as follows:
b. It is used in the form of dentifrices or mouth rinses. a. Antiseptic and astringent mouthwashes for soreness
2. Dental plaque: Stannous fluoride mouth rinses or gels under dentures
are effective in plaque control. b. Obtundent mouthwashes for sensitive oral lesions
a. Desensitizing agent: High doses of fluorides act as c. Detergent mouthwashes for cleaning and deodorizing
dental desensitizing agent by occluding dentinal tu- action. For example: Chlorhexidine, povidone iodine
bules and hardening the dentine surface. d. Prolonged use of concentrated solution may cause
adverse effects like staining the teeth.
Q. 2. Sialagogues 3. Therapeutic uses
a. 15–30 mL of diluted solution are used for gargling
Ans. and rinsing the mouth in soreness under dentures
1. Sialagogues are the drugs which increase the flow of sa- b. Sensitive oral lesions
liva. For example: Ginger and calomel, sugar-free gum, c. Postoperative and other bedridden patients for de-
tobacco, organic acids such as ascorbic, citric or malic odorizing the oral cavity and to maintain oral hygiene
2. Therapeutic uses: Xerostomia d. Halitosis and stomatitis
Q. 3. Mummifying agents Q. 5. Use of fluorides in caries
Ans. Ans.
1. Mummifying agents (Table 61.2) are the substances 1. Fluorides inhibit bacterial enzymes which produce ac-
used to harden and dry the pulp tissues. This hardening ids and therefore prevent decalcification of the teeth.
makes the tissue resistant to infection. 2. Fluorides convert the hydroxyapatite of enamel and
2. Commonly used astringents are a combination of astrin- dentine to fluorapatite which is more resistant to
destruction by the acids thus making the outer layers
of the enamel harder and more resistant to demineral-
TABLE 61.2 Mummifying Agents
ization.
Mummifying Mechanism Used in 3. Fluorides also stimulate remineralization of the enamel;
Agents of Action Combination with therefore fluorides are used in caries.
Liquid Precipitation Zinc oxide
formaldehyde of protein and glycerin
Q. 6. Chlorhexidine
Iodoform Liberating iodine Eugenol, phenol Ans.
Tannic acid Precipitation Tannic acid 1. Chlorhexidine is a biguanide compound which is a pow-
of protein and glycerol
erful, rapid acting antiseptic acting against a wide range
of Gram-positive and Gram-negative organisms and 5. Available as 5% aqueous concentrate and 1% water
against fungi at pH 5–8. miscible cream.
2 . Bacterial spores are prevented from germinating but are 6. Uses: It is used extensively for surgical scrub, neona-
not killed. tal bath, mouthwash, obstetrics and as general skin
3. It acts by disrupting the bacterial cell membrane and is antiseptic.
effective even in the presence of blood or pus.
4. It is nonirritating and has low potential for producing
contact dermatitis and photosensitivity.

General pharmacology
Some important definitions
l Pharmacology: Study of substances that interact with living system through chemical processes espe-
cially by binding to regularity molecules.

l Pharmacogenetics: Study of genetic variations that cause individual differences in drug response.
l Pharmacodynamics: Study of biological and therapeutic effects of drugs and their mechanism of action.
l Pharmacokinetics: Study of absorption, distribution, metabolism and excretion of drugs and their rela-
tionship to pharmacological response.

l Clinical pharmacology: Scientific study of drugs and includes pharmacodynamic and pharmacokinetic
investigations.
l Chemotherapy: Treatment of systemic infection with specific drugs with no or minimal effects on the
host cells.
l Pharmacy: Science of identification, selection, preservation, standardization, compounding and dis-
pensing of medicinal substances.

l Bioavailability: Percentage of drug that is absorbed from a given dosage and reaches the systemic
circulation following nonvascular administration.

l Biotransformation: Chemical alteration of a drug within a living organism.
Routes of drug administration:

Two main routes of drug administration are:
A. Local and
B. Systemic.
Systemic drug administration is of following types:
i. Oral
ii. Sublingual
iii. Rectal
iv. Cutaneous
v. Inhalational
vi. Nasal and
vii. Parenteral.
Parenteral route of drug administration includes:
a. Subcutaneous
b. Intramuscular
c. Intravenous
d. Intradermal.
Antagonism means when one drug decreases/inhibits the action of another
Type of Antagonism Mechanism Examples

Competitive/ reversible Agonist and antagonist compete for the same receptors and to Acetylcholine atropine
the extent that antagonist opposes pharmacological action of
agonist is decided by the occupation of receptors by two of it
Noncompetitive Antagonist inactivates receptors so that effective complex with Calcium channel blocker
agonist cannot be formed
Chemical Biological activity of drugs is increased/ decreased by chemical Acids, alkalies, BAL and
reaction arsenic
Physiological Two drugs acting on different receptors but on same physiological Adrenaline/ histamine
system
Functional Two agonists acting independently but causing two opposite Acetylcholine/ adrenaline
effects
Pharmacokinetic Interference in absorption/excretion/ metabolism of drug by Tetracycline/milk

other drugs phenobarbitone/ warfarin
Drugs acting on peripheral nervous system/ ANS

Local Anaesthetics
Injectible Low potency, short duration Procaine, chloroprocaine

Intermediate potency and duration Lidocaine (lignocaine), prilocaine
High potency & long duration Tetracaine (amethocaine), bupivacaine,
ropivacaine, dibucaine (cinchocaine)
Surface anaesthetics Soluble Cocaine, lidocaine, tetracaine, benoxinate
Insoluble Benzocaine, butyl aminobenzoate (butamben),

oxethazaine
Chemical Classification:
Esters Cocaine, procaine, chloroprocaine, tetracaine, benzocaine
Amides Lignocaine, mepivacaine, bupivacaine, dibucaine, prilocaine, ropivacaine
General Anaesthetics
Inhalational
Gas – Nitrous oxide
Liquids – Ether, halothane, enflurane, isoflurane, desflurane, sevoflurane.
Intravenous
Inducing agents – Thiopentone sodium, methohexitone sodium, propofol, etomidate
Slower acting drug – Benzodiazepines – Diazepam, lorazepam, midazolam
Dissociative anaesthesia – Ketamine
Neuroleptanalgesia – Fentanyl 1 Droperidol
Analgesics
Narcotic analgesics
Opiates (natural opium alkaloids) Phenanthrene derivatives Morphine, codeine, thebaine
Benzylisoquinolone derivatives Papaverine (non-analgesic), noscapine

(narcotic)
Synthetic Opioids
Semisynthetic derivatives of morphine Heroin, hydromorphone, oxymorphone, hydrocodone, oxycodone

Phenanthrenes (morphinans) Levorphanol
Piperidines Pethidine, alphaprodine, anileridine, piminodine, ethoheptazine
Benzomorphans Phenazocine, pentazocine
Diphenyl butane derivatives Methadone
Classification of NSAIDs
A. Nonselective COX inhibitors

Salicylates and congeners Aspirin, salicylic acid, sodium salicylate
Para-aminophenol derivatives Paracetamol
Pyrazolone derivatives Aminopyrine, antipyrine, phenylbutazone
Indoles Indomethacin
Heterocyclic aryl acetic acid derivatives Diclofenac, ketorolac
Propionic acid derivatives Ibuprofen, naproxen
Fenamates Mefenamic acid
Oxicams Piroxicam
Sulphonanilides Nimesulide
B. Selective COX-2 inhibitors
Celecoxib, rofecoxib ,valdecoxib
Cardiovascular drugs
Antihypertensives can be classified depending upon the site of action:
a) Drugs acting centrally (CNS):
Clonidine, methyldopa
b) Acting on autonomic ganglia:
Hexamethonium, mecamylamine, pempidine, etc.
c) Postganglionic sympathetic nerve endings:
Reserpine, guanethidine, bretylium, etc.
d) Vascular smooth muscle:
Sodium nitroprusside, hydralazine, calcium-channel blockers, minoxidil
e) Stimulating baroreceptors:
Veratrum alkaloids
f) Blocking renin-angiotensin-aldosterone axis:
Beta-adrenergic blockers, ACE inhibitors (enalapril, captopril)
g) Oral diuretics:
Thiazides
h) Alpha and beta antiagents
Diuretics:
Action Drug Site of Action

Carbonic acid anhydrase Acetazolamide Proximal convoluted tubule
Inhibitor, osmotic diuretics Mannitol, urea, glycerine Loop of Henle
Loop diuretics/high ceiling diuretics Frusemide, ethacrynic acid Thick ascending limb
Sodium chloride symport inhibitors Thiazide Distal convoluted tubule
Sodium potassium pump inhibitor/ Amiloride, triamterene Distal convoluted tubule and collecting tubule
potassium sparing diuretics
Aldosterone antagonists Spironolactone Distal convoluted tubule and collecting tubule
Chemotherapy
l Antibiotics are biological substances elaborated by microorganisms, which suppress the growth of other
microorganisms or destroy them in high dilution.

l Majority of antibiotics is obtained from fungi but some like bacitracin, colistin, polymixin-B are ob-
tained from bacteria. Some antibiotics are synthesized by chemical methods, e.g. chloramphenicol.
Type of action of antimicrobial agents
Bactericidal drugs
l Penicillins
l Cephalosporins
l Aminoglycosides
l Co-trimoxazole
l Polymyxin, colistin
l Rifampicin
l Isoniazid
l Vancomycin
l Ciprofloxacin
l Nalidixic acid
Bacteriostatic drugs
l Sulphonamides
l Erythromycin
l Ethambutol
l Nitrofurans
l Tetracyclines
l Chloramphenicol
l Lincomycin
Classification of antibiotics
i. Effective against gram 1ve bacteria
l Penicillins
l Macrolides
l Bacitracin
ii. Effective against gram -ve bacteria

l Streptomycin
l Gentamicin
l Paromomycin
iii. Effective against gram 1ve and -ve bacteria

l Ampicillin, amoxicillin, carbenicillin
l Cephalosporins
l Neomycin
iv. Effective against gram 1ve, 2ve, rickettsia and chlamydia

l Tetracycline
l Chloramphenicol
v. Effective against acid -fast bacilli (M. tuberculosis)

l Rifampicin
l Streptomycin, kanamycin
vi. Effective against protozoa

l Metronidazole
l Fumagillin
l Paromomycin
vii. Effective against fungi

l Nystatin
l Amphotericin B
l Griseofulvin
viii. Effective against malignancy

l Actinomycin D
l Mitomycin
l Azaserine
Drugs Mechanism of Action

Polymixin Alter cell wall permeability
Bacitracin
Amphotericin B
Penicillin Inhibit cell wall synthesis
Cephalosporins
Vancomycin
Drugs Mechanism of Action

Tetracycline Inhibit protein synthesis
Chloramphenicol
Erythromycin
Rifampicin Interfere with DNA function
Metronidazole
Aminoglycosides Misleading of m-RNA
Antiviral drugs Interfere with DNA synthesis
Fluoroquinolones Inhibit DNA gyrase
Ciprofloxacin
Sulphonamides Inhibit bacterial intake of folic acid
Generations of cephalosporins
Generation Effective Against Ineffective Against Examples

First Gram1ve organisms Gram-ve organisms Cephalothin
Pseudomonas Cephalexin
Cefadroxil
Second Gram1ve and-ve organisms Pseudomonas Cefuroxime
Cefoxitin
Cefaclor
Third Gram-ve enterobacteriaceae Gram 1ve cocci Cefotaxime
Pseudomonas Cefixime
Ceftizoxime
Ceftazidime
Fourth Similar to third generation but highly effective Methicillin resistant Cefepime
Staphylococci Cefpirome
Tetracyclines may be divided into three groups

i. Group I - Tetracycline
Chlortetracycline
Oxytetracycline
ii. Group II –
Demeclocycline
Methacycline
iii. Group III –
Doxycycline
Minocycline
Typical dentifrice components and their action
Component Material Purpose

Abrasive CaCO3, dibasic CaPO4 dehydrate, Removal of plaque/ stain polish tooth surface
hydrated alumina, hydrated silica, MgCO3
Detergents Sodium lauryl sulphate Aids debris removal
Colorants Food colorants Appearance
Flavouring Oils of spearmint and peppermint Flavour
Humectant Sorbitol/glycerin Maintains moisture control
Binder Carrageen Thickens
Continued
Component Material Purpose

Fluoride Sodium mono-fluorophosphates Prevents dental caries
Desensitizing agent KNO3 Promotes occlusion of dentinal tubules
Tartar control agents Disodium pyrophosphate Inhibits formation of calculus above the gingival margin
Antibiotic Prophylaxis Prior to Dental Treatment
Situation Drugs Dosage

Azithromycin or clarithromycin Adults: 500mg PO 1hr before procedure. Children:
15mg/kg PO 1hr before procedure
Allergic to penicillins Clindamycin Adults: 600mg IV within 30min before procedure
and unable to take oral Children: 20mg/kg IV within 30min before procedure
medications
Cefazolin Adults: 1g IM or IV within 30min before procedure

Children: 25mg/kg IM or IV within 30min before
procedure
Section V
Self-Assessment Questions
Multiple Choice Questions 585

Viva Questions 621
Section V
Self-Assessment Questions
Multiple Choice Questions
Section I
Dental Materials
1. Which of the following deoxidizing agent is added to dental alloys? 7. Which of the following are utilized in laminate impression
a. Palladium technique?
b. Silver a. Syringe agar and chilled tray alginate
c. Copper b. Syringe agar and tray agar
d. Zinc c. Syringe agar and impression compound
d. Chilled alginate and impression compound
2. Gypsum-bonded investment should not be heated above
a. 700°C 8. Which of the following polishing agents can be used to polish
b. 750°C amalgam restorations?
c. 800°C a. Garnet
d. 900°C b. Emery
c. Silex
3. The direction of sprue former should be at d. Alumina
a. 45°
b. 90° 9. In casting procedures the function of wetting agents is to
c. 95° a. Facilitate wetting of ring liner
d. 180° b. Facilitate mixing investment
c. Reduce contact angle of a liquid with wax surface
4. Over other base metal alloys advantage of titanium is
d. Promote better wax elimination
a. Low weight
b. Low cost
10. Under composite restorations which of the following materi-
c. Low strength
als should not be used as liners or bases?
d. Low melting point
a. Resin-modified GIC
5. All of the following impression materials harden by chemical b. Zinc oxide eugenol
reaction except c. Miracle mix
a. Zinc oxide eugenol d. Compomer
b. Impression compound
c. Alginate 11. The most heat producing and efficient burning zone in a sol-
d. Plaster of Paris dering flame is
a. Cold mixing zone
6. In a dentifrice commonly used desensitizing agent is b. Partial combustion zone
a. Sodium chloride c. Reducing zone
b. Potassium nitrate d. Oxidizing zone
c. Ammonium sulphate
d. Glycerine
1. d 2. a 3. a 4. a 5. b 6. b 7. a 8. c 9. c 10. b 11. c
585
12. The by-product of polymerization reaction of condensation 21. In metal ceramic crowns, the function of indium and tin is to
silicon is a. Decrease porosity
a. Hydrogen b. Improve bonding
b. Ethyl alcohol c. To form an opaque layer
c. Oxygen d. Improve thermal expansion
d. Methyl alcohol
22. Which dye material has a hazardous potential during fabrication?
13. Commonly used laser for curing composite resins is a. Improved stone
a. Nd:YAG b. Silver amalgam
b. CO2 c. Electrodeposited silver
c. ERYAG d. Epoxy resin
d. Argon
23. The role of magnesium chloride in zinc oxide eugenol
14. The polyacid modified composites are known as impression paste is
a. Compomers a. Accelerator
b. Hybrid ionomers b. Modifier
c. Polycarboxylates c. Plasticizer
d. Polyacrylates d. Retarder
15. The fraction of inhaled mercury vapour retained in the body is 24. Quartz in dental porcelain is
a. 45–55% a. Strengthener
b. 55–65% b. Binder
c. 65–85% c. Filler
d. 85–90% d. Crack minimizer
16. During casting subsurface porosity in metals can be avoided by 25. Space lattice refers to
a. Increasing sprue length a. Interatomic movement
b. Increasing sprue thickness b. Interatomic imbalance
c. Increasing metal temperature c. Arrangement of atoms
d. Increasing mould temperature d. Arrangement of molecules
17. Crosslinking in denture base resin is contributed by 26. Ammonia treated gold foil is called
a. Benzoyl peroxide a. Cohesive foil
b. Glycol dimethacrylate b. Noncohesive foil
c. N-paratoluidine c. Corrugated foil
d. Methyl methacrylate d. Noncorrugated foil
18. Which of the following hardness tests is independent of the 27. The modulus of elasticity refers to
ductility of the material? a. Flexibility
a. Rockwell hardness test b. Ductility
b. Vicker’s hardness test c. Stiffness
c. Knoop’s hardness test d. Malleability
d. Brinell hardness test
28. The alloy that possesses super elasticity is
19. Minimum thickness for type I zinc phosphate cement should be a. Nitinol
a. 15 µ b. Stainless steel
b. 25 µ c. Cobalt–chromium–nickel
c. 10 µ d. Gold–palladium
d. None of the above
29. Which of the following cements are truly adhesive to tooth
20. Which of the following cement base has the highest modulus structure?
of elasticity? a. Zinc oxide eugenol and zinc phosphate
a. Zinc polycarboxylate b. Silicates and polycarboxylates
b. Polymer reinforced ZnOE c. Silicates and zinc phosphates
c. Zinc phosphate d. Glass ionomer and polycarboxylate
d. Glass ionomer cement
12. b 13. d 14. a 15. c 16. a 17. b 18. c 19. b 20. c 21. b 22. c 23. a 24. c 25. c 26. b 27. c 28. a 29. d
Section | V Self-Assessment Questions 587
30. Back pressure porosity in castings is caused due to 39. For aesthetic areas where high lustre is required the restora-
a. High casting pressure tion used usually:
b. Low investment permeability a. Glass ionomer restoratives
c. Small size and improper direction of sprue b. Hybrid resin composites
d. Sprue c. Hybrid resin composites
d. Macrofilled resin composites
31. Type I gypsum product is also known as
a. Impression plaster 40. The water/powder ratio of alginate is
b. Class I stone/hydrocal a. 100 mL of water to 60 g of powder
c. Class II stone/densite b. 40 mL of water to 40 g of powder
d. Model plaster c. 40 mL of water to 15 g of powder
d. 15 mL of water to 40 g of powder
32. Frozen slab technique is applied in mixing
a. Zinc phosphate cement 41. In a high noble gold alloy percentage of gold is
b. GIC a. , 25%
c. Zinc polycarboxylate cement b. 25%
d. Resin cement c. . 40%
d. 100%
33. The function of flux is to
a. Prevent the oxidation of material during melting 42. Which of the following cements release fluoride?
b. Increase the melting point of the flux a. Glass ionomer
c. Prevent the contamination of the metal and the liner b. Silicate
d. All the above c. Polycarboxylate
d. All of the above
34. The best pickling solution for gypsum-bonded investment is
a. Hydrochloric acid 43. The main form of iron carbide in 18/8 stainless steel:
b. Nitric acid a. Martensite
c. Sulphuric acid b. Austenite
d. Phosphoric acid c. Ferrite
d. Pearlite
35. The setting expansion of gypsum products can be reduced by
a. Increased spatulation 44. To make vinyl polysiloxane hydrophilic, the following should
b. Adding potassium sulphate be added:
c. Less water/powder ratio a. Mineral oil
d. Allowing setting under water b. Surfactant
c. Water
36. Miracle mix is d. Plasticizer
a. Metal modified glass ionomer cement
b. Mixture of amalgam alloy and mercury 45. The compressive strength of dentine is approximately
c. Mixture of filler and resin in composite a. 468 MPa
d. Mixture of superoxol, hydrochloric acid and ether b. 162 MPa
c. 350 MPa
37. Dimensional stability of hydrocolloid impressions may be d. 266 MPa
achieved by
a. Using less water/powder ratio 46. Crystalline materials as compared to amorphous materials
b. Storing the impression under water have
c. Prolonged manipulation a. No space lattice
d. Using humidor b. Less stability
c. Well-defined melting point
38. Gases dissolved in molten metals are liberated when cooled, d. Hydrophobic property
giving rise to
a. Suck back porosity 47. Hardening solutions are used with impressions made of
b. Gas inclusion porosity a. Agar hydrocolloids
c. Localized shrinkage porosity b. Impression compound
d. Microporosity c. Plaster of Paris
d. Zinc oxide eugenol
30. b 31. a 32. a 33. a 34. a 35. b 36. a 37. d 38. b 39. c 40. c 41. c 42. d 43. b 44. b 45. d 46. c 47. a
48. The phenomenon by which porcelain appears different under c. The stress at the proportional limit
varying conditions of colour is called d. None of the above
a. Mesomerism
b. Metamerism 57. Compressive stress is obtained by dividing the external force
c. Refractive index by the
d. Translucency a. Area of the test specimen upon which the weight rests
b. Elasticity of the test specimen in strain
49. The type III gypsum product is also called c. Length of the test specimen beneath the force
a. Impression plaster d. Strain of the test specimen per unit length
b. Class I stone or hydrocal
c. Class II stone or densite 58. Which of the following atomic bonds are characterized by
d. Model plaster physical forces?
a. Ionic bonds
50. pH of which cement remains below 7 one month after inser- b. Van der Waals bonds
tion into the cavity? c. Metallic bonds
a. GIC d. Covalent bonds
b. Zinc phosphate
c. Resin cement 59. A colloidal state in which a liquid is suspended in another
d. Silicate cement liquid is called as
a. Solution
51. The significant properties of the glass ionomer restorative b. Suspension
material include c. Emulsion
a. Chemical bonding with enamel and dentine d. Sol
b. Biocompatibility
c. Release of fluoride with set material 60. Resistance of a liquid to motion is called
d. All of the above a. Viscosity
b. Creep
52. The EBA cement refers to c. Diffusion
a. Modified calcium hydroxide cement d. Springiness
b. Resin modified glass ionomer cement
c. Modified zinc oxide eugenol cement 61. A phenomenon by which a substance appears different under
d. Noneugenol zinc oxide cement varying conditions of colour is called as
a. Mesomerism
53. Stress is defined as b. Metamerism
a. An applied load or force c. Fluorescence
b. A deformation resulting from an applied load d. Refractive index
c. An external force opposing an applied load
d. An internal force opposing an applied load 62. Liquid which becomes more rigid as the rate of deformation
increases is termed as
54. Strain is defined as a. Thixotropic
a. An applied load or force b. Newtonian
b. A deformation resulting from an applied load c. Dilatant
c. An external force opposing an applied load d. Pseudoplastic
d. An internal force opposing an applied load
63. The zinc oxide eugenol impression pastes harden by
55. The proportional limit is a. Chemical reaction
a. The maximum stress in a structure b. Cold
b. The minimum force required to cause a structure to break c. Heat
c. The maximum stress that can be induced without perma- d. Pressure
nent deformation
d. The maximum elongation under tension that can be mea- 64. Fourth state of matter is
sured before failure a. Solid
b. Liquid
56. The modulus of elasticity is defined as c. Gas
a. The stress/strain ratio within the proportional limit d. Colloid
b. The strain at the proportional limit
48. b 49. b 50. d 51. d 52. c 53. d 54. b 55. c 56. a 57. a 58. b 59. c 60. a 61. b 62. c 63. a 64. d
65. All of the following statements about type II silicon impres- 73. Model plaster used to cast study models is
sion material are true except a. CaO
a. They evolve hydrogen when cast if they are not fully cured b. CaCO3
b. They exhibit a very low setting shrinkage c. (CaSO4)2.½ H2O
c. They have a lower tear resistance than polysulphide d. CaSO4. 2H2O
rubbers
d. They set by condensation polymerization 74. The product, which is obtained by calcining gypsum under
steam pressure at 120–130°C:
66. All of the following statements about an alginate impression a. Alpha-hemihydrates
are true except b. Beta-hemihydrates
a. It should be rapidly displaced from the mouth c. Calcium sulphate dihydrate
b. It may exhibit fluid exudates on the surface as a result of d. Orthorhombic anhydrate
imbibitions of water
c. It will take up water and expand if kept wet 75. Water/powder ratio of dental stone and plaster is respectively
d. It will shrink as a result of syneresis a. 0.28 and 0.6
b. 9.6 and 0.28
67. All of the following can be used to slow down the setting of c. 0.6 and 3.2
zinc oxide eugenol impression paste except d. 0.28 and 0.98
a. Adding a small amount of glycerine
b. Adding a small amount of water 76. Type IV dental gypsum is
c. Altering the amounts of the two pastes used a. Class II stone
d. Cooling mixing slab b. Densite
c. Class I stone or hydrocal
68. Which of the following is an example of rigid reversible d. Model or lab plaster
impression material?
a. Agar agar 77. Green strength with reference to plaster means
b. Plaster of Paris a. Dry strength
c. Impression compound b. Compressive strength
d. Elastomers c. Shear strength
d. The wet strength
69. An example of mucocompressive material is
a. Impression paste and impression compound 78. Type V dental gypsum is
b. Impression paste and impression plaster a. Dental stone of high strength
c. Alginate and agar agar b. Dental plaster of high strength
d. Impression paste and elastomers c. Dental stone of high strength and high expansion
d. Dye stone
70. Impression compound characterized by
a. Crystalline in structure with definite melting point 79. Teralba is
b. Amorphous in nature with high thermal conductivity a. Pieces of gypsum added to plaster of Paris
c. Amorphous in nature with low thermal conductivity b. Gypsum containing metal
d. Crystalline in nature with high thermal conductivity c. A constituent modelling wax
d. Gypsum containing resin
71. Minimum flow of impression compound at 45°C is
a. Greater than 50% 80. Plaster powder and stone mainly differ in
b. Greater than 65% a. Solubility
c. Greater than 75% b. Shelf life
d. Greater than 85% c. Chemical composition
d. Particle shape and porosity
72. Maximum flow of impression compound at mouth tem-
perature 81. Substance that accelerates setting reaction of stone irrespec-
a. Should be less than 6% tive of its concentration:
b. Should be less than 8% a. K2SO4
c. Should be less than 10% b. Borax
d. Should be less than 12% c. NaCl
d. KCl
65. d 66. b 67. b 68. c 69. a 70. a 71. d 72. a 73. c 74. a 75. a 76. a 77. d 78. c 79. a 80. d 81. a
82. Compared to dental stone, dental plaster exhibits 91. Epoxy resins polymerize by
a. High compressive strength a. Condensation reaction
b. Same compressive strength b. Copolymerization
c. Low W/P ratio c. Crosslinked polymerization
d. High setting expansion d. Branched polymerization
83. Type I gypsum product is 92. Plasticizer most commonly used in heat-cured acrylic resins is
a. Impression plaster a. Dibutylphthalate
b. Model plaster b. Hydroquinone
c. Hydrocal c. Benzyl alkonium
d. Densite d. Difunctional monomer
84. All of the following statements about the differences between 93. In resins plasticizers are added to
self-polymerizing acrylic resins and heat-cured resins are true a. Decrease the workability and increase brittleness
except b. Increase workability and decrease brittleness
a. The former have a lower molecular weight c. Decrease workability and brittleness
b. The former have higher residual monomer content d. Increase workability and brittleness
c. The former are more porous
d. The former have greater transverse strength 94. The first translucent filling material produced by Fletcher
was
85. The monomer in heat-cured denture base acrylic resins is a. Glass ionomer cement
a. Methacrylate b. Silicate cement
b. Ethyl methacrylate c. Composite resin
c. Methyl-ethyl methacrylate d. Hybrid-filled resin
d. Poly(methyl methacrylate)
95. After setting, the surface of silicate cement exhibits
86. Which area of denture exhibits porosity if curing occurs at severe crazing and increase in solubility and opacity
temperature more than 100°C? due to
a. Hard thick central area a. Increased temperature
b. Thin palatal area b. Covering with grease
c. Thin area of flanges c. Early moisture contamination
d. Porosity is uniformly distributed d. Dehydration
87. Which of the following is an example of a composite material? 96. The major clinical problem(s) associated with the silicate
a. A filled resin cement is/are
b. Colloidal silica a. Decreased working time
c. Gold alloy b. High solubility and disintegration in oral fluid
d. Wax c. Short clinical life in less hygienic area
d. Both b and c
88. The dimethyl-p-toluidine is used in
a. Thermal polymerization of acrylic 97. Which of the following is the drawback of the tooth-
b. Chemical polymerization coloured resin material developed in early periods?
c. Retarding the polymerization reaction a. Lack of colour stability
d. To inhibit the action of benzoyl peroxide b. High degree of polymerization shrinkage
c. High coefficient of thermal expansion
89. Methyl methacrylate used in dentistry is a d. All of the above
a. Synthetic thermoplastic resin
b. Synthetic thermoset resin 98. Who developed the basic polymer of the composite resin
c. Natural thermoplastic resin system?
d. Synthetic thermoset resin a. Dr Ray Bowen
b. Dr MG Buonocore
90. The boiling point of methyl methacrylate is c. Dr RG Craig
a. Below that of water d. Dr John Q Byram
b. Slightly above that of water
c. Equal to that of water
82. d 83. a 84. d 85. a 86. a 87. a 88. b 89. a 90. b 91. c 92. a 93. b 94. b 95. d 96. d 97. d 98. a
99. Which of the following cements have coefficient of thermal 108. In which of the following impression materials brush heap
expansion close to that of dentine? structure is found?
a. Silicate a. Zinc oxide eugenol
b. Glass ionomer b. Agar
c. Zinc phosphate c. Condensation silicone
d. Zinc polycarboxylate d. Polyether
100. Which according to ADA specification, the maximum thick- 109. Which is best material for RPD impression?
ness of luting agent should not exceed a. Impression plaster
a. 10 µm b. Irreversible hydrocolloid
b. 25 µm c. Reversible hydrocolloid
c. 50 µm d. None of the above
d. 75 µm
110. The type of spatula used to mix composite is
101. Which of the following is common to silicate and glass a. Plastic
ionomer cement? b. Stainless steel
a. Powder zinc oxide c. Iron
b. Powder aluminosilicate glass d. Glass
c. Liquid phosphoric acid
d. Liquid polyacrylic acid 111. The function of the coupling agent in a restorative resin is to allow
a. Adhesion of resin particles
102. Which of the following base or liner is contraindicated b. Bonding between filler crystals
beneath filled or unfilled resins? c. Bonding between filler and resin
a. Glass ionomer d. Bonding between tooth and resin
b. Calcium hydroxide
c. Polycarboxylate cement 112. Knoop hardness number (KHN) of composites is
d. Zinc oxide eugenol a. 40
b. 50
103. Polishable composites are c. 60
a. Microfilled resins d. 30
b. Unfilled resins
c. Conventional resins 113. KHN of dentine is
d. All composites a. 68
b. 58
104. Compomer is c. 48
a. Metal-modified glass ionomer cement d. 38
b. Polyacid-modified composite resin
c. Resin-modified glass ionomer cement 114. All of the following statements are true regarding acid etch-
d. Metal-modified composite resin ing except
a. 37% or 50% phosphoric acid is used
105. Which of the following cement has obtudant effect? b. Etching for a longer period results in greater penetration
a. Polycarboxylate of polymers
b. Zinc oxide eugenol c. It increases surface area
c. Calcium hydroxide d. It results in higher surface energy
d. Glass ionomer
115. After the acid etch treatment there is a complete remineral-
106. Which of the following cements should not be used under ization of enamel, if exposed to saliva within
composite restorations? a. 75 days
a. Polycarboxylate b. 45 days
b. Zinc oxide eugenol c. 55 days
c. Calcium hydroxide d. 65 days
d. Glass ionomer
116. Brinell hardness number of a dental gold alloy is directly
107. pH of polycarboxylate liquid is proportional to its
a. 2.5 a. Tensile strength
b. 5 b. Elongation
c. 1.7 c. Modulus of elasticity
d. 7 d. Modulus of resilience
99. a 100. b 101. b 102. d 103. a 104. b 105. b 106. b 107. c 108. b 109. b 110. a 111. c 112. d 113. a 114. b 115. b 116. a
117. Composites are retained in the tooth by the phenomenon of 126. A composite has
a. Cohesion a. Resin
b. Adhesion b. Filler
c. Atomic forces c. Both a and b
d. Mechanical interlocking d. None
118. Commonly used filler in composite resins is 127. Type of bonding between composite resins and tooth struc-
a. Colloidal silica ture is
b. Quartz a. Covalent bond
c. Aluminium b. Ionic bond
d. Glass c. Mechanical
d. Van der Waals forces
119. Which of the following are true of composites compared
with the unfilled resins except 128. Trituration means
a. Placed and finished at the same appointment a. Lysing amalgam alloy
b. More colour stable b. Mixing of amalgam alloy and mercury
c. Coefficient of thermal expansion close to the tooth structure c. Removal of excess of mercury
d. Finished surface is less smooth d. None of the above
120. Dental sealants are composed of 129. Dynamic creep is the

a. Glass ionomers a. Continuing alloying between alloy and mercury during
b. Methyl methacrylate the life of restoration
c. Bis-GMA b. Deformation of set amalgam during mastication
d. EBA resins c. Process of wetting the alloy by mercury
d. Spread of amalgam during packing
121. Composites are not being recommended for class II poste-
rior restorations mainly due to 130. In an amalgam filling the highest mercury concentration is
a. Poor colour matching found
b. Lacks sufficient strength a. At the margins of the restoration
c. Occlusal wear b. In the centre of the restoration
d. Frequent fractures at the isthmus c. In the deepest part of the restoration
122. Which of the following materials exhibits the best initial
marginal adaptation? 131. The dental amalgam best withstands the
a. Acid-etched composites a. Tensile stress
b. Amalgam b. Impact stress
c. Glass ionomer c. Shear stress
d. Unfilled resins d. Compressive stress
123. Which of the following is a composite material? 132. The copper content in low copper amalgam alloys is
a. A filled resin a. 6%
b. Colloidal silica b. 12–28%
c. Gold alloy c. 10–12%
d. Wax d. 12–20%
124. Radio opacity of composite resins is rendered by 133. All of the following are the features of the high copper amal-
a. Barium glass gam alloys except
b. Organic matrix a. Low marginal breakdown
c. Silica glass b. Low creep values
d. Fluoride particles c. High strength
d. Low corrosive resistance
125. The main advantage of composites compared to unfilled
direct filling resins is their 134. The main purpose of trituration is to
a. Higher modulus of elasticity a. Dissolve all the particles with mercury
b. Lower modulus of elasticity b. Coat the alloy particles with mercury
c. Esthetic excellence c. Reduce the size of the alloy particles
d. Lower thermal coefficient of expansion d. None of the above
117. d 118. a 119. b 120. c 121. c 122. a 123. a 124. a 125. d 126. c 127. c 128. b 129. b 130. a 131. d 132. a 133. d 134. b
135. Gillmore needle is used for testing the 144. The range of wavelength of visible light curing system is
a. Strength of plaster of Paris a. 800–1000 nm
b. Setting time of plaster of Paris b. 710–900 nm
c. Metal hardness c. 410–500 nm
d. Purity of noble metals d. 310–400 nm
136. Compared to lathe-cut alloy, spherical dental amalgam 145. For final impression in a patient with submucous fibrosis the
alloys material of choice is
a. Require less amalgamation time a. ZnOE
b. Require higher forces of condensation b. Putty silicon
c. Requires more mercury for trituration c. Regular body silicon
d. Have longer setting time d. Irreversible hydrocolloid
137. ADA specification number of dental amalgam alloy is 146. Which of the following cement base has the highest modulus
a. ADA specification no. 2 of elasticity?
b. ADA specification no. 3 a. ZOE
c. ADA specification no. 4 b. Zinc phosphate
d. ADA specification no. 1 c. Zinc polycarboxylate
d. GIC
138. The side effect of light cure composite resin system is
a. Iritis 147. As age advances the microleakage of an amalgam restoration
b. Cataract a. Decreases
c. Conjunctivitis b. Increases
d. Retinal damage c. Remains constant
d. Not variable
139. The weakest and most corrodible phase of dental amal-
gam is 148. The product that is formed on the surface of the amalgam
a. Ag2Hg3 restoration which frequently results in discolouration is
b. Sn8Hg a. Sulphide
c. CuSn6 b. Nitrate
d. CuSn c. Chloride
d. Oxide
140. Corrosion of amalgam restoration
a. Can extend up to a depth of 100–500 µm 149. Cavity varnish under amalgam restoration
b. Decreases if tin content of alloy increases a. Prevents the temperature changes from reaching the pulp
c. Is promoted by gamma phase of alloy particles b. Resists the forces of condensation
d. Is resisted the most by copper–tin phase in high copper c. Improves the marginal seal of the restoration
amalgams d. Prevents surface discolouration
141. Which of the following is true about agar hydrocolloid 150. The percentage of copper in high copper alloys is
impression material? a. 0–6%
a. Liquefies between 71–100°C b. 13–30%
b. Solidifies between 50–70°C c. 10–12%
c. Facilitates fabrication of metal dyes d. 12–20%
d. Cannot register fine surface details
151. Which of the following is not true about pin-retained amal-
142. Nanofillers are in the range of gam restorations?
a. 10–100 µm a. Conservative tooth preparation
b. 0.1–1 µm b. Can be completed in a single appointment
c. 0.01–0.1 µm c. Strength is increased
d. 0.005–0.01 µm d. Retention is increased
143. Torsional force is 152. Conventional dental amalgam alloy contains

a. Compression a. Silver, tin, copper and zinc
b. Shear b. Silver, mercury, copper and zinc
c. Tensile force c. Silver, tin, palladium and zinc
d. Transverse bending force d. Silver, copper, iridium and mercury
135. b 136. a 137. d 138. d 139. b 140. d 141. a 142. d 143. b 144. c 145. c 146. b 147. a 148. a 149. c 150. b 151. c 152. a
153. Contamination of zinc-containing amalgam by moisture dur- 162. Electralloy is an alloy of

ing trituration or condensation results in a. Gold and platinum
a. Marked expansion b. Cobalt and chromium
b. Increased setting time c. Gold and calcium
c. A sharp decrease in flow d. Tin and chromium
d. No change on amalgam
163. Which of the pattern for the metallic framework of a remov-
154. Advantages of pin-retained amalgam restoration are able partial denture is fabricated from
a. More conservative tooth preparation a. Inlay wax type II
b. Restoration can be completed in single visit b. Boxing wax
c. Retention is improved c. Modelling wax
d. All of the above d. Casting wax
155. The strength of dental investment for gold alloy is dependent 164. A true eutectic alloy has
on amount of a. Melting point below the melting point of either metal
a. Silica b. Melting point above the melting point of both metals
b. Carbon c. Melting point below that of high fusion metal
c. Gypsum d. Melting point above that of low fusing metal
d. Copper
165. Which of the following has two different phases in solid
156. Silicate cement is indicated in state?
a. Mouth breathers a. Eutectic alloy
b. Patients with high caries index b. Solid solution
c. Restoration of posterior tooth c. Intermetallic compound
d. Restoration of fractured tooth d. None of the above
157. Greatest potential hazard of mercury toxicity occurs due to 166. Softening heat treatment is also known as
a. Skin contact with mercury a. Annealing
b. Ingestion of amalgam during restoration b. Work hardening
c. Ingestion of amalgam scrap during removal c. Age hardening
d. Inhalation of mercury vapours d. Strain hardening
158. About cast cobalt–chromium alloys all of the following 167. Cold working or work hardening results in
statements are true except a. Increase in hardness
a. They have a modulus of elasticity twice that of gold alloys b. Increase in yield strength
b. They are more rigid than gold alloys c. Increase in ultimate tensile strength
c. They have higher ductility than gold alloys d. All of the above
d. They have a lower proportional limit than gold alloys
168. Which of the following gold alloys are used in majority of
159. The percentage contraction of gold alloys on solidifying is cast gold restorations?
approximately a. Type I
a. 0.4% b. Type II
b. 1.4% c. Type III
c. 2.4% d. Type IV
d. 3.4%
169. Which of the following properties of the crown and inlay
160. Addition of large amounts of platinum to a casting gold alloy will casting gold alloys decrease from type I to type IV?
a. Decrease its strength a. Proportional limit
b. Increase its fusion temperature b. Tensile strength
c. Decrease its tarnish resistance c. Hardness and strength
d. Blackens the alloy d. Elongation
161. Which of following wax coating is present on dental 170. Crucible indicated for casting base metal alloys is
floss? a. Carbon crucible
a. Bees wax b. Clay crucible
b. Japan wax c. Quartz crucible
c. Spermaceti wax d. Plastic crucible
d. Carnauba wax
153. a 154. d 155. c 156. b 157. d 158. c 159. b 160. b 161. c 162. c 163. d 164. a 165. a 166. a 167. d 168. b 169. d 170. c
171. The cohesive gold used as bulk filler is 180. The sprue in wax pattern should be placed at
a. Electralloy a. Right angle
b. Mat gold b. Wide angle
c. Spherical gold c. Acute angle
d. Gold foil d. Obtuse angle
172. The opacity in ceramics is achieved by adding 181. Which of the following cements is contraindicated in mouth
a. Boric oxide breathers?
b. Copper oxide a. Silicate
c. Silica b. ZOE
d. Titanium oxide c. Polycarboxylate
d. Zinc phosphate
173. Commonly used flux in dental ceramics is
a. Alumina 182. Which of the following is the feature of type III gold alloy?
b. Boric oxide a. Harder than type IV
c. Kaolin b. Used for small inlays
d. Silica c. Easily burnishable than type IV
d. Less gold than type IV
174. Porosity in porcelain can be prevented by
a. Thorough condensation 183. Binder in investment for dental castings
b. Rapid firing a. Provides adequate strength to the investment
c. High firing temperature b. Holds ingredients together
d. All of the above c. Provides rigidity
d. All of the above
175. Sprue should ideally be made of
a. Inlay wax 184. Percentage of zinc in ZOE cement is
b. Plastic rod a. 60%
c. Hollow plastic b. 70%
d. Hollow metal c. 80%
d. 90%
176. The fusing temperature (in °C) of pure gold is
a. 863 185. Dental wax pattern should be invested as soon as possible to
b. 1063 prevent
c. 1263 a. Distortion due to relaxation of internal stresses
d. 1463 b. Drying of the wax pattern
c. Continued expansion of wax
d. Reduction in flow of wax
177. Pickling is performed
a. To remove oxide film from casting
186. Gypsum-bonded investment should not be heated above
b. Polish the casting
a. 900°C
c. Improve the strength of casting
b. 1000°C
d. Avoid casting defects
c. 700°C
d. 800°C
178. To achieve a smooth polished surface of a cast gold alloy the
final polish is done by
187. Eugenol may be replaced in the zinc oxide eugenol cement
a. Pickling
by
b. Electropolishing
a. Acetic acid
c. Sand blasting
b. Alginic acid
d. Rouge
c. Phosphoric acid
d. Orthoethoxy acid
179. For crown and bridge the best tissue tolerated material is
a. Highly polished porcelain
188. Fluoride-rich materials include
b. Highly polished acrylic
a. Silicate cement
c. Highly polished metal
b. Glass ionomer cement
d. Highly glazed porcelain
c. Polycarboxylate cement
d. All of the above
171. b 172. d 173. b 174. a 175. d 176. b 177. a 178. d 179. d 180. c 181. a 182. c 183. d 184. b 185. a 186. c 187. d 188. d
189. The composition of glass ionomer cements is 195. Which of the following is common to both zinc eugenol
a. Aluminosilicate powder and phosphoric acid cement and polycarboxylate cement?
b. Aluminosilicate powder and polyacrylate liquid a. Liquid is polyacrylic acid
c. Zinc oxide powder and phosphoric acid b. Forms chemical bond to tooth structure
d. Zinc oxide powder and polyacrylate liquid c. Exhibit chelation reaction
d. Strength of cement
190. Which of the following dental cements promote the forma-
tion of reparative dentine? 196. Which of the following can accelerate the setting time of
a. Eugenol zinc oxide eugenol cement?
b. Calcium hydroxide a. Barium sulphate
c. Zinc oxide b. Zinc acetate
d. Silica c. Zinc sulphate
d. Barium chloride
191. In a light cure resin system benzoin methyl ether in a poly-
mer may be cured in the presence of 197. Which of the following cements is most irritant to pulpal
a. UV light tissues?
b. Infrared light a. Zinc phosphate
c. Visible light b. Silicate
d. Oiketone c. Glass ionomer
d. Polycarboxylate
192. To prevent porosity in self-cure acrylic resin, curing should
be carried out under 198. Which of the following dental material shows most tear
a. Cold water resistance?
b. Hot water a. Polysulphide
c. Tap water b. Condensation silicone
d. Vacuum pressure c. Addition silicone
d. Polyether
193. Advantage of light-activated composite resins is
a. Extended working time 199. Titanium casting is done
b. Reduced resistance to wear or abrasion a. Under vacuum
c. Better resistance to wear or abrasion b. Under air pressure
d. All of the above c. In specifically fabricated aluminium-vanadium crucibles
d. Using CAD-CAM techniques
1 94. Monophase elastomeric impression materials are based on
a. Putty 200. Which of the following are passivating alloys?
b. Heavy body a. Cr, Al, Ti
c. Regular body b. Cr, Mo, Ti
d. Light body c. Cr, Fe, Mo
d. Cr, Au, Ti
189. b 190. b 191. a 192. d 193. a 194. c 195. c 196. b 197. b 198. a 199. d 200. a
Section II
General Pathology
1. Bacteria are commonly engulfed by 9. Metastatic calcifications are seen in
a. Neutrophilic leucocytes a. Hypoparathyroidism
b. Large granular lymphocytes b. Vitamin D deficiency
c. Small lymphocyte c. Hypercalcaemia
d. Killer cells d. Hypothyroidism
2. Pulpal inflammation exhibits all of the following features except 10. Osteomalacia is mainly associated with
a. Release of serotonin a. Decrease in osteoid volume
b. Platelet aggregation in the blood vessels b. Decrease in osteoid surface
c. Release of inflammatory mediators c. Increase in osteoid maturation time
d. Vasoconstriction is produced d. Decrease in osteoid maturation time
3. The most common bone tumour occurring in children is 11. During oral prophylaxis gingival bleeding occurs in leukae-
a. Osteosarcoma mic patients because of
b. Ewing’s sarcoma a. Increased leukocyte count
c. Ameloblastoma b. Decreased leukocyte count
d. Multiple myeloma c. Deficiency of clotting factor
d. Platelet disorder
4. Phaeochromocytoma is a disorder primarily occurs due to defect in
a. Adrenal medulla 12. The average number of CD4 cells in body fluid is
b. Kidney a. 300–500/mm3
c. Lungs b. 800–1200/mm3
d. Thyroid c. 500–800/mm3
d. 400–600/mm3
5. All of the following are seen in adrenal deficiency except
a. Hypoglycaemia 13. Primary amyloidosis occurs in
b. Hypocalcaemia a. Tuberculosis
c. Hypotension b. Multiple myeloma
d. Hyponatraemia c. Hodgkin’s disease
d. Chronic osteomyelitis
6. In a blood sample antiserum A, antiserum B and Rh positive
factor are added. No agglutination is seen. The blood group is 14. Cytochrome C is associated with
a. O 1ve a. Glycolysis
b. O 2ve b. Apoptosis
c. AB 2ve c. Drug metabolization
d. AB 1ve d. Autolysis
7. Dystrophic calcifications are calcifications seen in 15. Extrahepatic cholestasis is seen in

a. Skin layers a. Haemolytic anaemia
b. Normal tissues b. Obstructive jaundice
c. Salivary glands c. Pancreatic carcinoma
d. Dead tissue d. Viral hepatitis
8. For karyotyping using light microscopy which of the following 16. To detect mutations all of the following methods are used
procedures is a routine technique? except
a. C–banding a. Single-stranded conformational polymorphism
b. G–banding b. Denaturating gradient gel electrophoresis
c. Q–banding c. Northern blot analysis
d. V–staining d. Gel electrophoresis
1. a 2. a 3. a 4. a 5. b 6. b 7. d 8. d 9. c 10. c 11. d 12. b 13. b 14. b 15. c 16. c

17. All of the following are pigment disorders except c. UV light

a. Vitiligo d. Vitamin C
b. Melanoma
c. Freckle 27. In which phase the synthesis of DNA occurs?
d. Seborrhoeic keratosis a. G1
b. S
18. Disappearance of nuclear chromatin is known as c. G2
a. Pyknosis d. M
b. Karyolysis
c. Karyorhexis 28. Which of the following is used to disinfect blood spills in the
d. None hospital?
a. Quaternary ammonium compounds
19. Dark-coloured urine and clay-coloured stools are seen in b. Sodium hypochlorite
a. Neonatal jaundice c. Plain soap and water
b. Haemolytic anaemia d. Cetavlon
c. Hepatocellular jaundice
d. Severe dehydration 29. All the following are caused by bradykinin except
a. Smooth muscle contraction
20. Cross-pleated sheet conformation of amyloidosis is deter- b. Dilatation of blood vessels
mined by c. Pain
a. Electron microscopy d. Opsonization
b. X-ray crystallography
c. Light microscopy 30. Lancefield group of streptococci belongs to
d. Congo red stain a. M-protein
b. Bile solubility
21. Epithelioid cells are present in all of the following except c. Carbohydrate (C) antigen on cell wall
a. Tuberculosis d. G-protein
b. Granulation tissue
c. Syphilis 31. Apoptosis is suggestive of
d. Sarcoidosis a. Liquefaction degeneration
b. Coagulation necrosis
22. Flow cytometry analysis is done for c. Neoangiogenesis
a. Blood glucose estimation d. Epithelial dysplasia
b. LDL fraction estimation
c. CD4/CD8 counts 32. Lepra cells are seen in abundance in
d. None a. Tuberculoid leprosy
b. Lepromatous leprosy
23. Acid phosphatase positivity is shown by c. Histoid leprosy
a. T lymphocytes d. Intermediate leprosy
b. B lymphocytes
c. Myelocytes 33. Highly infective stage of syphilis is
d. Monocytes a. Congenital
b. Primary
24. Amyloidosis most commonly occurs in c. Secondary
a. Spleen d. Tertiary
b. Kidney
c. Liver 34. All of the following cells contain the enzyme telomerase except
d. Heart a. Germinal
b. Somatic
25. Diabetic gangrene is caused by c. Haemopoietic
a. Vasospasm d. Tumour
b. Peripheral neuritis
c. Atherosclerosis 35. During phagocytosis the metabolic process causes the activa-
d. Vasodilation tion of
a. Oxidase
26. Which of the following retards healing of wounds? b. Hydrolase
a. Proteins c. Peroxidases
b. Cortisol d. Dehydrogenase
17. d 18. a 19. c 20. b 21. b 22. c 23. a 24. d 25. c 26. b 27. b 28. b 29. d 30. c 31. a 32. b 33. c 34. b 35. a
36. Fine needle aspiration cytology is not useful for diagnosing 45. Hydrolytic degeneration is characterized by
which of the following? a. Caseation
a. Tubercular lymphadenitis b. Coagulation
b. Papillary carcinoma of thyroid c. Liquefaction
c. Aneurysmal bone cyst d. Fibrinoid
d. Plasmacytoma
46. Incomplete fractures of the bone is known as
37. The cells which do not undergo mitotic divisions are a. Green stick fracture
a. Muscle cells b. Compound fracture
b. Endothelial cells c. Simple fracture
c. Neurons d. Comminuted fracture
d. Bone marrow cells
47. Myoma indicates a tumour of
38. Neointimal hyperplasia causes vascular graft failure as a a. Lymphoid tissue
result of hypertrophy of b. Melanocytes
a. Endothelial cells c. Muscle
b. Collagen fibres d. Minor mucous salivary gland
c. Smooth muscle cells
d. Elastic fibres 48. Amyloidosis is a metabolic defect of
a. AA protein
39. Dacron vascular graft is b. AL protein
a. Nontextile synthetic c. Polypeptides
b. Nontextile biologic d. Polysaccharides
c. Textile synthetic
d. Textile biologic 49. In a transected nerve regeneration by sprouting of axons takes
place in
40. Penicillin affects bacteria by interfering with a. Proximal end
a. Cellular respiration b. Distal end
b. Cellular oxidation c. Both ends
c. Cell wall synthesis d. None of the above
d. Cellular division
50. Feature common in all types of shock is
41. Condyloma lata is seen in
a. Decreased tissue perfusion
a. Lupus vulgaris
b. Hypertension
b. Wegener’s granulomatosis
c. Hypovolaemia
c. Syphilis
d. Vasoconstriction
d. Leprosy
51. The value of PTT is normal in
42. Sago spleen is the term used to describe the gross appearance
a. Thrombocytopenia
of spleen in
b. Factor II deficiency
a. Hypersplenism
c. Factor VIII deficiency
b. Amyloidosis
d. DIE
c. Chronic myelocytic leukaemia
d. Chronic malaria
52. In SABE the haematuria is which type of hypersensitivity
43. Increased number of columnar cells in lower oesophagus of a reaction?
patient suggests which of the following change? a. Type II
a. Dysplasia b. Type IV
b. Anaplasia c. Type III
c. Metaplasia d. Type I
d. Normal histology
53. Increase in size of an organ due to increase in size of cells is
44. Peripheral nerve regenerates at the rate of mm per day: known as
a. 1 a. Hyperplasia
b. 2 b. Hypertrophy
c. 0.5 c. Atrophy
d. 5 d. Dysplasia
36. c 37. c 38. a 39. b 40. b 41. c 42. b 43. c 44. a 45. c 46. a 47. c 48. c 49. a 50. a 51. a 52. c 53. b
54. Increased osmotic fragility is seen in c. Hydropic degeneration

a. Sickle cell anaemia d. Amyloid degeneration
b. Hereditary spherocytosis
c. Thalassaemia 63. In which of the following conditions leukocyte alkaline phos-
d. Chronic lead poisoning phates is elevated?
a. Pernicious anaemia
55. Increased conjugated and unconjugated bilirubins is seen in b. Sickle cell anaemia
a. Haemolytic jaundice c. Polycythemia vera
b. Hepatocellular jaundice d. Plummer-Vinson syndrome
c. Posthepatic jaundice
d. All of the above 64. The type of immunoglobulin most commonly increased in
multiple myelomas:
56. In a chronic alcoholic all the following may be seen in the a. IgA
liver except b. IgG
a. Fatty degeneration c. IgM
b. Chronic hepatitis d. IgD
c. Granuloma formation
d. Cholestatic hepatitis 65. Osteoclast shows an intense activity of which of the following
enzymes?
57. Schwannomas commonly occur in which of the following a. Alkaline phosphatase
nerves? b. Acid phosphatase
a. Eighth cranial nerve c. Esterase
b. Fifth cranial nerve d. Carbonic anhydrase
c. Peripheral nerve
d. Sympathetic nerve 66. Vascular involvement and thrombosis is seen in
a. Coccidioidomycosis
58. Kaposi’s sarcoma caused due to b. Aspergillosis
a. Bacteria c. Mucormycosis
b. Virus d. Histoplasmosis
c. Fungus
d. All of the above 67. For the microbiological assay of vitamin B12, the following
bacteria are used:
59. Caseation necrosis suggests a. Corynebacteria diphtheriae
a. Tuberculosis b. Streptococcus pyogenes
b. Sarcoidosis c. E. coli
c. Leprosy d. Lactobacillus
d. Midline lethal granuloma
68. For study of sex chromatin the suitable cells for convenience
60. Negri bodies are characteristic of are taken from
a. CMV infection a. Nails
b. HSV infection b. Skin
c. Poliomyelitis c. Hair
d. Rabies d. Buccal mucosa and gingival
61. Unidirectional migration of leucocytes towards a target is 69. White infarcts occur in one of the following organs:
known as a. Ovary
a. Diapedesis b. Lung
b. Margination c. Intestine
c. Pavementing d. Heart
d. Chemotaxis
70. Disappearance of nuclear chromatin is known as
62. Mallory’s degeneration seen in alcoholic liver disease is a a. Pyknosis
form of b. Karyolysis
a. Hyaline degeneration c. Karyorhexis
b. Fatty degeneration d. None
54. b 55. b 56. c 57. a 58. a 59. a 60. d 61. d 62. a 63. c 64. a 65. b 66. c 67. c 68. d 69. d 70. a
71. Following tissue injury earliest transient change observed 79. Neointimal hyperplasia causes vascular graft failure as a re-
will be sult of hypertrophy of
a. Neutropenia a. Endothelial cells
b. Monocytosis b. Collagen fibres
c. Lymphocytosis c. Smooth muscle cells
d. Neutrophilia d. Elastic fibres
72. Which of the following is used in oxygen-dependent killing? 80. Approximately what percentage of pulmonary emboli pro-
a. NADPH oxidase ceeds to infraction?
b. Super oxide dismutase a. 0–5%
c. Cytochrome oxidase b. 5–15%
d. Glutathione peroxidase c. 15–20%
d. 20–30%
73. In type I hypersensitivity reaction the immunoglobulin in-
volved is 81. In acute inflammation, all of the following vascular changes
a. IgE are observed except
b. IgM a. Vasodilation
c. IgA b. Stasis of blood
d. IgG c. Increased vascular permeability
d. Decreased hydrostatic pressure
74. What type of hypersensitivity reaction is Arthus reaction?
a. Localized immune complex
82. Fibrinoid necrosis may be observed in all of the following
b. Ag–Ab reaction
except
c. Compliment-mediated
a. Malignant hypertension
d. Ab-mediated
b. Polyarteritis nodosa
c. Diabetic glomerulosclerosis
75. Which one of the following is the most significant risk factor
d. Aschoff’s nodule
for development of gastric carcinoma?
a. Colonic cell metaplasia
b. Pyloric metaplasia 83. A simple bacterial test for mutagenic carcinogens is
c. Intestinal metaplasia a. Ames test
d. Ciliated metaplasia b. Redox test
c. Bacteriophage
76. When carcinoma of stomach develops secondarily to perni- d. Gene splicing
cious anaemia, it is usually located in the
a. Prepyloric region 84. Which one of the following stains is specific for amyloid?
b. Pylorus a. Periodic acid schiff (PAS)
c. Body b. Alzerian red
d. Fundus c. Congo red
d. Von-Kossa
77. Pleomorphic adenoma of the salivary gland arises most often
in the 85. Aschoff’s nodules are seen in
a. Parotid salivary gland a. Subacute bacterial endocarditis
b. Minor salivary glands b. Libman-Sacks endocarditis
c. Submandibular salivary gland c. Rheumatic carditis
d. Sublingual salivary gland d. Nonbacterial thrombotic endocarditis
78. The most important criterion with regard to the malignant 86. Which one of the following conditions is characterized by
behaviour of leiomyosarcoma is fatty change in liver?
a. Blood vessel penetration by tumour cells a. Hepatitis B virus infection
b. Tumour cells in lymphatic channels b. Wilson’s disease
c. Lymphocyte infiltration c. Hepatitis C virus infection
d. The number of mitoses per high power field d. Chronic alcoholism
71. d 72. a 73. a 74. a 75. c 76. d 77. a 78. d 79. d 80. b 81. d 82. c 83. a 84. c 85. c 86. d
87. All of the following bring about the cellular and flagellar 94. A diagnosis of chronic hepatitis is made if liver disease is
movement except present for a minimum of
a. Intermediate filaments a. 3 weeks
b. Actin b. 6 weeks
c. Tubulin c. 6 months
d. Myosin d. 3 months
88. The lipoxins belong to which of the following family of 95. In the oral cavity most common site of tuberculous
chemical mediators of inflammation? lesion is
a. Kinin system a. Buccal mucosa
b. Cytokines b. Lips
c. Chemokines c. Tongue
d. Arachidonic acid metabolites d. Palate
89. Which of the following is a procoagulation protein? 96. White infarcts occur in
a. Thrombomodulin a. Ovary
b. Protein C b. Lung
c. Protein S c. Intestine
d. Thrombin d. Heart
90. Which of the following is the most abundant glycoprotein
97. Mercury is toxic because it
present in basement membrane?
a. Complexes with haemoglobin to form methaemoglobin
a. Laminin
b. Inhibits haemoglobin synthesis, producing anaemia
b. Fibronectin
c. Inhibits anaerobic glycolysis
c. Collagen type 4
d. Binds to sulphhydryl groups
d. Fibrinogen
91. The blood normally does not clot intravascularly because 98. Lepra cells seen in leprosy are
a. Vitamin K antagonists are present in plasma a. Lymphocytes
b. Thrombin has a positive feedback on plasminogen b. Plasma cells
c. Sodium citrate in plasma chelates calcium ions c. Vacuolated histiocytes
d. Vascular endothelium is smooth and coated with glycocalyx d. Neutrophils
92. Pemphigus vulgaris is characterized by 99. All of the following host tissue responses can be seen in
a. Acanthosis acute infection except
b. Acantholysis a. Exudation
c. Auspitz’s sign b. Vasodilation
d. Wickham’s striae c. Margination
d. Granuloma formation
93. Which of the following tissue restores functional capacity
after injury, by hypertrophy? 100. The growth of uterus during pregnancy is an example of
a. Liver a. Hypertrophy
b. Adrenal cortex b. Hyperplasia
c. Cardiac muscle c. Both a and b
d. Peripheral nerve d. None of the above
87. a 88. d 89. d 90. a 91. d 92. b 93. c 94. c 95. c 96. d 97. d 98. c 99. d 100. c
Section III
Microbiology
1. Best method of sterilizing disposable syringes is 8. VDRL reactive mother gave birth to an infant. All of the
a. Gamma rays following would help in determining the risk of transmission
b. UV rays to the infant except
c. Hot air oven a. TPHA test on the serum sample of the mother
d. Boiling b. TPHA test on the serum sample of the infant
c. VDRL test on the paired serum sample of the infant and mother
2. All of the following are true about Vibrio cholerae except d. Time interval between the treatment of the mother and her
a. It is nonhalophilic delivery
b. Grows on simple media
c. Man is the only natural host 9. Which of the following parasitic infestation can lead to
d. Cannot survive in extracellular environment malabsorption syndrome?
a. Amoebiasis
3. Which of the following bacteria act by increasing C-AMP? b. Ascariasis
a. Vibrio cholerae c. Hookworm infestation
b. Staphylococcus aureus d. Giardiasis
c. E. coli heat-stable
d. Salmonella 10. All of the following vibrio species are halophilic except
a. V. cholerae
4. Botulinum affects all of the following except b. V. parahaemolyticus
a. Neuromuscular junction d. V. alginolyticus
b. Preganglionic junction d. V. fluvialis
c. Postganglionic nerves
d. CNS 11. All of the following statements are true regarding Clostridium
perfringens except
5. All of the following statements are true for Chlamydia psitta- a. It is the commonest cause of gas gangrene
cosis except b. It is normally present in human faeces
a. Acquired from bird’s droppings c. The principal toxin of C. perfringens is the alpha toxin
b. Causes urethritis d. Gas gangrene producing strains of perfringens produce
c. Causes pneumonia heat resistant spores
d. Treatment is tetracycline
12. All of the following are true with reference to infections of
6. All of the following diseases are associated with Epstein-Barr Escherichia coli except
virus infection except a. Enteroaggregative E. coli is associated with persistent
a. Infectious mononucleosis diarrhoea
b. Epidermodysplasia verruciformis b. Enterohaemorrhagic E. coli can cause haemolytic uraemic
c. Nasopharyngeal carcinoma syndrome
d. Oral hairy leukoplakia c. Enteroinvasive E. coli produces a disease similar to salmo-
nellosis
7. Which one of the following statement is true regarding patho- d. Enterotoxigenic E. coli is a common cause of travellers’
genicity of mycobacteria species? diarrhoea
a. M. tuberculosis is more pathogenic than M. bovis to the
humans 13. A bacterial disease that has been associated with the 3 “Rs”,
b. M. Kansasii can cause a disease indistinguishable from tu- i.e. rats, ricefields and rainfall is
berculosis a. Leptospirosis
c. M. Africanum infection is acquired from the environmental b. Plague
source c. Melioidosis
d. M. Marinum is responsible for tubercular lymphadenopathy d. Rodent-bite fever
1. a 2. d 3. a 4. d 5. b 6. b 7. b 8. b 9. d 10. a 11. d 12. c 13. a

14. Which of the following organisms are not able to survive 22. HIV can be detected and confirmed by
intracellularly? a. Polymerase chain reaction (PCR)
a. Neisseria meningitides b. Reverse transcriptase PCR
b. Salmonella typhi c. Real time PCR
c. Streptococcus pyogenes d. Mimic PCR
d. Legionella pneumophila
23. Which of the following infestation leads to absorption?
15. The commonest organism that causes acute meningitis in an a. Giardia lamblia
AIDS patient is b. Ascaris lumbricoides
a. Streptococcus pneumoniae c. Necater americana
b. Streptococcus agalactiae d. Ancylostoma duodenale
c. Cryptococcus neoformans
d. Listeria monocytogenes 24. The capsule of Cryptococcus neoformans in a CSF sample is
best visualized by
16. The most common pathogens responsible for nosocomial a. Grams stain
pneumonias in the ICU are b. India ink preparation
a. Gram-positive organisms c. Giemsa stain
b. Gram-negative organisms d. Methenamine-silver stain
c. Mycoplasma
d. Virus infections 25. Which of the following statements is true about hapten?
a. It induces brisk immune response
17. Exotoxins are b. It needs carrier to induce immune response
a. Lipid polysaccharide complex c. It is a T-independent antigen
b. Lipoprotein d. It has no association with MHC
c. Protein compound
d. Carbohydrate 26. Which of the following toxins acts by inhibiting protein
synthesis?
18. Tyndallization is carried out for a. Cholera toxin
a. One day b. Shiga toxin
b. Two successive days c. Pertussis toxin
c. 60 min d. LT of enterotoxigenic E. coli
d. Three successive days
27. In all of the following bacterial diarrhoeas toxins are impli-
19. Chlamydia trachomatis is associated with all of the following cated as the major pathogenetic mechanism except
except a. Vibrio cholerae
a. Endemic trachoma b. Shigella sp.
b. Inclusion conjunctivitis c. Vibrio parahaemolyticus
c. Lymphogranuloma venereum d. Staphylococcus aureus
d. Community-acquired pneumonia
28. Which of the following is correct regarding gas gangrene?
20. Viruses can be isolated by all of the following methods from a. It is due to Clostridium botulinum infection
clinical samples except b. Clostridial species are Gram-negative spore forming
a. Tissue culture anaerobes
b. Embryonated eggs c. The clinical features are due to the release of protein
c. Animals endotoxin
d. Chemically-derived media d. Gas is invariably present in the muscle compartments
21. Virus-mediated transfer of host DNA from one cell to another 29. The most sensitive method for detecting cervical Chlamydia
is known as trachomatis infection is
a. Transduction a. Direct fluorescent antibody test
b. Transformation b. Enzyme immunoassay
c. Transcription c. Polymerase chain reaction
d. Integration d. Culture on irradiated McConkey cells
14. c 15. c 16. b 17. c 18. d 19. d 20. d 21. a 22. b 23. a 24. b 25. b 26. b 27. c 28. d 29. c
30. Which of the following clinical features is not associated with 39. The earliest immunoglobulin to be synthesized by the fetus is
enteroviruses? a. IgA
a. Myocarditis b. IgG
b. Pleurodynia c. IgE
c. Herpangina d. IgM
d. Haemorrhagic fever
40. Mycotic abscesses are due to
31. Culture medium for Corynebacterium diphtheria: a. Bacterial infection
a. Loeffler’s serum slope b. Fungal infection
b. McConkey c. Viral infection
c. Sabouraud agar d. Mixed infection
d. Lowenstein Jensen medium
41. Which of the following statements is true?
32. Heat-labile instruments used in surgical procedures can be a. Agar has nutrient properties
best sterilized by b. Chocolate medium is selective medium
a. Absolute alcohol c. Enrichment media means addition of selective substances
b. Ultraviolet rays in a solid medium
c. Chlorine releasing compounds d. Nutrient broth is a basal medium
d. Ethylene oxide gas
42. Negri bodies are pathognomonic of
33. Smith Noguchi’s media is used for a. CMV infection
a. Salmonella b. HSV infection
b. Spirochaetes c. Poliomyelitis
c. Klebsiella d. Rabies
d. Bacillus
43. Which of the following immunoglobulins is not known to fix
34. In penicillin allergy, penicillin acts as a complement?
a. Hapten a. IgE
b. Antitoxin b. IgM
c. Super antigen c. IgA
d. Toxin d. IgG
35. All of the following are true for Bordetella pertussis except 44. Spores of which bacteria are used to test the efficacy of moist
a. It is a strict human pathogen heat sterilization?
b. It can be cultured from the patient during catarrhal a. Clostridium tetani
stage b. Streptococcus pyogenes
c. It leads to invasion of the respiratory mucosa c. Bacillus stearothermophilus
d. Infection can be prevented by an acellular vaccine d. Ureaplasma urealyticum
36. All of the following are true regarding Lyme’s disease except 45. For the microbiological assay of vitamin B12 the following
a. It is transmitted by ixodes tick bacteria is used:
b. Erythema chronicum migraines is seen a. Corynebacterium diphtheriae
c. Borrelia recurrentis is the causative agent b. Streptococcus pyogenes
d. Rodents act as natural hosts c. E. coli
d. Staphylococcus
37. Which of the following statements is true about rabies virus?
a. It is double-stranded RNA virus 46. Kaposi’s sarcoma is of
b. Contains a DNA-dependent RNA polymerase a. Bacterial origin
c. RNA has a negative polarity b. Viral origin
d. Affects motor neurons c. Fungal origin
d. Radiation origin
38. All of the following infections are often associated with acute
intravascular haemolysis except 47. Which of the following causes erysipelas?
a. Clostridium tetani a. Group B staphylococci
b. Bartonella bacilliformis b. Group A streptococci
c. Plasmodium falciparum c. Gonococci
d. Babesia microti d. Pneumococci
30. d 31. b 32. d 33. a 34. a 35. d 36. c 37. c 38. a 39. d 40. b 41. d 42. d 43. a 44. c 45. c 46. b 47. b
48. Most common fungus affecting diabetics is 57. The type of immunological response seen in transplant rejec-
a. Cryptococcus tion is
b. Aspergillus a. Type I
c. Rhodotorula b. Type II
d. Nocardia c. Type III
d. Type IV
49. Actinomycosis is caused by
a. Virus 58. The most resistant organisms to thermal inactivation are
b. Bacteria a. Bacterial spores
c. Fungus b. Virus
d. Unknown factor c. Spirochaetes
d. Streptococcus mutans
50. When subjected to paper electrophoresis, the fastest moving
fraction of protein in serum is 59. Disinfection of the rooms can be done by using
a. Albumin a. 20% phenol
b. a-globulin b. High efficiency particle arrestors
c. b-globulin c. Chlorine gas
d. g-globulin d. 40% formaldehyde vapour
51. The cells which produce antibodies are 60. Rideal Walker test is used to determine the efficiency of the
a. Plasma cell a. Dry heat sterilization
b. Helper T cell b. Disinfectant
c. Macrophage c. Moist heat sterilization
d. Natural killer cell d. Antibiotics
52. Polypeptide capsule is present in 61. Cold sterilization refers to the process of sterilization using
a. Corynebacterium diphtheriae a. Ultraviolet rays
b. Clostridium welchii b. Ultrasonic vibrations
c. Staphylococcus aureus c. Infrared rays
d. Bacillus anthracis d. Gamma rays
53. Bacteria that grow best at temperatures below 20°C are 62. Erythroblastosis fetalis can be prevented by injecting mother,
called at parturition with an antibody called
a. Mesophilic a. Rh (D) immunoglobulin
b. Psychrophilic b. Blocking antibody
c. Thermophilic c. Rh (E) immunoglobulin
d. Microaerophilic d. Antilymphocyte serum
54. Glassware are best sterilized by 63. For typing of class I histocompatibility antigens, a test that
a. Autoclaving can be used is
b. Hot air oven a. Cell-mediated lympholysis (CML)
c. Incineration b. Donor-recipient mixed lymphocyte response
d. Formaldehyde c. Primed lymphocyte typing
d. Antibody and complement mediated cytotoxicity
55. Which of the following are best demonstrated by negative
staining? 64. Hepatitis C virus belongs to which of the following groups?
a. Bacterial spores a. Picorna virus
b. Bacterial flagella b. Herpes virus
c. Bacterial capsule c. Hepadna virus
d. Bacterial fimbriae d. Flavi virus
56. By all of the following methods bacteria acquire characteris- 65. The distinguishing feature of a positive delayed type hyper-
tics except sensitivity skin test is
a. Through plasmids a. Erythema
b. Incorporating part of host DNA b. Necrosis
c. Through bacteriophages c. Induration
d. Through conjugation d. Vasculitis
48. b 49. a 50. a 51. a 52. d 53. a 54. b 55. c 56. b 57. d 58. a 59. d 60. b 61. d 62. b 63. d 64. d 65. a
66. In bacterial attachment to cell surfaces which of the following c. Decline

structures are involved? d. Stationary phase
a. Capsule
b. Pili 75. Monospot test is used to diagnose
c. Flagella a. Pernicious anaemia
d. Mesosomes b. Sickle cell anaemia
c. Infectious mononucleosis
67. Who first introduced solid media? d. Leukaemia
a. Louis Pasteur
b. Robert Koch 76. Australia antigen is associated with
c. Hensen a. AIDS
d. Ogston b. Hepatitis B surface antigen in acute hepatitis
c. Chronic leukaemia
68. For determining the virulence of staphylococci, the most im- d. Basal cell carcinoma
portant laboratory test is
a. Mannitol fermentation 77. Following hepatitis B infection through blood transfusion
b. Haemolysis of sheep erythrocytes disease manifests in
c. Detection of coagulase a. 1 week
d. The catalase test b. 6 weeks
c. 3 months
69. Human immunoglobulins are classified based on d. 6 months
a. Functional differences
b. Antigenic affinity 78. Causative agent of influenza is
c. Complement fixation a. Orthomyxo virus, which is a DNA virus
d. Structural differences b. Paramyxo virus, which is a RNA virus
c. Paramyxo virus, which is a DNA virus
70. Sulphur granules are a diagnostic feature of which of the fol- d. Orthomyxo virus, which is a RNA virus
lowing diseases?
a. Histoplasmosis 79. All are oncogenic except
b. Sulphide poisoning a. Varicella-zoster virus
c. Actinomycosis b. EB virus
d. Toxoplasmosis c. Papilloma virus
d. Herpes simplex virus
71. Tuberculin test is a screening test for
80. On a stained slide, Clostridium tetani appears as
a. Humoral immunity
a. Bunch of grapes
b. Cell-mediated immunity
b. Drumstick
c. Complement function
c. Chain of beads
d. Phagocyte dysfunction
d. Safety pin
72. Following active immunization with tetanus toxoid injection,
81. IL-1 is involved in
how often should a booster dose be given?
a. T-lymphocyte activation
a. Every year
b. decreased wound heal
b. Every 2 years
c. Gain in body weight
c. Every 5 years
d. Macrophage activation
d. Twice a year
82. The Gram-positive and negative bacteria differ in their
73. The principle on which autoclave works is a. Cell wall structure
a. Moist heat under pressure b. Cell membrane
b. Moist heat c. Nuclear material
c. Dry heat d. Nuclear membrane
d. Boiling
83. The mechanism by which most fungi cause disease is
74. Zero growth rate is observed during one of the phases of the a. Exotoxin production
bacterial growth curve. b. Lecithinase production
a. Lag c. Hypersensitivity
b. Exponential growth d. Coagulase production
66. b 67. b 68. c 69. b 70. c 71. b 72. c 73. a 74. d 75. c 76. b 77. a 78. d 79. a 80. b 81. a 82. a 83. c
84. Immunoglobulin that crosses placenta is c. Pseudomonas

a. IgM d. Klebsiella
b. Ig A
c. IgG 93. Grape bunch shaped colonies are seen in
d. IgD a. Streptococcus
b. Gonococci
85. Dry heat sterilization destroys microorganisms by c. E. coli
a. Oxidation d. Staphylococcus
b. Lysis
c. Hydrolysis of DNA 94. Dipicolinic acid is a substance found in bacterial
d. Coagulation of proteins a. Spores
b. Cell wall
86. Which of the following is an enrichment medium? c. Nucleus
a. Blood agar d. Cell membrane
b. Selenite F broth
c. MacConkey agar 95. Measles is highly infectious during which stage?
d. Nutrient broth a. Complicated stage
b. Exanthematous skin lesions
87. Serum sickness syndrome is an example of c. Catarrhal or respiratory droplets
a. Anaphylactic shock d. Convalescent stage
b. Angioneurotic oedema
c. Systemic arthus reaction 96. The most common complication of streptococcal sore throat is
d. Cell-mediated immunity a. Rheumatic fever
b. Scarlet fever
88. HIV is transmitted by all of the following routes except c. Pharyngitis
a. Sexual intercourse d. Blackwater fever
b. Needle prick injury
c. Blood transmission 97. Dark ground microscope is useful for the detection of
d. Saliva a. Spirochaetes
b. Streptococci
89. Certain viruses have been isolated in crystalline form and c. Staphylococci
have been found to be d. Pneumococci
a. Nucleoproteins
b. Phospholipids 98. Which of the following is a commonly found filamentous
c. Scleroproteins organism in dental plaque?
d. Flavoproteins a. Streptococci
b. Staphylococci
90. Amoebic liver abscess can be diagnosed by demonstrating c. Leptothrix
a. Cysts in the sterile pus d. Treponema
b. Trophozoites in the pus
c. Trophozoites in the faeces 99. Chronic multiple sinus tracts present at the angle of lower
d. Cysts in the stomach jaw, yellow purulent granular discharge is noticed you
should consider the following in the diagnosis:
91. Which of the following is an agglutination test in the diagno- a. Actinomyces
sis of typhoid? b. Tuberculosis
a. Widal test c. Staphylococci infection
b. Mantoux test d. Histoplasmosis
c. Eriks test
d. Wasserman test 100. A person with notched teeth or mulberry molars is likely to have:
a. Syphilis
92. Which of the following is anaerobic? b. Gonorrhoea
a. E. coli c. Thrush
b. Bacteroides d. Actinomycosis
84. c 85. a 86. b 87. c 88. d 89. a 90. b 91. a 92. b 93. d 94. a 95. c 96. a 97. a 98. c 99. a 100. a
Section IV
Pharmacology
1. Which of the following is a third generation cephalosporin? 9. The ratio of the median lethal dose to the median effective
a. Cefoperazone dose is known as
b. Cefuroxime a. Morbidity index
c. Cefoxitin b. Mortality index
d. Cefadroxil c. Anaesthetic index
d. Therapeutic index
2. Folic acid deficiency occurs on using
a. Aspirin 10. Which of the following is the least predictable reaction to
b. Phenytoin drug?
c. Chloramphenicol a. Idiosyncrasy
d. Cyclosporin b. Toxicity
c. Side effect
3. Which of the following is the intravenously given general d. Allergy
anaesthetics?
a. Propofol 11. Which of the following is the correct colour code of oxygen
b. Sevoflurane cylinder?
c. Naloxone a. Black cylinder with white shoulders
d. Isoflurane b. Black cylinder with grey shoulders
c. White cylinder with black shoulders
4. Tetracycline acts on which of the following? d. Grey cylinder with white shoulders
a. 30S ribosomes
b. 50S ribosomes 12. After diazepam sedation 50% ptosis of eyelid, blurring of
c. Cell membrane vision, slurring of speech indicates
d. Inhibiting DNA gyrase a. Tinel’s sign
b. Verill’s sign
5. Which one of the following local anaesthetics belongs to the c. Corman’s sign
ester group? d. Bell’s sign
a. Procaine
b. Bupivacaine 13. Myocardial depression is caused by which of the following?
c. Lignocaine a. Isoflurane
d. Mepivacaine b. Halothane
c. Desflurane
6. In patients with allergy to sulphonamides which of the follow- d. Sevoflurane
ing medications is contraindicated?
a. Levobunolol 14. Administration of which of the following corrects the haem-
b. Bimatoprost orrhage secondary to heparin?
c. Brinzolamide a. Vitamin K
d. Brimonidine b. Whole blood
c. Protamine
7. A diabetic patient developed cellulitis due to Staphylococcus d. Ascorbic acid
aureus, which was found to be methicillin resistant on the
antibiotic sensitivity testing. All the following antibiotics will 15. Persistent neutropenia is seen with prolonged usage of
be appropriate except a. Carmustine
a. Vancomycin b. Doxorubicin
b. Imipenem c. Vinblastine
c. Teicoplanin d. Cisplatin
d. Linezolid
16. Penicillin exerts its effect on bacteria by interfering with
8. Teratogenicity results when drugs are given during a. Cellular respiration
a. First trimester b. Cellular oxidation
b. Second trimester c. Cell wall synthesis
c. Third trimester d. Cellular division
d. After birth
1. a 2. b 3. a 4. a 5. a 6. c 7. b 8. a 9. d 10. a 11. a 12. b 13. b 14. c 15. c 16. c

17. What is the advantage of sublingual route of administration 26. Which one of the following muscle relaxant has the maximum
of drugs? duration of action?
a. Prevents first-pass effects a. Atracurium
b. Easy to administer b. Vecuronium
c. Lipid soluble c. Rocuronium
d. Can be spitted out with signs of toxicity d. Doxacurium
18. Which of the following is induction agent of choice in 27. The myocardium is sensitized to catecholamides by which
children? one of the following agents?
a. Methoxyflurane a. Isoflurane
b. Sevoflurane b. Halothane
c. Desflurane c. Ether
d. Isoflurane d. Propofol
19. Which of the following intravenous agent is the most suitable 28. Drug metabolism increased in all of the following by activat-
for day care surgical procedures? ing cytochrome enzyme except
a. Morphine a. Tetracycline
b. Ketamine b. Cimetidine
c. Propofol c. Rifampicin
d. Diazepam d. Phenobarbitone
20. Neuro adaptation to drug is same as 29. Curare poisoning is characterized by

a. Physical dependence a. Hypertension
b. Psychological dependence b. Hypotension
c. Addiction c. Does not release histamine
d. Habituation d. Hyperthermia
21. All of the following symptoms are seen with opiate with- 30. If t1/2 is 4 h, complete drug elimination occurs in how many
drawal except hours?
a. Diarrhoea a. 12 h
b. Lacrimation b. 20 h
c. Excessive speech c. 25 h
d. Mydriasis d. 30 h
31. Which one of the following is an antipseudomonal penicillin?

22. Nevirapine is a
a. Cephalexin
a. Protease inhibitor
b. Cloxacillin
b. Nucleoside reverse transcriptase inhibitor
c. Dicloxacillin
c. Nonnucleoside reverse transcriptase inhibitor
d. Piperacillin
d. Fusion inhibitor
32. For application in oral mucosa the antiseptic recommended is
23. Bisphosphonates act by
a. Hydrogen peroxide
a. Increasing the osteoid formation
b. Iodine
b. Increasing the mineralization of osteoid
c. Mebromine
c. Decreasing the osteoclast mediated resorption of bone
d. Decreasing the parathyroid hormone secretion
33. All of the following antibacterial agents act by inhibiting cell
24. Which of the following antibacterial agent should not be used wall synthesis except
along with d-tubocurarine? a. Carbapenem
a. Streptomycin b. Monobactam
b. Norfloxacin c. Cephamycin
c. Doxycycline d. Nitrofurantoin
d. Oflaxin
34. In which of the following phases of clinical trial of drugs
25. Penicillin-G is therapeutically used for all of the following except ethical clearance is not required?
a. Bacterial meningitis a. Phase I
b. Syphilis b. Phase II
c. Rickettsial infection c. Phase III
d. Anthrax d. Phase IV
17. a 18. b 19. c 20. a 21. d 22. c 23. c 24. a 25. c 26. d 27. b 28. b 29. b 30. b 31. d 32. b 33. d 34. d
35. Herxheimer reaction is seen in case of 44. Which of the following drugs does not produce an allergic
a. Penicillin used in actinomycosis reaction?
b. Penicillin used in syphilis a. Penicillins
c. Cephalexin used in syphilis b. Sulphonamides
d. Amoxicillin used in injection c. Cetirizine
d. Cephalosporins
36. COX-2 inhibitor is
a. Rofecoxib 45. Which of the following is not a nondepolarizing competitive
b. Aspirin neuromuscular blocker?
c. Uprofen a. Doxacurium
d. Paracetamol b. Decamethonium
c. Rocuronium
37. Which of the following corticosteroid is given by inhalation d. Mivacurium
route?
a. Beclomethasone 46. Which of the following is not a long-acting local anaesthetic?
b. Hydrocortisone a. Tetracaine
c. Dexamethasone b. Lidocaine
d. Prednisolone c. Bupivacaine
d. Dibucaine
38. The most effective bronchodilator is
a. Salbutamol 47. Drug metabolism can be induced by following factors except
b. Ephedrine a. Cigarette smoking
c. Isoprenaline b. Acute alcohol ingestion
d. Isoxsuprine c. Exposure to insecticides
d. Consume charcoal broiled meat
39. D-tubocurarine blocks the neuromuscular transmission by
48. Clinically significant drug interaction occurs between pyri-
a. Blocking acetylcholine receptors
doxine and all of the following drugs except
b. Preventing release of acetylcholine
a. Isoniazid
c. Destroying acetylcholine
b. Cyclosporine
d. Inactivating acetylcholine esterase enzyme
c. Levodopa
d. Hydralazine
40. The most common cause of antibiotic-related diarrhoea is
due to
49. Majority of drugs are transported across the cell membrane by
a. H. pylori
a. Passive diffusion
b. C. difficile
b. Active transport
c. K. pneumoniae
c. Facilitated transport
d. Shigella
d. Facilitated diffusion
41. The enzyme known to cause spontaneous thrombosis as an 50. Intrinsic staining of teeth due to calcium chelation is caused by
adverse reaction is a. Alizarin
a. Tyrosinase kinase b. Ampicillin
b. Aromatase c. Erythromycin
c. Asparaginase d. Tetracycline
d. Collagenase
51. The recovery period of primary herpetic gingivostomatitis is
42. Km value indicates shortened by which of the following medications?
a. Purity of enzyme a. Acyclovir
b. The maximum rate of drug elimination b. Zidovudine
c. Affinity c. Kenalog in Orabase
d. Half-life enzymes drug complex d. All of the above
43. Which of the following drug is safe to be used in lactating 52. Which of the following does not bind to GABA receptor chlo-
mothers? ride channels?
a. Erythromycin a. Ethanol
b. Chloramphenicol b. Alphaxalone
c. Ciprofloxacin c. Zolpidem
d. Ampicillin d. Buspirone
35. b 36. a 37. a 38. a 39. a 40. b 41. c 42. d 43. a 44. c 45. b 46. b 47. b 48. b 49. a 50. d 51. a 52. d
53. An antimicrobial which has antipseudomonal action is 61. Quinidine is used in treatment of
a. Cefpodoxime proxetil a. Hypertension
b. Ceforanide b. Angina pectoris
c. Cefotetan c. Atrial fibrillation
d. Cefoperazone d. Congestive heart failure
54. The bone marrow depression is caused by all of the following 62. Caffeine exhibits its central action on the
anticancer agents except a. Cerebral cortex
a. Chlorambucil b. Corpus callosum
b. Daunorubicin c. Hypothalamus
c. Doxorubicin d. Spinal cord
d. Flutamide
63. During administration of which of the following drugs, the
55. Which one of the following anticonvulsant drugs exhibits side cardiac arrhythmias are most commonly seen?
effects like granulocytopenia, gingival hyperplasia and facial a. Thiopental
hirsutism? b. Halothane
a. Phenytoin c. Ethyl ether
b. Valproate d. Nitrous oxide
c. Carbamazepine
d. Phenobarbitone 64. A distinct advantage of tetracyclines compared to penicillins
is that they
56. Sedation by which of the following routes can be reversed a. Have a wider range of antibacterial activity
most rapidly? b. Do not cause superinfections
a. Inhalation c. Are safer to use during pregnancy
b. Oral d. Have no side effects
c. Intravenous
d. Rectal
65. In treating opioid-dependent individuals, currently which of
the following drugs is widely used?
57. In management of a patient with an acute allergic reaction
a. Codeine
involving bronchospasm and hypotension the drug of
b. Methadone
choice is
c. Midazolam
a. Epinephrine
d. Pentazocine
b. Aminophylline
c. Dexamethasone
d. Diphenhydramine 66. Peripheral neuritis is a complication of
a. Isoniazid
58. The most rapid relief of symptoms of angina pectoris is found b. Griseofulvin
with the administration of c. Vincristine
a. Oxygen d. All of the above
b. Ibuprofen
c. Barbiturates 67. Felypressin is a
d. Meperidine (Demerol) a. Vasoconstrictor
b. Vasodilator
59. When administered intravenously in a high dose, epinephrine c. Coagulant
does not cause d. Anticoagulant
a. Increase liver glycogenolysis
b. Bronchiolar constriction 68. With use of which of the following drug the rebound phenom-
c. Evoking of extrasystoles in the heart enon is most commonly seen?
d. Restlessness and anxiety a. Epinephrine
b. Norepinephrine
60. Phenothiazines are mainly used to c. Phenylephrine
a. Produce muscle relaxation d. Levonordefrin
b. Suppress cough
c. Alter psychotic behaviour 69. Salbutamol is used in treatment of
d. Produce analgesia a. Cardiac asthma
b. Bronchial asthma
c. Pulmonary oedema
d. Cor pulmonale
53. d 54. d 55. a 56. a 57. a 58. d 59. b 60. c 61. c 62. a 63. b 64. a 65. b 66. d 67. a 68. a 69. b
70. In treating oral candidiasis, which of the following antibiotics 79. All of the following are alkylating agents except
is effective? a. Cyclophosphamide
a. Nystatin b. 5-FU
b. Bacitracin c. Busulfan
c. Penicillin d. Chlorambucil
d. Griseofulvin
80. Methotrexate is used in high doses in treating
71. In a patient with cardiac arrhythmia which of the following a. Osteosarcoma
cardiac depressants is contraindicated? b. Retinoblastoma
a. Lidocaine c. Rhabdomyosarcoma
b. Quinidine d. Ewing’s sarcoma
c. Phenytoin
d. Propranolol 81. Bisphosphonates act by
a. Increasing the osteoid formation
72. In all of the following conditions morphine is contraindicated b. Increasing the mineralization of osteoid
except c. Decreasing the osteoclast mediated resorption of bone
a. Pulmonary oedema d. Decreasing the parathyroid hormone secretion
b. Emphysema
c. Bronchial asthma 82. Which of the following drugs does not interfere with folic
d. Head injury acid metabolism?
a. Phenytoin
73. Diuretics cause loss of b. Gabapentin
a. Sodium c. Phenobarbitone
b. Calcium d. Primidone
c. Potassium
d. Iron 83. All of the following antibacterial agents act by inhibiting cell
wall synthesis except
74. Nitrous oxide is carried in the blood stream by a. Carbapenem
a. Haemoglobin b. Monobactam
b. White blood cells c. Cephamycin
c. Red blood cells d. Nitrofurantoin
d. Serum
84. Which of the following medications is contraindicated in pa-
75. All are short and rapid acting insulins except tients with allergy to sulphonamides?
a. Lispro a. Levobunolol
b. Aspart b. Bimatoprost
c. Glargine c. Brinzolamide
d. Glulisine d. Brimonidine
76. Which of the following is not an antiepileptic agent? 85. All of the following are part of the treatment of lithium toxic-
a. Phenytoin ity except
b. Topiramate a. Treating dehydration
c. Flunarizine b. Ingestion of polystyrene sulphonate
d. Carbamazepine c. Haemodialysis
d. Using an antagonist
77. All of the following statements about heparin are true
except 86. A highly ionized drug
a. Causes alopecia a. Is excreted mainly by the kidney
b. Nonteratogenic b. Can cross the placental barrier easily
c. Releases lipoprotein lipase c. Is well absorbed from the intestine
d. Causes hypokalaemia d. Is highly protein bound
78. Which of the following drugs causes orange coloured urine? 87. All of the following hormones have cell surface receptors except
a. Rifampicin a. Adrenalin
b. INH b. Growth hormone
c. Pyrazinamide c. Insulin
d. Ethambutol d. Thyroxine
70. a 71. b 72. a 73. c 74. c 75. c 76. c 77. d 78. a 79. b 80. a 81. c 82. b 83. d 84. c 85. d 86. a 87. d
88. Dry mouth during antidepressant therapy is caused by block- c. Medullary cortex
ade of which of the following receptors? d. Cerebrum
a. Muscarinic acetylcholine
b. Serotonergic 97. Local anaesthetics act by inhibiting
c. Dopaminergic receptors a. Motor fibres only
d. GABA b. Sensory fibres only
c. Both a and b
89. Which of the following is not penicillinase susceptible? d. None of the above
a. Amoxicillin
b. Penicillin G 98. Omeprazol is a drug of choice for treating
c. Piperacillin a. Peptic ulcer
d. Cloxacillin b. Amoebiasis
c. Malaria
90. Ethical clearance is not required in which of the following d. Cholera
phases of clinical trial of drug?
a. Phase I 99. Heroin contains
b. Phase II a. ASA
c. Phase III b. Acetyl morphine
d. Phase IV c. Pentazocine
d. Propoxyphene
91. Which one of the following statements about biguanides is
not true? 100. Which of the following is a naturally occurring local
a. Do not stimulate insulin release anaesthetic?
b. Decrease hepatic glucose production a. Cocaine
c. Renal dysfunction is not a contraindication for their use b. Procaine
d. Can be combined with sulphonylureas c. Lignocaine
d. Mepivacaine
92. Morphine can be used in all the following conditions except
a. Head injury
101. An anaesthetist orders a new attendant to bring the oxygen
b. Asthma
cylinder. He will ask the attendant to identify the correct
c. Hypothyroidism
cylinder by following colour code:
d. Diabetes
a. Black cylinder with white shoulders
b. Black cylinder with grey shoulders
93. Regarding sulphonamides, which of the following statements
c. White cylinders with black shoulders
is not true?
d. Grey cylinder with white shoulders
a. Sulphasalazine is well absorbed from GIT
b. Crystalluria can occur with sulphonamide administration
102. Which of the following fluoroquinolones does not require
c. Sulphonamide administration to newborn may cause
dose adjustment in a patient with creatinine clearance of
kernicterus
, 50 mg/min?
d. Sulphonamides are of value in treatment of infections due
a. Ciprofloxacin
to Norcardia species
b. Trovafloxacin
c. Lomefloxacin
94. BAL is useful in treating poisoning due to all of the following
d. Sparfloxacin
except
a. Lead
b. Organic mercury 103. Which of the following antibacterial should not be used with
c. Cadmium d-tubocurarine?
d. Arsenic a. Norfloxacin
b. Streptomycin
95. Ketamine is a c. Doxycycline
a. Short general anaesthetic agent d. Cefotaxime
b. Local anaesthetic agent
c. Antidepressive agent 104. All of the following are therapeutic uses of penicillin-G
d. Hypnotic agent except
a. Bacterial meningitis
96. The most resistant organ to GA is b. Rickettsial infection
a. Spinal cord c. Syphilis
b. Medulla oblongata d. Anthrax
88. a 89. d 90. d 91. c 92. a 93. a 94. c 95. a 96. b 97. b 98. a 99. b 100. a 101. a 102. b 103. b 104. b
105. All are symptoms of opiate withdrawals, except c. High Na1 levels
a. Diarrhoea d. Low K1 levels
b. Lacrimation
c. Mydriasis 114. The enzyme known to cause spontaneous thrombosis as an
d. Excessive speech adverse reaction is
a. Tyrosinase kinase
106. All the following increases drug metabolism by activating b. Aromatase
cytochrome enzyme except c. Asparaginase
a. Tetracycline d. Collagenase
b. Cimetidine
c. Rifampicin 115. Which of the following class of antibiotics are relatively
d. Phenobarbitone safer in patients on warfarin therapy?
a. Cephalosporins
107. Curare poisoning is characterized by b. Imidazoles
a. Hypertension c. Penicillins
b. Hypotension d. Macrolides
c. Does not release histamine
d. Oral route of administration is the best route 116. When a patient develops supraventricular tachycardia, with
hypotension under general anaesthesia, all of the following
108. Which is the most effective for asymptomatic amoebic treatments may be instituted except
cysts? a. Carotid sinus massage
a. Metronidazole b. Adenosine 3–12 mg IV
b. Diloxanide furoate c. Direct current cardioversion
c. Quiniodochlor d. Verapamil 5 mg IV
d. Furazolidone
117. Intramuscular route is to be precluded during the medica-
109. Sublingual route of drug administration is preferred due to tion of
a. Thin oral mucosa a. Antihypertensives
b. As it undergoes first-pass metabolism b. Antidiabetics
c. Irritating drugs can be given c. Anticoagulants
d. None of the above d. Antifibrinolytics
110. Which of the following actions is ascribed to delta type of 118. Drug efficacy refers to
opioid receptors? a. Range of diseases in which the drug is beneficial
a. Supraspinal analgesia b. Maximum intensity of response that can be produced by
b. Respiratory depression the drug
c. Euphoria c. The therapeutic dose range of the drug
d. Reduced intestinal motility d. The therapeutic index of the drug
111. Colloidal bismuth used in peptic ulcers causes 119. Which of the following medications shortens the recovery
a. Inhibition of proton causes period of primary herpetic gingivostomatitis?
b. Muscarinic blockade in stomach a. Acyclovir
c. It is against H. pylori b. Zidovudine
d. Coats the surface of ulcer c. Kenalog in orabase
d. All of the above
112. Activation of which of the following receptors would be
expected to decrease anxiety? 120. Which of the following does not bind to GABA receptor
a. Nicotinic cholinergic receptors chloride channels?
b. Glutamate receptors a. Ethanol
c. GABA A receptors b. Alphaxalone
d. Glucocorticoid receptors c. Zolpidem
d. Buspirone
113. Digitalis-induced automaticity is enhanced by
a. High K1 levels
b. High Ca11 levels
105. d 106. b 107. b 108. b 109. a 110. b 111. d 112. c 113. b 114. c 115. c 116. d 117. c 118. b 119. a 120. d
121. Which of the following antimicrobials has antipseudomonal 129. Which of the following drugs is currently widely used in
action? treating opioid-dependent individuals?
a. Cefpodoxime proxetil a. Codeine
b. Ceforanide b. Methadone
c. Cefotetan c. Alphaprodine
d. Cefoperazone d. Pentazocine
122. All of the following anticancer agents cause bone marrow 130. A patient, without prior medication, breathes a gas mix-
depression except ture consisting of 50% nitrous oxide and 50% per oxygen
a. Chlorambucil by volume. Which of the following effects would be
b. Daunorubicin expected?
c. Doxorubicin a. Analgesia
d. Flutamide b. Excitation
c. Surgical anaesthesia
123. Granulacytopenia, gingival hyperplasia and facial hirsutism d. Respiratory arrest
are all possible side effects of one of the following anticon-
vulsant drugs: 131. Which of the following is the current drug of choice for
a. Phenytoin status epilepticus?
b. Valproate a. Phenytoin
c. Carbamazepine b. Diazepam
d. Phenobarbitone c. Carbamazepine
d. Chlorpromazine
124. Which of the following is not an action of epinephrine when
administered intravenously in a high dose? 132. Secretory immunoglobulin is
a. Increases liver glycogenolysis a. IgG
b. Causes bronchiolar constriction b. IgA
c. Evokes extrasystoles in the heart c. IgM
d. Produces restlessness and anxiety d. IgE
125. Phenothiazines are used to
133. Zero order kinetics is seen with
a. Produce muscle relaxation
a. Phenytoin
b. Alter psychotic behaviour
b. Phenobarbital
c. Suppress coughing
c. Erythromycin
d. Produce analgesia
d. Digoxin
126. Salbutamol is used in
a. Cardiac asthma 134. Majority of drugs are transported across the membrane by
b. Bronchial asthma a. Passive diffusion
c. Pulmonary oedema b. Active transport
d. Cor pulmonale c. Facilitated transport
d. Filtration
127. The principal central action of caffeine is on the
a. Cerebral cortex 135. Action of nitroglycerin
b. Corpus callosum a. Slows SA node conductivity
c. Hypothalamus b. Blocks arrhythmia
d. Spinal cord c. Increases perfusion to heart
d. Is direct action on smooth muscle
128. A distinct advantage that tetracyclines have over penicillins
is that tetracyclines 136. Hypokalaemia is seen in therapy with
a. Have no side effects a. Digitalis
b. Do not cause superinfections b. Ibuprofen
c. Are safer to use during pregnancy c. Corticosteroids
d. Have a wider range of antibacterial activity d. Diazepam
121. d 122. d 123. a 124. b 125. b 126. b 127. a 128. d 129. b 130. c 131. b 132. b 133. a 134. a 135. d 136. a
137. Magnesium and aluminium are added in antacid because 146. Tannic acid is used in the following conditions except
a. Mg causes constipation, Al causes diarrhoea a. Bleeding gums
b. Mg causes diarrhoea, Al causes constipation b. Alkaloidal poisoning
c. Mg acts as buffering agent and Al antagonizes its c. Toothache
action d. Bleeding piles
d. Both increase gastric motility
147. All the following drugs cause dryness of mouth except
138. Nitrous oxide is carried in the blood stream by a. Atropine
a. Haemoglobin b. Chlorpheniramine
b. White blood cells c. Imipramine
c. Red blood cells d. Neostigmine
d. Serum
148. Serum sickness is caused by all the following drugs except
139. Ketamine is a a. Aspirin
a. Short general anaesthetic agent b. Penicillin
b. Local anaesthetic agent c. Sulphonamides
c. Antidepressive agent d. Chloroquine
d. Hypnotic agent
149. The organ most resistant to GA is
140. The dentist who first used ether as a general anaesthetic was a. Spinal cord
a. Martin b. Medulla oblongata
b. Morton c. Medullary cortex
c. Morrison d. Cerebrum
d. Murray
150. Local anaesthetics act by inhibiting
141. The dentist who first used nitrous oxide for the abolition of a. Motor fibres only
pain due to dental extraction was b. Motor and sensory fibres
a. Harper David c. Only sensory fibres
b. Harvey William d. None of the above
c. Horace Wells
d. Hunter John 151. The metabolism of a drug to a more potent or more toxic
form by the body is called
142. Which of the following is not a potassium sparing diuretic? a. Autotoxicosis
a. Spironolactone b. Teratogenesis
b. Bumetanide c. Mutagenesis
c. Triamterene d. Dependence
d. Amiloride
152. The antagonism between acetylcholine and atropine can be
143. A side effect of an antithyroid drug is best described as
a. Hypothyroidism a. Physical antagonism
b. Obesity b. Competitive receptor antagonism
c. Hypotension c. Physiological antagonism
d. Tremors d. Chemical antagonism
144. Xerostomia is treated with 153. Which of the following are definitely teratogenic to humans?
a. Neostigmine a. Anticancer drugs and thalidomide
b. Ephedrine b. Tetracyclines and corticosteroids
c. Scopolamine c. Barbiturates and oral anticoagulants
d. Atropine d. Antithyroid and anti-inflammatory drugs
145. Which of the following concentrations of ethanol exhibit the 154. Which of the following proteins has the greatest ability to
maximum antiseptic action? bind drugs?
a. 50% a. Albumin
b. 65% b. Fibrinogen
c. 70% c. Gamma globulin
d. 95% d. Beta globulin
137. b 138. c 139. a 140. b 141. c 142. b 143. a 144. a 145. c 146. c 147. d 148. d 149. b 150. c 151. a 152. b 153. a 154. a
155. Drug metabolism enzymes in liver are present in 164. The last sensation to be lost following LA administration:
a. Microsomes a. Pain
b. Cell membranes b. Touch
c. Nuclei c. Temperature sense
d. Ribosomes d. Deep pressure
156. In which of the following patients atropine is strongly 165. 1 mL of 2% lignocaine contains how many milligram of
contraindicated? drug?
a. Acute narrow angle glaucoma a. 10 mg
b. Peptic ulcers b. 15 mg
c. Bronchial asthma c. 20 mg
d. Drug-induced diarrhoea d. 200 mg
157. All of the following results in dry mouth except 166. Compared to 100,000 adrenaline, epinephrine 1:50,000 in an
a. Anticholinergics LA solution has the advantage of
b. Ganglion blocking agents a. Lesser capillary bleeding
c. Adrenergic agonists b. Greater depth of anaesthesia
d. Antihistamines c. Greater duration of anaesthetic action
d. Lesser toxic effects
158. Drug which induces natural sleep when administered in
therapeutic doses is called as 167. The most serious adverse effect of systemic local anaesthetic
a. Hypnotic toxicity is
b. Sedative a. Transient syncope
c. Soporific b. Postconvulsive central nervous system depression
d. Analgesic c. Postdepressive central nervous system convulsion
d. Hypotension
159. Which of the following is specific antagonist to benzodi-
azepine? 168. Aspirin is contraindicated with
a. Amphetamine a. Prednisolone
b. Flumazenil b. Theophylline
c. Meprobamate c. Warfarin
d. MAO inhibitors d. Oral contraceptives
160. Which of the following are long-acting barbiturates? 169. Which of the following has poor anti-inflammatory action?
a. Phenobarbitone and mephobarbitone a. Paracetamol
b. Secobarbitone and pentobarbitone b. Ibuprofen
c. Thiopentone and hexobarbitone c. Ketorolac
d. Pentobarbitone and thiopentone d. Diclofenac
161. Death in acute morphine poisoning is due to 170. Which of the following can be given safety in peptic ulcers?
a. Respiratory failure a. Aspirin
b. Cardiac arrest b. Diclofenac
c. Fall in BP and shock c. Brufen
d. Convulsions d. Paracetamol (acetaminophen)
162. The last sensation to be depressed by GA is 171. Antiarrhythmic action of phenytoin closely resembles that of
a. Taste a. Lignocaine
b. Pain b. Procainamide
c. Touch c. Digitalis
d. Hearing d. Verapamil
163. The first sensation lost after administration of local anaes- 172. The drug most commonly used during attack of angina
thetic is pectoris:
a. Proprioception a. Theophylline
b. Pain b. Isosorbide dinitrate
c. Pressure c. Sodium nitrate
d. Temperature d. Nitroglycerine or glyceryl trinitrate
155. a 156. a 157. c 158. c 159. b 160. a 161. A 162. d 163. b 164. d 165. c 166. a 167. b 168. b 169. a 170. d 171. a 172. d
173. Which of the following is a bacteriostatic drug? 182. Which of the following is not an action of the circulating
a. Erythromycin catecholamines?
b. Penicillin a. Dilation of pupils of eye
c. Vancomycin b. Dilation of bronchial muscles
d. Cephalosporin c. Liver glycogenesis
d. Increased heart rate
174. Fanconi-like syndrome is seen due to use of outdated drugs
of 183. Drug that is safe to administer to a patient who suffers from
a. Penicillin atrial tachycardia and is allergic to quinine and has no evi-
b. Doxycycline dence of congestive heart failure is
c. Tetracycline a. Digitoxin
d. Methacycline b. Quinidine
c. Procainamide
175. Grey baby syndrome is associated with which of the follow- d. Epinephrine
ing drugs?
a. Chloramphenicol 184. Gastric acid secretion has been shown to be most effectively
b. Tetracycline reduced with use of
c. Penicillin a. Anticholinergic drugs
d. Erythromycin b. Serotonin antagonists
c. H1 histamine receptor antagonists
176. Polyene antibiotics exhibit their action on d. H2 histamine receptor antagonists
a. Cell membrane
185. Which of the following can be used to calculate the drug
b. Cell wall
dose for children?
c. Cell nucleus
a. Young’s rule, considering the size of the child
d. Ribosomes
b. Smith’s rule, considering the adult dose
c. Clark’s rule, considering the weight of the child
177. The antagonist of heparin is
d. None of above
a. Protamine sulphate
b. EACA
186. One ounce is approximately
c. Menadione
a. 10 mL
d. Thrombin
b. 30 mL
c. 40 mL
178. Which of the following should be given preferably in perni-
d. 50 mL
cious anaemia?
a. Vitamin B12 187. Drug of choice for anthrax is
b. Folic acid a. Penicillin
c. Iron b. Tetracycline
d. None of the above c. Carbenicillin
d. Ciprofloxacin
179. Amide-type local anaesthetics are metabolized in the
a. Serum 188. Which of the following drug is not used in treatment of hy-
b. Liver pertension?
c. Spleen a. Reserpine
d. Kidneys b. Ephedrine
c. Methyldopa
180. Prolonged administration of streptomycin may result in d. Thiazide diuretic
damage to the
a. Optic nerve 189. DOT regimen means
b. Facial nerve a. Rifampicin 1 streptomycin—6 months
c. Auditory nerve b. Isoniazid 1 ethambutol—1 year
d. Trigeminal nerve c. Isoniazid 1 rifampicin—9 months
d. Rifampicin 1 streptomycin isoniazid—10 months
181. Which of the following affects the most to the granulation
healing tissue? 190. Which of the following is not a loop diuretic?
a. Cortisol a. Frusemide
b. Growth hormone b. Indapamide
c. Thyroxin c. Bumetanide
d. Adrenaline d. Ethacrynic acid
173. a 174. c 175. a 176. a 177. a 178. a 179. b 180. c 181. a 182. c 183. c 184. d 185. c 186. b 187. a 188. b 189. b 190. b
191. Indication for glucocorticoids includes all except 197. A patient receiving propranolol has an acute asthmatic
a. Rheumatic carditis attack while undergoing dental treatment; the most useful
b. Addison’s disease agent for the management of the condition would be
c. Anaphylactic shock a. Morphine
d. Glaucoma b. Epinephrine
c. Aminophylline
192. Tetracycline acts by d. Norepinephrine
a. Bactericidal effect
b. Interfering with cell wall synthesis 198. Of the following, the drug that does not produce neuromus-
c. Inhibiting protein synthesis cular blockade is
d. inhibiting nucleic acid synthesis a. Atropine
b. Physostigmine
193. Benzathine penicillin is given c. Succinylcholine
a. Orally d. Baclofen
b. Intravenously
c. Along with probenecid for the treatment of gonorrhoea 199. Following the administration of this drug, urine will have a
d. IM once a week in the treatment of syphilis red colour:
a. Rifampicin
194. Third generation cephalosporins
b. Clonidine
a. Are active orally
c. Methyldopa
b. Reach CNS in adequate concentration in meningitis
d. Sulphadiazine
c. Are ineffective against H. influenza infections
d. Are not very effective in Gram-negative infections
200. Hepatitis vaccine is given to the dentist
195. Sulphonamides a. To protect the dentist
a. Are weak bases b. To avoid carrier state
b. Alkalinization of urine reduces their excretion c. To protect the patient
c. Their metabolites are more soluble in alkaline urine d. None of the above
d. Do not precipitate in neutral or acidic pH of urine
196. First-pass metabolism occurs in

a. Heart
b. Within 1 hour after administration of drug
c. Liver
d. Brain
1 91. d 192. c 193. d 194. b 195. c 196. c 197. c 198. b 199. a 200. a

Viva Questions
Dental Materials
1. Name the micro hardness test methods. 16. In which stage of annealing is the rapid decrease in tensile
Ans. Knoop hardness test and Vickers hardness test. strength and increase in ductility of a wrought metal seen?
Ans. Recrystallization stage.
2. Which hardness test uses a hardened steel indenting tool?
Ans. Brinell hardness test. 17. Brinnel hardness number of a dental gold alloy is directly
proportional to what?
3. Ear prosthesis and intraocular prosthesis are made from Ans. Tensile strength.
which material?
Ans. Silicone. 18. What is the ultimate tensile strength?
Ans. Ultimate tensile strength (breaking point) is the stress at
4. What is the Brinell hardness number (BHN) of pure gold? the point of fracture.
Ans. 25.
19. What is the property of the material which describes the
5. What is Knoop hardness number of heat cure acrylic resin? resistance to abrasion known as?
Ans. 25–30. Ans. Hardness.
6. Define stress. 20. What does modulus of elasticity mean?
Ans. Stress is defined as an internal force opposing an applied Ans. Rigidity or stiffness of the material is known as modulus
load. of elasticity.
7. Define strain. 21. Silver-plated dyes use an electrolytic bath of which material?
Ans. Strain is defined as a deformation resulting from an Ans. Silver cyanide.
applied load.
22. Which physical property can be used to estimate indirectly
8. Define proportional limit. the proportional limit of gold alloys?
Ans. The maximum stress that can be induced without Ans. Brinell hardness number.
permanent deformation is known as proportional limit. 23. What is the ductility of a material a measure of?
9. Define the modulus of elasticity. Ans. Grain elongation.
Ans. The stress/strain ratio within the proportional limit is 24. The ability of the base to resist occlusal forces and to support
known as modulus of elasticity. the restoration is affected by which strength?
10. How do you compute compressive stress? Ans. Compressive strength.
Ans. Compressive stress is computed by dividing the external 25. The wetting of an adherent surface by an adhesive is related
force by the area of the test specimen upon which the weight to which property of adherent?
rests. Ans. Surface energy of the adherent.
11. How is the greatest stress which may be produced in a mate- 26. Name the hardness number which does not depend on the
rial such that stress is directly proportional to the strain ductility of metal.
known as? Ans. Knoop hardness number (KHN).
Ans. The proportional limit.
27. When a solid gets wet completely what is the contact angle?
12. What do you call the point at which a stress of a material Ans. 0°.
exhibits a specific limited deviation?
28. What is the ability of an alloy to withstand mechanical
Ans. Yield strength.
stresses without permanent deformation known as?
13. Define flow. Ans. Elastic limit.
Ans. Flow of a material refers to continued change of the 29. Give an example of the most rigid materials.
material under a given load. Ans. Cast chrome-cobalt (Cr-Co) alloys.
Or
30. Contact angle should be ideally how many degrees for proper
Flow is the deformation under a small static load, even that wetting?
associated with its own mass. Ans. Zero degrees.
14. Which wire exhibits shape memory? 31. Which orthodontic wire shows shape memory?
Ans. Nitinol wire. Ans. NiTi wire.
15. Name the atomic bonds characterized by physical forces. 32. What is torsional force?
Ans. Van der Waals bonds. Ans. Shear force.
33. Name any dental impression material that shows most tear 50. How is the cleaning of base metal alloy done?
resistance. Ans. Sand blasting with aluminium oxide.
Ans. Polysulphide.
51. Among wrought alloy, cobalt–chrome alloys, palladium al-
34. Which layer of tooth has the highest modulus of elasticity? loys and partial denture casting gold in hardened condition,
Ans. Enamel. which will produce the most rigid restoration for framework
35. Why does a material behave in certain ways above and below of same dimension?
the proportional limit on a stress-strain curve? Ans. Cobalt–chrome alloys.
Ans. On a stress-strain curve, a material behaves in certain 52. Austenite is an alloy of iron and carbon with the iron in
ways above and below the proportional limit because above the which form?
proportional limit a material functions in a plastic manner and Ans. Gamma form.
below the proportional limit it behaves in an elastic manner.
53. What is the yield strength of Austenite (NiTi alloy)?
36. Name the substance which acts as a cross-linking agent in
Ans. 560 MPa.
polysulphides.
Ans. Lead dioxide. 54. Name few passivating metals.
37. Which substance is recommended as an adhesive to trays Ans. Cr, AI, Ti.
with polysulphides? 55. Which zone of flame is used for melting the metal alloys?
Ans. Styrene – acrylonitrile. Ans. Reducing zone. ‘Flame – The flame can be divided into
38. While constructing a custom tray to use with polysulphide four zones, and the portion of the flame that is used to heat
rubber impression material, why should the thickness of ma- the soldering assembly should be neutral or slightly reducing
terial be uniform? part, because this produces the most efficient burning process
Ans. To allow uniform shrinkage. and the most heat’.
39. How will be the dies resulting from impressions taken from 56. Name one of the most biocompatible materials in oral cavity.
partially set elastomers during mixing? Ans. Titanium.
Ans. Shorter and narrower.
57. Name a universal bonding agent.
40. Mixing with latex gloves can prolong the setting time of Ans. Methoxyethyl trimellitic acid (META).
which impression materials?
Ans. Silicones. 58. Which is the most biocompatible among the elastomeric
impression materials?
41. Name the substance which acts as accelerator in silicone elas-
Ans. Polysulphide.
tomers.
Ans. Stannous octoate. 59. How do the zinc oxide–eugenol impression pastes harden?
Ans. Chemical reaction. The chemical reaction consists of
42. Name the impression material routinely used for automixing
hydrolysis of zinc oxide, which reacts with eugenol to form
system.
zinc eugenolate, which is a chelate. Water is needed to initiate
Ans. Polyvinyl siloxane.
the reaction and it is also a by-product of the reaction. This
43. Most accurate reproduction of details can be obtained by reaction is also known as autocatalytic reaction.
which impression material?
Ans. Polysulphides. 60. Name the fourth state of matter.
Ans. Colloid.
44. Which elastomers are best suited for multiple pouring of casts?
Ans. Polyvinyl siloxanes. 61. Name a common electrolyte used for plating copper indirect
dies.
45. Crater-like depressions are formed on casts by immediate Ans. Acidic copper sulphate.
pouring of which impressions?
Ans. Additional silicones. 62. Wax pattern is ideally invested immediately to decrease the
dimensional changes caused by what?
46. What is sublimation?
Ans. Relaxation of the internal stresses.
Ans. The conversion of a solid directly to gas is known as
sublimation. 63. What is hysteresis in a hydrocolloid gel?
47. Name the most commonly used titanium alloy for dental and Ans. Temperature lag between gelation and liquefaction tem-
medical purposes. perature is known as hysteresis, e.g. agar-agar (reversible
Ans. Ti 6A14V. hydrocolloid impression material).
48. What is the composition of cobalt–chromium alloys? 64. The dental amalgam is most resistant to which type of stress?
Ans. 60% cobalt, 30% chromium, rest 10% is made up by Ans. Compressive stress.
nickel, molybdenum, iron and carbon.
65. What is the term given to the phenomenon of moisture ab-
49. Which titanium is most elastic? sorption by an alginate impression?
Ans. Nickel titanium. Ans. Imbibition.
66. How do the type I and type II zinc oxide impression pastes differ? 83. What is balanced stone?
Ans. Type I and type II zinc oxide impression pastes differ in Ans. Balanced stone is dental stone in which accelerators or
their hardness after setting. retarders have been added according to need.
67. Name the impression with the least dimensional change 84. What is the main ingredient in dental plaster?
upon disinfection. Ans. Calcium sulphate hemihydrate.
Ans. Addition polysilicone.
85. The pattern for the metallic framework of a removable partial
68. Name the type III dental gypsum. denture is fabricated from which type of wax?
Ans. Dental stone. Ans. Casting wax.
69. Name the best material for duplicating cast. 86. Give examples of mouth temperature waxes.
Ans. Agar-agar. Agar and alginate both are useful for duplicating Ans. IOWA wax, KORECTA wax no.4, H-L physiologic paste
casts or models, but the most popular is agar because it can be and ADAPTOL are examples of mouth temperature waxes.
used many times. These waxes are designed to flow at mouth temperature.
These are used in fluid wax technique of recording posterior
70. Why palladium is added to polyvinyl siloxane?
palatal seal.
Ans. It acts as a scavenger.
71. When do syneresis seen in a hydrocolloid gel? 87. Setting expansion is advantageous in which materials?
Ans. Syneresis is seen as water loss. Ans. Gypsum investment materials, because the investment
expands to compensate for the casting shrinkage.
72. Immediate pouring of impressions is most critical in which
impression material? 88. By using which wax the standard perforated tray for use with
Ans. Condensation polysilicone. alginate impression materials could be brought to a more
customized contour?
73. What is a die? Ans. Utility wax.
Ans. A die is the replica of a single tooth.
89. Name three main sources from which the base constituents of
74. What does green strength with reference to plaster mean? dental waxes come from.
Ans. The wet strength. Wet strength or green strength is the Ans. Vegetables, minerals and insects.
strength obtained when excess water than that required for
hydration of hemihydrate is left in the specimen. 90. How much should be the gap between true end of casting
ring and wax pattern?
75. Water of reaction needed to react completely with 100 g of calcium Ans. 1/4 inch.
sulphate hemihydrates to convert it to calcium sulphate dihydrate?
Ans. 18.6 mL. 91. What is the other name of boxing wax?
Ans. Carding wax.
76. Name the product obtained by calcining gypsum under
steam pressure at 120–130°C or by dehydrating gypsum in 92. Resistance to corrosion in a cobalt–chrome casting is due to
the presence of sodium succinate. presence of which element?
Ans. a-Hemihydrates. Ans. Chromium. Elements like aluminium, chromium and
titanium have high affinity for oxygen and they form protec-
77. Model plaster (white) used to cast study models before mix-
tive oxide film which prevents further oxidation and corro-
ing with water, is largely composed of what?
sion. This is called PASSIVATION.
Ans. (CaSO4)2. 1/2 H2O.
93. Gypsum-bonded investment should not be heated over how
78. What type of bowl is used for mixing plaster of Paris?
much temperature?
Ans. A plastic bowl.
Ans. 700oC. At a temperature above 700°C, there is decompo-
79. What is the main difference between the powders of dental sition of gypsum investment with release of sulphur dioxide.
plaster and dental stone? Sulphur dioxide reacts with silver and copper to form their
Ans. Dental plaster (b-hemihydrate) and dental stone sulphides and thus contaminates the casting.
(a-hemihydrate) differ in particle size, shape and porosity.
94. Which zone of the flame is used for melting alloy during
Crystals of b-hemihydrate are more irregular in shape and
casting?
porous than a-hemihydrate.
Ans. Reducing zone of the flame.
80. What is the other name of type III dental gypsum?
95. Which dental cement accelerates the formation of reparative
Ans. Class I stone or hydrocal.
dentin?
81. What are the water/powder ratios of dental stone and plaster? Ans. Calcium hydroxide.
Ans. 0.28 and 0.6, respectively.
96. Electralloy is an alloy of which metals?
82. What is soluble plaster? Ans. Gold and calcium. The electrolytic precipitate of gold is
Ans. Impression plaster containing potato starch is called alloyed with 0.1% calcium. Calcium increases the strength by
soluble plaster. dispersion strengthening.
General Pathology
1. What is apoptosis? 19. What is common in all forms of shock?
Ans. Apoptosis is a pathological process associated with Ans. Impaired tissue perfusion.
cellular death.
20. What is the average number of CD4 cells in body fluid?
2. Cellular swelling and fatty change are example of which type Ans. 800–1200/mm3.
of injury?
21. Name the cell which secretes maximum amount of antibodies.
Ans. Reversible injury.
Ans. Plasma cell.
3. Myocardial infarct is an example of which necrosis?
22. Name the components of innate immunity that are active
Ans. Coagulation necrosis.
against viral cells.
4. Coagulation necrosis cannot be seen in which cells? Ans. NK cells (natural killer cells).
Ans. Brain.
23. Which component of neoplasm determines its biological
5. Which cells are the predominant cells after 48 h of inflammation? behaviour?
Ans. Monocytes. Ans. The parenchyma.
6. Name the principal chemical mediator of immediate phase of 24. What are the malignant neoplasms which arise from mesen-
acute inflammation. chymal tissue known as?
Ans. Histamine. Ans. Sarcomas.
7. Name the chemical mediator responsible for platelet 25. What is the tumour which shows origin from more than one
aggregation? germ layers known as?
Ans. Serotonin. Ans. Teratoma.
8. What is the first vascular reaction in inflammation? 26. What is the tumour which is a malformation presenting as a
Ans. Vasodilation. disorganized mass arising from mature tissue indigenous to
the particular site known as?
9. How does the migration of leukocytes from intravascular to
Ans. Hamartoma.
extravascular compartment occur?
Ans. Enlargement of interendothelial junctions. 27. Nuclear cytoplasmic ratio in malignant cells approaches what
ratio?
10. What does diapedesis connote?
Ans. 1:1.
Ans. Exodus of neutrophils from vascular compartment.
28. Barr body is found in which phase of the cell cycle?
11. Repair of inflammatory process begins within how many
Ans. Interphase.
hours?
Ans. 24 h. 29. What do you call the differential expression of the same gene
depending on the parent of origin?
12. What is the strength of surgical scar dependent on? Ans. Genomic imprinting.
Ans. Type of collagen produced.
30. What is pyknosis?
13. What effect have glucocorticoids on healing of wounds? Ans. Disappearance of nuclear chromatin is called as pyknosis.
Ans. Glucocorticoids decrease the inflammatory response
and fibroplasia. 31. Name the procedure used as routine technique for karyotyping
using light microscopy.
14. What does the granulation tissue consist of? Ans. G-banding.
Ans. Plasma cells, capillary sprouts and lymphocytes.
32. Which bacteria are used for the microbiological assay of VitB12?
15. What do you call a small flat, circumscribed discolouration of Ans. Escherichia coli.
skin/mucosa?
Ans. Macule. 33. What is anorexia nervosa?
Ans. Self-induced starvation.
16. Which cells in the body have the least regenerative potential?
Ans. Nerve cells. 34. Xerophthalmia, keratomalacia and metaplasia of columnar
epithelium are complex manifestations due to deficiency of
17. Fibrin is degraded by which enzyme? which vitamin?
Ans. Plasmin. Ans. Deficiency of vitamin A.
18. What do you mean by anasarca? 35. Beriberi results from the deficiency of which vitamin?
Ans. Anasarca is severe generalized swelling. Ans. Vitamin B1.
36. By what name is extensive cellulitis also known as? 44. Undermining ulcer is a feature of which disease?
Ans. Phlegmon. Ans. Tuberculosis ulcer.
37. Name the best test to evaluate syphilis after treatment. 45. Which disinfectant is used for blood spills in hospitals?
Ans. VDRL. Ans. Sodium hypochlorite.
38. Negri bodies are pathognomic of which infection? 46. What is the characteristic histopathological feature of
Ans. Rabies. pemphigus vulgaris?
Ans. Acantholysis.
39. What is the incubation period of Hepatitis B?
Ans. 3 months. 47. What is the reason for the typical ‘crew cut’ appearance seen
in sickle cell anaemia?
40. Define thrombosis.
Ans. Expansion of marrow leads to resorption of bone with
Ans. Formation of clotted mass in wall of noninterrupted
apposition of new bone on the skull.
cardiovascular system is known as thrombosis.
48. What does bronchiectasis mean?
41. Where do the mural thrombi form?
Ans. Bronchiectasis means a dilatation of the bronchi (gener-
Ans. In the heart or aorta.
alized or localized).
42. If a patient presents with cotton wool X-ray appearance,
49. Name the commonly occurring bone tumours in children.
hypercementosis and enlargement of maxillary dental bases,
Ans. Osteosarcoma and Ewing sarcoma.
he or she may be suffering from which bone disease?
Ans. Paget disease. 50. The secretion of which endocrine glands is not essential to
life?
43. McCune–Albright syndrome is associated with which bone
Ans. Adrenal medulla.
disease?
Ans. Fibrous dysplasia.
Microbiology
1. Who first introduced the solid media? 21. What is the mechanism of genetic transfer where a phage
Ans. Robert Koch. serves as a vehicle?
Ans. Lysogeny. In lysogenic or phage conversion, the phage
2. Name few discoveries of Robert Koch.
‘DNA’ confers genetic information to a bacterium. This
Ans. Tuberculus bacilli and Vibrio cholerae.
may influence the antigenic characteristics and change the
3. Name few live vaccines. bacteria into toxigenic. Example: diphtheria bacilli.
Ans. BCG, Yellow fever vaccine and Mumps.
22. Name the diagnostic tests used for identifying fungal infections?
4. Zero growth rate is observed during which of the phases of Ans. Direct microscopic examination of tissue specimen,
the bacterial growth curve? culturing of the species and immunological tests.
Ans. Stationary phase.
23. Name few characteristics of exotoxins?
5. What do you call the bacteria with tuft of flagella at one end? Ans. These are produced in minute amounts, released from
Ans. Lophotrichate. bacterial cell wall and destroyed by proteolytic enzymes.
6. Bacteria reproduce mainly by which method? 24. Give an example of naturally acquired passive immunity?
Ans. Binary fission. Ans. Placental transfer of antibodies.
7. Which is the best sterilization method for a hand-piece? 25. Name the predominant immunoglobulin in saliva?
Ans. Ethylene oxide gas. Ans. IgA.
8. What is the minimum time required for the sterilization of 26. Name the Immunoglobulin crossing placenta?
surgical instruments by moist heat at 134°C? Ans. IgG. IgG is major serum immunoglobulin and consti-
Ans. 3 min. tutes 80% of the total. It has a half-life of 23 days.
9. Bacterial spores are destroyed by which method of sterilization? 27. Name a few cells that have phagocytic property.
Ans. Autoclave. Ans. Lymphocytes, monocytes and macrophages.
10. What is the difference between sterilization and disinfection? 28. Give an example of immune complex hypersensitivity
Ans. Sterilization kills all spores but disinfection does not. reaction.
Ans. Serum sickness and Arthus reaction. Both Arthus reac-
11. Blood agar is what type of media? tion and serum sickness are examples of immune complex
Ans. Enriched media. diseases or type III hypersensitivity reactions. Arthus reaction
12. Give an example of negative staining. is a local manifestation of generalized hypersensitivity, while
Ans. India ink preparation. serum sickness is a generalized reaction.
13. Which media can be used for cultivation of viruses? 29. Name the type of immediately occurring reaction in which
Ans. Animal inoculation, tissue culture and embryonated eggs. antigens combine with antibodies already attached to the
surface of mast cells and basophils.
14. Name the type of media generally used to show streptococcal Ans. Type I hypersensitivity.
haemolysis.
30. The anaphylaxis should be treated first with which drug?
Ans. Differential media.
Ans. Epinephrine.
15. Name an oral anaerobic organism that form black colonies
31. What do you call the localized type III immune reaction?
on haemin-containing culture media.
Ans. Arthus reaction.
Ans. Bacteroides melaninogenicus.
32. Name the immunoglobulin used in the preparation of caries
16. Anaerobic bacteria can be cultured best in which media?
vaccine for the prevention of dental caries.
Ans. Robertson cooked meat medium.
Ans. IgA.
17. What is the usual concentration of agar used in agar medium?
Ans. 2%. 33. Give an example of heterophile antigen-based test.
Ans. Widal’s test.
18. Dark ground microscopy is useful to identify which organisms?
Ans. Spirochaetes. 34. Name the type of immunological response in transplant
rejection.
19. What is the main difference between Gram-positive and Ans. Type IV.
Gram-negative bacteria?
Ans. The cell wall structure. 35. Who has given the term ‘animalcules’ to oral microorganisms?
Ans. Leuwenhoek.
20. Name the component that sensitizes bacteria and virus to UV
irradiation? 36. Name the virulence factors of Neisseria gonorrhoeae.
Ans. Nucleic acids. Ans. Outer membrane proteins, IgA protease and pili.
37. What is the cause of resistance of Staphylococcus aureus? 44. ‘Grape bunch’-shaped colonies are seen in which organisms?
Ans. Elaboration of an enzyme that destroys penicillin. Ans. Staphylococcus.
Penicillin resistance is due to production of beta-lactamase
45. Widal test is positive in which infections?
or penicillinase, which inactivates penicillin by splitting the
Ans. Salmonella infections.
beta-lactam ring.
46. ‘Blue pus’ is associated with which infections?
38. What are the various names of granules in the Corynebacte-
Ans. Pseudomonas infections.
rium diphtheriae?
Ans. Metachromatic granules, Babes–Ernst granules and 47. Name the most common opportunistic infection in AIDS.
volutin granules. Ans. The most common opportunistic infection in AIDS
is candidiasis. The other common opportunistic infections
39. Rapid diagnosis of tuberculosis is possible with which staining?
in AIDS are oral candidiasis, herpes zoster, hairy cell
Ans. Auramine-rhodamine stain.
leukoplakia, salmonellosis, tuberculosis and Pneumocystis
40. Which is the commonest mycobacterial infection in tropical carinii.
countries?
48. Who discovered bacteriophage?
Ans. Mycobacterium tuberculosis.
Ans. Twort and d’Herelle. Bacteriophages are viruses that
41. On a stained slide, Clostridium tetani has what type of infect bacteria. They play an important role in the transmis-
appearance? sion of genetic information between bacteria by the process
Ans. Drum stick. of transduction.
42. Name the causative organism for gas gangrene? 49. What do you call the DNA covering material in a virus?
Ans. Clostridium welchii. Ans. Capsid.
43. Wasserman test is diagnostic of which disease? 50. The first vaccination was produced against which disease?
Ans. Syphilis. Ans. Smallpox.
Pharmacology
1. What does the term ‘pharmacodynamics’ stand for? 20. Salbutamol is most commonly used in treating which condition?
Ans. Action of drug on the body. Ans. Bronchial asthma.
2. Which is the most appropriate route for the administration 21. Name a selective bronchodilator.
of highly irritant drugs? Ans. Salbutamol.
Ans. Intravenous route.
22. Which is the most efficient respiratory stimulant?
3. Which site is used for the ‘pessary’? Ans. Doxapram.
Ans. Vagina.
23. Name a drug used in the treatment of cough which possesses
4. Which site is used for the suppositories? expectorant property.
Ans. Anal canal. Ans. Guaiphenesin.
5. ‘Glucuronide conjugation reaction’ is catalysed by which enzyme? 24. Name a few antitussive agents for the treatment of dry cough.
Ans. Microsomal enzymes. Ans. Codeine, pholcodine and noscapine.
6. Name an antagonist that acts on both sympathetic and para- 25. Name a cell stabilizer which prevents acute asthmatic attack?
sympathetic ganglia. Ans. Cromolyn sodium.
Ans. Hexamethonium.
26. Name the drug of choice in management of a patient with
7. What is the effect of acetylcholine on heart? an acute allergic reaction involving bronchospasm and
Ans. Hyperpolarization of SA nodal cells. hypotension.
Ans. Epinephrine.
8. Which is the drug of choice for myasthenia gravis?
Ans. Neostigmine. 27. Why magnesium and aluminium are added in antacid?
Ans. Magnesium causes diarrhoea, aluminium causes consti-
9. Name the most popular anticholinergic used for peptic ulcer
pation.
and gastritis.
Ans. Propantheline. 28. Excess of which hormones may be associated with increased
sensitivity to epinephrine?
10. Atropine is contraindicated in a patient with which disease?
Ans. Thyroid hormone.
Ans. Narrow angle glaucoma.
29. List some actions of epinephrine when administered intrave-
11. What are the effects of aspirin?
nously in a high dose.
Ans. Frank gastric bleeding, prolonged prothrombin time
Ans. Epinephrine when administered intravenously in a high
and platelet dysfunction.
dose increases liver glycogenolysis and evokes extrasystoles in
12. Narcotic overdose can be antagonized by which drug? the heart and produces restlessness and anxiety.
Ans. Naloxane.
30. Name an oral hypoglycaemic agent.
13. Less gastrointestinal bleed is seen in which NSAID? Ans. Glibenclamide.
Ans. COX2-specific inhibitors.
31. What is the highest risk associated with the use of oral con-
14. Aspirin is avoided in children with influenza infection traceptives?
because of the association of which syndrome? Ans. Thromboembolic disorders.
Ans. Reye syndrome.
32. Which drug is used therapeutically during allergic condi-
15. Paracetamol is contraindicated in which liver disorder? tions?
Ans. Chronic hepatitis. Ans. Epinephrine.
16. What does the salicylate overdose in children cause? 33. What are the primary features that separate the various insu-
Ans. Rye syndrome. lin preparations useful in the treatment of diabetes mellitus?
Ans. Onset and duration of action.
17. What is the effect of aspirin used in the treatment of myocar-
dial infarction? 34. Bleeding from the oral mucosa can be reduced by topical use
Ans. Aspirin inhibits thromboxanes. of which drug?
Ans. Epinephrine.
18. b2-Adrenergic receptor stimulating drugs are used in which
disease? 35. Name a long-acting nondepolarizing neuromuscular block-
Ans. Bronchial asthma. ing agent?
Ans. Pancuronium.
19. Name a few drugs which are contraindicated in bronchial
asthma. 36. Name a muscle relaxant which is a directly acting agent.
Ans. Morphine, propanolol and atropine. Ans. Dantrolene sodium.
37. Which muscle relaxant is a depolarizing blocker? 56. What is the competitive antagonist at the benzodiazepine site?
Ans. Succinylcholine. Ans. Flumazenil.
38. What is the mechanism of action of D-tubocurarine? 57. What is the mechanism of action of ‘phenytoin’?
Ans. D-tubocurarine reduces the frequency of channel opening. Ans. Prolongation of sodium ion channel inactivation.
39. Which types of paralysis occur by the depolarizing neuro- 58. Name the drug of choice for petit mal seizures?
muscular blockade? Ans. Valproate.
Ans. Fasciculations and then flaccid.
59. What are the actions of cardiac glycosides?
40. What is the effect of neostigmine on depolarizing neuromus- Ans. They increase myocardial contractility. They increase
cular blockade? cardiac output but they do not increase O2 consumption.
Ans. Neostigmine has no effect on neuromuscular blockade.
60. What are the actions of digitalis?
41. Name a most commonly used muscle relaxant for passing Ans. Diastole is shortened and systole is prolonged. It also
tracheal tube? causes the sensitization of SA node to acetylcholine.
Ans. Succinylcholine.
61. What is the mechanism of action of digitalis?
42. What is chlorzoxazone? Ans. Inhibition of Na1 K1 ATPase enzyme.
Ans. Chlorzoxazone is a centrally acting muscle relaxant.
62. Name the drug of choice for congestive heart failure in emergency.
43. What are the advantages of amide-linked local anaesthetics Ans. Ouabain.
(LAs)?
63. Which voltage-sensitive calcium channel is responsible for
Ans. They are not hydrolysed by plasma esterases. They have
pacemaker activity of SA node?
few hypersensitivity reactions and they bind to acid glycopro-
Ans. T-type (transient type) voltage-sensitive calcium channel.
tein in plasma.
64. Which calcium channel blocker has no effect on calcium
44. When a local anaesthetic is applied to the tongue, in which
channel recovery rate?
order does the loss of taste sensation occur?
Ans. Nifedipine.
Ans. Bitter, sweet, sour, salty taste.
65. What are the advantages of calcium channel blockers as
45. Among the somatic afferents, what is the order of blockade?
antihypertensive drug?
Ans. Pain, temperature, touch, deep pressure.
Ans. Calcium channel blockers are safe in asthma and angina
46. Corneal and laryngeal reflexes are lost in which stage of gen- patients.
eral anaesthesia?
66. Where does the maximum sodium reabsorption occur?
Ans. Stage-III plane-2.
Ans. The maximum sodium reabsorption occurs at the prox-
47. How can we avoid diffusion hypoxia, which is one of the imal tubule.
main side effects of N2O inhalation?
67. Name a high efficacy diuretic.
Ans. Continuing 100% O2 inhalation.
Ans. Furosemide.
48. Name an inducing agent used in general anaesthesia.
68. Name the site of action of furosemide.
Ans. Methohexitone sodium.
Ans. Thick ascending loop of Henle.
49. What is N2O? 69. Name the diuretic of choice in chronic renal failure (CRF).
Ans. N2O is a good analgesic and poor muscle relaxant. Ans. Furosemide.
50. Name an anaesthetic agent that sensitizes the heart to adrenalin. 70. Why high ceiling diuretics and aminoglycoside antibiotics
Ans. Fluothane (halothane). should not be prescribed in combination?
51. What is neurolept anaesthesia? Ans. Due to risk of ototoxicity.
Ans. Neurolept anaesthesia is a combination of fentanyl and 71. Name the drug which is contraindicated in haemophilia.
droperidol. Ans. Aspirin.
52. Antiseptic action of ethyl alcohol is maximum at which 72. Which drugs are avoided with warfarin?
concentrations? Ans. NSAIDs.
Ans. 70–90%.
73. Name the drug of choice in the management of life threatening
53 Toxic effects of methanol are mainly due to what? allergic reaction.
Ans. Formic acid. Ans. Adrenalin.
54. Name a short-acting barbiturate? 74. What is the antidote for heparin?
Ans. Pentobarbitone. Ans. Protamine sulphate.
55. What action does benzodiazepines have? 75. What is triflusal?
Ans. GABA facilitatory action. Ans. An antiplatelet drug.
76. What is the anticoagulant action of heparin, apart from 89. To achieve synergism, the MIC of each antimicrobial agent
releasing lypoprotein lipase in the blood? should be reduced to what percentage?
Ans. Inhibiting thrombin synthesis. Ans. 25% or less.
77. Excessive bleeding due to heparin overdose is controlled by 90. All cells do not divide at the same rate. Events in which
which drug? phase of the cell cycle determine when a cell is going to
Ans. Protamine sulphate. replicate?
Ans. GI phase.
78. Name the anticoagulant of choice during pregnancy.
Ans. Heparin. 91. Which anticancer agent does not cause bone marrow depres-
sion?
79. What is the role of heparin?
Ans. Flutamide.
Ans. It prevents prothrombin conversion to thrombin.
92. Name a few anticancer drugs which causes pulmonary
80. Name a proton pump inhibitor.
fibroses.
Ans. Omeprazole.
Ans. Busulfan, methotrexate and bleomycin.
81. Give an example of ulcer healing drug.
93. Persistent neutropenia is seen with which anticancer agents?
Ans. Carbenoxolone sodium.
Ans. Methotrexate.
82. How many times is ranitidine more potent than cimetidine?
94. ‘Granisetron’, an anticancer drug, has antiemetic properties
Ans. Five times.
because of what?
83. Name a thiazole ring containing H2 blocker. Ans. Serotonin receptor blocking action.
Ans. Famotidine.
95. Name a histamine receptor associated with acid secretion.
84. What is the maintenance dose of ranitidine for ulcer healing? Ans. H2 receptor.
Ans. 150 mg.
96. What is the duration of action of cetirizine?
85. Name a few anti-Helicobacter pylori drugs. Ans. 12–14 h.
Ans. Metronidazole, clarithromycin and tinidazole.
97. What are the actions of captopril?
86. What is the mechanism of action of metronidazole? Ans. Captopril abolishes pressor action of angiotensin I, but
Ans. Metronidazole damages the DNA and interferes with it does not abolish pressor action of angiotensin II.
DNA function.
98. Which prostaglandin is especially a natural ulcer protective?
87. What is the mechanism of action of amphotericin B? Ans. PGI2.
Ans. It causes leakage from cell membranes
99. Theophylline primarily affects which part of the brain?
88. Name a few drugs obtained from actinomycetes. Ans. Cerebral cortex.
Ans. Aminoglycosides, tetracylines and polyenes.
100. Give an example of mast cell stabilizer.
Ans. Ketotifen.
Section VI
Previous Years’ Question Bank
Section I Dental Materials 633

Section II General Pathology 641
Section III Microbiology 649
Section IV Pharmacology 657
Section VI
Previous Years’ Question Bank
Section I
Dental Materials
4. Electrochemical corrosion. [RGUHS Aug 96, Maharashtra
1. INTRODUCTION AND OVERVIEW
May 02]
OF MATERIALS OF DENTAL APPLICATIONS 5. Corrosion. [RGUHS Sep 01, Sep 04, TN 03]
1. List of American National Standards Institute/American Dental 6. Galvanic corrosion. [RGUHS Apr 02]
Association specifications for dental materials, instruments and 7. Thermal expansion. [TN 03]
equipments. 8. Dimensions of colour. [NTRUHS Oct 04]
9. Diffusion. [NTRUHS Dec 12 (OR)]
2. STRUCTURE OF MATTER
AND PRINCIPLES OF ADHESION Short Notes
1. Stress corrosion. [RGUHS Apr 05]
Short Notes 2. Dry corrosion. [RGUHS Sep 02]
1 . Space lattice. [RGUHS Aug 93, Aug 96] 3. Creep and flow. [RGUHS Feb 96]
2. Thermal expansion. [RGUHS July 91] 4. Coefficient of thermal expansion. [RGUHS Apr 98]
3. Surface energy. [RGUHS Mar/Apr 00] 5. Creep. [RGUHS Apr 98, Sep 01]
4. Space lattice. [RGUHS Sep 97] 6. Surface hardness. [RGUHS Sep 99]
5. Surface tension. [RGUHS Sep 99] 7. Hue, chroma and value. [RGUHS Apr 01, 09]
6. Contact angle. [RGUHS Sep 99] 8. Hue, chroma, value. [RGUHS Apr 02]
7. Intra-atomic bonds. [TN 05] 9. Tarnish and corrosion. [RGUHS Jun 91, 92, 93, 08]
8. Surface tension. [TN 02] 10. Types of corrosion. [RGUHS Dec 93, Oct 94]
11. Electrolytic corrosion. [TN 00]
12. Corrosion. [TN 00]
3. PHYSICAL PROPERTIES OF DENTAL 13. Dimensions of color. [NTRUHS Dec 12 (OR)]
MATERIALS 14. Yield strength. [NTRUHS June 13 (OR), (NR)]
Long Essays
4. MECHANICAL PROPERTIES OF DENTAL
1. Describe tarnish and corrosion. Write in detail about its effects
on various materials. [RGUHS Oct 87, Feb 93, Aug 98] MATERIALS
2. What is tarnish and corrosion? Describe types of corrosion.
[RGUHS Jul 90]
Short Essays
3. Dimensions of colour. [TN 05] 1 . Hardness. [RGUHS Apr 01, Jul 08, NTR UHS Apr/May 04]
2. Ductility and its measurement. [TN 08]
3. Hardness tests. [TN 05]
Short Essays 4. Define stress and strain. Name types of stresses and strains.
1 . Types of corrosion. [RGUHS Apr 98, Mar 05] How are these two properties important in study of dental
2. Corrosion of oral appliances. [RGUHS Apr 01] materials and explain about creep and flow? [RGUHS
3. Corrosion and tarnish. [RGUHS Mar 92, Aug 93, Sep 99, Dec 92]
Maharashtra 02] 5. Stress and strain relation. [NTR UHS Oct 02]
633
Short Notes Short Essays

1. Stress and strain. [RGUHS Dec 91, Oct 94, Jun 94, Sep 05] 1 . Evaluation of toxicity of dental materials. [RGUHS Apr 02]
2. Compressive and tensile stress. [RGUHS Mar 92, Jun 94, 2. Sensitization and stabilization of stainless steel. [RGUHS
Aug 98] Sep 02, NTRUHS Aug 05]
3. Modulus of elasticity. [RGUHS Aug 93, Mar 00, Apr 01] 3. Biocompatibility of dental materials. [NTRUHS Aug 05]
4. Proportional limit. [RGUHS Dec 91, Jun 93, NTRUHS 4. Biocompatibility. [NTRUHS Dec 12 (OR)]
Dec 12 (OR)]
5. Ductility and malleability. [RGUHS Dec 91, Jun 93, Jun 94,
Mar 94, Mar 05] Short Notes
6. Hardness. [RGUHS Jun 93, Dec 96] 1 . Toxic effects of materials. [RGUHS Sep 00]
7. Resilience. [RGUHS Sep 97, Sep 00] 2. Resin teeth. [RGUHS Sep 00]
8. Elastic limit. [RGUHS Apr 00]
9. Hardness tests. [RGUHS 96, RGUHS RS Sep 04]
10. Name types of strength. Discuss importance of strength in 8. IMPRESSION MATERIALS
study of dental materials. [RGUHS Dec 93]
11. Elasticity. [TN 00] Long Essays
12. Surface hardness. [TN 00] 1. What are ideal requisites of an impression material? Describe
13. Strain hardening. [TN 03] in detail about alginates. [RGUHS Mar 94, Aug 96]
14. Fusion temperature. [NTR UHS Jun 08] 2. Explain in detail composition, properties and uses of revers-
15. Creep and flow. [NTRUHS June 13 (OR), (NR)] ible hydrocolloid impression material. [RGUHS Jul 90]
3. Classify impression materials. Write in detail the composi-
tion, manipulation and uses of impression compound.
5. DENTAL POLYMERS [RGUHS Sep 97]
Long Essays 4. Classify hydrocolloid impression materials. Describe the
composition and manipulation of reversible hydrocolloids.
1. Describe polymerization mechanisms. Add a note on stages in Mention briefly about wet field technique. [RGUHS Apr 98]
addition polymerization. [RGUHS Apr 01] 5. Classify impression materials. Write composition of irrevers-
ible hydrocolloid and role played by each component.
[RGUHS Jun 99]
Short Essays 6. Classify impression materials and write in detail about the
1 . Addition polymerization. [RGUHS Apr 96] composition, chemical reaction and properties of irreversible
2. Chemical stages in addition polymerization. [TN Aug 04 hydrocolloid impression materials. [RGUHS Sep 99]
Modified, 08] 7. Classify impression materials. Describe the composition, set-
ting reaction and the various precautions to be observed to
minimize the failures in the case of alginate hydrocolloid
Short Notes impression materials. [RGUHS Sep 00]
8. State the properties and uses of rubber-based materials.
1 . Adhesive bonding. [TN 03] [RGUHS Aug 91]
2. Copolymerization. [NTR UHS Jun 08] 9. Advantages and disadvantages of elastomeric impression
material. [RGUHS Apr 02]
10. Classify impression materials. Write in detail the composi-
6. SOLID SOLUTIONS PHASES IN CAST tion, manipulation and uses of impression compound.
ALLOYS [RGUHS Sep 05]
11. Classify impression materials. Write a note on various uses of
Short Notes zinc oxide eugenol paste. [RS Sep 04, RGUHS Jun 93, Oct 94]
1 . Eutectic. [RGUHS Mar 88, Feb 93] 12. Classify impression materials and write in detail about com-
2. Solid solution. [RGUHS Mar 94] position, manipulation and uses of zinc oxide eugenol impres-
3. Quenching. [RGUHS Sep 99] sion material. [RGUHS Sep 04, NTRUHS AP Oct 04]
4. Solute and solvent. [RGUHS Sep 00] 13. What is the composition of zinc oxide eugenol paste? Give
various uses of this material. [Maharashtra May 02]
14. Mention the desirable qualities of impression materials. Classify
7. BIOCOMPATIBILITY OF DENTAL the impression materials, write in detail about the composition
MATERIALS chemistry and manipulation of alginate impression material.
[TN 07]
Long Essays 15. Define and classify impression materials. Discuss in detail the
composition gelation process manipulation and properties of
1. Tests for evaluation of biocompatibility. [TN 07] agar agar. [TN Aug 04 Modified, 08]
Section | VI Previous Years’ Question Bank 635
1 6. What are elastomers? Write in detail about the types, com- 1 5. Zinc oxide eugenol paste. [RGUHS Dec 92, Mar 00]
position properties and manipulation of addition silicone 16. Noneugenol paste. [RGUHS Sep 02]
impression material. [TN 05] 17. Classify impressions material. Write a note on various uses of
1 7. Give the ideal requirements of impression materials and clas- zinc oxide eugenol paste. [RGUHS Jun 93]
sify the materials available. Add a note on zinc oxide eugenol 18. What is hysteresis? What is its importance? [Maharashtra Jul/
impression pastes. [TN 00] Aug 05]
1 8. Write in detail about composition, manipulation and disad- 19. Syneresis and imbibition. [RGUHS Jun 91, 94]
vantages of irreversible hydrocolloid impression materials. 20. Duplicating materials. [RGUHS Dec 93]
[NTRUHS Apr 03] 21. Causes of failure of alginate impression. [RGUHS Jun 04]
19. Classify impression materials and describe in detail about con- 22. Zinc oxide eugenol paste. [RGUHS Dec 92, Dec 02]
tents, setting and properties of silicone rubber base impression 23. Composition of alginate. [TN Aug 04 Modified 08]
materials. [NTRUHS Oct 02] 24. Polyether. [TN 05]
20. Discuss in detail the composition, setting reaction, properties and 25. Laminate technique. [TN 05]
uses of alginate impression materials. [NTRUHS Dec 12 (OR)] 26. Role of trisodium phosphate in alginate. [NTR UHS Apr/May 04]
2 1. Classify dental impression materials. Write the composition 27. Uses of agar agar. [NTR UHS Oct 02]
and setting mechanism of reversible hydrocolloids. [NTRUHS 28. Mention accelerator and retarder for ZOE paste. [NTR UHS
June 13 (OR), (NR)] Oct 02]
Short Essays 9. GYPSUM PRODUCTS

1. Imbibition and syneresis. [RGUHS Sep 99, NTR UHS Oct 04] Long Essays
2. Properties and applications of alginate impression material.
[RGUHS Sep 02, Apr 03] 1. What are various gypsum products used in dentistry? De-
3. Impression compound. [RGUHS Apr 98] scribe the composition manipulation and setting reaction of
4. Zinc oxide eugenol impression paste. [RGUHS Apr 00, dental stone [RGUHS Apr 87, Apr 03]
Maharashtra May 02] 2. Write in detail the setting reaction of dental plaster and indi-
5. Zinc oxide eugenol impression paste. [RGUHS Mar 05] cate various uses in dentistry. [RGUHS Jan 89]
6. Silicone impression materials. [RGUHS Sep 04] 3. Classify gypsum products and write in detail about the chemis-
7. What are nonaqueous elastomers and write any one of its try and properties of type II gypsum product. [RGUHS Mar 00]
composition. [Maharashtra May 04] 4. Classify gypsum product and write in detail about the chemis-
8. Properties, advantages and disadvantages. [TN 07] try and properties of type II gypsum product. [RGUHS Apr 00]
9. Ideal requirements of impression materials. [TN 03] 5. What are the types of gypsum products used in dentistry?
10. Polysulphides. [TN 03] Describe in detail about the setting reaction and the various
11. Elastomers. [RGUHS Jul 08] factors which affect the dimensional stability of dental stone.
12. Duplicating materials. [NTR UHS Oct 04] [RGUHS Apr 01]
13. Reline technique for elastomeric impressions. [NTR UHS 6. What are different methods of manufacturing gypsum prod-
Oct 04] ucts? Write the setting reaction of gypsum. Mention the uses
14. Addition silicone, rubber base impression. [NTR UHS Apr/ of gypsum products. [RGUHS Sep 02]
May 04] 7. Discuss plaster of Paris in detail. [RGUHS Mar 05]
15. Condensation silicone impression materials. [NTR UHS Jun 08] 8. Define calcination. What is the process of calcinations?
[Maharashtra May 02]
9. Identify the different gypsum products with reference to their
Short Notes properties and setting characters. [TN 03]
10. Normal and hygroscopic setting expansions. [TN 03]
1. Syneresis and imbibition. [RGUHS Feb 96, NTR UHS Oct 02]
11. Give composition and explain setting reactions, properties,
2. Wet field technique. [RGUHS Sep 94, NTR UHS Jun 08]
manipulation and uses of silicone impression materials. [TN 00]
3. Irreversible hydrocolloids. [RGUHS Mar 95]
12. Enumerate various gypsum products and write in detail about
4. Imbibition and syneresis. [RGUHS Sep 97]
manufacturing and standardization of dental plaster and
5. Viscoelasticity. [RGUHS Apr 99]
dental stone. [NTR UHS Apr/May 04]
6. Imbibition. [RGUHS Sep 99]
13. Classify gypsum products. Write the composition, setting
7. Modified alginates. [RGUHS Apr 01]
reaction of dental plaster and dental stone. [NTR UHS Jun 08]
8. Syneresis. [RGUHS Sep 01]
9. Laminate technique. [RGUHS Apr 02]
10. Rubber base impression material. [RGUHS Oct 87, Aug 88] Short Essays
11. Addition silicones. [RGUHS Apr 99]
12. Crosslinking. [RGUHS Sep 00] 1. High strength, high expansion dental stone (type V). [RGUHS
13. Advantages of elastomeric impression materials. [RGUHS Apr 98]
Apr 03] 2. Calcium sulphate hemihydrate. [RGUHS Apr 99]
14. Impression compound. [RGUHS Apr 87, Aug 93] 3. Setting expansion. [RGUHS Apr 00]
4. Dye stone. [RGUHS Apr 01, NTR UHS Oct 04] 3. Composition and properties of inlay casting wax. [RGUHS
5. Hygroscopic setting expansion. [RGUHS Sep 04, NTRUHS Sep 02]
June 13 (OR), (NR)] 4. Manipulation of inlay wax. [RGUHS Mar 05]
6. Types of gypsum products. [TN 07] 5. Base plate materials. [RGUHS Mar 05]
7. Accelerators and retarders. [TN 07] 6. Ideal requisition of inlay wax. [TN 07]
8. Dye materials. [TN Aug 04 Modified] 7. Impression waxes. [TN 08]
9. Terra alba. [TN 08] 8. Base plate wax. [TN 05, NTR UHS Oct 04]
10. Factors controlling the setting time of plaster. [TN 05]
11. Dye stones. [TN 00, NTR UHS Oct 02]
12. Accelerators and retarders for gypsum products. [NTR UHS Short Notes
Jun 08] 1 . Inlay wax. [RGUHS Oct 87, Apr 99, Sep 00]
2. Composition of inlay wax. [RGUHS Mar/Apr 00]
Short Notes 3. Name types of inlay wax and other waxes used in dentistry.
[RGUHS Dec 93]
1. Dental stone. [RGUHS Feb 93, Mar 94, Sep 00, NTRUHS 4. Baseplate wax. [RGUHS Jun 92]
Dec 12 (OR)] 5. Types of wax. [RGUHS Dec 93]
2. Measurement of setting time of dental plaster. [RGUHS Aug 6. Inlay wax [RGUHS Jun 93]
95, NTR UHS Apr 03] 7. Desirable properties of inlay wax. [Maharashtra 02]
3. Vicat needle. [RGUHS Mar/Aug 88] 8. Sticky wax. [RGUHS Jul 08]
4. Hygroscopic expansion. [RGUHS Jul 90, Jun 91, Mar/Sep 94]
5. Setting expansion. [RGUHS Mar 00]
6. Impression plaster. [RGUHS Jun 94/Apr 99] 11. CASTING INVESTMENTS
7. Dental plaster. [NTRUHS June 13 (OR), (NR)] AND PROCEDURES
8. Bite registration paste. [RGUHS Sep 00]
9. Noneugenol paste. [RGUHS Sep 00] Long Essays
10. List various gypsum products and write about methods of
testing setting time. [RGUHS Jun 93] 1. What are types of investments? Describe the composition,
11. Enumerate the methods of controlling setting time of gypsum properties and manipulation of gypsum-bonded investment.
products. [Maharashtra Jul/Aug 05] [RGUHS Oct 87]
12. Describe the various gypsum products used in dentistry. [TN 00] 2. Classify investment materials. Discuss the role of thermal
13. Hardness tests. [RS Sep 04] expansion. [RGUHS Aug 95]
14. Plaster of Paris. [RGUHS Jul 08] 3. Classify investment materials and write in detail about
15. Wet and dry strength. [NTR UHS Apr 03] gypsum-bonded investment material. [RGUHS Sep 01]
16. Divestment. [NTRUHS June 13 (OR), (NR)] 4. What are the ideal requirements of a dye material used in
dentistry? Which is the material of your choice and why?
[RGUHS Apr 99]
10. DENTAL WAXES 5. Write in detail about casting defects. [RGUHS Mar 05]
6. Factors affecting hygroscopic expansion. [TN Aug 04
Long Essays Modified, 08]
1. Describe the composition, properties and manipulation of 7. Classify gypsum products and explain how each one is manu-
inlay wax. [RGUHS Apr. 87] factured. Discuss the properties, composition and manipula-
2. Classify and give the composition of various types of wax used tion of gypsum bonded investment. [TN 05]
in dentistry. [RGUHS Aug 88, Jul 90, Feb 93] 8. Classify dental investment materials. Discuss the composition
3. What are the ideal requisites of inlay wax? Write composition of gypsum-bonded investment. [RGUHS Jun 92]
of inlay wax. Enumerate reasons of wax distortion and method 9. Enumerate common causes of casting failures and what pre-
to control the same. [RGUHS Aug 93, Jul 08] cautions you will take to avoid the same. [RGUHS Apr 87,
4. Mention the different waxes used in dentistry. Write in detail Maharastra May 02]
the composition desirable properties and manipulation of 10. Discuss various steps in casting procedure of an inlay and add
inlay waxes. [RGUHS Sep 97] a note on shrinkage porosity. [NTR UHS Oct 04]
5. Requirements of inlay wax. [TN 05]
6. Manipulation of inlay casting wax. [TN 02]
7. Mention the various types of dental waxes. Describe in detail
Short Essays
the ideal requirements, composition and properties of inlay 1. Mention ideal requirements of investment materials. [RGUHS
casting wax. [TN 03] Mar 05]
2. Back pressure porosity. [RGUHS Sep 99, Apr 02]
3. Casting shrinkage. [RGUHS Apr 00]
Short Essays 4. Ideal requisites of a dye material and mention different types of
1 . Inlay wax. [RGUHS Sep 99, Sep 04] dye materials. [RGUHS Apr 03]
2. Causes and prevention of wax distortion. [RGUHS Apr 02] 5. Types and uses of casting machines. [RGUHS Apr 03]
6. Phosphate-bonded investments. [TN 02, 03, RGUHS Jun 89, 3 . Classify dental burs. State their function. [RGUHS Mar 92]
Apr 98, Maharastra 02] 4. Classify dental burs according to composition. What is rake
7. Dye materials. [TN 00] angle and clearance angle. [Mangalore University Jun 91]
8. Gypsum-bonded investments. [RGUHS Mar 94, RGUHS R 5. What are different types of abrasives and polishing agents?
Sep 97, NTR UHS Apr 03, Dec 12 (OR)] [RGUHS Dec 91]
9. Investment materials. [RGUHS Jul 90, Aug 95]
1 0. Causes for defective castings. [RGUHS Sep 97]
1 1. Dye material. [RGUHS Apr 98] Short Essays
1 2. Hygroscopic expansion. [TN 08] 1. Abrasives and polishing agents. [Mangalore University Jun 91,
1 3. Thermal expansion investment materials. [TN 05] 92, Dec 93, NTRUHS June 13 (OR), (NR)]
1 4. Electroformed dyes. [TN 03] 2. Describe the action of abrasives and state the requirements of
1 5. Hygroscopic setting expansion of casting investment. [TN 01] abrasive materials. [TN 07]
1 6. Sprue former. [RGUHS Jul 08] 3. Define abrasive and polishing agents. Give examples of each.
1 7. Casting defects. [NTRUHS June 13 (OR), (NR)] [Maharastra May 02]
4. Rake angle. [TN 00]
5. Dental bur design. [TN 03, NTR UHS Jun 08]
Short Notes 6. Polishing of metals. [TN 02]
1. Sprue. [RGUHS Mar 95, Sep 97, Sep 01] 7. Rake angle. [RGUHS Sep 99]
2. Divestment. [RGUHS Mar/Apr 00]] 8. Bur materials. [RGUHS Jul 08]
3. Hygroscopic expansion. [RGUHS Sep 99]
4. Phosphate-bonded investment. [RGUHS Sep 00]
5. Back pressure porosity. [RGUHS Sep 99] Short Notes
6. Pickling. [RGUHS Sep 99, 02, RS Sep 04] 1. Dental bur. [RGUHS Jul 91, Sep 92, Aug 95, Mangalore
7. Casting defects. [RGUHS Sep 00] University Dec 93, Jun 94, NTRUHS June 13 (OR), (NR)]
8. Sprue former. [RGUHS Sep 00] 2. Abrasives in dentistry. [RGUHS Mar 92, 95]
9. Microporosity. [RGUHS Sep 01] 3. Dentifrice. [RGUHS Mar/Apr 00, RGUHS R Apr 01, NTR
10. Reservoir. [RGUHS Apr 02] UHS Jun 08]
11. Epoxy resin dyes. [RGUHS Apr 03] 4. Pumice. [RGUHS Sep 97]
12. Coefficient of thermal expansion. [RGUHS Apr 03] 5. Diamond abrasives. [RGUHS R Sep 99]
13. Suck back porosity. [RGUHS Sep 04] 6. Diamond points. [RGUHS R Sep 00]
14. Dye. [RGUHS Sep 04] 7. Bonded abrasives. [RGUHS Apr 02]
15. What are various casting defects? [RGUHS Aug 91] 8. Rouge. [RGUHS Sep 04, Mar 05]
16. Describe briefly technique of casting. [RGUHS Mar 88, Jan 89] 9. Pickling. [RGUHS Sep 04]
17. Electroformed dye. [TN 03] 10. Diamond. [NTR UHS Oct 04]
18. Types of investment materials. [RGUHS Dec 93]
19. Pickling. [RGUHS Oct 87]
20. Porosities in metal casting. [RGUHS Jun 91] 13. BONDING
21. Casting defects. [RGUHS Oct 94, Mar/Apr 00]
22. Dye materials. [RGUHS Aug 93] Short Essays
23. Back pressure porosity. [RGUHS Apr 98] 1. The mechanism of etching in acid etch technique. [RGUHS
24. Casting shrinkage. [RGUHS Apr 99] Sep 97]
25. Porosities in dental cutting. [RGUHS Sep 92, Feb 96] 2. Bonding agents. [RGUHS Sep 97, NTR UHS Jun 08, NTRUHS
26. Divestment. [RGUHS Aug 96] June 13 (OR), (NR)]
27. Casting ring liners and their functions. [TN 08] 3. Pit and fissure sealants. [RGUHS Apr 02, Sep 04]
28. Casting shrinkage. [RGUHS Jul 08] 4. Acid etch technique. [RGUHS Sep 04]
29. Types of casting machines. [NTRUHS Dec 12 (OR)] 5. Dentine bonding agents. [TN 00]
12. FINISHING AND POLISHING Short Notes

MATERIALS
1. Pit and fissure sealants. [RGUHS Oct 94, Apr 98, Sep 01, RS
Long Essays Sep 04]
2. Sandwich technique. [RGUHS Mar 05]
1. Enumerate materials and methods while polishing chromium– 3. Dentine bonding agents. [RGUHS Sep 04]
cobalt alloys. [RGUHS Jan 89] 4. Acid etch technique. [RGUHS Sep 02]
2. State various abrasives used in dentistry. [RGUHS Jan 89] 5. Etching. [NTRUHS Dec 12 (OR)]
14. RESTORATIVE RESINS 2. Classify dental cements. Write composition, properties and
uses of polycarboxylate cements. [RGUHS Mar92, 95, NTR
Long Essays UHS Jun 08]
3. Classify dental cements. Discuss glass ionomer cement.
1. Classify composite resin restorative materials. Describe compo-
[RGUHS Feb 93, Aug 96]
sition, properties and uses of same. [RGUHS Sep 92, Aug 95]
4. Classify dental cements. Discuss in detail the composition,
2. What are anterior restorative materials? Discuss in detail com-
properties and uses of glass ionomer cements. [RGUHS Sep
posite resins. [RGUHS Apr 87]
99, Apr 03, Jul 08]
3. Classify composite resins and write in detail about the various
5. Mention the types of glass ionomer cement. What is the com-
constituents of composite resin and add a note on uses of light-
position of glass ionomer cement? Add a note on mechanism
activated composite resin. [RGUHS Apr 00]
of adhesion of glass ionomer to the tooth. [RGUHS Sep 02]
4. Classify composite restorative materials and write detail about
6. Classify dental cements and write in detail about manipulation,
the various components of composite resins. Add a note on
composition and uses of glass ionomer cement. [RGUHS
posterior composite. [RGUHS Sep 00]
Sep 04, Maharastra 02, RGUHS Sep 04 RS]
5. Hybrid composite resins. [TN 01]
7. Give the composition and biological properties of glass iono-
6. What are composite resins? Describe in detail the composition,
mer and dentine. Add a note on the recent modifications of
setting restorative materials. [RGUHS Sep 04]
GIC. [TN 00]
7. Classify composite resins. Discuss advantages and uses of light
8. Classify dental cements. Write the composition, setting reactions
cure composite resin. [RGUHS Jun 93, TN 00]
and properties of zinc polycarboxylate cements. [NTRUHS
8. Classify composite resins. Write the composition, properties
June 13 (OR), (NR)]
and uses of hybrid composites. [NTRUHS Dec 12 (OR)]
Short Essays
Short Essays
1. Polycarboxylate cement. [RGUHS Apr 99]
1. Posterior composites. [RGUHS Apr 01] 2. Calcium hydroxide. [RGUHS Sep 99]
2. Hybrid composites. [RGUHS Sep 01] 3. Liners and bases. [RGUHS Apr 2k]
3. Fillers and their role in composite resins. [RGUHS Apr 03] 4. Glass ionomer cement. [RGUHS Apr01, NTR UHS Oct 04,
4. Classification and uses of composite resins. [RGUHS Sep 02] Dec 12 (OR)]
5. Pit and fissure sealants. [TN 07] 5. Cavity varnish. [RGUHS Sep 01]
6. Dual cured composites. [TN 08] 6. Resin-modified glass ionomer. [RGUHS Sep 01]
7. Uses of composite resins. [TN 02] 7. Recent advances in glass ionomers. [RGUHS Apr02]
8. Microfilled composites. [TN 00] 8. Composition and uses of glass ionomer cements. [RGUHS
9. Advantages of resin cements. [NTR UHS Oct 04] Sep 97]
10. Contents and their role in composite resins. [NTR UHS Apr 03] 9. Manipulation of zinc phosphate cement. [RGUHS Apr 00,
Maharastra 02]
10. Polycarboxylate cement. [RGUHS Sep 01]
Short Notes
11. Classification and composition of glass ionomer cement.
1. Composite resin. [RGUHS Mar 95] [RGUHS Mar 05]
2. Filler in composite resin. [RGUHS Jul 90] 12. Zinc polycarboxylate cement. [RGUHS Mar 05, TN 01, 07]
3. Visual light cure composite. [RGUHS Sep 94] 13. Luting cements. [RGUHS Mar 05]
4. Microfilled composite resins. [RGUHS Apr 99] 14. Cavity varnish, liner and base. [RGUHS Sep 04, NTR UHS
5. Photo initiators. [RGUHS Apr 00] Jun 08]
6. Hybrid composite. [RGUHS Apr 01] 15. Composition of zinc phosphate cement. [Maharastra 02]
7. Coupling agents in composite resins. [RGUHS Sep 01] 16. Cavity base. [TN 07]
8. Composition of composite resin. [RGUHS Mar 05] 17. Root canal sealants. [TN 07]
9. Particle size in composite resins. [RGUHS Oct 94] 18. Modified zinc oxide eugenol cement. [TN 08]
10. Light-activated composites. [RGUHS Jun/Oct 94] 19. Cavity liners. [TN 02]
11. Micirofilled vs. conventional composite resins. [TN 03] 20. Glass cermets. [TN 00]
12. Crosslinking agents and their role in acrylic resins. [Oct 04] 21. Gutta percha. [TN 00]
13. Mention purpose of acid etching. [NTR UHS Apr/May 04] 22. Calcium hydroxide. [TN 00, RGUHS Jul 08]
14. Name any two pit and fissure sealants. [NTR UHS Apr 03] 23. Zinc phosphate cement. [TN 00]
15. Pit and fissure sealants. [NTRUHS Dec 12 (OR)] 24. Cavity liners and bases. [NTRUHS June 13 (OR), (NR)]
15. DENTAL CEMENTS Short Notes

1 . Liners and bases. [RGUHS Mar 88, Aug 96, 00]
Long Essays
2. Polycarboxylate cement [RGUHS Jun 89, Jun 91, Aug 93,
1. Describe the composition, properties and manipulation of every May 94].
glass ionomer cement. [RGUHS Mar 88, Sep 92, 94, R Apr 03] 3. Properties of luting cements. [RGUHS Jul 90, Mar 92]
4. Uses of glass ionomer cement. [RGUHS Jul 91, Aug 95] 5. Stages of annealing. [RGUHS Apr 02]
5. Pulp protecting cements. [RGUHS Jul 91, Mar 92] 6. High copper silver amalgam. [RGUHS Sep 04, Mar 05,
6. Cavity varnish. [RGUHS Jul 91, Aug 93, Sep 00, TN 07, Maharastra 02]
NTRUHS Dec 12 (OR)] 7. Amalgam capsule. [TN 02]
7. Zinc phosphate cement. [RGUHS Sep 94] 8. Copper amalgam. [TN 02]
8. Calcium hydroxide cement. [RGUHS Mar 95, Aug 00] 9. Delayed expansion of amalgam. [TN 00]
9. Metal-modified GIC. [RGUHS Aug 96] 10. Eames technique. [TN 00, 07]
1 0. Zinc oxide eugenol cement. [RGUHS Aug 95] 11. Admixed amalgam alloys. [NTR UHS Oct 04]
1 1. Manipulation of zinc phosphate cement. [RGUHS Mar 00] 12. Types of silver alloys. [NTRUHS Dec 12 (OR)]
1 2. Cavity liners. [RGUHS Jun 91, 93, Dec 91, Sep 97] 13. Toxicity tests. [NTRUHS June 13 (OR), (NR)]
1 3. Calcium hydroxide. [RGUHS Apr 98, Mar 05] 14. Factors affecting success of amalgam restorations. [NTRUHS
1 4. Uses of polycarboxylate cement. [RGUHS Apr 98] June 13 (OR), (NR)]
1 5. Composition of glass ionomer cement. [RGUHS Apr 98,
Maharastra 02]
1 6. Cement. [RGUHS Sep 99] Short Notes
1 7. Uses of calcium hydroxide. [RGUHS Apr 00] 1. High copper alloy. [RGUHS Apr 87, Apr 99, Mar 00]
1 8. Intermediate restorative materials. [RGUHS Sep 00] 2. Alloy composition of amalgam. [RGUHS Mar 94: 9S]
1 9. Sandwich technique. [RGUHS Apr 02, Apr 03, NTRUHS 3. Delayed expansion. [RGUHS Jun 92, Sep 94, NTR UHS Jun 08]
Dec 12 (OR)] 4. Creep in amalgam. [RGUHS Aug 96, NTR UHS Jun 08]
2 0. Metal-modified glass ionomer cement. [RGUHS Oct 94] 5. Admixed alloy. [RGUHS Mar 94, 95]
2 1. Biological property of silicate cement. [RGUHS Oct 94] 6. Delayed expansion of amalgam. [RGUHS Sep 99]
2 2. Advantages and disadvantages of zinc polycarboxylate ce 7. Eames technique. [RGUHS Sep 99]
ments. [TN 03] 8. Percolation. [RGUHS Apr 01]
9. Amalgam bond. [RGUHS Apr 0l]
10. Gamma-2 phase in silver amalgam. [RGUHS Apr 03, Mar 05]
16. DENTAL AMALGAM 11. Creep in amalgam. [RGUHS Sep 04]
Long Essays 12. Trituration. [RGUHS Sep 04]
13. Discuss advantages of high copper amalgam. [RGUHS Dec 93,
1. Discuss type, physical properties and uses of dental amalgam Oct 94]
alloys. Add a note on high copper alloys. [RGUHS Jun 89, 14. Mercury: alloy ratio. [RGUHS Jun 93]
Aug 93] 15. Setting reaction of dental amalgam. [TN 05]
2. Discuss in detail properties of various dental amalgams. 16. Mercury health hazards. [TN 03]
[RGUHS Aug 91] 17. Mercury toxicity. [TN 08]
3. State various merits and demerits of dental amalgams. [RGUHS 18. Tarnish. [NTRUHS June 13 (OR), (NR)]
Mar 92]
4. Give the composition of dental amalgam alloys and write in
detail about the manipulation and properties of high copper 17. DIRECT FILLING GOLD
dental amalgam. [RGUHS Sep 99]
5. Define an alloy. Give the composition of dental amalgam alloy. Long Essays
Write the various stages of manipulation of amalgam alloy. 1. In what forms are gold used in dentistry? Describe in detail the
[RGUHS Apr 02] various types of direct filling gold available. Briefly mention
6. What is an amalgam? Describe the composition of various sil- degassing techniques. [RGUHS Apr 98]
ver amalgam alloys used for restorations and also describe the 2. Classify direct filling gold and explain its physical properties,
manipulation of the alloy for a restoration. [TN 00] manipulation and advantages. [TN Aug 04 Modified, 08]
7. Write in detail about definition, classification, composition,
manipulation, advantages, disadvantages and uses of dental
amalgam. [TN 07] Short Essays
8. Write in brief about the setting reaction of both low and high
1 . Cohesive and noncohesive gold. [RGUHS Sep 99]
copper amalgam alloy. What are the phases formed during the
2. Types of gold alloy. [RGUHS Sep 99]
reaction with a note on factors effecting its strength? [TN 08]
3. Mat gold. [RGUHS Sep 01]
9. Classify silver amalgam alloys. Give the composition and role
4. Stages of annealing. [TN Aug 04 Modified, 08]
of each constituent of silver alloy. [Maharastra 02]
Short Essays Short Notes

1 . Cohesive and noncohesive gold. [RGUHS Mar/Apr 00]
1 . Trituration of dental amalgam. [RGUHS Sep 97]
2. Gold foil. [RGUHS Sep 00]
2. Spherical amalgam alloy. [RGUHS Apr 98]
3. Degassing. [RGUHS Apr 02]
3. Trituration. [RGUHS Sep 99, TN 03]
4. Mat gold, electrolytic gold. [RGUHS Jun 89, NTR UHS Oct 04]
4. High copper alloy. [RGUHS Apr 00]
5 . Gold foil. [RGUHS Sep 92, TN 07] 1 2. Composition of porcelain. [RGUHS Sep 02, Mar 05]
6. Karat and fineness. [TN 08, NTRUHS Dec 12 (OR)] 13. Firing of porcelain. [RGUHS Dec 91]
7. Zones of flame. [NTRUHS Dec 12 (OR)] 14. State three requirements of metal ceramic alloys. [Maharastra
8. Forms of direct filling gold. [NTRUHS June 13 (OR), (NR)] Jul/Aug 05]
15. Classify dental ceramics and write in detail about metal
ceramic restorations. [TN 03]
18. DENTAL CERAMICS
Long Essays 19. DENTURE BASE RESINS
1. Define dental porcelains. Describe in detail the composition
and manipulation of dental porcelain. [RGUHS Sep 92, Jun 94]
Long Essays
2. Classify dental casting alloys. Describe about mechanical prop- 1. What are denture base resins? Describe properties and ma-
erties and add note on dental ceramics. [RGUHS Apr/Sep 01] nipulation technique of heat cure acrylic denture base resin.
3. Classify dental porcelains. Describe the methods of condensa- [RGUHS Mar/Aug 88, 96, Maharastra 02]
tion and firing procedures. [RGUHS Oct 87, Jun 89] 2. Name various denture base materials. Discuss in detail physi-
4. Discuss the composition, types, physical properties, manipu- cal and chemical phases of acrylic resin. [RGUHS Feb 96]
lation, advantages and disadvantages of dental porcelains. 3. Write in detail the composition and the properties of denture
[TN 05] base resins and add a note on light-activated denture base
5. What are metal ceramic restorations? What are ideal require- resins. [RGUHS Sep 01]
ments for meta ceramic restorations? Mention its composition. 4. What are soft-liners? Write the composition, properties and
[RGUHS Jan 91, Dec 92, 93] uses of tissue conditioners. [RGUHS Apr 02]
5. Classify denture base resins. Write the composition and action
of each constituent of heat-cure acrylic. Add a note on porosity
Short Essays and its causes in dental acrylic resins. [RGUHS Apr 03,
1. Dental porcelain. [TN 07] Maharastra 06]
2. Requirements of metal ceramic alloys. [TN 08] 6. Classify the denture base materials. Give the ideal properties
3. Aluminous porcelain and its advantages. [TN 01] of denture base resins. What care will you take to avoid the
4. Firing of porcelain in jacket crown. [TN 00] processing defects of acrylic resin material? [Maharastra 02]
5. Aluminous porcelain. [RGUHS Apr 99] 7. Mention the composition and the role of each ingredient of
6. Classification and uses of dental porcelain. [RGUHS Apr 03] heat-cure denture base resins. Describe its properties. [TN 08]
7. Chrome–cobalt alloy. [TN 08] 8. Describe the ideal requirements of denture base materials.
8. Benefits and drawbacks of metal ceramics. [TN 08] Explain the chemical stages of polymerization and the curing
9. Dicor. [TN 05] cycles of heat-cure acrylics. [TN 03]
10. Objects of alloying. [TN 05] 9. What are the ideal requirements of denture base materials?
11. Metal ceramics. [TN 03] Describe the composition and setting of base acrylic resins.
12. Benefits and drawbacks of metal ceramics. [TN Aug 04 [TN 01]
Modified] 10. Define porosity and the causes of porosity while using poly-
13. Properties desirable in metal ceramic alloys. [NTR UHS methyl methacrylate acrylic resin and the methods to prevent
Oct 04] the same. [TN 02]
14. Baking stages in dental porcelain. [NTR UHS Oct 04]
15. Composition of restorative porcelain. [NTR UHS Jun 08]
16. Castable ceramics. [NTRUHS Dec 12 (OR)]
Short Essays
17. Methods of strengthening ceramics. [NTRUHS June 13 (OR), 1. Resilient denture liners. [RGUHS Apr 98, TN 00]
(NR)] 2. Tissue conditioners. [RGUHS Sep 99, TN 05]
3. Separating media. [RGUHS Sep 99, TN 07]
4. Denture relining materials. [RGUHS Apr 01]
Short Notes 5. Curing. [TN Aug 04 Modified, 08]
1. Aluminous porcelain. [RGUHS Apr 87, Feb 93, Jun 94] 6. Requirements of denture base resin. [TN 05]
2. Condensation and firing of porcelains. [RGUHS Jan 89] 7. Porosity in acrylic resin. [TN 03, NTR UHS Oct 02]
3. Ceramic crown. [RGUHS Mar 94] 8. Curing cycle of denture base resin. [RGUHS Mar 05, NTR
4. Glazing. [RGUHS Mar 94] UHS Apr 03]
5. Castable ceramics. [RGUHS Apr 98, Mar 00] 9. Name various denture base materials. Discuss the causes of
6. Role of feldspar in porcelain. [RGUHS Sep 02] porosity in acrylic resin. [RGUHS Dec 91, Jun 94]
7. Dicor. [RGUHS Apr 00] 10. Self-cure acrylic resin. [NTR UHS Apr/May 04]
8. Types of glazes used in dental porcelain. [RGUHS Sep 01] 11. Heat-cure acrylic resin. [NTR UHS Jun 08]
9. Uses of glazing in dental porcelain. [RGUHS Apr 02] 12. Soft liners for dentures. [NTR UHS Apr 03]
10. Advantages of castable ceramics. [RGUHS Apr 03] 13. Autopolymerizing acrylic resins. [NTR UHS Oct 02]
11. Platinized foil. [RGUHS Sep 02] 14. Physical stages of polymerization. [NTRUHS Dec 12 (OR)]
Short Notes 1 5. Crazing in acrylic resin. [NTR UHS Apr 03]

16. Physical stages in mixing of heat-cure acrylic resins. [NTR
1. Condensation polymerization. [RGUHS Jun 89] UHS Oct 02]
2. Chemical stages in polymerization. [RGUHS Mar 95] 17. Soft liners. [NTRUHS June 13 (OR), (NR)]
3. Cold-cure acrylic. [RGUHS Apr 87] 18. Internal porosity of denture base. [RGUHS Aug 06]
4. Autopolymerizing resin. [RGUHS Mar 94]
5. Light-activated denture base resin. [RGUHS Mar 94]
6. Porosity in denture base. [RGUHS Mar 88, Aug 95, NTR 20. DENTAL IMPLANTS
UHS Jun 08]
7. Denture cleansers. [RGUHS Sep 00] Short Essays
8. Tissue conditioners. [RGUHS Apr 01] 1 . Acid etch technique. [RGUHS Sep 99]
9. Denture reliners. [RGUHS Mar 05] 2. Dental implants material. [RGUHS Mar 05]
10. What is the copolymerization? Name its advantages. [RGUHS
Dec 92]
11. Porosity in denture. [RGUHS Jun 94] Short Notes
12. Relining denture bases. [RGUHS Dec 91]
13. Explain various curing cycles for acrylic resins. [Maharastra 1 . Implant materials. [TN 01, 03, NTRUHS June 13 (OR), (NR)]
Jul/Aug 05] 2. Types of implants. [RGUHS Sep 09]
14. Purpose of soft liners. [NTR UHS Apr/May 04] 3. b titanium alloy. [NTR UHS Jun 08]
Section II
General Pathology
1. CELL INJURY, CELL DEATH 7. Wear and tear pigment. [NTR-NR Oct 04]
8. What is fatty liver? What are the causes? [NTR-NR Apr 03]
AND ADAPTATIONS
9. Describe pathogenesis and pathology in fatty changes.
Long Essays [RGUHS Sep 02]
10. Hypertrophy. [RGUHS Apr 00]
1. Define necrosis. Write different types of necrosis, give exam- 11. Metaplasia. What is it? Give examples. [NTR-NR Oct 02]
ples. [NTR-NR Apr 00] 12. Hypertrophy. Define and give examples. [NTR-NR Apr 03]
2. Classify necrosis and discuss nuclear changes. [BUHS Mar 95] 13. Define hyperplasia and give examples. [RGUHS Mar/Aug 05]
3. Define and classify gangrene. Write about diagnosis and man- 14. Hemosiderosis. [RGUHS Aug 06, TN Oct 99 Revised]
agement of wet gangrene. [BUHS Mar 92]
4. Define gangrene. Give an account of different varieties of
gangrenes with examples. [BUHS Mar 88] Short Notes
5. Mention types of degeneration. Discuss pathogenesis and
1. Apoptosis. [NTR-OR Apr 97]
macroscopic appearance of fatty liver. [RGUHS Aug 96]
2. Gangrene. [NTR-OR Oct 97, R Apr 99, NTR-NR Oct 02, Oct 03]
6. Define necrosis. Classify and discuss about different types of
3. Gas gangrene. [NTR-OR Apr 90]
necrosis. [TN Oct 96 New regulation]
4. Types of gangrene. [NTR-OR Apr 94]
7. Define and classify degeneration. Discuss the aetiopathogenesis
5. Pathological calcification. [NTR-NR Oct 04]
and pathology of fatty liver. [NTR-NR Oct 04]
6. Dystrophic calcification. [NTR-OR Oct 97, Apr 00, NTR-NR
8. Mention the type of degeneration. Discuss pathogenesis and
Apr 01, Apr 04, TN Apr 96, Feb 09 Modified, Apr 00, Oct 00
microscopic appearance of fatty liver. [BUHS Aug 96]
Modified]
7. Dystrophic and metastatic calcification. [NTR-NR Apr
Short Essays 03, Aug 92, 95, Sep 06, TN Apr 99 Revised regulations,
Modified]
1 . Characteristics of dry gangrene. [NTR-NR Oct 05] 8. Hyaline change. [NTR-OR Apr 89]
2. Types of necrosis with examples. [NTR-NR Oct 04] 9. Hyaline calcification. [NTR-OR Jun 87]
3. Dry gangrene. [RGUHS Aug 06] 10. Definition and types of necrosis. [NTR-OR Oct 93]
4. Coagulative necrosis. [BUHS Sep 94] 11. Types of necrosis with examples. [NTR-OR Jun 87]
5. Lab diagnosis and prophylaxis of gas gangrene. [BUHS Sep 97] 12. Aetiology of cell injury. [NTR-OR Oct 92]
6. What is dystrophic calcification? Give two examples. [RGUHS 13. Free radical injury. [NTR-OR Jan 92]
Aug 05] 14. Reversible cell injury. [NTR-OR Apr 89]
15. Define and classify gangrene with examples. [RGUHS Sep 02, 12. Define inflammation. Classify chemical mediators of acute
Sep 04] inflammation and discuss their role briefly. [TN Oct 99
16. Enumerate the types of necrosis and define the coagulative Revised]
necrosis. [RGUHS Mar 06] 13. Describe briefly serological diagnosis of syphilis. [NTR-OR
17. Fatty degeneration. [RGUHS Apr 99] Apr 00]
18. What is pathologic calcification? Classify the same giving 14. Define granuloma. What are the causes and pathology of
examples. [RGUHS Mar 04] granuloma? [NTR-NR Oct 02]
19. Calcification. [RGUHS Mar 87, Feb 91] 15. Write briefly on cervicofacial actinomycosis. [BUHS Apr 94,
20. Enumerate the types of necrosis giving examples. [RGUHS RGUHS Apr]
Mar 04] 16. Define and classify granuloma. Describe the aetiopathogenesis
21. Coagulative necrosis. [RGUHS Sep 94] and pathology of tuberculosis. [BUHS Apr 87, Jun 89, RGUHS
22. Define and classify gangrene. [RGUHS Sep 04] Apr 87, Jun 89, Mar 92]
23. Necrosis. [TN Aug 08 Modified, Feb 09 Modified] 17. Write briefly about aetiopathogenesis of tuberculosis. Describe
24. Dry gangrene. [TN Feb 07 Modified] the complications of secondary pulmonary tuberculosis.
25. Hyperplasia. [TN Feb 06 Modified] [BUHS Sep 98, RGUHS Sep 98]
26. Hypertrophy and hyperplasia. [TN Apr 99 Revised regulations] 18. What is a granuloma? List common examples of a granuloma,
27. Lipofusion. [NTR-OR Apr 94] describe the pathogenesis and effects of any one. [TN Oct 98
28. Fatty liver. [NTR-OR Oct 98, Aug 01, TN Aug 06 Modified] New revised]
29. Melanin pigment. [NTR-OR Apr 94]
30. Exogenous pigment. [NTR-OR Oct 91]
31. Microscopy of fatty liver. [NTR-NR Apr 05] Short Essays
32. Aetiology of fatty liver. [RGUHS Mar/Sep 04] 1. Phagocytosis—recognition, engulfment and degradation.
33. Fatty degeneration. [RGUHS Apr 99] [RGUHS Mar 04]
34. Fatty change. [TN Aug 08 Modified] 2. Classify and discuss chemical mediators of acute inflamma-
35. Causes of ischemia. [NRT-NR Apr 02] tion. [RGUHS Sep 04]
36. Atrophy. [NTR-OR Apr 84, Oct 98] 3. Chemotaxis. [NTR-NR Oct 04, BUHS Feb 96, RGUHS Sep 02,
37. Metaplasia. [NTR-OR Jul 90, Oct 92] Sep 04, Mar 05]
38. Hyperplasia. [NTR-OR Jan 89, TN Aug 06 Modified, Oct 96 4. Phagocytosis. [NTR-NR Oct 02, BUHS Mar 95]
Old regulation] 5. Chemical mediators of inflammation. [NTR-NR Oct 03]
39. Hypertrophy. [NTR-OR Jul 89, RGUHS Apr 00] 6. Inflammation. [BUHS Mar 92]
40. Define metaplasia giving examples. [RGUHS Mar 04] 7. Cardinal signs of inflammation. [RGUHS Mar 03]
41. Antioxidants. [NTR-OR Oct 88] 8. Discuss the vascular and cellular events of inflammation. [TN
Feb 07 Modified]
9. Classify leprosy. Describe the pathology of tuberculoid leprosy.
2. ACUTE AND CHRONIC [TN Aug 06 Modified]
INFLAMMATION 10. Oral lesions of syphilis. [BUHS Mar 94]
11. What is Ghon’s complex? Mention the lab diagnosis of tuber-
Long Essays culosis. [RGUHS Mar/Sep 04]
1. Describe briefly the vascular phenomenon of inflammation.
[NTR-OR Jan 89]
2. Define inflammation. Describe the various vascular changes Short Notes
of inflammation. [NTR-NR Feb 01] 1. Chemotaxis. [NTR-OR Jun 87, Jan 92, RGUHS Feb 96, Sep 99,
3. Define inflammation. What are the cardinal signs of inflam- Sep 02, TN Apr 96 Regulation, Aug 08 Modified]
mation? [NTR-OR Apr 98] 2. Phagocytosis. [NTR-OR Jan 88, Apr 99, NTR-NR Mar 95,
4. Define inflammation. Discuss cellular events in acute inflam- Oct 05, TN Aug 05 Modified]
mation. [NTR-NR Apr 04] 3. Lymphokines. [NTR-OR Jan 92]
5. Define inflammation and discuss about different cellular 4. Varieties of inflammation. [NTR-OR Oct 97]
events in acute inflammation. [BUHS Aug 93] 5. Signs of inflammation. [NTR-OR Apr 85]
6. Define inflammation and discuss the role of chemical media- 6. Vascular phenomenon in inflammation. [NTR-OR Oct 89,
tors in the process of the inflammation. [RGUHS Apr 99] Apr 93]
7. Define inflammation and discuss about different cellular 7. Chemical mediators of acute inflammation. [RGUHS Mar 04]
events. [RGUHS Aug 93, Mar 97] 8. Mention the role of histamine in inflammation. [RGUHS
8. Describe vascular changes in inflammation. [RGUHS Mar 94] Mar 06]
9. Define inflammation and discuss the role of chemical media- 9. Difference between transudate and exudates. [RGUHS Aug 93]
tors in the process of inflammation. [RGUHS Apr 99] 10. Exudate. [RGUHS Aug 96]
10. What are types of exudation? Describe the sequelae of pyo- 11. Gumma. [NTR-OR Apr 96, RGUHS Sep 98, Apr 99, Sep 02]
genic abscess. [RGUHS Oct 87, Jan 89] 12. Granuloma. [NTR-OR Apr 97, Feb 01, NTR-NR Apr 04,
11. Define inflammation. What are the chemical mediators? Write RGUHS Aug 95, TN Apr 98 Old Revised]
in detail about the role of chemical mediators in inflamma- 13. Morphology of granuloma. [NTR-NR Mar 05]
tion. [TN Feb 05 Modified] 14. Granulomatous inflammation. [NTR-OR Oct 90]
1 5. Actinomycosis. [NTR-OR Apr 99, Apr 00, NTR-NR Apr 03, 3 . Factors delaying wound healing. [RGUHS Mar 06]
Apr 06, TN Feb 05 Modified] 4. Gangrene. [NTRUHS Dec 12 (NR & OR)]
1 6. Primary complex. [NTR-OR Oct 98, Apr 99, Apr 00, TN
Oct 00 Modified, Apr 98 Old Revised]
1 7. Congenital syphilis. [NTR-NR Apr 04, TN Oct 00 Revised Short Notes
regulations] 1. Fracture healing. [NTR-OR Oct 98]
1 8. Lepromatous leprosy. [NTR-NR Oct 03, TN Aug 08 Modi- 2. Granulation tissue. [NTR-OR Oct 96, TN Oct 00 Revised
fied, Oct 98 New/Old revised] regulations]
1 9. Pathological lesions of syphilis. [NTR-OR Jun 87] 3. Healing of oral structures. [NTR-NR Aug 01]
2 0. Chronic granulomatous inflammation. [RGUHS Aug 05] 4. Factors influencing wound healing. [NTR-NR Sep 94,
2 1. Ghon’s complex. [RGUHS Apr 99] Apr 06]
2 2. What is tuberculoid granuloma? Give three examples. 5. Healing by second intention. [NTR-NR Apr 04, TN Oct 99
[RGUHS Mar 04] Modified]
2 3. Cellular events in acute inflammation. [TN Feb 08 Modified] 6. Sequential stages in wound healing by first intention. [NTR-
2 4. Primary tuberculosis. [TN Feb 06 Modified] NR Oct 05]
2 5. Oral manifestations of syphilis. [TN Apr 00 Modified] 7. Wound healing by first intention. [TN Feb 06 Modified]
2 6. Chronic inflammation. [TN Apr 99 Revised regulations] 8. Healing of wound by primary intention. [TN Apr 98 Old
2 7. Tuberculoid type of leprosy. [TN Apr 99 Modified] revised]
2 8. Microscopy of tubercle. [NTR-NR Oct 05] 9. Primary union. [TN Oct 96 Old regulation]
2 9. Chancre. [RGUHS Apr 03] 10. Pathologic calcification. [NTRUHS June 13 (NR & OR)]
3 0. Giant cells. [RGUHS Apr 03]
3 1. Lepra reaction. [RGUHS Apr 03]
3 2. Mention cell derived chemical mediators of acute inflamma- 4. HAEMODYNAMIC DISORDERS,
tion. [NTRUHS June 13 (NR & OR)] THROMBOSIS AND SHOCK
Long Essays
3. TISSUE REPAIR: REGENERATION,
HEALING AND FIBROSIS 1. Describe aetiopathogenesis of oedema. [NTR-OR Apr 97]
2. Discuss aetiopathogenesis of nutritional oedema. [NTR-OR
Long Essays Oct 97]
3. Define oedema. Discuss pathogenesis and causes of oedema.
1. Describe the healing of a fracture. Enumerate the causes for [NTR-OR Jun 89, Feb 96, RGUHS Feb 96, TN Feb 07
nonhealing of fracture. [NTR-OR Oct 98] Modified]
2. Describe the healing of wound by primary union. Mention the dif- 4. What are the types of exudation? Describe the sequelae of
ferences between primary and secondary union. [NTR-OR Jul 89] pyogenic abscess. [NTR-OR Oct 87, Jun 89]
3. Describe types and factors influencing wound healing. [BUHS 5. Define oedema. Write the types of oedema. Describe the
Feb 96] pathogenesis of oedema. [TN Feb 06 Modified]
4. Define repair. Discuss factors, which influence the process of 6. Define oedema. Mention the different types of oedema and
repair. Describe briefly healing by secondary union. [BUHS their cause. [TN Apr 98 Old revised]
Aug 88, Aug 98] 7. Classify inflammatory exudates. Give example. What are the
5. Define healing. Mention types of wound healing. Describe differences between an exudate and a transudate? [TN Oct 96
healing of a fracture and factors influencing the same. [BUHS New regulation]
Mar 88, Feb 91, Aug 95, Aug 96, Mar 98] 8. Define shock. Discuss classification and pathogenesis of
6. Define repair and regeneration. Describe difference between shock. [NTR-OR Jan 90, Mar 95, RGUHS Jan 90, Mar 95,
primary healing and secondary healing. [RGUHS Mar 04] TN Apr 99 Modified, Oct 96 New regulation]
7. What are the types of wound healing? Describe healing of a 9. Define shock. Discuss types, pathogenesis and pathology of
clean incised wound. What are the factors affecting wound shock. [NTR-OR Jan 92]
healing? [TN Aug 07 Modified] 10. Discuss the aetiology, pathogenesis and pathology of shock.
8. Define repair. Describe the process of healing of a surgical [NTR-OR Apr 93, TN Apr 96 Regulation]
wound. Enumerate the factors influencing healing process. [TN 11. Define shock. What are the factors leading to irreversible
Apr 00 Modified] shock? [NTR-NR Oct 03]
9. Describe the stages in healing of a fracture. Mention five 12. Define thrombosis. Discuss the aetiopathogenesis of thrombus.
factors that can cause delayed healing. [TN Apr 99 Revised [NTR-NR Oct 05]
regulations] 13. Define thrombosis. Discuss in brief the pathogenesis of throm-
bus formation. [NTR-OR Apr 99, TN Apr 00 Regulations]
14. Define a thrombus. Mention the type and discuss the fate of
Short Essays thrombus. [NTR-OR Jan 88]
1 . Granulation tissue. [NTR-OR Oct 96, NTR-NR Oct 03] 15. Define embolism. Give an account of various types of emboli.
2. Complications of wound healing. [NTR-OR Oct 03] [BUHS Aug 92]
16. Define thrombosis. Discuss the pathogenesis and fate of 2 3. Evolution of thrombus. [RGUHS Mar 95]
thrombus. [BUHS Jan 89, Jul 90, Mar 94] 24. Fat emboli. [RGUHS Jan 90]
17. What is a thrombus? Describe its pathogenesis and fate. [TN 25. Air emboli. [RGUHS Feb 96]
Oct 98 New Revised] 26. Caisson’s disease. [RGUHS Aug 93]
18. Define infarction. Describe the pathology of infarct. [NTR- 27. Fate of thrombus. [RGUHS Aug 93, 95, TN Apr 99
OR Apr 96, RGUHS Sep 99] Modified, Oct 00 Revised regulations, NTRUHS June 13
19. Describe morphology and microscopic structure of cardiac (NR & OR)]
infarction. [RGUHS Apr 03] 28. Air embolism. [TN Aug 05 Modified, Aug 06 Modified]
20. Define shock. What are the types of shock? Discuss the 29. Infarct. [NTR-OR Oct 89]
mechanism of septic shock. [NTRUHS June 13 (NR & OR)] 30. Infarction. [NTR-OR Jan 90, Aug 01, TN Feb 05 Modified,
Feb 09 Modified]
31. Types of infarction. [NTR-OR Apr 89]
Short Essays 32. Air embolism. [TN Oct 99 Modified]
1. Angioedema. [NTR-NR Apr 06]
2. Types of oedema. [NTR-NR Apr 04]
3. Types of exudates with examples. [NTR-NR Apr 05]
5. DISEASES OF THE IMMUNE SYSTEM
4. Exudate. [BUHS Oct 87, Aug 96] Long Essays
5. Define oedema and mention two types. [RGUHS Aug 05]
6. Difference between transudate and exudates. [BUHS Aug 93] 1. Define hypersensitive reaction. Explain type IV hypersensitive
7. Irreversible shock. [NTR-OR Apr 02] reaction. [RGUHS Aug 06]
8. Classification of shock. [NTR-OR Oct 99] 2. Define hypersensitivity. [TN Oct 00 Modified]
9. Fate of thrombus. [NTR-NR Sep 06] 3. Classify with suitable examples the hypersensitivity reactions.
10. Fat emboli. [BUHS Jan 90] [TN Oct 00 Modified]
11. Caisson’s disease. [BUHS Feb 96] 4. Describe the immune mechanism of tissue injury in type
12. Air emboli. [BUHS Aug 93] I anaphylaxis. [TN Oct 00 Modified]
13. Evolution of thrombus. [BUHS Mar 95] 5. Define amyloidosis. Discuss in detail the aetiopathogenesis
14. Red infarct—how is it caused? How many types of infarcts of amyloidosis. Add a note on its staining characteristics. [TN
are there? [NTR-NR Apr 03] Oct 96 New regulation, Feb 08 Modified]
Short Notes Short Essays

1. Oedema. [NTR-OR Apr 00] 1. Classification of amyloidosis. [NTR-OR Oct 97, TN Feb 08
2. Pedal oedema. [NTR-OR Oct 90] Modified]
3. Pulmonary oedema. [NTR-OR Oct 93] 2. Anaphylaxis. [NTR-OR Jan 90, Mar 92, Oct 99]
4. Difference between transudate and exudates. [NTR-OR Apr 95] 3. Microscopy of sago spleen. [NTR-NR Oct 04, BUHS Aug 93]
5. Types of oedema. [RGUHS Apr 99] 4. Amyloidosis. [BUHS Jul 92]
6. Pathogenesis of oedema. [TN Aug 05 Modified, Feb 08 5. Define and classify amyloidosis. Enumerate the staining reac-
Modified] tions. [RGUHS Apr 03]
7. Mechanism of oedema formation. [TN Oct 99 Revised] 6. Pathological changes in amyloidosis. [RGUHS Mar 04,
8. Types of exudates. [TN Oct 99 Modified] Sep 04]
9. Nutmeg liver. [NTR-OR Jan 88, NTR-NR Apr 04, RGUHS 7. Structure of immunoglobulin. [NTR-OR Apr 00]
Sep 02]
10. Types of shock. [NTR-NR Apr 06]
11. Stages of shock. [NTR-OR Apr 85]
Short Notes
12. Anaphylactic shock. [NTR-NR Sep 06] 1. Atopy. [NTR-OR Oct 98, TN Feb 07 Modified]
13. Mechanism of shock in burns. [NTR-OR Oct 99] 2. B lymphocytes. [NTR-OR Apr 84]
14. Describe stages and end result in shock. [RGUHS Apr 03] 3. Cell-mediated immunity. [NTR-OR Apr 98, Apr 99, Feb 01]
15. Embolism. [NTR-OR Apr 98, Feb 01] 4. Routes of transmission of HIV. [NTR-OR Oct 96]
16. Atrial thrombus. [NTR-OR Oct 89] 5. Type I hypersensitivity reaction. [NTR-OR Oct 92]
17. Fat embolism. [NTR-NR Apr 98, Oct 02, Oct 05, TN Oct 99 6. Define amyloidosis. [TN-Feb 08 Modified]
Revised, Aug 07 Modified, Feb 09 Modified] 7. Sago spleen. [NTR-OR Aug 93, Oct 94, TN Aug 05 Modified]
18. Pulmonary embolism. [NTR-OR Oct 92, Apr 93] 8. Amyloidosis. [NTR-OR Jul 89, Jul 92]
19. Thrombosis. [RGUHS Apr 99] 9. Amyloidosis of liver. [NTR-NR Apr 00]
20. Pulmonary embolism. [RGUHS Apr 00] 10. Special stains of amyloid. [NTR-OR Apr 84]
21. Define thrombosis. Discuss fate of thrombus. [RGUHS 11. Source and nature of amyloid. [NTR-OR Apr 95]
Sep 04, Mar 05] 12. Special stains for demonstrating amyloid. [NTR-NR Sep 06]
22. Define the embolism and discuss the thromboembolism. 13. Lymphokines. [NTR-OR Jan 92]
[RGUHS Aug 05] 14. Histamine. [NTRUHS Dec 12 (NR & OR)]
6. NEOPLASIA 7 . Chemical carcinogenesis. [BUHS Mar 94]

8. Basal cell carcinoma. [NTRUHS Dec 12 (NR & OR)]
Long Essays
1. Explain the characteristics of benign and malignant tumours. Short Notes
[NTR-NR Mar 05]
2. Define neoplasia. Give the difference between benign and 1. Oncogenes. [NTR-OR Jan 92, Oct 96]
malignant tumours. [NTR-NR Apr 03] 2. Oncogenic viruses. [NTR-OR Oct 93]
3. Define neoplasia. Classify tumours. Discuss the modes of 3. Spread of tumours. [NTR-OR Apr 96, Apr 99, Apr 98, NTR-
spread of malignant tumours. [NTR-NR Apr 06] NR Feb 01]
4. Define neoplasia. Write the difference between benign and 4. Chemical carcinogens. [NTR-OR Apr 84]
malignant tumours. [NTR-OR Aug 01] 5. Spread of malignant tumours. [NTR-OR Jul 89]
5. Mention the differences between the benign and malignant 6. Characteristics of malignant cells. [NTR-OR Apr 88, TN
tumours. Discuss the methods of spreading of tumours. Apr 00 Modified]
[NTR-OR Jun 87] 7. Lab diagnosis of cancer. [BUHS Mar 96]
6. Describe the features of malignant cells. Discuss the mode of 8. Stages of cancer. [R Sep 98, R Sep 02]
spread of malignant tumours. [NTR-OR Apr 84] 9. Characteristics of malignancy. [TN Aug 07 Modified]
7. Classify the tumours. What are the differences between 10. Oncogenes. [NTR-OR Jan 92, RGUHS Apr 99]
malignant and benign tumours? [NTR-OR Oct 95] 11. Burkitt’s lymphoma. [NTR-OR Apr 98]
8. Write briefly about the spread of the tumours. [BUHS Aug 91, 12. Virus-related human tumours and examples. [RGUHS Sep 03]
Aug 95] 13. Describe the oncogenesis by chemical carcinogen. [RGUHS
9. Discuss differences between benign and malignant tumours. Mar 06]
Add a note on paraneoplastic syndrome. [BUHS Jan 90, Aug 93, 14. Mention the types of physical carcinogens. Describe the car-
Sep 94] cinogenesis due to ionizing radiation. [RGUHS Mar/Sep 04]
10. Define and classify neoplasia. Describe differences between 15. Aetiology of oral cancer. [TN Apr 00 Modified]
benign and malignant tumours. [RGUHS Apr 03, TN Aug 06 16. Ionizing radiation [TN Oct 98 New revised]
Modified] 17. Tumour markers. [NTR-OR Oct 91]
11. Discuss differences between benign and malignant tumours. 18. Paraneoplastic syndrome. [NTR-OR Jul 84]
Discuss methods of spread of tumours. [RGUHS Apr 03] 19. Osteoid osteoma. [NTRUHS Dec 12 (NR & OR)]
12. Describe the various methods of spread of tumours. [TN 20. Leukemoid reaction. [NTRUHS June 13 (NR & OR)]
Feb 09 Modified, Oct 99 Modified] 21. Ewing’s sarcoma. [NTRUHS June 13 (NR & OR)]
13. Define tumour. Enumerate the differences between benign 22. Dysplasia. [NTRUHS June 13 (NR & OR)]
and malignant neoplasms. [TN Oct 98 New revised, Aug 08
Modified]
14. Explain the term neoplasia. Compare the characters of benign
7. GENETIC AND PAEDIATRIC DISEASES
and malignant tumours with suitable examples. Write briefly Short Essay
about carcinogens. [TN Oct 00 Revised regulations]
15. Define neoplasia. Mention seven important differences be- 1. Down’s syndrome. [NTR-OR Jan 89]
tween benign and malignant tumours. Describe the gross and
microscopic appearance of squamous cell carcinoma of the
tongue. [TN Oct 98 New/Old revised] Short Notes
16. Discuss about injury caused by ionizing radiation. [RGUHS 1 . Chromosome mutation. [NTR-OR Apr 86]
Mar 97] 2. Inborn errors of metabolism. [NTR-OR Oct 87]
17. Define carcinogenesis. Discuss in detail the chemical carcino- 3. What is erythroblastosis fetalis? [RGUHS Aug 05]
genesis. [RGUHS Mar 06] 4. Cystic hygroma. [NTR-NR Sep 06]
18. Define metastasis. Describe the various routes of metastasis
and add a note on mechanism. [NTRUHS Dec 12 (NR & OR)]
8. ENVIRONMENTAL AND NUTRITIONAL
Short Essays DISORDERS
1 . Metaplasia. [NTR-NR Apr 06] Long Essay
2. Name the pathways of spread of malignant tumours. [NTR-NR
Apr 04] 1. Classify vitamins. Discuss the role of vitamin D in rickets.
3. Staging of cancer. [RGUHS Apr 02, Sep 03] [TN Oct 96 Old regulation]
4. Spread of tumours. [RGUHS Sep 04, Mar 05]
5. Characteristics of malignancy. [BUHS Oct 87, Jun 89, Mar 95, Short Essays
Aug 96, Sep 97]
6. Differences between benign and malignant tumours. [BUHS 1 . Pellagra. [NTR-NR Apr 03]
Aug 88, Mar 94, Feb 96, RGUHS Sep 98, Sep 99, Mar 04, Sep 04] 2. Osteomalacia. [NTR-NR Oct 03]
3 . Microscopic picture of osteomalacia. [NTR-NR Oct 93] 11. HAEMATOPOIETIC AND LYMPHOID
4. Manifestations of vitamin A deficiency. [NTR-NR Apr 02]
SYSTEMS
5. Manifestations of rickets. [RGUHS Aug 06]
6. Mention two differences between kwashiorkor and marasmus. Long Essays
[RGUHS Aug 05]
1. Define and classify anaemias. Describe the peripheral blood
picture of iron deficiency anaemia. [NTR-NR Oct 87, Feb 91,
Short Notes Sep 06]
2. Classify anaemia. Describe laboratory diagnosis of iron defi-
1. Rickets. [NTR-OR Oct 85, R Jul 90, Sep 94, Sep 98]
ciency anaemia. [BUHS Oct 87, Feb 91, RGUHS Mar 06]
2. Scurvy. [NTR-OR Oct 98, R Jun 89, Aug 91, Apr 99, TN
3. Define anaemia. Describe in detail clinical features, peripheral
Oct 98, Apr 00 Regulations, New/Old revised, Aug 07
blood and bone marrow findings in megaloblastic anaemia.
Modified]
[RGUHS Mar 04, Sep 04]
3. Kwashiorkor. [NTR-OR Apr 90]
4. Define and classify anaemias. Discuss about the clinical
4. Vitamin B12. [NTR-OR Oct 94]
features, peripheral smear and bone marrow study in iron
5. Vitamin B12 deficiency. [NTR-OR Jun 87]
deficiency anaemia. [TN Aug 05 Modified]
6. Protein-energy malnutrition. [NTR-OR Oct 99]
5. Classify leukaemia. Describe clinical picture, blood and bone
7. Manifestations of scurvy. [RGUHS Sep 04, R Sep 04]
marrow findings in acute leukaemia. [BUHS Jul 90]
8. Enumerate causes and investigations in vitamin D deficiency.
6. Define leukaemia. Describe aetiology, clinical features and
[RGUHS Sep 02, R Sep 02]
blood picture of chronic myeloid leukaemia. [RGUHS Sep 02,
9. Enumerate clinical features of rickets. [RGUHS Mar 04]
Apr 03]
10. Actinomycosis. [NTRUHS Dec 12 (NR & OR)]
7. Discuss classification and aetiology of leukaemia. Describe
peripheral blood and bone marrow picture of chronic myeloid
9. INFECTIONS AND INFESTATIONS leukaemia. [BUHS Apr 87, Sep 94]
8. What are the causes of continuous bleeding after tooth extrac-
Short Essays tion? How do you investigate the cause? [BUHS Mar 87,
Mar 88, Feb 93, Sep 94]
1 . Lab diagnosis of enteric fever. [NTR-NR Apr 06]
9. Discuss the causes of haemorrhage and describe the complica-
2. Urinary sediment. [BUHS Jan 90, Mar 92, RGUHS Sep 96,
tions. [TN Oct 96 Old regulation]
Sep 04, Mar 05]
3. Lepromatous leprosy. [NTRUHS Dec 12 (NR & OR)]
Short Essays
Short Notes 1. Clinical features of anaemia. [NTR-OR Oct 93]
2. Blood picture in iron deficiency anaemia. [NTR-OR Apr 87,
1. Amoebiasis. [NTR-OR Oct 91]
NTR-NR Apr 04]
2. Candidiasis. [NTR-OR Apr 89]
3. What is leucocytosis? What are the causes? [NTR-NR
3. Rhinosporidium. [NTR-OR Apr 00]
Apr 03]
4. Amoebic infection. [NTR-NR Aug 01]
4. Peripheral blood smear of vitamin B12 deficiency? [RGUHS
5. Cysticercus cellulose. [NTR-NR Oct 03]
Apr 00]
6. Fungus affecting hair. [NTR-NR Apr 00]
5. Causes of neutrophilic leucocytosis. [NTR-NR Apr 06]
7. Bacterial food poisoning. [NTR-OR Oct 98]
6. What is leucocytosis? What are the causes? [NTR-NR
8. Candidiasis—what is it? What are the causes? [NTR-NR
Apr 03]
Oct 02]
7. Blood picture of chronic myeloid leukaemia. [NTR-NR
9. Rhinosporidiosis. [RGUHS Feb 07]
Oct 02]
10. Stages of phagocytosis. [NTRUHS Dec 12 (NR & OR)]
8. Agranulocytosis. [RGUHS Aug 06]
9. Leukaemoid reaction. [RGUHS Mar 06]
10. HEART AND BLOOD VESSELS 10. Chronic myeloid leukaemia. [RGUHS Apr 99, TN Apr 99
Revised regulations]
Short Essays 11. Classification of acute myeloid leukaemia. [RGUHS Apr 00]
12. Peripheral blood picture of acute lymphatic leukaemia.
1 . Hypertension. [BUHS Mar 92] [RGUHS Sep 99, Sep 04, Mar 05]
2. Describe the morphology and microscopy of cardiac infarction. 13. What is disseminated intravascular coagulation? Describe the
[RGUHS Sep 03] aetiopathogenesis of the same. [RGUHS Sep 04]
14. Bleeding time. [NTR-NR Aug 01]
Short Notes 15. Thrombocytopenia. [NTR-NR Oct 03, Apr 04, Apr 06]
16. Classical haemophilia. [NTR-NR Oct 05]
1 . Hyperlipidemia. [NTR-OR Oct 92] 17. Lab diagnosis of ITP. [NTR-NR Mar 05]
2. Atheromatous plaque. [NTR-OR Jan 90] 18. Von Willebrand’s disease. [NTR-NR Apr 02]
1 9. Causes of prolonged bleeding time. [NTR-NR Sep 06] 32. Leukaemoid reaction. Describe causes, peripheral smear and
2 0. Haemophilia. [RGUHS Feb 91] bone marrow findings. [RGUHS Mar 04]
2 1. Pancytopenia. [RGUHS Mar 05] 33. Classification of acute myeloid leukaemia. [RGUHS Sep 98]
2 2. Anticoagulants. [RGUHS Mar 05] 34. What is eosinophilia? Enumerate four causes of eosinophilia.
2 3. Prothrombin time. [BUHS Jan 89] [RGUHS Mar 04]
2 4. Thrombocytopenia. [BUHS Jul 90, Aug 95] 35. Leukaemoid reaction. [TN Oct 98 New/Old Revised]
25. Laboratory investigations in bleeding disorders. [BUHS Aug 96, 36. Agranulocytosis. [RGUHS Aug 06, TN Apr 96 Regulation]
RGUHS Mar 05] 37. Haemophilia A. [NTR-OR Oct 97, TN Oct 96 Old Regula-
26. Laboratory diagnosis of multiple myeloma—blood, bone marrow tion, Apr 00 Regulations, Feb 06 Modified]
and urine findings. [RGUHS Mar 04] 38. Pancytopenia. [NTR-OR Apr 97, Oct 98]
2 7. Sickle cell anaemia. [NTRUHS Dec 12 (NR & OR)] 39. Bleeding time. [NTR-OR Apr 98, Aug 01]
40. Immune thrombocytopenia purpura. [NTR-OR Jan 92]
41. Idiopathic thrombocytopenic purpura. [RGUHS Aug 05, TN
Short Notes Feb 05 Modified]
1. ESR. [NTR-OR Apr 96, NTR-NR Aug 03, TN Aug 05 42. What is the intravascular disseminated coagulation? Describe
Modified] the aetiopathogenesis of the same. [RGUHS Mar 04]
2. Anaemia. [NTR-OR Apr 88] 43. Burkitt’s lymphoma. [NTR-NR Apr 98]
3. Thalassemia. [NTR-OR Oct 90] 44. Lymphoma. [BUHS Aug 88]
4. Aplastic anaemia. [NTR-OR Apr 99] 45. Multiple myeloma. [RGUHS Apr 00]
5. Pernicious anaemia. [NTR-OR Oct 89, NTR-NR Apr 06] 46. Wintrobe tube. [NTRUHS Dec 12 (NR & OR)]
6. PCV. [TN Apr 98 Old revised, RGUHS Oct 98] 47. Peripheral blood and bone marrow picture in megaloblastic
7. Sickle cell anaemia. [NTR-OR Apr 93] anaemia. [NTRUHS June 13 (NR & OR)]
8. Megaloblastic anaemia. [NTR-OR Oct 89, TN Oct 00 Modi-
fied, Feb 09 Modified)
9. Clinical features of anaemia. [NTR-OR Oct 93]
12. LUNG
10. Packed cell volume. [NTR-OR Jan 92, NTR-NR Feb 01] Short Essays
11. Hereditary spherocytosis. [NTR-OR Apr 86]
12. Blood picture of iron deficiency anaemia. [NTR-OR Apr 99, 1. Lab diagnosis of Corynebacterium diphtheriae in brief. [NTR-
RGUHS Apr 99, TN Feb 07 Modified] OR Apr 00]
13. Bone marrow in megaloblastic anaemia. [NTR-NR Apr 96] 2. ARDS—describe causes and pathogenesis. [RGUHS Oct 02]
14. Blood picture in megaloblastic anaemia. [NTR-NR Apr 05]
15. Peripheral blood smear in iron deficiency anaemia. [NTR-OR
Jan 89, Apr 99]
Short Note
16. Peripheral and bone marrow picture in B12 deficiency. [NTR- 1. Lobar pneumonia. [NTR-OR Apr 87]
OR June 87]
17. Blood picture in megaloblastic anaemia including bone
marrow findings. [NTR-NR Oct 03] 13. DISEASES OF ORAL CAVITY
18. Lab diagnosis of anaemias. [RGUHS Aug 06] AND SALIVARY GLANDS
19. Blood and bone marrow picture in B12 deficiency anaemia.
[RGUHS Mar 06] Short Essays
20. Megaloblastic anaemia blood picture. [RGUHS Sep 98,
1. Cancrum oris. [NTR-NR Mar 05, BUHS Feb 93, RGUHS
Mar 99]
Sep 04, Mar 05, NTRUHS June 13 (NR & OR)]
21. Peripheral smear of vitamin B12 deficiency. [RGUHS Apr 00]
2. Adenocarcinoma. [TN Apr 96 Regulation]
22. Laboratory findings in megaloblastic anaemia. [TN Feb 08
3. Leukoplakia of mouth. [NTR-OR Oct 04]
Modified]
4. Microscopy of ameloblastoma. [NTR-NR Oct 05]
23. Haemosederin. [TN Oct 96 Old Regulation, Oct 00 Revised
5. Epulis. [BUHS Oct 87]
regulations, Feb 05 Modified]
6. Leukoplakia. [BUHS Mar 88]
24. Peripheral smear picture in vitamin B, deficiency anaemia.
7. Ameloblastoma. [RGUHS Sep 98]
[TN Apr 00 Modified]
8. Vincent’s angina. [RGUHS Mar 05]
25. Eosinophilia. [NTR-NR Sep 06]
9. Pleomorphic adenoma. [BUHS Aug 96, Feb 97]
26. Acute leukaemia. [NTR-OR Apr 93]
27. Acute myeloid leukaemia. [NTR-OR Apr 93, Apr 00]
28. Blood picture in chronic myeloid leukaemia. [NTR-NR Short Notes
Oct 04]
29. Classify acute leukaemias. [RGUHS Sep 98] 1 . Epulis. [NTR-OR Oct 98, RGUHS Oct 87, Sep 98]
30. Classification of leukaemias. [RGUHS Aug 05] 2. Adamantinoma. [NTR-OR Apr 93, TN-Apr 96 Regulation]
31. Peripheral smear layer findings in acute leukaemia. [RGUHS 3. Leukoplakia. [NTR-OR Mar 88, Apr 97, Apr 00, TN Apr 00
Mar 06] Regulations]
4. Dental caries. [NTR-OR Apr 99] 5 . Osteosarcoma. [BUHS Aug 88, Aug 91, Mar 95]
5. Oral candidiasis. [NTR-NR Feb 01] 6. Fibroma. [BUHS Jun 89]
6. Cancrum oris. [NTR-OR Feb 93, Apr 93]
7. Ameloblastoma. [NTR-OR Oct 97, RGUHS Sep 98,
Apr 03] Short Notes
8. Dentigerous cyst. [NTR-OR Apr 96] 1 . Sequestrum. [NTR-OR Jan 89, RGUHS Apr 00]
9. Pleomorphic adenoma. [NTR-OR Apr 97, Oct 98, TN Oct 99 2. Osteoporosis. [NTR-OR Oct 93]
Revised, TN Aug 07 Modified, NTR-NR Feb 96, Aug 96, 3. Osteomyelitis. [NTR-OR Jan 88, RGUHS Apr 99]
Sep 06] 4. Osteosarcoma. [NTR-NR Mar 05, RGUHS Aug 88, 91,
10. Pleomorphic adenoma of salivary glands. [NTR-OR Apr 97, Mar 95]
NTR-NR Oct 04] 5. Osteoclastoma. [NTR-NR Oct 05, RGUHS Mar 88]
11. Microscopic picture of pleomorphic adenoma. [NTR-NR Oct 03] 6. Pyogenic osteomyelitis. [NTR-OR Oct 04]
12. Premalignant lesions. [BUHS Feb 93] 7. Osteoclastoma—clinical features, X-ray findings and morphology.
13. Microscopic features of Warthin’s tumour. [RGUHS Mar 06] [RGUHS Aug 05]
14. Describe the pathology and behaviour of ameloblastoma.
[RGUHS Apr 03]
15. Enumerate premalignant lesions. Discuss in detail about 18. SKIN
leukoplakia. [RGUHS Sep 04, Mar 05]
16. Typhoid ulcer. [RGUHS Aug 06] Short Essays
1. Basal cell carcinoma. [NTR-OR Apr 97, Oct 97, NTR-NR
14. LIVER, GALLBLADDER AND BILIARY Mar 05]
2. Describe gross and microscopic picture and behaviour of basal
TRACT cell carcinoma. [RGUHS Aug 02]
3. Squamous cell carcinoma (epithelioma). [NTR-OR Apr 00,
Short Note TN Feb 06 Modified]
1. Idiopathic haemochromatosis. [TN Aug 07 Modified]
Short Notes
15. MALE AND FEMALE GENITAL SYSTEM 1 . Rodent ulcer. [NTR-OR Jan 89]
2. Malignant melanoma. [NTR-OR Oct 94, TN Feb 05 Modified]
Short Essay 3. Basal cell carcinoma. [NTR-NR Oct 02, TN Aug 08 Modified,
1. Teratoma. [BUHS Apr 87] RGUHS Apr 00]
4. Squamous cell carcinoma. [NTR-NR Apr 87, NTR-NR Mar 05]
5. Oral squamous cell carcinoma. [TN Oct 00 Modified]
Short Note 6. Carcinoma in situ. [TN Apr 99 Modified]
7. Premalignant lesions. [RGUHS Feb 93]
1. Define teratoma. [NTR-NR Oct 02]
16. ENDOCRINE SYSTEM 19. NERVOUS SYSTEM

Short Note
Long Essay
1. Immunization of rabies. [NTR-OR Apr 00]
1. Define diabetes mellitus. Discuss laboratory diagnosis and
complications of diabetes mellitus DM? [RGUHS Sep 04,
Mar 05] 20. MISCELLANEOUS
Short Essays
Short Essay
1. Mention the diseases transmitted through blood transfusion
1. Thyrotoxicosis. [TN Oct 98 New/Old revised] and screening tests. [RGUHS Aug 04]
2. Mention stains used for the demonstration of amyloid.
[NTRUHS June 13 (NR & OR)]
17. MUSCULOSKELETAL SYSTEM
Short Essays Short Notes
1 . Microscopic picture of osteosarcoma. [NTR-NR Apr 03] 1 . Bombay blood group. [RGUHS Apr 03]
2. Microscopic picture of osteoclastoma. [NTR-NR Oct 02] 2. Anticoagulants used in blood bank. [RGUHS Sep 03]
3. Osteomyelitis. [RGUHS Apr 99] 3. Specific gravity of urine. [RGUHS Mar 06]
4. Osteoclastoma. [BUHS Mar 88]
Section III
Microbiology
PART I:GENERAL MICROBIOLOGY
1. HISTORICAL INTRODUCTION 1 2. Bacterial fimbriae. [RGUHS Mar 06]
13. Bacterial flagella. [TN Aug 07 Modified]
Short Notes 14. Anatomy of bacterial cell. [TN Aug 05 Modified]
1. Koch’s postulates. [NTR-OR Oct 92, RGUHS MAR 95, TN
Oct 98 New revised scheme) 3. STERILIZATION AND DISINFECTION
2. Louis Pasteur. [NTR-NR Oct 03]
3. Autoclave. [TN Apr 00 New regulation] Long Essays
4. Robert Koch. [TN Apr 96 Regulation]
1. Define sterilization. Describe an autoclave. [NTR-OR Oct 98]
2. Define sterilization. Add a note on moist heat sterilization.
2. MORPHOLOGY AND PHYSIOLOGY [NTR-NR Apr 05]
OF BACTERIA 3. Define sterilization and disinfection. Add a note on moist heat
sterilization. [NTR-NR Mar 05]
Long Essays 4. Define sterilization and classify sterilization methods. Write
briefly about chemical methods of sterilization. [NTR-OR
1. Draw a neat diagram of bacterial cell. Add a note on bacterial Aug 01]
cell wall. [NTR-NR Apr 06] 5. Discuss the methods of sterilization of an operation theatre
2. Describe the morphology of bacterial cell with a neat labelled and instruments required for oral surgical procedures. [NTR-
diagram and explain briefly. [NTR-OR Apr 99] OR Apr 93]
3. Classify bacteria depending on their shape. Describe cell wall 6. Define sterilization. Classify sterilization methods and write
of bacteria. [TN Aug 06 Modified] about physical methods of sterilization. [NTR-NR Apr 03, TN
Oct 96 Old regulation]
Short Essays 7. What are the methods of bacterial sterilization? Describe
merits and demerits of each. [BUHS Feb 91]
1. Define various structures of bacterial cell with a diagram. 8. Define and classify sterilization. Write briefly on dry heat
[BUHS Mar 95] method of sterilization. [BUHS Feb 96, TN Oct 00 Revised
2. Growth curve. [NTR-NR Oct 02] regulations]
3. Gram stain. [NTR-NR Oct 02] 9. What are the methods of bacterial sterilization? Describe
4. Importance of gram stain. [NTR-NR Oct 05] merits and demerits of each. [BUHS Feb 91]
5. Ziehl-Neelsen stain. [NTR-NR Oct 04] 10. Define and classify sterilization. Write briefly on dry heat
6. Different types of spores. [NTR-NR Oct 04] method of sterilization. [BUHS Feb 96]
7. Draw a diagram of spore and label. [NTR-NR Oct 04] 11. Define sterilization. What are the various methods of moist
8. Different morphological forms of bacteria. [NTR-NR Apr 06] heat sterilization? [TN Feb 08 Modified]
9. Bacterial growth curve. [NTRUHS Dec 12 (NR & OR)] 12. Discuss in detail about sterilization by autoclaving. [TN Feb
10. Inclusion bodies. [NTRUHS June 13 (NR & OR)] 08 Modified]
13. Define and differentiate sterilization and disinfection. What
are the methods of moist heat sterilization? [TN Apr 00
Short Notes Modified]
1. Flagella. [NTR-OR Oct 91, Oct 04] 14. Define sterilization. Discuss the moist heat methods of steril-
2. Bacterial capsule. [NTR-OR Apr 86, Oct 02, TN Oct 96 New ization. [TN Apr 98 Old revised]
regulation]
3. Capsulated bacteria. [NTR-OR Jan 88]
4. Bacterial spore. [NTR-OR Mar 05, TN Feb 08 Modified]
Short Essays
5. Morphology of bacterial cell. [NTR-OR Aug 01] 1 . Moist heat. NTR-OR Jan 88]
6. Bacterial growth curve. [NTR-OR Jun 87, Oct 05] 2. Principle of autoclave. [NTR-NR Apr 06]
7. AFB stain. [NTR-QR Jan 89] 3. Uses of hot air oven. [NTR-NR Oct 02]
8. Acid fact staining. [NTR-OR Jan 92] 4. Name four different causes of disinfection. [NTR-NR
9. Gram staining. [NTR-OR Apr 93] Mar 05]
10. Ziehl-Neelsen stain. [NTR-OR Apr 06] 5. Chemical disinfectants. [BUHS Mar 94, RGUHS Mar 99]
11. Fimbriae. [BUHS Aug 96] 6. Hot air oven. [NTRUHS Dec 12 (NR & OR)]
Short Notes 5. CULTURE METHODS

1. Sterilization. [NTR-OR Apr 97] Long Essay
2. Seitz filter. [NTR-OR Jan 89]
3. Hot air oven. [NTR-OR Oct 97, TN Feb 06 Modified] 1. Describe anaerobic culture methods. [NTR-OR Oct 90]
4. Autoclave. [NTR-OR Jan 87, Feb 01, NTR-NR Oct 05,
Sep 06, TN Oct 96 New regulation, Apr 98 Old revised, Oct 00
Modified, Aug 05 Modified, Feb 09 Modified, NTRUHS
Short Essays
June 13 (NR & OR)] 1 . McIntosh and Filde’s anaerobic jar. [NTR-OR Apr 95]
5. Sterilization by heat. [NTR-NR Jan 92,TN Apr 99 Modified, 2. Anaerobic culture methods.
Apr 99 Revised regulations] 3. Two methods of demonstration of motility of bacteria.
6. Moist heat sterilization. [NTR-NR Oct 03] [NTRUHS June 13 (NR & OR)]
7. Different methods of sterilization. [NTR-NR Oct 04]
8. Disinfectants. [NTR-NR Oct 04, TN Oct 98 New/Old
revised] Short Notes
9. Chemical disinfectants. [NTR-OR Apr 84, TN Oct 99 1 . Cultivation of bacteria. [NTR-OR Jan 89]
Modified, Apr 96 Old regulation] 2. Anaerobic cultivations of bacteria. [TN Oct 96 New regulation]
10. Antiseptics and disinfectants. [NTR-OR Jan 88]
11. Tyndallization. [BUHS Jan 89]
12. Cold sterilization. [RGUHS Feb 07, TN Aug 07 Modified] 6. IDENTIFICATION OF BACTERIA
13. Bacterial filters. [TN Apr 98 Old/Revised regulation]
Short Essay
1. Urease test. [NTR-OR Oct 90]
4. CULTURE MEDIA
Long Essays Short Notes
1. Define and classify culture media with examples. Write briefly 1 . Indole test. [NTR-OR Oct 94]
on selective and anaerobic media. [RGUHS Apr 03] 2. Voges-Proskauer test. [NTR-OR Apr 85]
2. Classify culture media. Describe anaerobic culture methods.
[TN Feb 07 Modified]
7. BACTERIAL TAXONOMY AND
BACTERIAL GENETICS
Short Essays
1 . Enriched media. [NTR-NR Oct 03] Short Notes
2. Mention four selective media. [NTR-NR Oct 04] 1 . Transfer factor. [NTR-OR Apr 88]
3. Name three selective media and their uses. [NTR-NR Oct 06] 2. Methods of genetic transfer. [RGUHS Mar 06]
4. Name three enriched media and their uses. [NTR-NR 3. Transduction. [TN Oct 98 New revised]
Oct 02]
5. Name two enriched media and two transport media. [NTR-NR
Oct 05] 8. INFECTION
6. Robertson’s cooked meat media. [BUHS Feb 96]
7. Media for cultivation of bacteria. [RGUHS Oct 01]
Long Essay
1. Mention the infections transmitted by the blood and blood
products. Write in detail about any one agent. [NTR-OR Apr 98]
Short Notes
1 . Blood agar. [NTR-NR Oct 02] Short Essay
2. Blood culture. [NTR-OR Apr 89]
3. Enriched media. [NTR-OR Apr 98] 1. Endotoxin and exotoxin. [NTR-NR Oct 03]
4. Transport media. [NTR-NR Feb 01, TN Aug 06 Modified, Feb
08 Modified]
5. Enrichment media. [NTR-OR Oct 94]
Short Notes
6. Preparation of blood agar medium. [NTR-OR Apr 93] 1 . Sources of infection. [NTR-OR Apr 99, NTR-NR Oct 03]
7. Selective media. [RGUHS Oct 00] 2. Exotoxin and endotoxin. [BUHS Jan 89, RGUHS Aug 05]
8. Anaerobic culture media. [TN Feb 05 Modified, NTRUHS Dec 3. Universal precautions against blood and body-fluid borne
12 (NR & OR)] pathogens. [TN Apr 00 New regulations]
9. IMMUNITY Short Notes

Long Essays 1 . Complement system. [BUHS Feb 93]
2. Functions of complement. [TN Oct 00 Revised regulations]
1. Define and classify immunity. Discuss acquired immunity.
[NTR-NR Oct 02]
2. Classify immunity and describe active immunity with example. 12. STRUCTURE AND FUNCTION OF
[TN Feb 09 Modified] IMMUNE SYSTEM, IMMUNE RESPONSE
AND IMMUNODEFICIENCY DISEASES
Short Essays
Short Essays
1 . Types of active immunity with examples. [NTR-NR Oct 04]
2. Acquired immunity. [RGUHS Sep 04, Mar 05] 1 . Cytokines. [NTR-OR Apr 94]
3. Difference between active and passive immunity. [NTRUHS 2. Lymphokines. [NTR-OR Jan 91]
Dec 12 (NR & OR)] 3. Lymphokines. [BUHS Apr 87]
4. Major histocompatibility complex (MHC). [RGUHS Aug 06]
Short Notes
Short Notes
1 . Active immunity. [NTR-NR Sep 06, NTR-OR Jan 89]
2. Acquired active immunity. [NTR-OR Apr 00] 1 . B lymphocytes. [NTR-OR Apr 84]
3. Cell-mediated immunity. [NTR-OR Apr 98, Apr 99, Feb 01] 2. Cytokines. [RGUHS Sep 04, Mar 05]
4. Mechanism of innate immunity in an individual. [NTR-NR Apr 06]
5. Differences between active and passive immunity. [NTR-NR
Mar 05] 13. HYPERSENSITIVITY
6. Passive immunity. [BUHS Aug 95]
Long Essay
1. Define and classify hypersensitivity. Write in detail about
10. ANTIGENS AND ANTIBODIES: type-I hypersensitivity. [NTRUHS June 13 (NR & OR)]
IMMUNOGLOBULINS AND ANTIGEN–
ANTIBODY REACTIONS
Short Essays
Short Essays 1 . Anaphylaxis. [BUHS Feb 93, TN Oct 99 Revised]
1 . Immunoglobulin A (IgA). [NTR-OR Oct 94] 2. Delayed hypersensitivity. [RGUHS Sep 98]
2. IgG. [RGUHS Apr 04] 3. Type I hypersensitivity. [RGUHS Apr 03]
3. Secretory immunoglobulins. [RGUHS Oct 99] 4. Type II hypersensitivity. [RGUHS Apr 00]
4. Precipitation reaction. [RGUHS Aug 06]
5. Agglutination reaction. [NTRUHS Dec 12 (NR & OR)]
Short Notes
1. Define and classify hypersensitivity. Describe anaphylaxis.
Short Notes [BUHS Mar 94]
1 . Immunoglobulin. [NTR-OR Oct 92] 2. Define hypersensitivity and discuss reactions. [BUHS
2. Name of the immunoglobulins. Write about IgA. [NTR-OR Apr 00] Sep 94]
3. Structure of immunoglobulin. [NTR-OR Apr 98, Apr 00, NTR- 3. What is hypersensitivity? Write briefly on type III hypersen-
NR Apr 03] sitivity. [RGUHS Mar 97]
4. IgE. [BUHS Feb 96] 4. Define and classify hypersensitivity. Describe in detail of
5. Immunoglobulin M. [RGUHS Aug 06] principle and mechanism of hypersensitive reaction. [RGUHS
6. ELISA. [NTR-OR Apr 00] Mar 04]
7. Agglutination. [NTR-OR July 89, TN Apr 00 Modified] 5. Serum sickness. [NTR-NR Apr 03]
8. Coombs’ test. [NTR-OR Aug 00, NTR-NR Aug 01, TN Feb 05 6. Type I hypersensitive reaction. [NTR-OR Oct 92]
Modified] 7. Classify hypersensitive reactions. [NTR-NR Feb 01]
8. Immediate type of hypersensitive reaction. [NTR-OR Apr 84]
9. Classify hypersensitivity and write about serum sickness.
11. COMPLEMENT SYSTEM [NTR-NR Feb 01]
10. Tuberculin test. [RGUHS Mar 98]
Short Essay 11. Anaphylaxis. [TN Oct 98 New revised]
1. Interferon. [BUHS Mar 95] 12. Antibiotic sensitivity test. [TN Oct 96 New regulation]
14. AUTOIMMUNITY, IMMUNOLOGY OF 15. MISCELLANEOUS

TRANSPLANTATION AND MALIGNANCY Short Essays
AND IMMUNOHEMATOLOGY
1 . Nosocomial infection. [NTR-OR Jan 90, TN Oct 99 Revised]
Short Essay 2. Castanedos method of culture. [NTR-NR Apr 03]
3. Antibiogram. [RGUHS Oct 04]
1. Allograft reaction. [BUHS Apr 87]
Short Notes
Short Note
1 . Stool examination. [NTR-OR Apr 96, Apr 97]
1. Autoimmune diseases. [BUHS Jun 89]
2. Hospital infections. [NTR-OR Jan 92]
3. Apoptosis. [RGUHS Apr 01]
PART II : SYSTEMIC BACTERIOLOGY

16. STAPHYLOCOCCUS, 10. Describe the cultural characteristics and classification of
STREPTOCOCCUS, PNEUMOCOCCUS streptococci. Discuss the pathology of cariogenic strepto-
cocci. [NTR-OR Jun 87]
AND NEISSERIA 11. C-reactive protein. [BUHS Feb 88]
Long Essays 12. Media used for gonococcus. [NTR-OR Jan 90]
1. Describe the morphology, staining characters and pathogenicity

of Staphylococcus. Add a note on laboratory diagnosis of Short Notes
staphylococcal infections. [TN Oct 98 New/Old revised scheme]
2. Classify staphylococci. Describe the morphology, cultural 1. Name the pyogenic cocci. Describe the pathogenesis and
characteristics and reactions of Staphylococcus aureus. De- laboratory diagnosis of staphylococci. [RGUHS Mar 06]
scribe the pathological lesions caused by staphylococci. [NTR- 2. Coagulase test. [NTR-OR Jun 87, TN Apr 99 Revised
OR Apr 94, TN Apr 96 Regulation] regulations]
3 . Write in brief about the nonsuppurative lesions of streptococci. 3. Name four diseases caused by Staphylococcus aureus. [NTR-
[TN Aug 07 Modified] NR Mar 05]
4. Write in detail about the morphology, pathogenesis, laboratory 4. Staphylococcal infections. [RGUHS Feb 07]
diagnosis and the treatment of streptococci. [TN Feb 06 Modified] 5. Describe the morphology, cultural characteristics and suppu-
5 . Classify streptococci. Describe the toxins and lesions produced rative lesions caused by staphylococci. [TN Aug 07 Modified]
by b-haemolytic streptococci. Add a note on the laboratory 6. Enumerate all the pyogenic cocci. [TN Feb 06 Modified]
diagnosis. [TN Oct 99 Modified] 7. Describe morphology, pathogenicity and laboratory diagnosis
6 . Classify Staphylococci. Describe the lesions caused by of Staphylococcus. [TN Aug 05 Modified]
S. aureus and laboratory diagnosis of S. aureus infection. 8. Write in detail about bacterial suppurative lesions. [TN Feb
[NTRUHS Dec 12 (NR & OR)] 05 Modified]
9. Name the organisms causing septicaemia. [TN Feb 05
Modified]
Short Essays 10. Add a note on coagulase delivered by Staphylococcus. [TN
1 . Few qualities of pathogenic staphylococci. [NTR-NR Oct 03] Feb 05 Modified]
2. Lesions caused by Staphylococcus aureus. [NTR-NR Oct 02] 11. Lesions produced by Staphylococcus aureus. [TN Oct 00
3. Staphylococcus aureus. [RGUHS Sep 98] Revised regulations]
4. Enumerate pyogenic organisms. Describe morphology, cultural 12. Classify Streptococcus. Mention the streptococcal species in
characteristics and lesions produced by Staphylococcus pyogens. the lesions of oral cavity and pharynx. [BUHS Nov 86]
[BUHS Mar 92, Mar 93, Feb 97] 13. Describe the morphology, cultural characteristics, toxins and
5. Toxins of streptococci. [NTR-OR Jan 90] virulence factors produced by streptococci. [BUHS Feb 91]
6. Name four diseases caused by Streptococcus pyogenes. [NTR- 14. Classify streptococci and describe pathogenesis, laboratory
NR Oct 05] investigations. [BUHS Feb 94]
7. Nonsuppurative lesions caused by Streptococcus pyogenes. 15. Classify streptococci and describe the laboratory investiga-
[NTR-NR Oct 04] tions of streptococci pyogenes. [RGUHS Mar/Sep 05]
8. Antistreptolysin O test. [RGUHS Mar 04] 16. Poststreptococcal complications. [NTR-NR Aug 01]
9. Discuss streptococci under the following headings: 17. Viridians streptococci. [RGUHS Aug 05, TN Apr 99 Revised
a. Morphology regulations]
b. Classification 18. Subacute bacterial endocarditis (SBE). [BUHS Jan 89]
c. Dental caries 19. Streptococcal infections. [TN Feb 09 Modified]
d. Laboratory diagnosis [TN Aug 08 Modified] 20. Sore throat. [TN Oct 98 New revised]
2 1. Toxins and enzymes produced by Streptococcus. [TN Oct 96 Short Notes

New regulation]
2 2. Morphology and cultural characteristics of Pneumococcus. 1 . Give an account of tubercular bacilli. [BUHS Jan 89, Aug 92]
[NTR-OR Oct 97] 2. Describe morphology, cultural characteristics, pathogenicity and
23. Discuss laboratory investigations of meningitis. [BUHS Jan 89] laboratory diagnosis of Mycobacterium tuberculosis. [BUHS
2 4. Morphology and cultural characters of pneumococci. [NTR- Mar 95, Aug 96]
OR Oct 97] 3. BCG. [NTR-OR July 89, TN Aug 05 Modified, Oct 96 New
2 5. Laboratory diagnosis of pneumococcal infections. [RGUHS regulation]
Mar 06] 4. Tuberculin test. [BUHS Mar 88]
2 6. Bacteria causing meningitis. [NTR-OR Oct 91] 5. Antibiotic sensitivity test. [TN Feb 06 Modified]
6. Lab diagnosis of Mycobacterium leprae. [NTR-OR Apr 84]
17. CORYNEBACTERIUM
19. CLOSTRIDIUM
Long Essays
Short Essays
1. Briefly describe the pathogenesis, laboratory diagnosis and
prophylaxis of Corynebacterium diphtheriae. [TN Oct 00 1 . Prophylaxis of tetanus. [NTR-NR Apr 06]
Modified] 2. Triple antigen. [RGUHS Apr 00]
2. Mention the organisms found in the oral cavity describe the
pathogenesis and laboratory diagnosis of diphtheria. [TN Apr 99
Short Notes
Revised regulations]
3. Describe the morphology, cultural characters and diagnosis of 1. Discuss in detail about organisms causing gas gangrene.
Corynebacterium diphtheriae. Add a note on immunization. [BUHS Jun 89]
[NTR-NR Feb 01, Oct 05, NTR-OR Apr 97, RGUHS Oct 97] 2. Classify Clostridium. Describe laboratory diagnosis and pro-
phylactics of gas gangrene. [BUHS Feb 96]
3. Describe morphology, cultural characteristics, toxins liberated
Short Essays and lesions produced by clostridial strains. [BUHS Oct 87,
1. Immunization against diphtheria. [BUHS Aug 93] Jan 90, RGUHS Aug 96]
2. Describe the morphology, cultural characteristics of Coryne- 4. Prophylaxis of tetanus. [NTR-OR Apr 99]
bacterium diphtheriae. [NTR-NR Oct 04] 5. Immunization against tetanus. [NTR-OR Jan 92, NTR-NR
3. Describe laboratory diagnosis and prophylaxis of diphtheria. Oct 98, TN Apr 99 Modified]
[BUHS Mar 94] 6. Cultural characteristics of Clostridium tetany. [NTR-OR Oct 94]
4. Describe morphology, cultural characteristics and laboratory 7. Define shock. Describe the causes and pathogenesis of shock.
diagnosis of Corynebacterium. [BUHS Aug 88, Jul 90, Aug 95] [TN Apr 99 Modified]
5. Name different species of genus Corynebacterium. [RGUHS 8. Oral microbial flora. [TN Oct 96 New regulation]
Aug 05]
6. DPT vaccine. [NTR-OR Oct 98, TN Aug 06 Modified]
20. NONSPORING ANAEROBES
7. Triple vaccine. [NTR-OR Oct 92]
8. Cultivation of Corynebacterium diphtheriae. [NTR-OR Apr 89] Short Essays
9. Lab diagnosis of Corynebacterium diphtheriae. [NTR-OR Apr
00, TN Apr 98 Old revised] 1 . Bacteroids. [RGUHS Aug 06]
1 0. Name two media used for cultivation of Corynebacterium 2. Lactobacillus. [RGUHS Sep 04, Mar 05]
diphtheriae. [NTR-NR Mar 05]
Short Notes
18. MYCOBACTERIUM (TUBERCULOSIS, 1. Enumerate the nonsporing anaerobes present as normal resi-
ATYPICAL MYCOBACTERIA AND dent flora in the mouth. Mention the various oral anaerobic
MYCOBACTERIUM LEPRAE) infections. [BUHS Apr 87]
2. Lactobacillus. [BUHS Mar 88]
Short Essays
1 . Mantoux test. [BUHS Mar 95] 21. ENTEROBACTERIACEAE
2. Describe the morphology, cultural characters and pathogenicity of (COLIFORMS-PROTEUS, SHIGELLA
Mycobacterium tuberculosis. Add a note on laboratory diagnosis
of pulmonary tuberculosis. [NTR-NR Sep 06, TN Oct 99 Revised] AND SALMONELLA)
3 . Classify leprosy. Describe morphology, propagation and labo-
Short Essay
ratory diagnosis of Mycobacterium leprae. [BUHS Aug 91]
4. Tuberculin Test (Mantoux test). [NTRUHS Dec 12 (NR & OR)] 1. Lab diagnosis of enteric fever. [NTR-NR Apr 06]
Short Notes 4. Discuss laboratory diagnosis of syphilis. [BUHS Oct 87]

5. Describe morphology, cultural characteristics, pathogenicity
1. Widal test. [NTR-OR Jan 88, Apr 00, TN Oct 98 New/Old and laboratory diagnosis of Treponema pallidum. [BUHS
revised, Feb 06 Modified, Aug 08 Modified] Aug 93]
2. Widal reaction. [NTR-OR Apr 97] 6. VDRL test. [NTR-OR Apr 99]
3. Enterotoxins. [NTR-OR Apr 94] 7. Vincent’s angina. [NTR-OR Oct 97, NTR-NR Mar 05]
4. Bacterial antigens. [TN Feb 05 Modified] 8. Borrelia vincentii. [NTR-OR Jun 87]
5. Laboratory diagnosis of enteric fever. [TN Oct 98 New revised] 9. Congenital syphilis. [NTR-OR Apr 98]
10. Standard test for syphilis. [NTR-OR Apr 00, TN Feb 05
Modified]
22. VIBRIO
11. Serological tests for diagnosis of syphilis. [NTR-OR Oct 90,
Short Essay Apr 93]
12. Laboratory diagnosis of syphilis. (TN Oct 99 Modified, Apr
1. Describe the morphology, cultural characteristics and toxins 96 Regulation]
of Vibrio cholerae. Discuss briefly about cholera. [NTR-OR
Jan 92]
25. ACTINOMYCETES, RICKETTSIACEAE
Short Note AND CHLAMYDIAE
1. Cholera. [NTR-OR Oct 89, Oct 99] Short Essays
1 . Cervicofacial actinomycosis. [BUHS Feb 87]
2. Actinomycosis. [NTR-OR Oct 99, NTR-NR Apr 06]
23. PSEUDOMONAS, YERSINIA,
PASTEURELLA, FRANCISELLA,
HAEMOPHILUS, BORDETELLA Short Notes
AND BRUCELLA 1. Actinomycosis. [NTR-OR Apr 93, Apr 99, Apr 00, TN Oct 98
New/Old Revised, Oct 99 revised, Feb 07 Modified]
Short Note 2. Inclusion bodies. [NTR-NR Apr 03]
1. Whooping cough. [NTR-OR July 89]
26. MISCELLANEOUS
24. SPIROCHAETES: TREPONEMA Short Essays
PALLIDUM, BORRELIA VINCENTII
1 . Malignant pustule. [NTR-NR Apr 03]
Short Essays 2. Define septicaemia and bacteraemia. [NTR-NR Sep 06]
3. Mention four bacteria causing meningitis. [NTR-NR
1. Name two sexually transmitted bacterial diseases. [NTR-NR Oct 04]
Mar 05] 4. Mention four bacteria causing respiratory infection. [NTR-NR
2. Serological tests for syphilis. [BUHS Sep 94] Oct 04]
3. Borrelia Vincentii. [NTRUHS Dec 12 (NR & OR)] 5. DPT vaccine. [RGUHS Sep 06]
6. Triple vaccine. [RGUHS Apr 00]
7. Bacterial vaccine. [RGUHS Apr 90]
Short Notes
1. Describe the serological diagnosis of syphilis. [NTR-OR
Apr 00]
Short Notes
2. Classify spirochetes. Discuss morphology, pathogenesis of 1 . Cryptococcosis. [NTR-OR Oct 88]
Treponema pallidum. Mention the diagnosis of syphilis. [NTR- 2. Bacterial food poisoning. [NTR-OR Oct 98]
OR Jan 88] 3. Normal flora of upper respiratory tract. [NTR-NR Oct 04]
3. Describe the morphology, pathogenicity, cultural characteristics and 4. Postship to coccal complications. [NTR-NR Aug 01]
laboratory diagnosis of Treponema pallidum. [NTR-NR Oct 03] 5. Antibacterial agents on anaerobic bacteria. [RGUHS Oct 01]
PART III : MEDICAL VIROLOGY

27. GENERAL PROPERTIES OF VIRUSES 3 . Poliomyelitis prophylaxis. [TN Oct 00 Revised Regulations]
4. Immunization against poliomyelitis. [TN Oct 98 New/Old
Short Essays revised]
1 . Name three RNA viruses. [NTR-NR Sep 06]
2. Three methods of isolation of viruses. [NTR-NR Oct 03] Short Notes
3. Mention 4 antiviral agents. [NTRUHS June 13 (NR & OR)]
1 . Polio vaccine. [NTR-OR Apr 99]
2. Immunoprophylaxis in poliomyelitis. [NTR-NR Sep 06]
Short Notes 3. Killed vaccines. [TN Oct 00 Modified]
1 . Isolation of viruses. [NTR-NR Feb 01] 4. Name four vaccines. [NTR-NR Oct 05]
2. Cultivation of viruses. [NTR-QR Apr 98, Oct 98, TN Oct 98
New revised] 32. ORTHOMYXO AND PARAMYXO
3. Classification of viruses. [TN Apr 00 Regulations]
VIRUSES
28. BACTERIOPHAGE: STRUCTURE Short Essay
AND SIGNIFICANCE 1. Mumps viral infection. [RGUHS Feb 07]
Short Essays
Short Note
1 . Bacteriophage. [NTR-QR Oct 94]
2. Define definitive host with example. [NTRUHS June 13 1. Mumps. [NTR-OR Apr 96]
(NR & OR)]
33. ARBO AND RHABDO VIRUSES

29. POXVIRUSES
Short Essays
Short Note 1 . Kyasanur forest disease (KFD). [NTR-OR Mar 92]
1. Transport media. [TN Aug 08 Modified] 2. Japanese encephalitis. [NTR-OR Jan 90]
30. HERPES VIRUSES Short Notes

Short Essay 1 . Arboviruses. [NTR-OR Apr 84]
2. Immunization of rabies. [NTR-OR Apr 00]
1. Herpes virus. [BUHS Oct 87, Feb 91] 3. Rabies vaccine. [TN Aug 08 Modified]
Short Notes 34. HEPATITIS VIRUSES

1 . Herpes simplex. [NTR-OR Jan 88] Short Essays
2. Cytomegalo virus. [NTR-OR Apr 96]
3. Herpes simplex viral infections. [RGUHS Aug 06, Aug 07 1 . Danes particles. [NTR-NR Apr 03]
Modified, TN Apr 00 Modified] 2. Lab diagnosis of hepatitis B [TN Aug 05 Modified]
3. Prophylaxis against hepatitis B. [NTR-NR Apr 06]
31. ADENOVIRUSES
AND PICORNAVIRUSES Short Notes
1. Describe morphology, spread, prevention and lab diagnosis of
Short Essays hepatitis B-virus. [NTR-OR Apr 00]
1 . Immunology of poliomyelitis. [NTR-OR Feb 89] 2. Hepatitis B virus. [NTR-OR Oct 96, NTR-NR Oct 05, TN
2. Sabin vaccine. [BUHS Jan 90] Apr 99 Modified, Apr 00 Modified, Feb 09 Modified]
3. Hepatitis B virus lab diagnosis. [TN Feb 08 Modified]
4. Describe pathogenicity and laboratory diagnosis of hepatitis B
Short Notes virus. [TN Feb 07 Modified]
1 . Polio vaccine. [TN Aug 08 Modified] 5. Hepatitis vaccine. [TN Feb 05 Modified]
2. Vaccine for polio. [TN Feb 06 Modified] 6. Serum hepatitis. [TN Oct 00 Modified]
35. ONCOGENIC VIRUSES 3. Mode of transmission of HIV. [NTRUHS June 13 (NR

& OR)]
Short Notes
1 . Oncogenic virus. [NTR-OR Apr 94] Short Notes
2. Cytomegalo viruses. [NTR-OR Apr 96]
3. Human papilloma virus. [NTR-OR Apr 97] 1 . Modes of transmission of HIV. [NTR-NR Oct 04]
2. Human immunodeficiency virus. [RGUHS Sep 04, Mar 05]
3. VDRL test. [TN Apr 99 Revised Regulations, Feb 08
36. HUMAN IMMUNODEFICIENCY Modified]
VIRUS (HIV)/AIDS
Short Essays
1 . Diagram of AIDS virus. [NTR-NR Apr 03]
2. Mention four modes of infection of HIV. [NTR-NR Oct 05]
PART IV : MEDICAL MYCOLOGY

37. FUNGAL DISEASES 3. Candida albicans. [NTR-OR Feb 01, NTR-NR Sep 06, TN
Apr 98 Old/Revised, TN Aug 07 Modified]
Long Essay 4. Culture methods of Candida albicans. [NTR-OR Apr 98]
5. Moniliasis. [RGUHS Aug 05]
1. Give an account of infections caused by Candida albicans.
6. Opportunistic fungal infections. [NTR-OR Aug 01, TN
Describe laboratory diagnosis of Candida. [TN-Aug 06
Oct 99 Modified]
Modified]
7. Mention two oral fungal infections. [NTR-NR Oct 04]
8. Opportunistic mycosis. [TN Feb 08 Modified, Feb 09 Modified]
Short Notes 9. Candidal infections. [TN Apr 00 Regulations]
10. Candidiasis. [NTR-OR Apr 89]
1 . Mycetoma. [NTR-OR Apr 96] 11. Enumerate the lesions caused by Candida albicans. [NTRUHS
2. Oral thrush. [NTR-NR Mar 05, TN Oct 00 Modified] Dec 12 (NR & OR)]
PART V : MEDICAL PARASITOLOGY

38. PROTOZOANS 9. Erythrolytic schizogony. [NTR-OR Apr 83]
10. Human cycle of malarial parasite. [NTR-NR Oct 05]
Long Essays 11. Diagnosis of malaria or diagnosis of the malarial infection.
[NTR-OR Oct 98, Aug 01]
1. Discuss the aetiology, pathogenesis and diagnosis of intestinal
12. Laboratory diagnosis of malaria. [NTR-NR Apr 06]
amoebiasis. [NTR-OR Jan 92]
13. Malarial parasites. [RGUHS Sep 03]
2. Describe the morphology and life cycle of Entamoeba histolyt-
14. Oral protozoal parasites. [RGUHS Apr 99]
ica. Write about laboratory diagnosis of intestinal amoebiasis.
15. Plasmodium vivax life cycle in mosquito. [RGUHS Aug 06;
[NTR-NR Oct 04]
TN Feb 07 Modified]
3. Describe the life cycle of malarial parasites in man. Give a
16. Plasmodium vivax life cycle in the human. [RGUHS Feb 07]
brief description of pathological lesions produced in man by
17. Laboratory diagnosis of intestinal amoebiasis. [RGUHS
the malarial parasites. [NTR-OR Apr 84]
Oct 00, Apr 01]
18. Plasmodium falciparum. [TN Aug 05 Modified]
Short Notes 19. Benign tertian malaria. [TN Oct 00 Revised regulations]
20. Life cycle of Entamoeba histolytica. [TN Oct 98 New revised]
1 . Amoebic infection. [NTR-OR Aug 01]
2. Amoebic dysentery. [NTR-NR Apr 06]
3. Entamoeba gingivalis. [NTR-OR Apr 99] Short Essays
4. Entamoeba histolytica. [NTR-OR Jan 88, TN Feb 09 Modified]
5. Morphology of Entamoeba gingivalis. [NTR-OR Apr 98, Apr 99] 1 . Blackwater fever. [NTR-OR Apr 96, NTR-NR Oct 04]
6. Laboratory diagnosis of Entamoeba histolytica in brief. [NTR- 2. Complications of Plasmodium falciparum. [NTR-NR Oct 02]
OR Oct 98] 3. Name the species of malarial parasites infecting humans.
7. Microfilaria. [NTR-OR Apr 00, NTR-NR Oct 02, Oct 03] [NTR-NR Mar 05]
8. Gametocytes of malaria. [NTR-OR Jun 87, Apr 93] 4. Kala-azar. [RGUHS Aug 00]
5 . Name two complications caused by Plasmodium falciparum. 2. Describe the morphology, life cycle and pathogenesis of Wucher-
[NTRUHS Dec 12 (NR & OR)] eria bancrofti. Discuss the diagnosis of filariasis. [NTR-OR Oct 90]
3. Hydatid cyst. [NTR-OR Apr 84, NTR-NR Apr 03, TN Aug 06
Modified]
39. HELMINTHES 4. Casoni’s test. [NTR-OR Jan 89]
5. Hookworm infestations. [NTR-OR Jul 89]
Short Essay 6. Cystericercus cellulosae. [NTR-OR Oct 91, Apr 97, NTR-NR
1. Ankylostoma duodenale. [RGUHS Oct 02] Oct 03]
7. Life cycle of Ascaris lumbricoides. [NTR-OR Apr 96, TN Aug 07
Modified]
Short Notes 8. Life cycle of Ancylostoma duodenale. [NTR-OR Apr 97]
9. Pathogenesis and clinical manifestations of Ancylostoma
1. Enumerate the common tapeworms. Describe the morphology, duodenale. [RGUHS Apr 01]
life cycle and laboratory diagnosis of Taenia solium. [NTR-OR 10. Mycetoma. [TN Feb 06 Modified]
Apr 89] 11. Yaws. [TN Apr 00 Modified]
PART VI : DENTAL MICROBIOLOGY

40. DENTAL MICROBIOLOGY Short Notes
Long Essays 1. Dental caries. [NTR-OR Apr 96, Apr 99, NTR-NR Oct 02, Apr 06]
2. Dental plaque. [NTR-NR Oct 04]
1. Enumerate the organisms causing white patch on the throat. 3. Vincent’s angina. [NTR-OR Oct 97, NTR-NR Apr 05]
Describe the laboratory diagnosis of diphtheriae. [BUHS Oct 4. Congenital syphilis. [NTR-NR Apr 04]
99, RGUHS Aug 05] 5. Lactobacilli. [BUHS Apr 99]
2. Discuss normal oral flora. What is the pathogenesis of dental 6. Development of oral flora. [BUHS Nov 86]
plaque formation. [TN Apr 00 Regulations] 7. Prevention of dental caries. [RGUHS Mar 06]
8. Bacteria causing dental caries. [TN Feb 07 Modified]
9. Microbiology of dental caries. [TN Oct 99 Revised]
Short Essays 10. Aetiology of dental caries. [TN Oct 98 New revised]
1 . Oral thrush. [NTR-NR Oct 03] 11. Oral microbial flora. [TN Apr 96 Regulation]
2. Oral candidiasis. [NTR-OR Feb 01] 12. Lockjaw. [NTR-OR Oct 97, Apr 99]
3. Cultural methods of Candida albicans. [NTR-OR Apr 98] 13. Bacteria in oral cavity. [NTR-NR Apr 03]
4. Oral lesions in congenital syphilis. [NTR-NR Apr 06] 14. Microbial flora of oral cavity. [NTR-QR Aug 01]
5. Name the microorganisms causing dental caries. [NTR-NR 15. Koplik’s spots. [NTR-NR Apr 03, Oct 04]
Sep 06] 16. Oral antiseptics. [RGUHS Aug 01]
6. Morphology diagnosis and diseases caused by Candida 17. Oral spirochetes. [RGUHS Aug 05]
albicans. [NTR-OR Apr 99] 18. Prevention of dental caries. [RGUHS Aug 06]
7. Periodontal infection. [RGUHS Apr 03] 19. Acute ulcerative gingivitis. [NTRUHS June 13 (NR & OR)]
8. Candidiasis—what is it? What are the causes? [RGUHS Sep 02] 20. Normal flora of human mouth. [NTRUHS June 13 (NR & OR)]
Section IV
Pharmacology
PART I : GENERAL PHARMACOLOGICAL PRINCIPLES
1. DEFINITIONS, ROUTES OF DRUG 2. Describe the routes of drug administration, their merits and
demerits with suitable examples. [NTR-OR Jan 91, RGUHS
ADMINISTRATION
Apr 98]
Long Essays 3. What are the routes of drug administration? Explain advan-
tages and disadvantages of various routes. [BUHS Jan 90]
1. Describe the various sources of drugs in pharmacology with 4. Enumerate all routes of drug administration. Discuss merits
suitable examples. Add a note on different methods of drug and demerits of oral and intravenous routes of administrations.
administration. [NTR-OR Apr 84] [BUHS Jan 86, RGUHS Apr 03]
5. Describe the routes of administration of drugs with examples. Short Essays

Discuss advantages and disadvantages of intravenous route.
[RGUHS Mar 05] 1 . Drug metabolism. [RGUHS Apr 99]
6. Enumerate the routes of administration of drugs giving suitable 2. Channels of drug exertion. [RGUHS Sep 94]
examples. What are the advantages and disadvantages of oral 3. Modification in renal exertion. [RGUHS Sep 94]
route of administration? [RGUHS Apr 02] 4. Define the term prodrug giving an example. [RGUHS Sep 98,
7. Enumerate the routes of administration of drugs. Write the BUHS Mar 94, RGUHS Sep 98]
advantages and disadvantages of intravenous (IV) route of 5. First-pass metabolism. [RGUHS Sep 01]
administration. [NTRUHS June 13 (NR & OR)] 6. Bioavailability. Factors influencing it by oral route with
examples. [BUHS Mar 94, RGUHS Sep 98]
7. Oxidizing agents. [NTRUHS June 13 (NR & OR)]
Short Essays
1. Enumerate all routes of drug administration. Discuss merits Short Notes
and demerits of oral and intravenous routes of administration. 1. Bioavailability. [NTR-OR Oct 98, RGUHS Apr 00]
[RGUHS Jan 86] 2. Mention two factors which affect bioavailability. [NTR-NR
2. Describe the routes of administration of drugs with examples. Oct 04]
[RGUHS Apr 99] 3. Biotransformation. [NTR-OR Apr 95, Apr 98, RGUHS Mar 06]
3. Sublingual route of administration. [RGUHS Apr 87, Jul 90, 4. Drug metabolism. [NTR-OR Apr 93]
R Apr 98] 5. Pharmacokinetics. [NTR-OR Apr 92]
4. Intravenous route. [RGUHS Sep 99] 6. What is plasma half-life? [NTR-NR Oct 02]
5. Name two drugs administered by sublingual route. Mention 7. Define prodrug and give example. [NTR-OR Feb 83]
two advantages of this route. [RGUHS Apr 87, Sep 98] 8. Methods of prolonging the effects of a drug. [NTR-OR Feb 83]
6. Mention different routes of administration of drugs. Write in de- 9. Prodrug. [RGUHS Mar 94]
tail about sublingual route of administration. [RGUHS Apr 99] 10. First pass metabolism with suitable examples. [NTR-NR Sep 06,
7. Name the two drugs administered by sublingual route of RGUHS Sep 98]
administration. Mention two advantages of this route. [RGUHS 11. Define prodrug. Give two examples. [NTRUHS Dec 12 (NR
Sep 98] & OR)]
Short Notes 3. PHARMACODYNAMICS

1. New drug delivery. [NTR-OR Oct 99] Long Essays
2. Parenteral administration of drugs. [NTR-OR Feb 90]
1. Describe the various factors that modify the dosage and action
3. Sublingual route of administration of drug. [NTR-OR Jun 87,
of drugs. [NTR-OR Sep 83]
RGUHS Jan 89]
2. Discuss factors modifying drug action with examples. [BUHS
4. Various routes of drug administration. [NTR-OR Apr 91]
July 90, RGUHS Aug 06]
5. Advantages and disadvantages of oral route. [NTR-NR
3. Describe the principles and mechanism of action of drugs with
Apr 04]
examples. Add a note on enzyme induction. [BUHS July 91,
6. Advantages and disadvantages of inhalation route. [NTR-NR
RGUHS Jul 91]
Feb 02]
7. Advantages and disadvantages of intravenous route of admin-
istration. [NTR-NR Oct 05] Short Essays
8. Intravenous route. [BUHS Apr 87, RGUHS Sep 92] 1 . Pharmacodynamics. [NTR-OR Apr 96]
9. Drug nomenclature. [RGUHS Mar 04] 2. Factors modifying drug action. [NTR-OR Apr 85]
10. Explain the advantages of IV route of drug administration. 3. Placebo. [BUHS Mar 92]
[RGUHS Mar 06] 4. Physiological antagonism. [RGUHS Aug 05]
11. Two merits and two demerits of intravenous route of admin- 5. Drug antagonism. [NTR-OR Jan 89, Aug 01, Apr 96, Oct 96,
istration of drugs. [RGUHS Mar 04] NTR-NR Apr 03, Mar 05, Apr 06, Sep 06, RGUHS Mar 94,
12. Write four advantages of oral route of drug administration. Sep 95, NTRUHS Dec 12 (NR & OR)]
[NTRUHS Dec 12 (NR & OR)] 6. Explain three types of drug antagonism with examples.
[RGUHS Aug 06]
2. PHARMACOKINETICS
Short Notes
Long Essays
1 . Tachyphylaxis. [NTR-OR Jul 89, NTR-NR Oct 04]
1. Describe the various methods to prolong the duration of action 2. Drug synergism. [NTR-OR Apr 99, Feb 01]
of a drug. [NTR-OR Jul 89] 3. Bioassay. [RGUHS Apr 00]
2. Explain the means of biotransformation of drugs in the body 4. Synergism. [BUHS Apr 87, RGUHS Apr 87]
with examples. [RGUHS Mar 97] 5. Placebo. [RGUHS Mar 92]
6 . Drug antagonism. [RGUHS Mar 95] Short Notes

7. Tachyphylaxis. [RGUHS Jun 89, Sep 92; R Apr 00]
8. What is tachyphylaxis? Give two examples. [RGUHS Mar 04] 1 . Drug resistance. [RGUHS Sep 98]
2. Anaphylactic reaction. [RGUHS Jun 86]
3. Idiosyncrasy. [RGUHS Jul 90]
4. ADVERSE DRUG EFFECTS 4. Addiction. [RGUHS Jul 90]
5. Teratogenicity. [RGUHS Mar 95; Apr 99]
Short Essays 6. Adrenaline in anaphylactic shock. [RGUHS Mar 05]
1 . Write in detail the drug toxicity in man. [NTR-OR Jan 89] 7. Hypersensitive reaction. [NTR-OR Dec 86]
2 . Adverse drug reactions. [RGUHS Apr 99] 8. Drug resistance. [RGUHS Sep 98; Aug 05]
3 . Anaphylactic reaction. [RGUHS Aug 88, Jan 91] 9. Anaphylactic reaction. [BUHS Jun 86]
PART II: DRUGS ACTING ON AUTONOMIC NERVOUS SYSTEM

5. CHOLINERGIC SYSTEM AND DRUGS 6. ANTICHOLINERGIC DRUGS
Long Essay AND DRUGS ACTING ON AUTONOMIC
GANGLIA
1 . Classify cholinergic drugs with examples. Write the mecha-
nism of action, uses and adverse effects of neostigmine. [NTR- Long Essays
NR Sep 06]
1. Classify anticholenergic drugs. Discuss the pharmacology and
uses of atropine. Mention the symptoms of atropine poisoning
Short Essays and line of treatment. [NTR-OR Oct 86]
2. Classify anticholenergic drugs. Discuss the adverse effects and
1 . Irreversible anticholinesterases. [RGUHS Apr 87] uses of atropine. [BUHS Sep 92]
2 . Neostigmine. [RGUHS Jun 89] 3. Discuss the pharmacological actions of atropine. Mention
3 . Compare neostigmine and physostigmine. [RGUHS Mar 94] some atropine substitutes and their uses in the therapy. [BUHS
4 . Therapeutic uses of atropine. [RGUHS Apr 02] Jan 89]
5 . Role of atropine in organophosphorus poisoning. [RGUHS Sep 99]
6 . Therapeutic uses of reversible anticholinesterases. [RGUHS
Mar 04, Sep 04] Short Essays
7. What is the organophosphorus poisoning? Describe the treatment.
[NTR-OR Oct 86] 1 . Compare atropine and cocaine. [RGUHS Apr 87, Aug 93]
8 . Neostigmine is used in the treatment of diaphragmatic paraly- 2. Atropine. [RGUHS Mar 92, Feb 93, 96]
sis caused by d-tubocurarine. [NTR-NR Feb 02] 3. Homatropine. [RGUHS Jan 91, Apr 99]
4. Atropine poisoning. [RGUHS Jan 89]
5. Atropine sulphate—mechanism of action. [NTR-OR Jan 92]
Short Notes 6. Uses and adverse effects of atropine. [RGUHS Feb 07]
7. Rationale of using atropine in organophosphorus poisoning.
1. Neostigmine. [RGUHS Oct 87, Feb 93, R Apr 00]
[RGUHS Sep 99, Sep 02]
2. Pralidoxime. [RGUHS Sep 98]
8. Explain the rationale of using pralidoxime in organophospho-
3. Oximes in organophosphorus poisoning. [RGUHS Apr 03]
rus poisoning. [RGUHS Mar 06]
4. Neostigmine in myasthenia gravis. [RGUHS Apr 03]
9. Atropine substitutes. [NTRUHS Dec 12 (NR & OR)]
5. Neostigmine—uses and adverse effects. [NTR-OR Oct 97]
6. Physostigmine use in atropine poisoning. [NTR-NR Oct 03]
7. Therapeutic uses of atropine. [RGUHS Apr 02]
Short Notes
8. Compare physostigmine and neostigmine. [RGUHS Feb 07]
9. Irreversible anticholinesterases. [BUHS Apr 87] 1. Atropine. [NTR-OR Feb 90, Apr 97, RGUHS Jun 86,
1 0. Compare neostigmine and physostigmine. [BUHS Mar 94, Sep 94]
RGUHS Mar 06] 2. Atropine derivatives. [NTR-OR Apr 93]
1 1. Role of atropine in organophosphorus poisoning. [RGUHS 3. Therapeutic uses of atropine. [NTR-NR Oct 05]
Sep 99] 4. Mention two atropine substitutes. [RGUHS Sep 98]
1 2. Oximes. [RGUHS Aug 06] 5. Atropine poisoning. [BUHS Apr 87]
1 3. Neostigmine in myasthenia gravis. [RGUHS Apr 03] 6. Scopolamine. [RGUHS Sep 98]
1 4. Mention the rationale of using pilocarpine in glaucoma. 7. Uses of hyoscine in motion sickness. [RGUHS Apr 03]
[NTRUHS June 13 (NR & OR)] 8. Mention four adverse effects of atropine. [NTR-NR Oct 04]
1 5. Mention the rationale of using oximes in organophosphate 9. Rationale of using atropine in preanaesthetic medication.
poisoning. [NTRUHS June 13 (NR & OR)] [NTR-NR Apr06]
10. Rationale of using atropine in organophosphorus poisoning. Short Notes

[NTR-NR Apr 04]
11. Mention two atropine substitutes used as mydriatic. [NTR- 1. Adrenaline. [RGUHS Jul 91, Sep 92, Sep 99, NTR-OR
NR Apr 03] Oct 87, Feb 1990, Apr 97]
12. Scopolamine. [RGUHS Sep 98] 2. Dopamine. [RGUHS Mar 99]
13. Atropine and scopolamine. [RGUHS Aug 05] 3. Compare adrenaline and ephedrine. [RGUHS Apr 87, Aug 93]
4. Reserpine. [RGUHS Jan 90]
5. Pharmacotherapy of shock. [RGUHS Sep 92]
7. ADRENERGIC SYSTEM AND DRUGS 6. Adrenaline and noradrenaline. [RGUHS Mar 1905]
7. Prazosin. [RGUHS Apr 00]
Long Essays 8. Adrenaline in anaphylactic shock. [RGUHS Apr 03]
1. Discuss the pharmacological actions and some important uses 9. Salbutamol in bronchial asthma. [RGUHS Mar 05]
of sympathomimetic drugs. [NTR-OR Apr 93] 10. Noradrenaline. [NTR-OR Apr 96]
2. Classify sympathomimetics. Write the therapeutic uses and 11. Epinephrine. [NTR-OR Dec 86]
adverse effects of adrenaline. [NTR-NR Apr 04] 12. Isoprenaline. [NTR-OR Jul 89]
3. Classify sympathomimetics. Write cardiovascular actions of 13. Uses of the adrenaline. [NTR-NR Sep 06]
adrenaline. Mention uses of adrenaline. [NTR-NR Oct 02] Or,
4. Classify adrenergic drugs. Write all the uses of adrenaline and Therapeutic uses of adrenaline. [NTR-OR Feb 01]
isoprenaline. [RGUHS Mar 95]
5. Classify adrenergic agents. Discuss the actions and uses of 8. ANTIADRENERGIC DRUGS
adrenaline. [BUHS Mar 92, RGUHS Sep 00]
6. Describe the differences in action of adrenaline, noradrenaline (ADRENERGIC RECEPTOR ANTAGONISTS)
and isoprenaline. Write their uses indicating the routes of
Long Essays
administration and usage. [BUHS Jun 86]
7. Classify adrenergic drugs depending on the clinical uses with 1. Enumerate beta blockers. Write their pharmacological actions
suitable examples. Explain the pharmacological actions and and adverse effects of propranolol. [NTR-OR Apr 99]
adverse effects of adrenaline. [RGUHS Mar 06] 2. Classify b-blockers. Describe the pharmacological action, thera-
peutic uses and adverse effects of propranolol. [NTR-NR Mar 05]
3. Classify beta-adrenergic receptor blockers and describe what
Short Essays are the actions and uses of propranolol. [RGUHS Aug 88]
1. Pharmacological basis of administrating lignocaine with
adrenaline. [NTR-OR Oct 95] Or, Short Essays
Adrenaline is combined with lignocaine. [NTR-NR
1 . Adrenergic alpha blockers. [RGUHS Aug 93]
Mar 05]
2. Beta adrenergic blocking drugs. [RGUHS Jan 90, Sep 94, Aug 95]
Or, 3. Propranolol. [RGUHS Jun 89, Sep 94, Feb 96, Apr 98, Apr 99,
Write the rationale of combining xylocaine with adren- Apr 00, BUHS Jul 90, Aug 96]
aline for local anaesthesia. [RGUHS Apr 02] 4. Cardioselective beta blockers. [RGUHS Mar 02]
2. Ephedrine. [BUHS Jan 90, RGUHS Jan 90] 5. Name four alpha adrenergic blockers. Write the uses of alpha
3. Amphetamine. [RGUHS Jan 91] adrenergic blockers. [NTRUHS June 13 (NR & OR)]
4. Adrenaline in anaphylactic shock. [RGUHS Apr 03]
Or,
Adrenaline in anaphylaxis. [NTR-OR Oct 91]
Short Notes
5. Mention one indication for the use of adrenaline and ligno- 1. Classify beta adrenergic blocking agents. [RGUHS Aug 88,
caine and explain the basis for the same. [RGUHS Aug 00, Apr 98, Apr 99, BUHS Sep 94, Aug 95]
Feb 07] 2. Classification of beta blockers. [NTR-OR Oct 85, RGUHS
6. Rationale of using adrenaline in anaphylactic shock. [RGUHS Mar 95, Apr 99, Sep 99]
Mar 05] 3. Propranolol. [RGUHS Jul 90, Aug 96 Apr 00; NTR-OR Feb
7. What is dopamine? Mention one use and route of administration. 90, Apr 00]
[RGUHS Apr 02] 4. Timolol. [RGUHS Mar 94, Mar 04]
8. What is prazosin? Mention one therapeutic use. [RGUHS 5. Cardioselective beta blockers. [NTR-OR Aug 01, NTR-NR
Sep 02] Apr 03]
9. Rationale of using adrenaline in anaphylactic shock. [RGUHS 6. Alpha adrenergic blocking agents. [NTR-OR Oct 90]
Mar/Sep 04] 7. Propranolol is contraindicated in bronchial asthma. [NTR-OR
10. Rationale of using dobutamine in cardiogenic shock. [NTR- Oct 93]
OR Oct 03] 8. Labetalol. [RGUHS Aug 05]
11. Compare adrenaline and noradrenaline. [RGUHS Mar 05] 9. Uses and adverse effects of beta blockers. [RGUHS Aug 06]
PART III : AUTOCOIDS AND RELATED DRUGS

9. HISTAMINES AND ANTIHISTAMINES 2. Classify nonsteroidal anti-inflammatory drugs. Explain the
mechanism of action and uses of ibuprofen. [NTR-NR
Short Essays Sep 06]
3. Classify nonnarcotic analgesics. Discuss the actions and uses
1. Mention four newer antihistamines with four advantages. of salicylates. [NTR-OR Jun 87]
[NTR-NR Mar 05] 4. Classify nonsteroidal anti-inflammatory drugs. Mention the
2. Mention four therapeutic uses of H1 blockers. [NTR-NR Apr 04] therapeutic uses and adverse effects of aspirin. [NTR-NR
3. Autocoids. [BUHS Aug 95] Feb 02; RGUHS Mar 06]
4. Antihistamines. [BUHS Feb 96, RGUHS Apr 99] 5. Classify nonsteroidal anti-inflammatory drugs. Describe the
5. Enumerate two nonsedative antihistamines and mention four pharmacological actions and therapeutic uses of salicylates.
uses of them. [RGUHS Feb 07] [NTR-OR Apr 93, Apr 99, Feb 01]
6. Morphine and pethidine. [RGUHS Apr] 6. Enumerate antipyretic analgesics. Describe the pharmaco-
7. Therapeutic uses of H1 blockers. [RGUHS Mar 04] logical actions, uses and side effects of acetyl salicylic acid.
[NTR-OR Apr 96]
Short Notes 7. Classify nonsteroidal anti-inflammatory drugs. Describe the
pharmacological actions, uses and adverse effects of propi-
1. Autocoids. [RGUHS Aug 95, Feb 96] onic acid derivatives. [NTR-OR Oct 98]
2. Antihistamines. [RGUHS Apr 99] 8. Classify analgesics. Discuss the pharmacology, therapeutic
3. Describe the therapeutic uses of antihistamines. [RGUHS uses and toxicity of salicylates. [BUHS Aug 95; RGUHS
Mar 05] Sep 00]
4. H1 blockers. [NTR-OR Apr 99] 9. Classify analgesics. Enumerate the action of salicylates, men-
5. Cyproheptadine. [NTR-OR Apr 95] tion two contraindications of aspirin. [BUHS Jan 89, RGUHS
6. Nonsedative antihistamines. [NTR-OR Aug 01] Apr 98]
7. Therapeutic uses of H1 blockers. [NTR-OR Oct 96] 10. Classify analgesics. Compare morphine and aspirin. Write
8. Nonsedative antihistamines. [NTR-NR Oct 03] contraindications to morphine. [BUHS Oct 87]
9. Cetirizine. [RGUHS Sep 00, Sep 02] 11. Enumerate nonsteroidal anti-inflammatory drugs with suit-
10. Ergometrine. [RGUHS Jan 90] able examples. Explain the mechanism of action, uses and
11. Promethazine. [RGUHS Sep 04] adverse effects of aspirin. [RGUHS Feb 07]
12. Name four antihistamines. [NTRUHS June 13 (NR & OR)] 12. Classify analgesics. Write briefly on the adverse effects
produced by them. How would you treat a case of aspirin
poisoning? [BUHS Jan 86]
10. 5-HYDROXYTRYPTAMINE, 13. Define the term analgesics. List four nonsteroidal anti-
ITS ANTAGONISTS AND DRUG THERAPY inflammatory drugs belonging to four different chemical
OF MIGRAINE, PROSTAGLANDINS, groups. Mention therapeutic uses of aspirin. Explain the
pharmacological basis of anyone of its uses. [RGUHS
LEUKOTRIENES (EICOSANOIDS)
Sep 02]
AND PLATELET-ACTIVATING FACTOR
Short Essay Short Essays
1. Selective COX-2 inhibitors. [RGUHS Aug 05, Mar 06] 1 . Opioid antagonists. [RGUHS Apr 03]
2. Low-dose aspirin is administrated prophylactically. [NTR-NR
Oct 04]
Short Notes 3. Rationale of using aspirin in postmyocardial infarction. [NTR-
1 . Prostaglandins. [RGUHS Mar 94, NTR-OR Mar 04] NR Apr 04]
2. Ergometrine. [BUHS Jan 90] 4. Classify analgesics, compare morphine and aspirin. Write the
contraindications to morphine. [RGUHS Oct 87]
5. Mention the antidote for paracetamol poisoning. How does it
11. NONSTEROIDAL act? [NTR-NR Oct 03]
ANTI-INFLAMMATORY DRUGS
AND ANTIPYRETIC ANALGESICS Short Notes
Long Essays 1. Aspirin. [RGUHS Jul 91, Sep 92, Feb 93, Sep 98, Apr 99,
NTR-OR Dec 86, Feb 90]
1. Classify nonsteroidal anti-inflammatory drugs and mention
2. Paracetamol. [NTR-OR Oct 97, RGUHS Aug 98, Jul 91]
their clinical uses. [NTR-OR Apr 93]
3. Aspirin postmyocardial infarction. [RGUHS Apr 03] 12. ADDITIONAL DRUGS FOR
4. Nimesulide. [NTR-NR Oct 02]
RHEUMATOID ARTHRITIS AND DRUGS
5. Phenyl butazone. [NTR-OR Jan 92]
6. Acetyl salicylic acid. [NTR-OR Apr 97] FOR GOUT
7. Aspirin as an anti-inflammatory agent. [NTR-OR Jul 89]
8. Aspirin and paracetamol. [RGUHS Aug 06]
Short Notes
9. Therapeutic uses and contraindications of aspirin. [RGUHS 1 . Probenecid and penicillin in chemotherapy. [RGUHS Sep 00]
Aug 05] 2. D-penicillamine. [RGUHS Sep 04]
10. Mention four non-steroidal anti-inflammatory drugs. [NTRUHS 3. Methotrexate. [RGUHS Mar 05]
Dec 12 (NR & OR)] 4. Role of glucocorticoids in rheumatic arthritis. [NTR-OR Oct 97]
5. Rationale of using probenecid with penicillin. [NTR-NR Oct 03]
PART IV : RESPIRATORY SYSTEM

13. DRUGS FOR COUGH AND 2. Salbutamol. [RGUHS Jul 90, Aug 96]
BRONCHIAL ASTHMA 3. Disodium cromoglycate. [RGUHS Jan 89]
4. Aminophylline. [RGUHS Apr 00]
Short Essays 5. Mention two drugs used to suppress dry cough. [RGUHS
Apr 02]
1. Mention two drugs used to suppress dry cough. [NTR-NR Apr 06]
6. Mention two drugs used in acute bronchial asthma. Write the
2. Noscapine. [RGUHS Aug 98]
rationale of using any one drug. [RGUHS Sep 02]
3. Disodium cromoglycate. [BUHS Jan 89]
7. Salbutamol. [NTR-NR Apr 03]
4. Salbutamol in bronchial asthma. [RGUHS Mar/Aug 05]
8. Aminophylline. [NTR-OR Feb 01]
5. Pharmacotherapy of status asthmaticus. [RGUHS Aug 05, Mar 06]
9. Nasal decongestants. [NTR-NR Apr 06]
6. Mention two drugs used to suppress the dry cough. [RGUHS
10. Mention four nasal decongestants. [NTR-NR Apr 03]
Apr 02]
11. Rationale of using salbutamol in bronchial asthma. [NTR-NR
7. List three groups of drugs used in bronchial asthma with an
Feb 02]
example. [RGUHS Aug 06]
12. Beclomethasone. [RGUHS Mar 05]
8. Mention two drugs used in acute bronchial asthma. Write the
13. Explain the mechanism of action of sodium cromoglycate.
rationale of using any one drug. [RGUHS Sep 02]
[RGUHS Feb 07]
14. Name four bronchodilators. [NTRUHS June 13 (NR & OR)]
Short Notes
1. Noscapine. [RGUHS Aug 88]
PART V : HORMONES AND RELATED DRUGS

14. ANTERIOR PITUITARY HORMONES, 15. INSULIN, ORAL HYPOGLYCAEMICS
THYROID HORMONE AND THYROID AND GLUCAGON
INHIBITORS
Long Essays
Long Essays 1. Classify antidiabetic drugs and write about the oral antidiabetic
1. Enumerate the antithyroid drugs. Explain the action of the drugs. [NTR-OR Jul 89]
thioamides giving the indications, advantages and adverse 2. Describe the different preparations of insulin. Add a note on
effects of each. [NTR-OR Aug 98, RGUHS Apr 98] their merits and demerits. [NTR-OR Sep 84]
3. Mention the various insulin preparations with their advantages
and disadvantages. [NTR-OR Apr 97]
Short Essays 4. Mention insulin preparations and discuss their pharmacologi-
1 . Radioactive isotopes. [RGUHS Mar 05] cal actions and adverse effects. [NTR-OR Jun 87]
2. Antithyroid drugs. [RGUHS Aug 95] 5. Classify drugs used in diabetes mellitus. Write the mechanism
3. Radioactive iodine. [NTRUHS June 13 (NR & OR)] of action, adverse effects and uses of sulphonylureas. [NTR-
NR Oct 02, Oct 03]
6. Classify oral antidiabetic drugs. Discuss the pharmacological
Short Notes actions and uses of glibenclamide. [BUHS Jan 89]
1 . Lugol’s iodine. [RGUHS Aug 88, Jan 89, Jan 90] 7. Classify antidiabetic drugs. Write mechanism of action, thera-
2. Iodine. [RGUHS Jan 90, Sep 94] peutic uses and effects of insulin. [RGUHS Apr 00]
8 . Mention the hormones secreted by pancreas. What is dia- 5. Describe the therapeutic uses and adverse effects of glucocor-
betic coma? What are the principles of treatment? [BUHS ticoids. How do the synthetic glucocorticoids differ from the
Jan 86] natural one? [BUHS Jan 86]
Short Essays Short Essays

1. Mention different insulin preparation. [RGUHS Apr 00] 1 . Synthetic corticosteroids. [RGUHS Aug 96]
2. Antidiabetic action of sulphonylurea. [RGUHS Feb 96] 2. Adverse effects of corticosteroids. [RGUHS Sep 99]
3. Oral antidiabetic drugs. [RGUHS Aug 93] 3. Side effects of glucocorticoids. [RGUHS Mar 92]
4. Insulin and sulphonylurea. [RGUHS 2006] 4. Adverse effects of prednisolone. [RGUHS Apr 02]
5. Preparations of insulin. [RGUHS Mar 04] 5. Therapeutic uses of glucocorticoids. [RGUHS Apr 03]
6. Four adverse effects of insulins. [NTR-NR Apr03] 6. Mechanism of action and adverse effects of dexamethasone.
7. Mention four advantages of newer insulins. [RGUHS Sep 02] [RGUHS Aug 06]
8. Sulphonylurea is not effective in treating diabetes mellitus. 7. Explain why glucocorticoid therapy should not be stopped
Explain. [RGUHS Apr 02] abruptly. [RGUHS Feb 07]
9. Newer insulins are preferred to conventional insulins. Why? 8. Abrupt cessation of prolonged administration of glucocorti-
[RGUHS Oct 04] coids is hazardous. Explain. [RGUHS Aug 05]
10. Give reason—glibenclamide is not useful in treating child-
hood diabetes mellitus. [RGUHS Mar 05]
Short Notes
1. Side effects of glucocorticoids. [RGUHS Apr 00, Apr 02]
Short Notes 2. Prednisolone. [NTR-OR Apr 98]
1. Insulin. [NTR-OR Feb 83, Feb 90, RGUHS Jan 90] 3. Betamethasone. [NTR-OR Feb 90]
2. Newer insulins. [RGUHS Jan 91] 4. Hydrocortisone. NTR-OR Apr 97]
3. Sulphonylurea. [RGUHS Sep 99] 5. Adverse effects of prednisolone. [NTR-NR Feb 02]
4. Give reason—glibenclamide is not useful in treating child- 6. Adverse effects of glucocorticoids. [NTR-OR Apr 99]
hood diabetes mellitus. [RGUHS Apr 02] 7. Therapeutic uses of glucocorticoids. [NTR-NR Apr 03]
5. Mention four advantages of newer insulins. [RGUHS 8. Uses and adverse effects of glucocorticoids. [NTR-OR
Sep 02] Oct 99, NTR-NR Oct 02]
6. Tolbutamide. [NTR-OR Apr 96] 9. Adverse effects of adrenocorticosteroids. [NTR-OR Apr 99,
7. Glibenclamide. [NTR-OR Oct 98, NTR-NR Sep 06] Feb 01]
8. Newer insulin. [NTR-OR Apr 00, NTR-NR Mar/Oct 05] 10. ACTH. [NTR-OR Dec 86]
9. Insulin preparations. [NTR-OR Jan 92, RGUHS Feb 07] 11. Synthetic corticosteroids. [BUHS Aug 96]
10. Preparations of insulin. [NTR-NR Apr 02] 12. Side effects of glucocorticoids. [BUHS Mar 92]
11. Protamine zinc insulin (PZI). [NTR-OR Apr 93] 13. Adverse effects of corticosteroids. [RGUHS Sep 99]
12. Adverse effects of insulin. [NTR-OR Aug 01] 14. Therapeutic uses of prednisolone. [NTR-NR Apr 06]
13. Oral antidiabetic drugs. [RGUHS Aug 99] 15. Mention four nonhormonal uses of glucocorticoids. [NTR-
14. Antidiabetic action of sulphonylurea. [BUHS Feb 96] NR Mar 05]
15. Mention different insulin preparations. [RGUHS Apr 00] 16. Two differences between hydrocortisone and dexamethasone.
16. Compare insulin and sulphonylurea. [BUHS Aug 92] [NTR-NR Sep 06]
17. Name four oral hypoglycemic drugs. [NTR-NR Apr 06] 17. Name four glucocorticoids. [RGUHS Mar 06]
18. Sulphonylurea. [RGUHS Sep 99, Mar 06] 18. Glucocorticoids should not be stopped abruptly. Why?
[NTRUHS Dec 12 (NR & OR)]
16. CORTICOSTEROIDS
17. GONADAL HORMONES (SEX
Long Essays HORMONES) AND THEIR ANTAGONISTS
1. Classify glucocorticoids. Describe the mechanism of action,
adverse effects and therapeutic uses. [NTR-NR Oct 04]
Short Essays
2. Enumerate the synthetic corticosteroids. Describe their 1 . Anabolic steroids. [RGUHS Nov 86]
pharmacology, uses and toxicity. [BUHS Apr 87] 2. Combination of oestrogen and progesterone in oral contracep-
3. Enumerate glucocorticoids. Describe therapeutic uses and ad- tives. [RGUHS Apr 00]
verse effects of any one of them. [BUHS Aug 91, Feb 93,
RGUHS Mar 97]
4. Name the adrenocorticosteroids. Write all glucocorticoid prep- Short Notes
arations. Give the uses of it and toxicity of glucocorticoids. 1 . Oral contraceptives. [NTR-OR Jul 89, RGUHS Mar 94]
[BUHS Mar 95] 2. Anabolic steroids. [BUHS Nov 86]
18. OXYTOCIN AND DRUGS ACTING 2. What is normal plasma calcium level in the body? Describe
the role of different hormones and vitamins influencing body
ON UTERUS
calcium levels. [NTR-OR Apr 84]
Short Note
1. Oxytocin. [RGUHS Aug 95] Short Essays
1 . Agonists influencing calcium metabolism. [NTR-OR Apr 85]
19. DRUGS AFFECTING CALCIUM 2. Vitamin D deficiency. [RGUHS Apr 00]
BALANCE
Short Notes
Long Essays
1 . Calcium carbonate. [RGUHS Jul 91]
1. Write drugs acting on calcium metabolism. Describe the 2. Vitamin D. [RGUHS Jun 89, Aug 96, NTR-OR Oct 98, Apr 00]
pharmacological actions of parathyroid hormone. [NTR-OR 3. Parathyroid hormone. [NTR-OR Oct 97]
Feb 83]
PART VI : DRUGS ACTING ON PERIPHERAL NERVOUS SYSTEM

20. SKELETAL MUSCLE RELAXANTS 21. LOCAL ANAESTHETICS
Long Essays Long Essays
1. Classify skeletal muscle relaxants. Describe the pharmacological 1. Classify local anaesthetics and write in detail about xylocaine.
actions, therapeutic uses and adverse effects of d-tubocurarine. [NTR-OR Feb 90]
[NTR-OR Apr 00] 2. Classify local anaesthetics. Write their mechanism of action.
2. List two classes of skeletal muscle relaxants acting at neuro- Mention the types of local anaesthetics. [NTR-NR Oct 05]
muscular junction. Mention two therapeutic uses of them. 3. Classify local anaesthetics. Discuss the uses and toxicity of
[RGUHS Mar 99] lignocaine. [NTR-OR Jan 88]
4. Classify local anaesthetics. Mention their mechanism of action
and various methods of producing local anaesthesia. [NTR-NR
Short Essays Oct 03]
5. Classify local anaesthetics. Enumerate the various methods of
1. Compare d-tubocurarine and succinylcholine. [BUHS Jan 90, producing local anaesthesia by drugs. Describe the pharma-
RGUHS Jan 90] cology of xylocaine. [NTR-OR Apr 85]
2. Classify skeletal muscle relaxants. [RGUHS Aug 96] 6. Classify local anaesthetics. Compare lignocaine hydrochlo-
3. Rationale of using neostigmine in myasthenia gravis. [NTR- ride and cocaine. [BUHS Aug 88]
NR Oct 05] 7. Classify local anaesthetics. Discuss uses and adverse effects
4. Succinylcholine and d-tubocurarine. [RGUHS Feb 07] of lignocaine. [BUHS Feb 93, RGUHS Apr 99]
5. Write rationale of using neostigmine in d-tubocurarine poison- 8. Classify the local anaesthetics with suitable examples. Describe
ing. [RGUHS Apr 02, Mar 05] the different techniques employed to induce local anaesthetics.
6. Neostigmine is used in the treatment of diaphragmatic paralysis Explain how the action of lignocaine can be prolonged. [RGUHS
caused by d-tubocurarine. [NTR-NR Feb 02] Mar 00]
7. Classify skeletal muscle relaxants. [BUHS Apr 96] 9. Classify local anaesthetics. Discuss the mechanism of action,
8. Write the rationale of using neostigmine in d-tubocurarine adverse effects and therapeutic uses of lignocaine. Add a note
poisoning. [RGUHS Apr 02] on the advantages of lignocaine. [RGUHS Apr 03]
10. Classify local anesthetics with examples. Explain mechanism
of action and therapeutic uses of lignocaine. Add a note
Short Notes on complications of spinal anaesthesia. [NTRUHS Dec 12
(NR & OR)]
1 . Skeletal muscle relaxants. [NTR-OR Oct 97, RGUHS Aug 87]
2. Succinylcholine. [RGUHS Oct 87]
3. D-tubocurarine. [RGUHS Aug 93, 95] Short Essays
4. Pancuronium. [NTR-OR Jan 89, NTR-OR Apr 93]
5. Succinylcholine. [NTR-OR Oct 94, RGUHS Apr 02] 1 . Lidocaine. [RGUHS Jun 89, Mar 94]
6. Diazepam. [RGUHS Sep 04] 2. Uses of adrenaline in lidocaine. [RGUHS Jul 90, Sep 98,
7. Mention two skeletal muscle relaxants and their two uses. Apr 99]
[NTRUHS June 13 (NR & OR)] 3. Toxicity of lidocaine. [RGUHS Oct 87]
4 . Lidocaine and mepivacaine. [RGUHS Apr 00] 5. Cocaine. [RGUHS Jun 91]
5 . Mechanism of local anaesthetic. [RGUHS Apr 02] 6. Procaine. [RGUHS Aug 93, 95, NTR-OR Jan 89]
6 . Differentiate general anaesthetics and local anaesthetics. 7. Mention different types of local anaesthesia. [RGUHS
[RGUHS 03] Mar 04]
7 . Write the rationale of combining xylocaine with adrenaline for 8. Xylocaine. [NTR-OR Apr 97]
lignocaine. [NTR-OR Mar 05] 9. Sequential blockade. [NTR-OR Jan 92]
10. Intravenous anaesthetics. [NTR-NR Oct 04]
11. Mechanism of action of local anaesthetics. [NTR-NR Apr 03]
Short Notes 12. Toxicity of lidocaine. [BUHS Oct 87]
1. Lidocaine. [BUHS Apr 87, RGUHS Jul 91, Mar 94, NTR-OR 13. Lidocaine and mepivacaine. [RGUHS Apr 00]
Apr 98, Apr 99, Feb 01, NTR-NR Apr 06] 14. Mechanism of action of lidocaine. [RGUHS Apr 02]
2. Procaine hydrochloride. [RGUHS Apr 00] 15. Uses of adrenaline in lidocaine. [RGUHS Sep 98, Apr 99,
3. Topical local anaesthetics. [BUHS Jul 91, RGUHS Jul 91] Sep 99, Apr 02]
4. Adrenaline in lidocaine. [RGUHS Apr 00] 16. General anaesthesia and local anaesthesia. [RGUHS Aug 01]
PART VII : DRUGS ACTING ON CENTRAL NERVOUS SYSTEM

22. GENERAL ANAESTHETICS 7. Ketamine. [RGUHS Apr 02, NTR-OR Apr 99]
8. Halothane. [NTR-OR Oct 98]
Long Essays 9. Methotrexate. [NTR-OR Apr 97]
1. Enumerate general and local anaesthetics used in dental 10. Diethyl ether. [NTR-OR Jan 92, Oct 96]
practice. Describe the pharmacological actions, merits and 11. Thiopentone sodium. [NTR-OR Apr 85]
demerits of nitrous oxide as a sole general anaesthetic agent. 12. Preanaesthetic medication. [NTR-OR Apr 85]
[NTR-OR Dec 86] 13. Diazepam and atropine in preanaesthetic medication. [NTR-
2. Classify general anaesthetics. Write pharmacology of nitrous OR Apr 90]
oxide. [BUHS Aug 96, RGUHS Sep 99] 14. Benzodiazepine. [RGUHS Apr 99, Sep 00]
15. Ether and halothane. [RGUHS Aug 06]
16. Compare nitrous oxide and halothane. [BUHS Aug 88]
Short Essays 17. Compare nitrous oxide and diethyl ether. [BUHS Apr 87]
1. Operative procedure involved in stage II of GA. [RGUHS Mar 92]
2. Ether. [RGUHS Jun 89]
3. Compare nitrous oxide and diethyl ether. [RGUHS Apr 87]
23. ETHYL AND METHYL ALCOHOL
4. Compare nitrous oxide and halothane. [RGUHS Aug 88]
Short Essay
5. Benzodiazepine. [RGUHS Apr 99, Sep 00]
6. Adrenaline—its therapeutic uses, routes of administration. 1. Ethyl alcohol is used in methyl alcohol poisoning. Write the
[RGUHS Sep 99] rationale. [NTR-NR Apr 04]
7. Ketamine. [RGUHS Apr 02]
8. Two advantages and two disadvantages of halothane. [NTR-
NR Oct 02] Short Notes
9. Two advantages and two disadvantages of ether as general
anaesthetic. [NTR-NR Apr 03] 1 . Ethyl alcohol. [NTR-OR Feb 90]
10. One indication for combining nitrous oxide and halothane. 2. Methyl alcohol. [NTR-OR Jan 89]
Explain its rationale. [NTR-NR Sep 06]
11. Diazepam and its uses. [BUHS Jun 86, Aug 93]
12. Operative procedures involved in stage of GA. [BUHS 24. SEDATIVES/HYPNOTICS
Mar 92]
13. Intravenous anaesthetics. [NTRUHS June 13 (NR & OR)]
Long Essays
1. Classify hypnotics. Mention the pharmacological actions,
management of poisoning of barbiturates. [NTR-OR Feb 83]
Short Notes 2. Classify hypnosedatives. Discuss the pharmacological actions,
1. Classify general anaesthetics. [RGUHS Aug 96, Sep 99] uses and adverse effects of benzodiazepines. [NTR-OR Apr 98]
2. Why adrenaline is used along with good anaesthetic infiltra- 3. Define sedative hypnotics. Classify them. What are the advan-
tion. [RGUHS Sep 99] tages of benzodiazepines over barbiturates as sedative hypnotics?
3. Ether. [NTR-OR Apr 96, RGUHS Aug 95] [NTR-NR Apr 03]
4. Nitrous oxide. [NTR-OR Jan 89, RGUHS Jan 91] 4. Classify benzodiazepines. Explain their mechanism of action
5. Diazepam. [RGUHS Jun 86, Aug 93] and therapeutic uses. Mention their advantages over barbitu-
6. Preanaesthetic medication. [RGUHS Jul 91] rates as sedative hypnotics. [NTR-NR Oct 04]
5. Classify barbiturates. Discuss thiopentone sodium. [BUHS 3. Phenytoin is contraindicated during pregnancy. [NTR-NR
Nov 86] Mar 05]
6. Define sedatives, hypnotics and tranquilizers. Name the various 4. Phenytoin sodium in grand mal epilepsy. [RGUHS Aug 05]
barbiturate poisoning. [BUHS Mar 95] 5. Enlist the advantages and disadvantages of thiopentone
7. Classify hypnotics. Describe the uses, adverse effects and sodium. [RGUHS Mar 06]
treatment of barbiturates poisoning. [BUHS Apr 87] 6. Valproic acid—mechanism. [NTR-GR Apr 91]
8. Classify sedative hypnotics. Explain the mechanism of action 7. Carbamazepine. [NTRUHS Dec 12 (NR & OR)]
and adverse effects of diazepam. Enumerate its therapeutic
uses. [RGUHS Aug 05]
Short Notes
1 . Phenobarbitone. [RGUHS Jun 86, Jul 90]
Short Essays 2. Carbamazepine. [RGUHS Mar 05]
1. Classify barbiturates and write its uses and dose. [RGUHS R 3. Sodium valproate. [NTR-OR Oct 00, NTR-NR Apr 02]
Apr 00] 4. Phenytoin sodium. [NTR-OR Oct 97]
2. Two advantages of diazepam over phenobarbitones as hyp- 5. Diphenylhydantoin sodium. [NTR-GR Apr 93, NTR-NR Apr 06]
notic. [NTR-NR Sep 06] 6. Mention two drugs that cause gingival hyperplasia. [NTRUHS
3. Uses of benzodiazepine. [BUHS Feb 96] June 13 (NR & OR)]
4. Benzodiazepines as preanaesthetic medication. [RGUHS Aug 06] 7. Write two drugs used in grand mal epilepsy. [NTRUHS
June 13 (NR & OR)]
Short Notes
26. ANTIPARKINSONIAN DRUGS
1. Adverse effects of barbiturates. [RGUHS Sep 94]
2. Uses of benzodiazepine. [RGUHS Feb 96] Long Essay
3. Flumazenil. [RGUHS Mar 94]
4. Classify barbiturates, discuss thiopentone sodium. [RGUHS 1. Classify the drugs used in parkinsonism and discuss pharma-
Nov 86] cology and adverse effects of l-DOPA. [BUHS Mar 94]
5. Define sedatives, hypnotics and tranquilizers. [RGUHS Mar 95]
6. Classify hypnotics. [RGUHS Apr 87]
7. Diazepam. [NTR-OR Jan 92, Oct 97]
Short Essays
8. Benzodiazepines. [NTR-OR Jan 89] 1. What is dopamine? Mention one use and route of administra-
9. Phenobarbiturates. [NTR-OR Apr 96] tion. [NTR-NR Apr 06, RGUHS Apr 02, Mar 05]
10. Indications of diazepam. [NTR-NR Oct 02] 2. Levodopa is used in parkinsonism. [RGUHS Apr 99]
11. Classify barbiturates and write the uses and doses. [RGUHS
Apr 00]
12. Urine should be alkalized in acute barbiturate poisoning. Short Notes
Why? [RGUHS Apr 01] 1 . Pyridoxine is given with INH. [RGUHS Sep 99]
13. Why diazepam is preferred over phenobarbitone as sedative 2. Levodopa. [NTR-OR Oct 01]
– hypnotic. [NTRUHS Dec 12 (NR & OR)] 3. Dopamine. [NTR-OR Apr 84, RGUHS Mar 99]
4. Mention four drugs used in Parkinsonism. [NTRUHS Dec 12
25. ANTIEPILEPTIC DRUGS (NR & OR)]
Long Essays 27. DRUGS USED IN MENTAL ILLNESS:

1. Classify the drugs used in epilepsy. Write the mechanism of ANTIPSYCHOTIC AND ANTIANXIETY
action and adverse effects of diphenylhydantoin sodium.
[NTR-GR Aug 01]
DRUGS
2. Enumerate the antiepileptic drugs belonging to different Short Essays
groups. Explain the actions of phenytoin. How will you man-
age a case of convention precipitated during tooth extraction? 1 . Chlorpromazine. [RGUHS Sep 92]
[RGUHS Aug 98, Apr 99] 2. Neuroleptanalgesia. [RGUHS Apr 03]
3. Classify antiepileptic agents. Mention the mechanism of action 3. Mention two uses and two adverse effects of chlorpromazine.
and clinical uses of dilantin sodium. [BUHS Apr 94] [RGUHS Apr 02, NTR-NR Oct 02, Apr 06]
4. Anxiolytics. [NTRUHS June 13 (NR & OR)]
Short Essays
Short Note
1 . Diphenylhydantoin sodium. [RGUHS Aug 95, Sep 02]
2. Sodium valproate. [RGUHS Apr 02] 1. Chlorpromazine. [RGUHS Jun 90, Aug 95, NTR-OR Aug 01]
28. OPIOID ANALGESICS 10. Naloxone. [NTRUHS June 13 (NR & OR)]
AND ANTAGONISTS
Long Essays Short Notes
1. Pentazocine. [NTR-OR Oct 98, RGUHS Jul 05]
1. Classify narcotic analgesic group of drugs and write about
2. Uses of morphine. [NTR-OR Oct 91]
morphine. [NTR-OR Feb 90]
3. Codeine. [RGUHS Aug 05]
2. Classify narcotic analgesics. Discuss the uses and dangers of
4. Morphine. [RGUHS Mar 92, Feb 96]
morphine. Name morphine antagonists available. [NTR-OR
5. Procaine and cocaine. [RGUHS Aug 06]
Oct 96]
6. Adverse effects of morphine. [BUHS Sep 95]
3. Classify narcotic analgesics. Describe the actions, therapeutic
7. Therapeutic uses of morphine. [BUHS Sep 96]
uses and toxic effects of morphine. [NTR-OR Apr 85]
8. Contraindications of morphine. [BUHS Sep 94]
4. Classify analgesics. Discuss indications, contraindications for
9. Compare morphine and pethidine. [BUHS Apr 87]
the use of morphine giving reason. [BUHS Jun 86]
10. Write the CNS pharmacological actions of morphine. [BUHS
5. What are narcotic analgesics? Describe the pharmacological
Feb 96]
actions, uses and toxicity of opium alkaloids. [BUHS Aug 93]
11. Dextropropoxyphene. [RGUHS Mar 92]
12. Four drugs used in mental depression. [NTR-NR Apr 03]
Short Essays 13. Newer antidepressants. [NTR-NR Apr 00]
1. Morphine is contraindicated in head injury. [NTR-NR Oct 05]

2. Pentazocine. [BUHS Jul 93] 29. CNS STIMULANTS AND COGNITION
3. Dextropropoxyphene. [BUHS Mar 92] ENHANCERS
4. Morphine is used in acute left ventricular failure. [RGUHS
Apr 03] Short Essay
5. Mention the three contraindications for the use of morphine.
1. Analeptic drugs. [RGUHS Jan 90]
[RGUHS Aug 06]
6. Compare the two: morphine and pethidine. [RGUHS Apr 87]
7. Contraindications of morphine. [RGUHS Sep 94] Short Notes
8. Morphine is contraindicated in hypertension. [RGUHS Mar 04]
9. Rationale of using imipramine in mental depression. [NTR- 1 . Analeptics. [RGUHS Mar 92, Aug 95, Apr 98, NTR-OR Dec 86]
NR Apr 06] 2. Neuroleptics. [BUHS Aug 95]
PART VIII : CARDIOVASCULAR DRUGS

30. DRUGS AFFECTING 5 . Write the cardiac toxicity of digoxin. [RGUHS Mar 06]
6. Name two high ceiling diuretics and its two uses. [NTRUHS
RENIN-ANGIOTENSIN SYSTEM June 13 (NR & OR)]
AND PLASMAKININS
Short Note 32. ANTIARRHYTHMIC DRUGS
1. Enalapril. [NTR-OR Feb 01, RGUHS Mar 04] Short Essays
1 . Why procainamide is preferred to procaine. [RGUHS Feb 93]
31. CARDIAC GLYCOSIDES AND DRUGS 2. Nifedipine. [RGUHS Sep 02]
FOR CHF
Short Essay Short Notes
1. Therapeutic uses and adverse effects of digoxin. [NTR-OR 1 . Procainamide. [RGUHS Jan 89, Sep 99]
Apr 99] 2. Verapamil. [RGUHS Feb 93, BUHS Feb 94, NTR-OR Aug 01]
2. Digoxin is used in congestive cardiac failure. [RGUHS Apr 99] 3. Classification of antiarrhythmic drugs. [NTR-OR Oct 93]
3. Rationale of using digoxin in atrial fibrillation. [NTR-NR
Feb 02]
33. ANTIANGINAL AND OTHER
ANTI-ISCHAEMIC DRUGS
Short Notes
Long Essays
1 . Digitoxin. [RGUHS Apr 87, Jun 89, Aug 93, NTR-OR Jul 89]
2. Digoxin in atrial fibrillation. [RGUHS Apr 03] 1. Classify vasodilators. Describe the pharmacological actions
3. Nitroglycerine. [NTR-NR Sep 06] of nitrates, their clinical uses and side effects. [NTR-OR
4. Therapeutic uses of digoxin. [NTR-NR Apr 04] Feb 83]
2. Enumerate four antianginal drugs belong to different groups. 4. Classify drugs used in the treatment of hypertension. Discuss
Write the mechanism of action, uses and adverse effects of the pharmacological actions, uses and adverse effects of the
short acting drugs used for acute anginal attack. [RGUHS ACE inhibitors. [NTR-OR Apr 98]
Mar 06] 5. Classify antihypertensive drugs. Write the pharmacology of beta-
adrenoreceptor blocking drugs. [RGUHS Apr 98, RGUHS Apr 99]
Short Essays
Short Essays
1 . Drugs used in treatment of angina pectoris. [RGUHS Apr 99]
2. Cardioselective beta blockers. [RGUHS Apr 02] 1. Captopril. [RGUHS Sep 92]
3. Acute anginal pain. [RGUHS Oct 87] 2. Calcium channel blocking drugs in treatment of hypertension.
4. Nifedipine. [RGUHS Sep 04] [RGUHS Apr 00]
5. Calcium channel blockers in cardiovascular disorders. [RGUHS 3. Compare chlorothiazide and propranolol. [RGUHS Jan 89]
Aug 05] 4. List two centrally acting antihypertensive drugs. Mention the
6. List three drugs used in angina pectoris with one example for adverse effects of any one of them. [RGUHS Sep 99]
each group. [RGUHS Feb 07] 5. Calcium channel blockers. [NTR-NR Apr 02]
7. List one cardioselective and one nonselective beta-receptor 6. Rationale of using clonidine in hypertension. [NTR-NR
antagonists. Mention two therapeutic uses of them. [RGUHS Apr 04]
Sep 99] 7. Rationale of using beta blockers in hypertension. [NTR-NR
Oct 05]
8. Prazosin. [RGUHS Apr 00]
Short Notes 9. Propranolol. [RGUHS Sep 98, Sep 99]
1. Nifedipine. [RGUHS Jan 89, NTR-OR Apr 95, NTR-NR 10. Chlorothiazide diuretics in hypertension. [RGUHS Aug 06]
Oct 02, Oct 05] 11. Mention thiazides as an antihypertensive drug. [RGUHS Sep 02]
2. Name of drugs causing gingival hyperplasia. [RGUHS Sep 99] 12. What is prazosin? Mention one therapeutic use of it. [RGUHS
3. Nitroglycerine. [NTR-OR Oct 96] Sep 02]
4. Acute anginal pain. [BUHS Oct 87]
5. Drugs used in the treatment of angina pectoris. [RGUHS
Apr 99]
Short Notes
1. Propranolol. [RGUHS July 90, Sep 98, 99]
2. Clonidine. [RGUHS Aug 93, NTR-OR Apr 00]
34. ANTIHYPERTENSIVE DRUGS 3. Reserpine. [RGUHS Apr 87, Jan 90]
4. Mention two uses and two adverse effects of thiazide.
Long Essays [RGUHS Sep 02]
1. Classify antihypertensive drugs. Describe the pharmaco- 5. Name four drugs used in hypertension. [RGUHS Mar 04]
logical actions of any two commonly used drugs. [NTR-OR 6. Enalapril. [NTR-OR Feb 01, NTR-NR Feb 02]
Apr 96] 7. ACE inhibitors in hypertension. [NTR-OR Oct 98]
2 . Classify the drugs used on the treatment of hypertension. State 8. Four drugs used in hypertension. [NTR-NR Feb 02]
the mechanism of action, indications and adverse effects of any 9. Propranolol—antihypertensive actions and adverse effects.
three of them. [NTR-OR Jan 92] [NTR-OR Feb 91]
3 . Classify the drugs used in hypertension. Write the pharmaco- 10. ACE inhibitor drugs. [NTR-OR Oct 92, NTR-NR Oct 00]
logical actions and adverse effects of angiotensin converting 11. Captopril. [BUHS Sep 92]
enzyme (ACE) inhibitors. [NTR-NR Apr 2006] 12. Compare chlorothiazide and propranolol. [BUHS Jan 89]
PART IX : DRUGS ACTING ON KIDNEY

35. DIURETICS AND ANTIDIURETICS 7. Hydrochlorothiazide and frusemide. [RGUHS Mar 95]
8. Mention two therapeutic uses and two adverse effects of
Short Essays frusemide. [RGUHS Apr 02]
9. Compare hydrochlorothiazide and frusemide. [RGUHS
1 . Compare acetazolamide and frusemide. [RGUHS Oct 87]
Mar 05]
2. Classify diuretics and write mechanism of action of thiazides.
10. Classify diuretics. Write mechanism of action of thiazides.
[RGUHS Sep 99]
[RGUHS Sep 99]
3. Compare frusemide and spironolactone. [RGUHS Mar 94,
Mar 06]
4. Compare chlorothiazide and spironolactone. [RGUHS Oct 88] Short Notes
5. Chlorothiazide. [RGUHS Jan 90, Apr 98] 1 . Frusemide. [RGUHS Feb 96, NTR-OR Apr 97, Oct 97, Apr 00]
6. Classify diuretics. Write mechanism of action of thiazides. 2. Chlorothiazide. [RGUHS Jan 90]
[RGUHS Sep 99] 3. Potassium sparing diuretics. [RGUHS Jul 91]
4. Spironolactone. [RGUHS Sep 99] 15. Name two loops diuretics. Mention two uses of them. [NTR-NR
5. Osmotic diuretics. [RGUHS Aug 96] Apr 03]
6. Thiazides. [RGUHS Sep 98] 16. Mention two uses and two adverse effects of thiazides. [NTR-
7. Mannitol. [NTR-OR Oct 86] NR Oct 02]
8. Loop diuretics. [NTR-OR Jan 92, NTR-NR Oct 03] 17. Rationale of combining spironolactone with frusemide. [NTR-NR
9. Thiazide diuretics. [NTR-OR Jul 89, NTR-NR Mar 05] Sep 2006]
10. Potassium sparing diuretics. [NTR-OR Apr 88] 18. High sealing diuretics. [RGUHS Aug 05]
11. Name two loop diuretics. Mention two uses of them. [NTR- 19. Mention two uses and two adverse effects of thiazides.
NR Apr 03] [RGUHS Sep 03]
12. Triamterene and frusemide. [RGUHS Apr 05] 20. Enlist three diuretic drugs and one different use for each.
13. Name four diuretics. [NTR-NR Oct 05] [RGUHS Feb 07]
14. Rationale of combining thiazides with spironolactone. [NTR-NR 21. Mention two therapeutic uses and two adverse effects of
Oct 04] frusemide. [RGUHS Apr 02, Mar 05, Mar 06]
PART X : DRUGS AFFECTING BLOOD AND BLOOD FORMATION

36. HAEMATINICS 37. DRUGS AFFECTING COAGULATION,
AND ERYTHROPOIETIN BLEEDING AND THROMBOSIS
Long Essays Long Essays
1. Explain the mechanism of iron absorption in the body. Add a 1. Enumerate the agents used to control bleeding. Discuss their
note on different iron preparations. [NTR-OR Sep 84] actions and uses. [NTR-OR Jun 87]
2. Classify anticoagulants. Discuss the mechanism of action, uses
and adverse effects of the coumarin derivatives. [NTR-OR Oct 97]
Short Essays 3. Classify styptics. Describe the role of vitamin K when bleeding
1 . Parental iron preparations. [RGUHS Mar 92, Aug 96] is due to oral anticoagulation therapy. [RGUHS Sep 00]
2. Cyanocobalamin. [RGUHS Aug 95] 4. Describe how heparin and dicumarol act as anticoagulants.
3. Adverse effects of cyanocobalamin. [RGUHS Sep 99] Indicate their route of administration, duration of action and
4. List two anticoagulants acting by different mechanism. Men- name their antagonists. [BUHS Jun 86]
tion any two uses of them. [RGUHS Sep 98] 5. Classify anticoagulants and explain in detail about pharmaco-
5. Preparations of iron. [RGUHS Sep 02, NTR-OR Jun 87, Feb 01] logical action, pharmacodynamics, therapeutic uses and toxic-
6. Iron-sorbitol-citric acid. [RGUHS Aug 05] ity of heparin. [BUHS Apr 94, RGUHS Apr 00]
7. Desferrioxamine in iron poisoning. [RGUHS Apr 03]
8. Adverse effects of cyanocobalamin. [RGUHS Sep 99]
9. Ferrous gluconate is used in microcytic hypochromic anaemia.
Short Essays
[RGUHS Apr 99] 1. Styptics. [RGUHS Feb 96]
2. Anticoagulants. [RGUHS Aug 95]
3. Compare heparin and oral anticoagulants. [RGUHS Apr 00]
Short Notes 4. Dicumarol poisoning. [RGUHS Jan 89]
1. Drugs for anaemia. [RGUHS Sep 94] 5. Compare heparin and dicumarol. [RGUHS Apr 87, Jan 90]
2. Iron preparations. [RGUHS Mar 94, NTR-NR Mar 03] 6. Adverse effects of cyanocobalamin or vitamin B12. [RGUHS
3. Ferrous sulphate. [RGUHS Jun 89, Feb 93, R Apr 99, NTR- Sep 99]
OR Apr/Oct 96] 7. Dicoumarol and heparin. [RGUHS Mar 05]
4. Vitamin B12. [NTR-OR Feb 83, Apr 97] 8. Explain the mechanism of action of streptokinase and mention
5. Folic acid. [NTR-OR Apr 98] one use of it. [RGUHS Aug 06]
6. Cyanocobalamin. [BUHS Aug 95, NTR-OR Apr 85] 9. Name two oral anticoagulants. Mention one drug treating
7. Drugs used in microcytic anaemia. [NTR-OR Jan 92] toxicity of oral anticoagulants. [RGUHS Sep 02]
8. Drugs used for pernicious anaemia. [NTR-OR Apr 93] 10. Coagulants. [NTRUHS Dec 12 (NR & OR)]
9. Indications for parenteral use of iron. [NTR-OR Oct 89]
10. Mention two oral and parenteral preparations. [NTR-NR Feb 02]
11. Vitamin C is given with iron in the treatment of anaemia.
Short Notes
[NTR-NR Feb 02] 1 . Vitamin K deficiency. [RGUHS Apr 00]
12. List two coagulants acting by different mechanism. Mention 2. Styptics. [RGUHS Sep 92, Mar 05, NTR-OR Jun 87]
any two uses of them. [RGUHS Sep 98] 3. Streptokinase. [RGUHS Mar 05]
4. Heparin. [NTR-OR Apr 97, Apr 99, TR-OR Apr 00, NTR-NR 19. Compare heparin and dicumarol. [BUHS Apr 87, RGUHS
Sep 06] Mar 05]
5. Vitamin K. [NTR-OR Apr 93, Apr 96, Apr 98] 20. Compare heparin and oral anticoagulants. [RGUHS Apr 00]
6. Fibrinolytics. [NTR-NR Oct 05]
7. Fibrinolytic agents. [NTR-OR Aug 01, NTR-NR Apr/Oct 03]
8. Hemostasis. [NTR-OR Sep 83]
38. HYPOLIPOPROTEINAEMIC DRUGS
9. Warfarin. [NTR-OR Apr 98] AND PLASMA EXPANDERS
10. Warfarin sodium. [NTR-OR Apr 96]
11. Oral anticoagulants. [NTR-NR Apr 04] Short Essays
12. Therapeutic uses of vitamin K. [NTR-OR Dec 86] 1. Plasma expanders. [RGUHS Mar 05, NTRUHS Dec 12 (NR &
13. Mechanism of action of heparin. [NTR-OR Oct 02] OR)]
14. Drugs used in pernicious anaemia. [NTR-OR Apr 93, Apr 98] 2. What is plasma expander? Give two examples. [NTR-NR
15. Vitamin K is used in the overdosage of warfarin. [NTR-NR Oct 05]
Oct 03]
16. Anticoagulants. [BUHS Aug 95]
17. Dicumarol poisoning. [BUHS Jan 89]
Short Note
18. Adverse effects of vitamin B12. [RGUHS Sep 99] 1. Plasma expanders. [RGUHS Apr 87, NTR-NR Oct 04]
PART XI : GASTROINTESTINAL DRUGS

39. DRUGS FOR PEPTIC ULCER 1 5. Metoclopramide. [RGUHS Aug 05 NTR-OR Aug 05]
16. Cimetidine and ranitidine. [RGUHS Feb 07]
Long Essay 17. Ranitidine is preferred to cimetidine. [BUHS Oct 87]
18. Antihistamine drugs in peptic ulcers. [RGUHS Sep 99]
1 . What is antacid? Classify with suitable examples. Mention
19. Classify drugs used in treatment of peptic ulcers. [RGUHS
the merits and demerits of NaHCO3 as an antacid. [NTR-OR
Apr 99]
Apr 84]
20. What is omeprazole? Mention its two uses. [NTR-NR Apr 03]
21. Mention two prokinetic drugs and their adverse effects.
Short Essays [NTR-NR Oct 02]
22. Give two reasons for prescribing ranitidine over cimetidine.
1 . Classify drugs used in treatment of peptic ulcer. [RGUHS [NTR-NR Apr 04]
Apr 99] 23. Rationale of combining aluminium hydroxide gel and magne-
2 . Antihistaminic drugs in peptic ulcer. [RGUHS Sep 98] sium trisilicate as antacids. [NTR-NR Apr 06]
3 . H2 blockers. [RGUHS Oct 87, Apr 99, 00] 24. Sucralfate. [BUHS Aug 93]
4. Cimetidine. [RGUHS Sep 99] 25. H2 antagonists. [BUHS Aug 88]
5. Ranitidine. [RGUHS Sep 02] 26. Carbenoxolone sodium. [BUHS Apr 87]
6. Antacids. [RGUHS Mar 04] 27. Proton pump inhibitors. [RGUHS Mar 04]
7. Amoxycillin and gentamicin. [RGUHS Mar 05] 28. Omeprazole is used in peptic ulcers. [RGUHS Apr 00, Aug 06]
29. Explain the mechanism of action of omeprazole. [RGUHS
Aug 06]
Short Notes 30. Aspirin is contraindicated in peptic ulcers. [RGUHS Apr 03]
1. H2 antagonist. [RGUHS Apr 87] 31. Mention four proton pump inhibitors. [NTRUHS Dec 12 (NR
2. Cimetidine. [RGUHS Aug 93, Sep 99] & OR)]
3. Antacids. [RGUHS Jan 90, Mar 95]
4. Sucralfate. [RGUHS Aug 88]
5. Carbenoxolone sodium. [RGUHS Apr 00] 40. EMETICS, ANTIEMETICS AND OTHER
6. Omeprazole is used in peptic ulcer. [RGUHS Apr 03, Sep 04, GASTROINTESTINAL DRUGS
NTR-NR Oct 05]
7. Ranitidine. [NTR-OR Oct 92, Aug 01, NTR-NR Oct 05] Short Essays
8. Omeprazole. [NTR-OR Feb 01, NTR-NR Apr 06] 1 . Compare promethazine and ranitidine. [RGUHS Jan 89]
9. The antacids. [NTR-OR Apr 85, Jan 92] 2. Emetics. [RGUHS Jul 91, Aug 96, Sep 98]
10. Magnesium sulphate. [NTR-OR Apr 96] 3. Metoclopramide. [RGUHS R Apr 98, 00, R Sep 98]
11. Prokinetic drugs. [NTR-NR Oct 04, Sep 06] 4. Prokinetic agents. [RGUHS Apr 03]
12. Aluminium hydroxide. [NTR-OR Apr 95, Apr 97, Apr 1998, 5. Rationale of using domperidone as antiemetics. [NTR-NR
Oct 99] Apr 03]
13. What is omeprazole? Mention its two uses. [NTR-NR Apr 03] 6. Domperidone is preferred over metoclopramide in vomiting.
14. H2 blockers. [RGUHS Apr 99, Apr 00, Oct 02] [NTR-NR Mar 05]
7 . Name two antiemetics drugs and mention their adverse effects. 2. List two purgatives giving an indication for each of them.
[RGUHS Feb 07] [RGUHS Sep 98]
8 . Antiemetics. [NTRUHS June 13 (NR & OR)] 3. ORS. [RGUHS Sep 04]
4. Rationale of using loperamide in diarrhoea. [NTR-NR
Apr 06]
Short Notes
1. Metronidazole. [RGUHS Apr 99]
2. Name two drugs used to suppress vomiting. [RGUHS Mar 04]
Short Notes
3. Metoclopramide. [NTR-OR Apr 96, Apr 00] 1. Bulk purgatives. [RGUHS Jun 89]
4. Rationale of using metoclopramide in vomiting. [NTR-NR 2. Magnesium sulphate. [NTR-OR Oct 96, RGUHS Sep 99]
Feb 02] 3. Name two osmotic purgatives. [RGUHS Apr 02, Mar 05]
5. Rationale of using domperidone as antiemetics. [NTR-NR Apr 03] 4. Mention two drugs used in noninfective diarrhoea. [RGUHS
6. Mention two prokinetic drugs and their two adverse effects. Mar 04]
[NTR-NR Oct 03] 5. Loperamide. [NTR-NR Mar 05]
7. Antiemetics. [RGUHS Aug 96, Sep 99] 6. Liquid paraffin. [NTR-OR Jun 87, Jul 89]
8. Promethazine. [RGUHS Mar 04] 7. Saline purgatives. [NTR-OR Apr 99]
9. Prokinetic drugs. [RGUHS Apr 03] 8. Osmotic purgatives. [NTR-NR Apr 03]
10. Compare promethazine and ranitidine. [BUHS Jun 89] 9. Anthraquinone preparations. [NTR-OR Apr 84]
10. Hazards of use of purgatives. [NTR-OR Dec 86]
11. ORS. [RGUHS Mar 04]
41. DRUGS FOR CONSTIPATION 12. Osmotic purgatives. [RGUHS Mar 06]
AND DIARRHOEA 13. Drugs used as purgatives. [RGUHS Apr 98, Apr 00]
14. List two purgatives giving an indication for each. [RGUHS
Short Essays Sep 98]
1. Drugs used as purgatives. [RGUHS Apr 98, 00]
PART XII : ANTIMICROBIAL DRUGS

42. GENERAL CONSIDERATIONS 3. Classify drugs used in the treatment of infections caused by
Gram-negative organisms. Discuss the mechanism of action,
Long Essays uses and adverse effects of fluoroquinolones. [NTR-OR Oct 97]
4. Classify sulphonamides. Discuss the mechanism of action,
1 . Mention some examples of antibiotics and describe the mecha-
adverse effects and uses of co-trimoxazole. [BUHS Mar 92]
nism of action and side effects of two commonly used antibiot-
ics. [NTR-OR Sep 83]
2. Classify antimicrobial agents based on the mechanism of Short Essays
action with examples. Explain four advantages of combined
use of antimicrobials with examples. [RGUHS Feb 07] 1. Classify sulphonamides. Write important adverse effects.
[RGUHS Apr 00]
2. Co-trimoxazole. [RGUHS Jul 90, Feb 96, R Sep 99]
Short Essay 3. Ciprofloxacin should not be used in children. [NTR-NR Oct 04]
4. Rationale for combining sulfamethoxazole and trimethoprim.
1 . What is superinfection? Give two examples. [NTR-NR Apr 03] [NTR-NR Mar 05]
5. Sulfonamides are not very effective in the presence of pus.
Short Note Explain. [NTR-NR Oct 04]
6. Explain the mechanism of action of co-trimoxazole. [RGUHS
1 . Superinfection. [NTR-OR Oct 98] Mar 06]
43. SULPHONAMIDES, CO-TRIMOXAZOLE Short Notes

AND QUINOLONES 1. Co-trimoxazole. [NTR-OR Apr 85, Jun 87, Apr 97, Oct 98,
Apr 00, NTR-NR Oct 05, RGUHS Jan 91, Aug 93]
Long Essays 2. Rationale of combination of sulfamethoxazole with trime-
1 . Enumerate fluoroquinolones. Write their therapeutic uses and thoprim. [RGUHS Mar 04]
adverse effects. [NTR-NR Oct 05] 3. Clarify sulphonamides. Discuss the mechanism of action,
2 . Enumerate fluoroquinolones. Mention their antimicrobial spec- adverse effects and uses of co-trimoxazole. [RGUHS Mar 92]
trum, therapeutic uses and adverse effects. [NTR-OR Aug 01] 4. Ciprofloxacin. [NTR-OR Oct 98, Apr 99]
5 . Long-acting sulphonamides. [NTR-OR Jan 88, Jul 89] 9. Rationale of combining amoxicillin and clavulanic acid.
6. Classify sulphonamides. Write important adverse effects. Write one indication of this combination. [NTR-NR Sep 06]
[RGUHS Apr 00] 10. Penicillin acts as a bactericidal agent. [BUHS Jun 86]
7. Mention two topically used sulfonamides. [NTRUHS Dec 12 11. Probenecid and penicillin in chemotherapy. [RGUHS Sep 99]
(NR & OR)] 12. Cloxacillin and the staphylococcal infections. [RGUHS
Aug 05]
13. Amoxicillin is combined with clavulanic acid. [RGUHS
44. BETA-LACTAM ANTIBIOTICS Mar 04]
14. Name four semisynthetic penicillin preparations. [RGUHS
Long Essays Mar 06]
1. Discuss the mechanism of benzyl penicillin action, uses and
adverse effects. [NTR-OR Oct 98]
2. Classify drugs used in the treatment of infections caused by Short Notes
Gram-positive organism. [NTR-OR Apr 00] 1. Semisynthetic penicillin. [RGUHS Sep 92]
3. Define the terms chemotherapeutic agents and antibiotics. 2. Broad-spectrum penicillin. [RGUHS Jun 86, R Apr 99, BUHS
Describe the newer penicillins. [NTR-OR Apr 84] Sep 92]
4. Classify penicillins. Describe the mechanism of action, 3. Ampicillin. [RGUHS Oct 87, Sep 99, Mar 05]
antibacterial spectrum and the therapeutic uses of ampicillin. 4. Cephalosporins. [BUHS Jul 91, RGUHS 91]
[NTR-NR Mar 05] 5. Penicillin acts as a bactericidal agent. [RGUHS Sep 99]
5. Define antibiotics. Classify penicillins. Explain their mecha- 6. Amoxicillin. [RGUHS Jun 89, NTR-OR Jan 88, Jul 89, Apr 00]
nism of actions, toxicity and important uses of penicillins. 7. D-penicillamine. [NTR-NR Sep 06]
[NTR-OR Jan 92] 8. Semisynthetic penicillins. [NTR-NR Oct 02, Oct 03, BUHS
6. Classify penicillins. Discuss the therapeutic uses and adverse Jan 91]
effects of benzyl penicillin. [BUHS Jul 90] 9. Beta-lactamase inhibitors. [NTR-OR Apr 98, RGUHS
7. Enumerate various penicillins and give its toxicity. Write Mar 06]
the treatment of penicillin in anaphylactic shock. [BUHS 10. Oral penicillin. [RGUHS Mar 04]
Mar 95] 11. Ampicillin and amoxicillin. [RGUHS Mar/Aug 06]
8. Define antibiotic. Describe the benzyl penicillin and mention 12. Uses of benzyl penicillin. [BUHS Aug 95]
about newer penicillins and their uses. [BUHS Aug 93] 13. Broad-spectrum penicillins. [RGUHS Oct 04]
9. Classify semisynthetic penicillins. Describe the spectrum of 14. Extended-spectrum penicillins. [RGUHS Sep 98, Apr 06]
action, adverse effects and therapeutic uses of amoxicillin. 15. Adverse effects of penicillin. [BUHS Aug 96]
[RGUHS Mar 04] 16. Amoxicillin and gentamicin. [RGUHS Apr 03]
10. Classify semisynthetic penicillins. Discuss the mechanism of 17. Penicillinase-resistant penicillin. [RGUHS Aug 97]
action, adverse effects and therapeutic uses of amoxicillin.
[RGUHS Aug 05]
11. Classify penicillin. Write in brief the therapeutic uses of 45. TETRACYCLINES AND
penicillin G. Add a note on treatment of acute anaphylactic CHLORAMPHENICOL
shock due to intramuscular injection of procaine penicillin.
[RGUHS Apr 02] Long Essays
12. Enumerate beta-lactam antibiotics. Write antibacterial spec-
1. Enumerate tetracyclines. Write their antimicrobial spectrum
trum, adverse effects and therapeutic uses of amoxicillin.
and therapeutic uses. [NTR-OR Feb 01]
[NTRUHS June 13 (NR & OR)]
2. Enumerate tetracycline preparations. Write their therapeutic
13. Classify semisynthetic penicillins. Describe the antibacterial
uses and adverse effects. [NTR-NR Apr 03]
spectrum, uses and adverse effects of Ampicillin. [NTRUHS
3. Explain broad-spectrum antibiotics. Describe the mechanism
Dec 12 (NR & OR)]
of action, therapeutic uses and toxic effects of tetracyclines.
[NTR-OR Apr 85]
Short Essays 4. Describe the clinical uses and toxicity of tetracyclines. How will
you treat a case of superinfection due to tetracycline therapy?
1 . Oral penicillins. [RGUHS Aug 95] [NTR-OR Dec 86]
2. Adverse effects of penicillin. [RGUHS Aug 96] 5. Enumerate tetracycline preparations. Write about therapeutic
3. Uses of benzyl penicillin. [RGUHS Aug 96] uses and adverse effects. [RGUHS Sep 02]
4. Cephalosporins. [RGUHS Mar 94] 6. Enumerate tetracyclines. Write their therapeutic uses and
5. Extended-spectrum penicillin. [RGUHS Apr 03] adverse effects of the same. [RGUHS Apr 06]
6. Enumerate four wider spectrum penicillins. [NTR-NR Apr 04] 7. List four tetracyclines. Explain the pharmocokinetic differ-
7. Rationale of using probenecid with penicillin. [NTR-NR Oct 02] ences among tetracyclines. [RGUHS Sep 99]
8. What is d-penicillamine? Mention its two uses. [NTR-NR 8. What are broad-spectrum antibiotics? Discuss adverse of
Apr 04] indiscriminate use of tetracyclines. [BUHS Nov 85, Sep 92]
9 . What are broad-spectrum antibiotics? Enumerate various tetra- Short Notes

cyclines. Discuss the adverse effects of tetracyclines. [BUHS
1 . Aminoglycoside antibiotics. [RGUHS Oct 99, BUHS Feb 96]
Jan 91, RGUHS Apr 98, Mar 06]
2. Streptomycin. [RGUHS Mar 97]
3. Gentamicin. [RGUHS Feb 93, NTR-OR Apr 97, Apr 98]
Short Essays
1. Tetracyclines. [RGUHS Aug 95] 47. MACROLIDE AND OTHER
2. Differences between oxytetracycline and doxycycline. ANTIBACTERIAL DRUGS IN TREATMENT
[RGUHS Apr 03, BUHS Sep 94]
3. Adverse effects of broad-spectrum antibiotics. [RGUHS
OF URINARY TRACT INFECTIONS
Sep 94] Long Essay
4. Tetracycline should not be given with antacids. [NTR-NR Oct
02, Oct 03] 1. Enumerate macrolide antibiotics. Describe the antimicrobial
5. Give reasons for not prescribing tetracyclines to a child of five spectrum and therapeutic uses of erythromycin. [RGUHS
years. [NTR-NR Apr 02] Mar 04]
6. Tetracyclines are contraindicated during pregnancy and infancy.
[NTR-NR Oct 04]
Short Essays
7. Enlist four tetracyclines. [RGUHS Mar 06]
8. Adverse effects of tetracycline. [RGUHS Jan 89] 1 . Four therapeutic uses of erythromycin. [NTR-NR Apr 03]
9. Adverse effects of chloramphenicol. [BUHS Oct 87, RGUHS 2. Erythromycin. [RGUHS Jun 86, Aug 96]
Oct 87]
10. Tetracyclines are contraindicated during pregnancy. [RGUHS
Apr 03] Short Notes
11. Mechanism of action and adverse effects of chloramphenicol. 1 . Erythromycin. [RGUHS Jan 86, Aug 96]
[NTRUHS June 13 (NR & OR)] 2. Gentamicin. [NTR-OR Jul 89, Jan 92, Oct 96, Apr 98]
3. Streptomycin. [NTR-OR Feb 90]
4. Macrolide antibiotics. [RGUHS Mar 06]
Short Notes
1 . Tetracyclines. [NTR-OR Apr 98]
2. Doxycycline. [NTR-OR Apr 99] 48. ANTITUBERCULAR DRUGS
3. Chloramphenicol. [NTR-OR Oct 92]
4. Tetracyclines and doxycycline. [RGUHS Feb 07]
Long Essays
5. Adverse effects of broad-spectrum antibiotics. [BUHS Mar 94] 1. Classify drugs used in tuberculosis. Write the pharmacology of
6. Tetracyclines are contraindicated during pregnancy. Why? any two commonly used drugs. [NTR-OR Apr 97]
[NTRUHS Dec 12 (NR & OR)] 2. Enumerate the drugs used in the treatment of tuberculosis.
Write the mechanism of action and adverse effects of any one
of them. [NTR-NR Apr 02]
46. AMINOGLYCOSIDE ANTIBIOTICS 3. Discuss drugs used for treating tuberculosis. Discuss any one
of antitubercular drugs. [BUHS Jan 86]
Long Essays 4. Discuss chemotherapy of pulmonary tuberculosis. Mention
1. Enumerate aminoglycoside antibiotics. Write the antimicrobial mechanism of action, adverse effects of three commonly used
spectrum, side effects and therapeutic uses of gentamicin. drugs. [BUHS Jan 90]
[NTR-OR Apr 00]
2. Enumerate aminoglycoside antibiotics. Write the antimicrobial
spectrum, therapeutic uses and adverse effects of any one of Short Essays
them. [NTR-NR Feb 02] 1. Pyridoxine should be administered with isonicotinic acid
3. Classify drugs used in the treatment of infections caused by hydrazide (INH). [NTR-NR Mar 05]
Gram-negative organisms. Discuss the mechanism of action, 2. Mention four adverse effects of rifampicin. [NTR-NR Mar 05]
uses and adverse effects of fluroquinolones. [NTR-OR Oct 97] 3. One use and mechanism of action of INH. [NTR-NR Sep 06]
4. What are aminoglycoside antibiotics? Briefly state the pharma- 4. Mention two important uses of rifampicin and its two adverse
cological actions, adverse effects and uses of anyone of them. effects. [NTR-NR Oct 02]
[RGUHS Mar 05] 5. Rationale of combining INH with pyridoxine in the treatment
of tuberculosis. [NTR-NR Oct 05]
6. INH. [RGUHS Aug 95, Apr/Sep 99]
Short Essays 7. DOTS in chemotherapy of TB. [RGUHS Mar 04]
1 . Aminoglycoside. [RGUHS Feb 96] 8. Mention the six drugs used in tuberculosis. [RGUHS Feb 07]
2. Mention two therapeutic uses and two adverse effects of genta- 9. INH is combined with pyridoxine in the treatment of tubercu-
micin. [NTR-NR Oct 05] losis. [RGUHS Sep 99, Apr 03]
10. Explain why multidrug therapy is used in the treatment of 51. ANTIVIRAL DRUGS
tuberculosis. [RGUHS Mar 06]
Short Essay
Short Notes 1. Antiviral drugs. [RGUHS Jan 90]
1. INH. [RGUHS Aug 95, Apr/Sep 99]

2. Rifampicin. [BUHS Oct 87, NTR OR Feb 01, NTR-NR Short Notes
Oct 04, RGUHS Oct 87]
1 . Acyclovir. [NTR-OR Apr 98]
3. DOTS in chemotherapy of tuberculosis. [RGUHS Sep 04]
2. Zidovudine. [RGUHS Aug 00]
4. Pyridoxine with isoniazid. [RGUHS Sep 04]
5. Dapsone. [NTR-OR Oct 96, Oct 97]
6. Isoniazid. [NTR-OR Oct 98] 52. ANTIMALARIAL DRUGS
7. Pyrazinamide. [NTR-OR Apr 93]
8. Isonicotinic acid hydrazine. [NTR-OR Oct 98] Long Essay
9. INH (isonicotinic acid hydrazide). [NTR-OR Apr 99]
10. Four adverse effects of rifampicin. [NTR-NR Feb 02] 1. Classify the drugs used in malaria and briefly outline mecha-
11. Isoniazid acetylator status in TS chemotherapy. [RGUHS nism of action, clinical uses and toxicity of chloroquine.
Aug 05] [RGUHS Mar 94]
49. ANTILEPROTIC DRUGS Short Notes

1 . Emetine. [RGUHS Apr 99]
Short Essays 2. Chloroquine. [BUHS Apr 87, NTR-OR Oct 97]
1. Mention the four drugs used in lepra reaction. [NTR-NR Oct 02] 3. Mention four antimalarial drugs. [NTRUHS Dec 12 (NR &
2. Enlist three drugs for leprosy. [RGUHS Aug 06] OR)]
3. Treatment of lepra reaction. [NTRUHS Dec 12 (NR & OR)]
53. ANTIAMOEBIC AND OTHER
Short Notes ANTIPROTOZOAL DRUG
1 . Dapsone. [RGUHS Jul 90, Feb 93] Long Essay
2. Schedule for treatment of leprosy. [RGUHS Sep 98]
3. Multidrug therapy in leprosy. [RGUHS Apr 00] 1. Define chemotherapy. Classify the drugs used in treatment of
4. Lepra reaction. [RGUHS Mar 94, NTR-NR Feb 02] amoebiasis and malaria. [RGUHS Apr 87, Aug 95, Apr 99]
5. DDS. [NTR-OR Oct 96, Oct 97]
6. Treatment of lepra reaction. [NTR-NR Mar 05]
7. Mention four drugs used in lepra reaction. [NTR-NR Oct 03] Short Essays
8. Multidrug therapy in leprosy. [RGUHS Apr 00] 1. Therapeutic uses of metronidazole in dentistry. [RGUHS Sep 04,
9. Schedule for treatment of leprosy. [RGUHS Sep 98] Mar 04]
2. Four uses of metronidazole. [NTR-NR Sep 06]
3. Mention three uses and three adverse effects of metronidazole.
50. ANTIFUNGAL DRUGS [RGUHS Aug 06]
Short Essays
1 . Amphotericin B. [RGUHS Mar 04] Short Note
2. Antifungal drugs. [RGUHS Mar 05]
1. Metronidazole. [NTR-OR Jan 92, Oct 97, Jul 98, RGUHS
3. Name four drugs used in fungal infections. [NTR-NR Apr 06]
Oct 87, Aug 88, Jul 90, Apr 99]
Short Notes
54. ANTIHELMINITICS
1 . Name two broad-spectrum antifungal drugs. [RGUHS Jan 91]
2. Nystatin. [RGUHS Jan 90, Mar 05] Short Essay
3. Antiviral drugs. [RGUHS Apr 92]
1. Treatment of hookworm infestation. [RGUHS Mar 94,
4. Griseofulvin. [NTR-OR Feb 01]
Aug 95]
5. Ketoconazole. [NTR-OR Apr 98]
6. Amphotericin B. [BUHS Jul 90]
7. Antifungal drugs. [BUHS Apr 92]
Short Note
8. Mention four antifungal drugs. [NTRUHS June 13 (NR &
OR)] 1. Paperizine citrate. [NTR-OR Feb 90]
PART XIII : CHEMOTHERAPY OF NEOPLASTIC DISEASES

55. ANTICANCER DRUGS 2. Name two antibiotics used in cancer therapy. [RGUHS R Sep
02, RGUHS Sep 02, Apr 04, Mar 05]
Short Essays 3. Antimetabolites. [NTR-NR Oct 02, RGUHS R Mar 05]
4. Methotrexate. [NTR-OR Jul 87, Aug 01]
1 . List four toxic effects of alkylating agents. [RGUHS Sep 98]
5. Name vinca alkaloids. [NTR-NR Mar 05]
2. Vinca alkaloids. [RGUHS Sep 98]
6. Cyclophosphamide. [NTR-OR Oct 97]
3. Name two antimetabolites used in cancer therapy. [RGUHS
7. Antibiotics in cancer chemotherapy. [NTR-OR Oct 98]
Apr 02]
8. What is methotrexate? Mention two of its uses. [NTR-NR
4. List four toxic effects of alkylating agents. [RGUHS Sep 98]
Apr 04]
5. Methods to ameliorate the toxicity of anticancer drugs. [NTR-
9. Name four antimetabolites used in cancer therapy. [NTR-NR
NR Sep 06]
Oct 05]
10. Name four antimetabolites used in cancer chemotherapy.
Short Notes [NTRUHS June 13 (NR & OR)]
1. Nitrogen mustard. [RGUHS Mar 92]
PART XIV : MISCELLANEOUS

56. IMMUNOSUPPRESSANTS, GENE 58. CHELATING AGENTS
THERAPY AND DRUGS ACTING ON SKIN Short Essays
AND MUCOUS MEMBRANES
1 . Dimercaprol. [RGUHS Jun 89, Sep 99]
Short Essay 2. Chelating agents. [BUHS Sep 92, RGUHS Aug 96, Sep 98]
3. EDTA. [RGUHS Sep 99]
1. Uses of astringents in dental practice. [RGUHS Sep 98]
4. Name four chelating agents. [NTR-NR Feb 02, RGUHS Apr
02, Mar 05]
Short Notes 5. Dimercaprol used in arsenic poisoning. [RGUHS Sep 99]
6. Define chelation. Mention four chelating agents. [RGUHS Mar 01]
1 . Tannic acid. [RGUHS Jan 90]
2. Clove oil. [RGUHS Mar 92]
3. Counter irritants. [NTR-OR Apr 84, NTR-OR Feb 90]
Short Notes
4. Astringents. [BUHS Jun 89, RGUHS Apr 98] 1 . Chelating agents. [RGUHS Sep 92, Mar 05, Feb 07]
2. BAL. [RGUHS Mar 97, Sep 98]
3. Dimercaprol. [RGUHS Mar 97, NTR-NR Oct 04]
57. ANTISEPTICS, DISINFECTANTS 4. EDTA. [NTR-OR Jun 87]
AND ECTOPARASITICIDES 5. Desferrioxamine. [NTR-NR Aug 06]
6. Heavy metal antagonists. [NTR-OR Aug 01]
Long Essay
1. Define and classify antiseptics. Write in detail about mecha- 59. VITAMINS
nism of action, different preparations and uses of phenol.
[RGUHS Sep 99] Short Essays
1 . Pyridoxine. [RGUHS Jul 91]
Short Essays 2. Ascorbic acid. [RGUHS Nov 86, Sep 98]
3. Thiamin deficiency. [RGUHS Apr 00]
1 . Acriflavine. [RGUHS Jul 90] 4. Ascorbic acid deficiency. [RGUHS Apr 00]
2. Chlorhexidine. [RGUHS Feb 93, Mar 04] 5. Name two fat-soluble vitamins and mention two uses of any-
3. Potassium permanganate. [RGUHS Jun 89] one. [RGUHS Sep 02]
4. Uses of antiseptics in dentistry. [RGUHS Jan 91, RGUHS R
Sep 98]
5. Bleaching agents. [RGUHS Mar 05]
Short Notes
6. Commonly used antiseptics. [BUHS Jan 91, RGUHS Mar 05] 1 . Ascorbic acid. [RGUHS Mar 92, Feb 93, RGUHS R Apr 00]
7. Antiseptics and disinfectants. [NTRUHS Dec 12 (NR & OR)] 2. Vitamin C. [NTR-OR Feb 01]
3 . Vitamin B6. [NTR-OR Dec 86] fluoride is used for this purpose? Give a short account of fluo-
4. Vitamin B12 (cyanocobalamin). [NTR-OR Apr 97] ride toxicology. [RGUHS Sep 02]
5. Pyridoxine. [BUHS Jul 91] 2. Classify disinfectants and antiseptics used in dental practice
6. Ascorbic acid. [BUHS Nov 86, RGUHS Sep 98] with suitable examples. Describe their general uses in den-
tistry. What are the specific uses of clove oil and eugenol?
[RGUHS Mar 05]
60. VACCINES AND SERA
Short Essay Short Essays
1. What procedure will be adapted so that tetanus does not result
1 . Describe briefly obtundents. [NTR-NR Sep 06]
from your treatment? How will you treat a case of tetanus?
2. Dentifrices. [RGUHS Aug 00]
[RGUHS Oct 87]
3. Disclosing agents. [RGUHS Mar 04]
4. Bleaching agents. [RGUHS Mar 05]
Short Note 5. Dental Abrasives. [NTRUHS Dec 12 (NR & OR)]
1. Posterior pituitary extract given by IV drop before delivery

only. [RGUHS Oct 01] Short Notes
1 . Fluorides in dentistry. [TN Apr 00]
61. DENTAL PHARMACOLOGY 2. Sialogogues. [RGUHS Aug 00]
3. Mummifying agents. [RGUHS Sep 98]
Long Essays 4. Mouthwashes. [NTRNR Dec 12]
1. Discuss fluoride pharmacology in relation to its utility as an 5. Use of fluorides in caries. [RGUHS Mar 05]
anticaries agent. What are the different formulations in which 6. Chlorhexidine. [TN Apr 04]
Index
A Acute myeloblastic leukaemia Agar, 24 Amoebic infection, 193

Abdominal actinomycosis, 131 (AML), 199 Agar agar, 23 Amoxicillin, 533–535
Abortive transduction, 265 Acute myeloid leukaemia, 200, Agar sol, 18 Amphetamine, 399
Abrasion, 51 204, 211 Agglutination, 276 Amphotericin B, 553
Abrasive and polishing Acute rheumatic fever, 293, 295 Agglutination test, 313 Ampicillin, 530, 534, 535
agents, 46 Acute toxicity, 572 Agranulocytic angina, 212 Amyloid, 163, 164, 170
Abrasives, 574 Acyclovir, 556 Agranulocytosis, 203, 212 Amyloidosis, 163, 165, 169
Absorption, 368, 427 ADA specifications, 3, 32, 39 AIDS virus, 333 of kidney, 164
Acarbose, 424 Adaptive immunity, 269–271 Air bubbles, 16, 35 of liver, 170
Accelerators, 19 Addictions/drug dependence, Air emboli, 155 Antioxidants, 119
Acetyl salicylic acid or 380, 382 Air embolism, 149, 155 Anabolic steroids, 437
aspirin, 409–412 Addisonian megaloblastic Air voids, 16 Anaemia, 111, 115, 190, 196
Acetylation, 369 anaemia, 208 Albendazole, 560 Anaerobic chambers, 243
Acetylcholine, 383 Addition polymerization, 11 Albumin, 508 Anaerobic culture
Acetylene gas, 38 Adenovirus, 185, 332 Alcohol, 251, 458 media, 259
Acid etch technique, 49 ADH mechanism, 143 Algid malaria, 343 methods, 260, 263
Acid fast bacilli, 248 Adhesion, 60, 122, 268 Alginate, material, 14–17 Anaerobic media, 256–257
Acid phosphatase, 201 Adhesive, 4 Alkaline pyrogallol method, Anaerobic organisms, 263
Acquired active immunity, 273 Administration, 497 260, 261, 263 Anaerobic pouches, 260
Acquired drug resistance, 320 Admixed alloy powder, 71 Alkylating agents, 561 Anaerobiosis, 263
Acquired immunity, 271 Admixed alloy, 74 Alkylbenzoates, 17 Anaesthesia, 454, 455
Acquired resistance, 381 Adrenaline, 382, 394, 396 Allergic asthma, 418 Analeptic drugs, 476
Acriflavine, 567 Adrenergic a–blockers, 401 Allergic conjunctivitis, 418 Analgesic action, 409, 411
Acrylic resins, 54 Adrenergic drugs, 394–395 Allergic reactions, 380, 432 Analgesics, 409
ACTH, 436 Adrenergic neuron Allergic rhinitis, 418 Anamnestic reaction, 310
Actinomycosis, 131, 134, 319 blockers, 485 Allergy, 161, 280, 282 Anaphylactic atopic
Actions, 456–457, 476, 500 Adrenocorticosteroids, 435 Allograft reaction, 286 reaction, 169
dexamethasone, 434 b Adrenoceptor Alloyed electrolytic Anaphylactic reaction, 381
insulin, 425 stimulants, 398 precipitate, 79, 85 Anaphylactic shock, 159, 382,
Activators, 53 b-Adrenergic blockers, 402 Alpha haemolysin, 292 400, 528, 531
Active immunity, 269, 270 a-Adrenergic blocking Altered vascular Anaphylaxis, 166, 280, 306
Active immunization, 299, 306 agents, 403 permeability, 130, 133 Anaplasia, 173
Acute barbiturate Adult respiratory distress Alumina-silica ratio, 56 Ancylostoma duodenale, 347–48
poisoning, 460, 464 syndrome, 214 Aluminium hydroxide gel, 513 Angina pectoris, 401, 480–484
Acute glomerulonephritis, Advantages over ampicillin, 533 Aluminium hydroxide, 511–12 Angioedema, 157
294–95 Adverse drug Aluminium oxide, 44 Angiogenesis, 139
Acute high altitude reactions, 378, 380 Aluminous porcelain, 87, 89 Angiotensin antagonists, 477
oedema, 158 Adverse effects, 384, 390, 393 Amalgam alloys, 70, 78 Angiotensin converting
Acute inflammation, 120, 121 oral iron, 498 Amalgam corrosion, 5 enzyme (ACE)
Acute iron poisoning, 497–498 penicillin, 531 Ameloblastoma, 216, 219 inhibitors, 485
Acute left ventricular Adverse reactions, 465–466 Amidase test, 301 Animal inoculation, 307, 322
failure, 474 Aerosol and gaseous Aminoglycoside, 541–542 Annealing, 82, 83
Acute leukaemia, 199 disinfectants, 253 Ammonium sulphide, 5, 7 Anode, 8
Acute lymphatic Aesthetic filling materials, 50 Aminophylline, 418 Antacids, 511, 512, 513, 540
leukaemia, 212 Aesthetics, 33, 57 Amniotic fluid embolism, 150 Antagonists, 486
Acute lymphoblastic leukaemia African Burkitt’s Amoebiasis, 193, 558 Anthraquinone
(ALL), 200 lymphoma, 333 Amoebic dysentery, 345 preparations, 518
677
Antiallergic action, 434 Ascaris lumbricoides, 348 Bile culture, 192 Cancer therapy, 562, 563
Antiamoebic drugs, 558 Ascorbic acid, 191, 569, 570 Bioassay, 378 Cancrum oris, 219
Antianginal drugs, 480 Aspiration prophylaxis, 453 Bioavailability, 371 Candelilla wax, 31
Antiarrhythmic drugs, 447 Aspirin, 410–411, 513 Biochemical tests, 313 Candida albicans, 336, 338
Antibiotic prophylaxis, 306 Astringents, 501, 503–504 Biocompatibility, 13, 81 Candidal infections, 338, 555
Antibiotic resistance, 320 Atherosclerosis, 223 Biological carcinogens, 176 Candidiasis, 336
Antibiotic sensitivity tests, 290 Atopic reaction, 162 Biotransformation, 368–369 Candle jar method, 260
Antibiotics, 519, 526, 563 Atopy, 168, 285 Bis-GMA, 53, 54 Carbamazepine, 466
Antibodies, 273 Atrial fibrillation, 478 Bite registration material, 26 Carbide burs, 45
Antibody detection, 334 Atropine, 386, 387, 388, 389 Blackwater fever, 343 Carbidopa, 468–469
Anticariogenic properties, 57 Atropine poisoning, 388, 391 Bleaching agents, 567, 575 Carbimazole, 421, 422
Anticholinergic agents, 452 Atropine substitutes, 388, 392 Bleeding time, 209 Carcinogenesis, 175
Anticholinergic drugs, 388 Autoclave, 249–251, 252, 254 Blood agar, 256, 258, 288, 292 Carcinoid tumour, 222
Anticoagulants, 230, 500, Autocoids, 405, 406 Blood culture, 192, 258 Carcinoma in situ, 185, 229
503–04 Autoimmune diseases, 286 Blood smear, 205 Carcinomas, 171
Anticonvulsants, 461 Autoimmunity, 285 Blood transfusion, 230 Cardiac oedema, 143
Antidiabetic action, 427 Autonomic nervous system, Blow torch, 48 Cardiac toxicity, 478
Antidiabetic drugs, 423, 427 470, 473 b-Blockers, 400, 403, 487 Cardinal signs of
Antiemetics, 453, 515, 516 Autopolymerizing resins, 96 Body weight, 373 inflammation, 128
Antiepileptic drugs, 464 Avascular necrosis, 432 Bonded abrasives, 47 Cardiogenic shock, 145, 154
Antifungal drugs, 554, 555 Bonded stones, 47 Cardioselective b–blockers,
Antigen detection, 334, 337 B Bonding agents, 48, 49 403, 483, 484
Antigen–antibody B lymphocytes, 168, 279 Bone marrow findings, 196, Caries, 351
reactions, 276 Back pressure porosity, 41, 43 197, 210, 211 Carnauba wax, 29, 31
Antihistamines, 405 Bacteraemia, 321 Bone morrow Cartilaginous metaplasia, 114
Antihistaminic drugs, 510 Bacterial appendages, 268 examination, 201 Caseous necrosis, 109, 110
Antihypertensive drug, 484, 488 Bacterial capsule, 246 Borderline reactions, 136 Casoni’s test, 348
Anti-inflammatory action, 409 Bacterial cell, 242 Bordetella pertussis, 314 Castable ceramics, 88
Antileprotic drugs, 553 Bacterial fimbriae, 247 Borrelia vincentii, 318 Castaneda’s method, 287
Antimalarial drugs, 557, 559 Bacterial food poisoning, 194 Bowen’s disease, 227, 229 Casting, 7, 48
Antimetabolites, 562, 563 Bacterial gastroenteritis, 523 Brinell hardness test, 10 Casting alloys, 5
Antimicrobial drugs, 521 Bactericidal agent, 532 Broad-spectrum Casting defects, 34
Antiparkinsonian drugs, 467 Bacteriostatic drugs, 535 antibiotics, 537, 538 Casting machines, 36, 40
Antiplatelet (antithrombotic) Barbiturate poisoning, 460 Broad-spectrum antifungal Casting ring lining, 35
effect, 410, 411–412 Barbiturates, 459t, 462, 463 antibiotics, 555 Casting waxes, 29, 31
Antipsychotic drugs, 470 Barcol hardness test, 9, 10 Bronchial asthma, 419, 420, Catalase peroxidase test, 301
Antipyretic action, 409–410 Basal cell carcinoma or rodent 432, 434 Cavity liners, 62, 68
Antisecretory drugs, 386, 389 ulcer, 183 Bronchodilators, 420 Cavity varnishes, liners and
Antiseptics, 565, 567, 572, 574 Basal cell carcinoma, 183, Brown atrophy, 113 bases, 13
Antispasmodics, 386, 389–390 227, 228, 229 Buchner’s tube, 260 Celecoxib, 413
Antistreptolysin O test, 294 Baseplate materials, 31 Buerger’s disease, 110 Cell culture, 322
Antithyroid drugs, 420 Baseplate waxes, 32 Bulk purgatives, 517 Cell injury, 116
Antitubercular drugs, 546, 550 Basic/basal media, 258 Bulk technique, 51 Cell stimulating reactions, 283
Antiviral drugs, 555, 556 BCG, 303 Burkitt’s lymphoma, 181, 182, Cell-derived mediators, 124
Aphthous ulcer, 221 Bead technique, 51 185, 213 Cell-mediated immunity, 168
Aplastic anaemia, 198 Beclomethasone, 419 Cellular events, 121
Apomorphine, 514 Bends, 155 C in acute inflammation,
Apoptosis, 115 Benign hypertension, 195 Caisson disease, 149, 155, 160 121, 130
Arboviruses, 329 Benign tertian malaria, 346 Calcinosis, 115 Cementation, 51
Argon laser lamps, 52 Benign tumours, 170 Calcitonin, 440 Central nervous system,
Arnold’s steam sterilizer, 254 Benzodiazepine, 454, 457 Calcium channel blockers, 469–470, 472
Arsenic poisoning, 568 Benzoyl peroxide initiator, 12 479, 481, 482, 485 Centrally acting muscle
Arterial emboli, 157t Benzyl penicillin, 531, 536 Calcium hydroxide relaxants, 461
Arterial thrombi, 147 Beta haemolysin, 292 cement, 55, 69 Centrally acting skeletal
Arthritides, 431–432, 434 Beta-hemihydrate, 30 Calcium hydroxide, 13 muscle relaxants, 442–44
Arthus reaction, 167, 284, 380 Betamethasone, 435 Calcium metabolism, 440 Cephalosporins, 528, 532, 535
Artificial culture media, 258 Beta-propiolactone (BPL) Callus, 137 Ceramic or refractory dye
Artificial gas, 36 vaccine, 229, 329 Campylobacter enteritis, 545 materials, 40
Aryl sulphatase test, 301 Biguanides, 424, 429, 429t Cancer, 178, 185 Ceramic–cellulose, 35
Index 679
Cerebral ischaemia, 147 Clotting system, 125 C-reactive protein, 294 Dental plaque, 351
Cerebral malaria, 343 Clove oil, 565, 572 Creep in amalgam, 77 Dental plaster, 26, 28
Cerebral oedema, 144 Cloxacillin, 533, 536 Cresol, 566 Dental porcelain, 88
Ceresin, 31, 32 Coagulants, 499 Crystallization, 26 Dental stone, 27, 29
Cervicofacial Coagulase test, 294 Cultivation of bacteria, 257 Dentifrices, 574
actinomycosis, 319 Coagulation proteins, 125 of virus, 322 Dentigerous cyst, 220
Cetirizine, 407 Coagulative necrosis, 109, Culture, 289, 290, 350, 351 Dentin bonding agents, 49
Chancre, 136 111–112, 116, 117, 153 Culture media, 256 Denture base materials, 93
Charcot-Leyden crystals, 341 Cocaine, 390, 450 Culture of bacteria, 263 Denture base resins, 94
Chelating agents, 567, 568 Codeine, 475 Curing dentures, 30 Denture cleansers, 95
Chelation, 19 Coefficient of thermal Cushing’s syndrome, 432, 433 Denture relining materials, 95
Chemical activation, 12 expansion, 32, 51, 95 Cutaneous infections, 325 Denture resins, 90
Chemical Cohesive and noncohesive Cutaneous lesions, 190 Deoxopellets, 262
carcinogenesis, 175–176 gold, 84 Cutaneous route, 362 Depolarizing blockers, 443
Chemical disinfectants, 250 Cold welding, 83 Cutting efficiency, 59 Depressant actions, 472
Chemical mediators, 123, 129 Collagen diseases, 434 Cyanide poisoning, 481 Depression, 376
Chemical sterilization, 253 Columnar metaplasia, 114 Cyanocobalamin, 496, 570 Dermatologic disorders
Chemotactic factors, 281 Combined immunization, 299 Cyclization, 369 (cutaneous syndrome), 175
Chemotaxis, 130, 132, 135 Combining antacids, 512 Cyclophosphamide, 563 Dermatophitidis, 337
Chemotherapy, 526, 534, 551 Compacted gold, 81 Cyproheptadine, 406 Dermoid cyst, 179, 222
of TB, 549 Complement system, 125, 277 Cyst, 339 Desferrioxamine, 498, 568
Chlamydia trachomatis, 545 Complete denture, 25 Cysticercus cellulosae, 193 Desmopressin, 500
Chlamydospores, 337, 350 Compomers, 54 Cytogenetics, 201 Desorbing or degassing, 79, 82
Chlorhexidine, 567, 575 Composite resin restorative Cytokines, 278, 279 Detergents, 574
Chlorine, 261 material, 50 Cytolytic reaction, 382 Dexamethasone, 434, 436
Chlorohexidine, 566 Composite resins, 12, 63 Cytolytic toxins, 292 Dextran, 508
Chloramphenicol, 540 Composition of alginate, 15t Cytomegalovirus, 325 Dextropropoxyphene, 474
Chloroquine, 557–558 Compression moulding Cytotoxic oedema, 144 Diabetes mellitus, 222, 428
Chlorothiazide, 490, 492 technique, 91 Diabetic coma, 426
Chlorothiazide diuretics, 488 Compressive strain, 11 Diabetic ketoacidosis, 223
Chloroxylenol, 566 Compressive strength, 11, 29 D Diabetic microangiopathy, 223
Chlorpromazine, 469, 471 Compressive stress, 11 Dammar resin, 29, 31 Diaminodiphenyl sulfone, 553
Chokes, 155 Condensation, 73 Dane particle, 330, 331 Diamond abrasives, 46
Cholera, 314 polymerization resins, 96 Dapsone, 551, 553 Diaphoresis, 224
Cholinergic drugs, 383 silicone, 23t, 24t Decompensated shock, 146 Diarrhoeas, 523
Christensen’s urease Confirmatory tests, 334 Decompression sickness, 149 Diatoms, 44
medium, 264 Congenital infection, 325 Decreased plasma oncotic Diazepam, 455, 456, 462, 464
Chromic oxide, 45 Congenital lesions, 325 pressure, 142 Dicor, 89
Chromosome mutation, 186 Congenital syphilis, 134, 318 Decyclization, 369 Dicumarol poisoning, 504
Chronic inflammation, 120 Congestive cardiac failure, 481 Deeper tissues, 364 Diethyl ether, 454, 456
Chronic leukaemiae, 200 Conjugation, 264, 266 Defective castings, 35 Differential media, 258
Chronic myeloid Contact angle, 4 Deformation, 11 Digitoxin, 478
leukaemia, 201, 203, 211 Continuous cell lines, 323 Degassing techniques, 80 Digoxin, 477
Chronic toxicity, 572 Conventional insulins, 429 Dehydration, 26 Dimensional stability, 17
Cimetidine, 510, 512, 513 Convulsion precipitated, 465 Delayed expansion, 78 Dimercaprol, 567–568
Cimetidine, ranitidine and Coombs’ test, 276 Delayed hypersensitivity Dimethacrylate
famotidine, 453 Copolymerization, 93 reaction, 162, 382 monomers, 11
Circulating antigen, 193, 311 Copolymers, 93 Delta haemolysin, 292 Dimorphic fungi, 337
Circumferential dentigerous Corrosion, 5–6, 7 Demonstration of circulating Diphenylhydantoin sodium,
cyst, 220 Corticosteroids, 431, 433 antigen, 311 465, 467
Classification Corynebacterium diphtheriae, Dental acrylic resins, 89 Diphtheriae, 214, 299
of impression materials, 14 297, 299, 301 Dental amalgam, 78 Dipping method, 30
of semisynthetic Co-trimoxazole, 524–525, 526 Dental amalgam alloys, 73 Direct filling gold, 82, 86
penicillins, 533 Coumarin derivatives, 501 Dental burs, 47 Direct posterior composites, 54
of sulphonamides, 525 Counter irritants, 564 Dental caries, 218, 350, 352 Direct wax pattern, 30
Clavulanic acid, 534–535 Coupling, 13 Dental cements, 57, 59 Directly acting agents, 442–44
Clearance angle, 46, 47 Cox-2 Inhibitors as Dental ceramics, 86 Disclosing agents, 574
Clonidine, 485, 486, 487 NSAIDs, 415 Dental implant materials, 96 Disinfectants, 259, 572
Clostridium tetani, 308, 571 Craniotabes, 188 Dental investments, 38 Disodium cromoglycate, 417
Disseminated intravascular EBA cements, 69 Epulis, 215 Filtration, 255

coagulation, 207 Echinococcus Ergometrine, 408 Fimbriae or pili, 244
Distant spread, 172, 174, 177, granulosus, 347 Ergot alkaloids, 408 Final setting time, 28
179, 181 Ectopic hormone Eroded areas, 57 Finishing abrasives, 44
Distortion, 22, 35 production, 175 Erythema nodosum leprosum Fins on casting, 33
Diuretics, 484–485, 489, 494 Eczema herpeticum, 325 (ENL) reaction, 136 Firing of porcelain, 85
Divestment, 43 EDTA, 49, 567 Erythroblastosis fetalis, 187 First set response, 286
Dizziness, 561 Egg vaccines, 229, 329 Erythrocytic schizogony, 342 First-pass metabolism, 370
DNA oncogenic viruses, 185 Eicosanoids, 124 Erythromycin, 544–545, 546 Flame desorption, 82
DNA probes, 266 Elastic limit, 11 Erythropoiesis, 201 Flaming, 252
DNA viruses, 323, 332 Elasticity, 20 ESR, 207 Flexural strength, 11
Doderlein’s bacillus, 309 Elastomers, 28 Ethamsylate, 500 Flow technique, 51
Domperidone, 515, 516 Eleck’s gel precipitation test, Ether, 453, 454, 455, 456 Fluid electrolytes, 8
Dopamine, 397, 400, 468 214, 298, 300 Ethyl alcohol, 458 Flumazenil, 463
Dough or gel stage, 94 Electrochemical corrosion, 6, 8 Ethyl silica-bonded Fluorescent treponemal
Down’s syndrome, 186 Electroformed dyes, 41 investments, 38, 39 antibody (FTA) test, 316
Doxycycline, 539, 540, 541 Electrolyte concentration cell, 7 Eugenol, 19t, 572 Fluorides
DPT vaccine, 300 Electrolytic cell, 8 Exfoliative diseases, 289 formulations, 572
Drug action, 372, 374–376 Electrolytic gold, 84 Exfoliative toxins, 292 in caries, 575
Drug administration, 361, 365 Electrolytic or electrochemical Exoerythrocytic cycle, 342, 344 in dentistry, 575
Drug antagonism, 377, 378 or wet corrosion, 7 Exoerythrocytic pharmacology, 572
Drug cumulation, 382 Electrolytic precipitate, 79, 85 schizogony, 342 toxicity, 572
Drug dependence, 374 Electromotive force (EMF), 6 Exogenous pigments, 111 Fluoroquinolones, 520, 522
Drug excretion, 370 Electroplating bonding, 47 Exothermic reaction, 28 Flute or chip space, 47
Drug metabolism, 369, 371 Eliciting dose, 280 Exotoxic shock, 145 Foil, 85
Drug nomenclature, 367 Elisa test, 193, 311, 334 Exotoxins, 267, 268 Folate antagonists, 562
Drug resistance, 320, 381 Embolism, 148, 155, 156, 160 Explant culture, 322 Folate deficiency, 197
Drug synergism, 378 Embolization, 148, 155 Extended-spectrum Folic acid, 498
Drug toxicity, 378 Embryonated eggs, 322 penicillins, 532 deficiency, 196
Drugs, 373, 507, 510, 517, Emergence of resistance, 521 External porosity, 31, 95 Foreign bodies, 137
547, 553, 554 Emetics, 514 External void, 34 Formaldehyde, 256
Drugs acting centrally to Emetine, 558 Extraintestinal amoebiasis, 344 Formulations, 554
reduce BP, 486 Enalapril, 477, 488 Extraintestinal lesions, 340 Forward pressure
Drugs acting Enamel bonding agents, 48 Exudates, 131, 158 hypothesis, 143
calcium metabolism, 438 Endocrinal uses, 431, 436 Exudation, 128, 153 Fractional sterilization, 249
epilepsy, 464 Endocrinopathies (endocrine Fracture toughness, 65
hypertension, 488 syndromes), 175 Fractures, 10
to suppress dry cough, 418 Endogenous mediators, 123, 129 F Free radical injury, 116
Dry calcinations, 26 Endogenous pigments, 111, 118 Faeces, 370 Free radicals, 12
Dry corrosion or chemical Endothelial injury, 121 Faeces culture, 192, 309 Functions of antibodies, 275
corrosion, 6, 8 Endotoxic shock, 145 Fat embolism, 149, 160 Fungal infections, 554
Dry gangrene, 110 Endotoxins, 267–268 Fat necrosis, 109, 110, 116 Fungi, 337
Dry heat, 256 Engulfment stage, 123 Fate of thrombus, 154, 160 Fungus affecting hair, 194
D-tubocurarine, 442, 443, 445 Enrichment media, 257, 258 Fat-soluble vitamins, 569 Fused porcelain, 86
Ductility and malleability, 10 Entamoeba histolytica, 339 Fatty degeneration, 117 Fused quartz, 37
Duplicating models, 15 Enteric fever, 192, 309, 311 Fatty liver, 111–112 Fusiform bacilli, 318
Duration of action, 367, 430, Enterotoxins, 314 Feldspar, 88
446, 450 Enzyme immunoassays Ferrous sulphate, 498 G
Dye materials, 27, 40 (EIA), 317 Fibrin, 501, 503 Galvanic corrosion, 8
Dye preparation, 35 Enzymes, 293, 296, 375 Fibrinogen, 500 Galvanic shock, 8
Dye stone, 27, 41 Eosinophilia, 211 Fibrinoid necrosis, 109, 110 Gametocytes of
Dysplasia, 216 Ephedrine, 397, 399 Fibrinolytic agents, 506 malaria, 346
Dystrophic Epidermoid carcinoma, 227 Fibrinolytic system, 126 Gametogony, 342, 345
calcification, 113, 115 Epistaxis, 209 Fibrocaseous tuberculosis, 128 Gamma haemolysin, 292
Epithelial metaplasia, 113, 119 Fibroma, 183 Gamma-2 (g2) phase, 78
Epithelioid cells, 133, 135 Fibrous ceramic aluminous Ganglion blockers, 485
E Epithelioma, 183, 227 silicate, 35 Gas bubbles, 155
Eames technique, 77 Epoxy resin dyes, 42 Fibrous scar, 152 Gas embolism, 149, 155
EB virus, 326 Epstein-Barr virus, 326 Figure ‘8’ motion, 16 Gas gangrene, 111, 304, 307
Index 681
Gas inclusion porosities, 41 Gum dammar, 29 Herpes virus, 185, 332 Hypertension, 195, 482, 484,
Gaspak system, 260 Gumma, 133 Herpetic lesions, 325 486, 488
Gastrokinetic drugs, 453 Gypsum, 25 Herxheimer reaction, 135 Hyperthyroidism, 420
Gaucher’s disease, 186, 187 Gypsum products, 26 Hexachlorophene, 566 Hypertrophy and
Gel theory, 25 Gypsum: alpha-hemihydrate, 37 Hexuronic acid, 191 hyperplasia, 117
Gelatin foam, 501, 504 Gypsum-bonded Hibitane, 566 Hypertrophy, 114, 119
Gene amplification, 180 investments, 37, 38, 39 High copper alloys, 70, 71 Hypnosedatives, 460
Gene transfer High copper amalgam, 76, 78 Hypnotics, 460, 461, 463
(by transposons), 320 H High expansion dye stones, 26 Hypochlorites, 251
General anaesthetics, 448, 451 H agglutination, 310 High strength, 26 Hypoglycaemia, 223
Genetic transfer, 264, 266 H1 blockers, 404, 406 Histamine, 124, 133, 281 Hypolipidaemic drugs, 508
Genital infections, 293 H2 blockers, 510 Histamine receptor, 453 Hypoparathyroidism, 439
Genital lesions, 325 (H2 receptor) blocking Histocompatibility Hypovolaemic shock, 145,
Gentamicin, 533–534, agents, 453 antigens, 278 154, 159
542–543, 544 Haematocrit, 208 HIV infection, 333, 335 Hypoxic encephalopathy, 146
Germination, 248 Haematogenous spread, 172, Homatropine, 391
Germ tubes, 337 174, 178–179, 181 Hooke’s law, 11 I
Ghon’s complex, 131, 135 Haematologic disorders, 432 Hookworm infestation, 349 Id reaction, 337
Ghon’s focus, 135 Haemochromatosis, 221 Hospital acquired Ideal anaesthesia, 451
Giant cells, 136 Haemodynamic changes, 120 infection, 286 Idiosyncrasy, 379, 381
GICs, 57 Haemolytic anaemia, 198 Hospital infections, 287 Idiosyncratic effects, 381
Gillmore needles, 28 Haemolytic toxins, 292 Hot air oven, 252, 254, 255 IgA, 276
Gingival hyperplasia, 483 Haemophilia, 206 Hue, value and chroma, 8 IgD, 276
Glass ionomer cements, 13, 59 Haemophilus influenzae, 521 Human cycle, 341 IgE, 276, 290
Glasses or ceramics, 52–53 Haemorrhagic diasthesis, 190 Human immunodeficiency IgG, 275, 284
Glazes, 88 Haemorrhagic virus (HIV) infection, 335 IgM, 275, 288
Glibenclamide, 428, 429 gastroenteropathy, 146 Human insulin, 425, 427 Imbibition and syneresis, 23
Glomerular filtration, 370 Haemosiderin, 210 Human papilloma virus, 332 Immediate type of hypersensi-
Glove boxes, 260 Haemosiderosis, 114 Humoral or antibody-mediated tive reaction, 161, 284
Glucagon, 426 Haemostasis, 506 immunity, 270 Immobilization, 137
Glucocorticoids, 416, 420, Halothane, 454, 455, 457 Hutchinson’s teeth, 318, 350 Immune complex, 283
431–432, 436 Hand mixing, 75 Hutchinson’s triad, 135 Immune complex
Glucocorticoid therapy, 435 Hansen’s bacillus, 302 Hyaline change, 116 reaction, 163
Glucuronide conjugation, 369 Hard deposits, 5 Hyaluronidase, 292 Immune response, 303
Glucosidase inhibitors, 424–425 Hard liners, 93 Hybrid composite, 54 Immunity, 269, 270, 272
Glutathione conjugation, 369 Hardness tests, 9, 10 Hydatid cyst, 348 Immunization, 229, 297, 307
Glycine conjugation, 369 Head injury, 473 Hydrochlorothiazide, 491 Immunoglobulin A (IgA), 273
Gold foil, 79, 83 Headache, 561 Hydrocolloid impression Immunological factors, 285
Gold inlay, 35 Healing of a fracture, 136–137 materials, 17 Immunological test, 334
Gold restorative material, 83 Heat, 263 Hydrocolloids, 23 Impact strength, 11
Gonococcal infections, 523 Heat activation, 12 Hydrocortisone, 435, 436 Implantation, 173, 178
Gonorrhoea, 523 Heat cure acrylic denture base Hydrogen peroxide, 251 Impression, 26, 52
Gram stain, 245 resins, 90, 91 Hydrogen sulphide, 5, 7 compound, 22
Gram-negative Hematological findings, 198 Hydrolysis, 369 materials, 14, 24, 26
bacteria, 242–243 Hemozoin, 342, 345 Hydrostatic pressure, 120 plaster, 25–26, 27
Gram-negative Hepadna virus, 185 Hygroscopic expansion, 40, 43 trays, 16, 18
septicaemia, 523 Heparin, 502, 503, 504, 506 Hygroscopic setting expansion Improved dental stone or dye
Gram-positive bacterial cell Heparin antagonist, 502, 503 (HSE), 39–40 stone, 39
wall, 252 Hepatic amoebiasis, 341, 344 Hyoscine, 393 Inactivated radical, 12
Gram-positive cocci, 295 Hepatitis A, 331 Hyperaemia, 152 Inactive molecule, 12
Gram-stained smear, 350, 351 Hepatitis B antigen, 332 Hypercoagulability, 151 Incineration, 252
Grand mal epilepsy, 466 Hepatitis B surface antigen of blood, 156 Incomplete casting, 33, 34
Granulation tissue, 139, 140 (HBsAg), 330, 332 Hyperglycaemia, 222, 433 Increased capillary
Granuloma, 126, 133, 135, Hepatitis B vaccine, 331 Hyperparathyroidism, 439 permeability, 142, 158
215–216 Hepatitis B, 331t Hyperplasia, 114, 119, 216 Incubation period, 327
Griseofulvin, 554 Hepatitis B virus, 330, 331 Hypersensitivity, 161, 282, Indicator media, 258, 259
Ground quartz, 53 Hereditary spherocytosis, 210 283, 294, 306 Indole test, 264
Growth curve, 244 Herpes simplex viral Hypersensitive reactions, 161, Induction or initiation
Guinea worm, 349 infections, 324 284, 395 period, 12
Infant brain vaccines, 229, 329 J Light-activated denture base Malignant melanoma, 184, 228
Infarction, 152, 161 Japanese B encephalitis, 328 resins, 96 Malignant neoplasms, 172
Infecting dose, 268 Jarisch-Herxheimer reaction, Light-activated resins, 12 Malignant pustule, 319
Inflammation, 120, 121, 132 528, 531 Light-cured composites, 52 Malignant tumours, 171, 172
Inflammatory exudate, Juvenile diabetes, 430 Lignocaine, 448, 449 Malleability, 10
121–122 Liners and bases, 62 Mannitol, 493
Inhalation, 362 Lioresal, 445 Mantoux test, 304
Inhalation route, 367 K Lipofuscin, 118 Marasmus, 190
Initial setting time, 28 Kahn test, 316 Liquefaction (colliquative) Marginal leakage, 54
Initiator carcinogens, 175, 181 Kala-azar, 343 necrosis, 109–110 Marginal percolation, 54
Injectable anaesthetics, 450 Kaposi sarcoma, 333 Liquefaction necrosis, 116 Margination and rolling, 121
Injectable polio vaccine, 326 Karat and fineness of gold, 85 Liquid paraffin, 518 Marjolin’s ulcer, 227
Inlay casting wax, 31 Ketamine, 456 Live viral vaccines, 327 Marrow findings, 197
Inlay pattern, 30 Ketoconazole, 555 Lobar pneumonia, 215 Mat foil, 79, 84
Inlay restoration, 29 Kieselguhr, 44 Local agents (styptics), 499t Mat gold, 79, 83, 84
Inlay wax, 32, 35 Killed polio vaccine, 327 Local anaesthesia, 399 Maxillofacial prosthetics, 25
Innate immunity, 272, 273 Killed viral vaccines, 327 Local anaesthetics, 446, 449 Mechanical articulators, 31
Inoculation, 267 Killing or degradation Local haemosiderosis, Mechanism of action, 394,
Insomnia, 461 stage, 123, 129 114–115 417, 419, 423
Insulating medium, 24 Kinins, 125 Local invasion, 172, 174, 177 of chloroquine, 557
Insulin, 424–425, 426, 427 Knoop hardness test, 10 Local routes, 363–364, 366 Medicinal uses, 537
Insulin preparations, 425–426 Koch’s postulates, 241 Localized shrinkage or shrink- Megakaryocytes, 201
Insulin resistance, 428 Koplik’s spots, 328, 352 spot porosity, 41–43 Megaloblastic anaemia, 196
Interferon, 277 Kwashiorkor, 190, 191 Localized shrinkage, 42 Meglitinide analogues, 424
Intermediate restoration, 64 Kyasanur forest disease Lock jaw, 308 Melanin pigment, 118
Intermediate restorative (KFD), 328 Log (logarithmic) or exponen- Melanophores, 118
materials, 69 tial phase, 244 Meningitis, 296, 297
Internal porosity, 33, 95 L Long-acting Mental depression, 474, 475
Interstitial oedema, 144 Labetalol, 404 sulphonamides, 526 Mepivacaine, 448, 450
Intestinal amoebiasis, 340, 344 Laboratory infections, 267 Loop diuretics, 485, 493 Mercury: alloy ratio, 77
Intestinal lesion, 340 Laboratory tests, 193, 311, 351 Loperamide, 517, 518 Merozoites, 342, 344
Intracutaneous test, 214, 300 Lactobacillus, 309, 351 Loss of gloss method, 28 Mesenchymal metaplasia, 114
Intradermal test, 344 b-Lactamase inhibitors, 536 Lugol’s iodine, 422 Metal ceramics, 87
Intravenous anaesthetics, 450 Lag phase, 244–245 Luting cement, 61, 67 Metal restorations, 6
Intravenous iron Laminate technique, 24 Lymphadenitis, 128 Metal spatula, 16
therapy, 199 Lardaceous spleen, 167 Lymphatic permeation, 172 Metallic materials, 10
Intravenous route, 364–365 Large irregular voids, 34 Lymphatic spread, 172, 174 Metal-modified GICs, 68
Intrinsic drug resistance, 320 Leakage, 121 Lymphoid leukaemoid Metaplasia, 113, 119, 177
Investment materials, 42 Lenti virinae, 332 reaction, 212 Metastasis, 172
Involucrum, 225 Lepra reaction, 136, 552–553 Lymphokines, 132, 170, 279 Metastatic calcification, 115
Iodine, 257, 422 Lepromatous leprosy, 134, 136 Lysogenic bacterium, 265 Metastatic lesions, 340
Ion channels, 376 Leprosy, 130, 136, 553 Lysogenic conversion, Metformin, 429, 429t
Ionizing radiation, 180, 253 Leukaemia, 199, 201 265–266 Methohexitone, 457
Ipecacuanha, 514 Leukaemic cells, 201 Lysosomal enzymes of Methotrexate, 416, 563
Iron deficiency anaemia, 198, Leukaemoid reaction, 212 leucocytes, 125 Methyl alcohol poisoning, 458
210, 211 Leukocyte activation, 122 Methylation, 369
Iron preparations, 494 Leukocytosis, 202 M a-Methyldopa, 485
Iron–sorbitol–citric acid, 497 Leukoplakia, 216, 218 MacConkey’s medium, 288 Metoclopramide, 514, 515
Irreversible anticholinesterases, Leukotriene receptor Macrolide antibiotics, 544, 546 Metronidazole, 516, 559–60
385, 388 antagonist, 420 Macrophages, 122, 123 Microbial flora of oral
Irreversible hydrocolloids, 17 Levodopa, 468, 469 Magnesium sulphate, 518 cavity, 352
Irreversible shock, 146, 154 Lidocaine, 448, 450 Magnesium trisilicate, 513 Microfilaria, 345
Irritation, 376 Light activated denture base Major histocompatibility Microporosity, 34, 41
Ischaemia, 118, 152, 157 resins, 92, 96 complex, 278 Micrsomal enzymes, 369
Ischaemic necrosis, 151, 155 Light activation, 12 Malaria, 346, 558 MMR vaccines, 328
Isolation of viruses, 323 Light cure denture base Malarial parasites, 341, 346 Mode of action, 411, 446
Isoniazid, 547 technique, 91 Malignancy, 178 Mode of transmission, 131
Isonicotinic acid (INH), 549 Light devices, 12 Malignant cells, 177 Model plaster, 26, 29
Isoprenaline, 396 Light emitting diodes, 52 Malignant hypertension, 195 Models, 29
Index 683
Modifiers, 25, 29, 37 Neuromyopathic Omeprazole, 512 Papillary cystadenoma

Modifying chemicals, 38 syndromes, 175 Oncogenes, 180 lymphomatosum, 220
Modifying drug action, 376 Neutral red test, 301 Oncogenic viruses, 185, 332 Papova virus, 185
Modulus of elasticity, 10 New drug delivery Ophthalmic lesions, 325 Paracetamol, 412–414, 415
Moist heat, 248, 253 systems, 366 Opioid analgesics, 452, 472 Paraffin wax, 29, 31
sterilization, 255 Newer insulins, 428, 429, 430 Opportunistic infections, 268 Paraneoplastic
Molten wax, 30 Niacin test, 301 Oppurtunistic mycosis, 338 syndromes, 174, 182
Mongolism, 186 Niemann-Pick disease, 187 Opsonization, 123, 129 Parathormone, 441
Monkey fever, 328 Nifedipine, 481, 483 Oral anticoagulants, 504, 507 Parathyroid hormone,
Monomer, 11 Nimesulide, 415 Oral antidiabetic drugs, 427 438–440, 441
Morphine, 472–473, 474, 475 Nitrate reduction test, 302 Oral antiseptics, 352 Parenteral administration of
Moulds, 29, 35 Nitric oxide (NO), 125 Oral cancer, 182 drugs, 363–364
Mounting casts, 29 Nitrogen mustard, 563 Oral candidiasis, 219, 351 Parenteral iron, 496
Mounting plaster, 29 Nitroglycerine, 483 Oral cavity, 352 therapy, 199
Mouthwashes, 575 Nitrous oxide, 451, 454, 456 Oral contraceptives, 437 Parkinsonism, 467, 468
Mulberry/Moon’s/Fournier’s Noble metal, 5, 6, 46 Oral flora, 352 Passivation, 5, 7
molars, 135 Noncohesive gold foil, 79 Oral hypoglycaemic Passive cutaneous anaphylaxis
Mulling, 73 Nondepolarizing (competitive) drugs, 423 test, 341, 344
Multidrug therapy (MDT) blockers, 443 Oral iron, 495, 497 Passive immunity, 271, 272
regime, 550, 552 Nonendocrinal uses, 431–432 preparations, 497 Passive immunization, 299, 306
Multiple myeloma, 213 Noneugenol paste, 24 therapy, 199 Pastes, 12
Mummifying agents, 575 Nonhealing of fracture, Oral polio vaccine, 326, 327 Pasteurization of milk, 249, 252
Mumps, 328 136–137 Oral route, 361, 364, 367, 368 Pathological calcification, 115
Mumps viral infection, 327 Nonhormonal uses, 436 Oral squamous cell Pavementing, 122
Mural thrombi, 147 Nonionising radiation, 253 carcinoma, 184 Pellagra, 189
Mutation, 186 Nonmicrosomal enzymes, 369 Oral thrush, 351 Pelvic actinomycosis, 131
Myasthenia gravis, 387, 445 Non-neural vaccines, 229 Ordinary petri dish, 261 Penicillins, 526, 528, 529, 530
Mycobacterium leprae, 134 Nonproprietary name, 367 Organ culture, 322 Pentazocine, 473, 475
Mycobacterium Nonradiation carcinogens, 176 Organic nitrates, 480–481, 484 Peptic ulcers, 513
tuberculosis, 135, 301 Nonsedative Organophosphorus poisoning, Periodic acid Schiff test, 201
Mycoplasma antihistamines, 404, 407 385, 386, 387 Peripheral smear, 197, 212
pneumoniae, 545 Nonselective beta receptor, 483 Orodental conditions, 537 Permeability factors, 123, 129
Mydriatics, 386, 390, 392 Nonspecific antigens, 310 Orofacial actinomycosis, 319 Pernicious anaemia, 208, 507
Myeloid leukaemoid Nonspecific esterase, 201 ORS, 517, 518 Pernicious malaria, 343
reaction, 212 Nonsteroidal anti-inflammatory Osmotic diuretics, 493 Pethidine, 474
Myocardial infarction, 194 drugs, 410–411 Osmotic purgatives, 518 Phagocytic vacuole, 129
Myocardial ischaemia, 147 Nonsynthetic reactions, 369 Osseous callus formation, 137 Phagocytosis, 122, 129, 132
Nonsystemic antacids, 509 Osseous metaplasia, 114 Phagolysosome, 123
Noradrenaline, 398 Osteoarthritis, 431 Phagosome, 123
N Noscapine, 418 Osteoclastoma, 225, 226 Pharmacodynamics, 376
Narcotic analgesics, 471 Nosocomial infection, 286 Osteomalacia, 188, 189 Pharmacokinetics, 372, 384,
Nasal decongestants, 419 NSAIDs, 411, 412–413 Osteomyelitis, 224 385, 387, 404, 407, 418
Native immunity, 272, 273 Nucleus, 243 Osteoporosis, 226 Pharmacological actions, 384,
Natural active immunity, 273 Nutmeg liver, 159 Osteosarcoma, 225, 226 389, 390–391, 392, 394
Natural resistance, 381 Nutrient agar slope, 288 Ototoxicity, 542 of adrenaline, 396–399
Necrosis, 109, 112–113, 116 Nutrient broth with red hot Oxidation reaction, 8 Pharmacotherapy, 419,
Negative rake angle, 46 iron pieces, 260 Oxidation, 369 431–432, 434–435
Neomycin, 543 Nutrient broth, 258 Oxidizing agents, 254 of shock, 398
Neoplasia, 170, 174 Nystatin, 555 Oximes, 387 Phase of decline, 245
Neostigmine, 383, 384, 385 Oxygen concentration cell, 7 Phenobarbitone, 466
Neovascularization, 139 O Oxytetracycline, 539 Phenobarbiturate, 462
Nephrotoxicity, 542 Obtundents, 573 Oxytocin, 438, 571 Phenol, 251–252, 566
Neural vaccines, 229 Ocular lesions, 189 Ozone, 251 Phenol derivatives, 566
Neuroleptanalgesia, 470 Oedema, 141, 153, 157, 158 Phenothiazines, 470, 471
Neuroleptic drugs, 476 and haemorrhage, 152 P Phenytoin, 464, 466
Neuroleptics, 476 in acute tubular injury, 143 Palladium-silver alloys, 13 Phenytoin sodium, 465, 466
Neuromuscular blockage, 542 in glomerulonephritis, 143 Pancreas, 426 Phosphate diabetes, 188
Neuromuscular blocking in nephrotic syndrome, 143 Pancuronium, 443, 445 Phosphate-bonded investments,
agents, 442–44 Oestrogen, 437 Pancytopenia, 212 37, 38, 39, 43
Phosphorus stick method, 261 Pour and cure fluid resin Pyaemia, 321 Resins, 12
Photosensitivity, 380 technique, 91 Pyogenic abscess, 153 Respiratory infections, 293
Physical carcinogens, 180 Powder/liquid ratio, 59 Pyogenic infections, 293 Restorative materials, 14
Physiological functions, 496 Pox virus, 332 Pyogenic osteomyelitis, 224 Retroviruses, 332
Physostigmine, 385 Pralidoxime, 387, 394 Pyrazinamide, 551 Reversal reaction, 553
Pickling, 36, 42 Prausnitz-Kustner reaction, 276 Pyridoxine, 469, 550, 569 Reversible
Pierre Fauchard, 3 Prazocin, 399, 487 Pyrimidine antagonists, anticholinesterases, 386
Pinhole porosity, 34, 41 Preanaesthetic medication, 562–563 Reversible hydrocolloid
Piperazine citrate, 561 393, 452, 457, 463, 473 (agar agar) impression
Pit and fissure sealants, 48, 49 Precipitation reaction, 275 material, 17, 23t
Q
Placebo, 373, 377, 378 Precystic stage, 339 Rh factor, 213
Quartz and binder, 33
Plasma, 500 Prednisolone, 435 Rheumatic arthritis, 416
Quartz fillers, 53
Plasma calcium level, 439 Pregnancy, 466 Rhinosporidiosis, 194, 337
Quartz-tungsten-halogen
Plasma expander, 507 Preliminary impressions, 15 RIA, 352
lamps, 52
Plasma half-life, 372 Premalignant lesions, 220, 227 Ribonucleoside/nucleotide
Quaternary ammonium salts
Plasma proteases, 124, 125 Preparation of iron, 495–496 synthesis, 369
(quats), 251
Plasma protein binding, 368 Pressure technique, 51 Rickets, 188, 189
Quaternary compounds, 392
Plasma protein-derived Primary cell cultures, 323 Rifampicin, 547, 549, 550, 551
Quellung reaction, 246
mediators, 124 Primary healing, 139t Rim lock trays, 18
Quenching (for gold alloys), 36
Plasmids, 266 Primary mediators, 281 RNA oncogenic viruses, 185
Plasmodium falciparum Primary syphilis, 134 RNA viruses, 323, 332
infection, 343 Primary tuberculosis, 135 R Robert Koch, 241
Plasmodium vivax, 346 Primary union, 138, 141 Rabies vaccines, 329 Robertson’s cooked meat
Plaster of Paris, 24, 28 Procainamide, 479 Radiation carcinogens, 176 broth, 257, 263
Plasticized acrylic resin, 92 Procaine, 479 Radioactive iodine, 421 Rockwell hardness test, 10
Plasticizer, 19 Procaine hydrochloride, 449 Rake angle, 59 Rodent ulcer, 183, 227, 228
Platelet-activating factor, 124 Procallus formation, 137 Ranitidine, 511, 512, 513, 514 Rofecoxib, 413
Platinised foil, 79, 84 Procarcinogens, 175–176, 181 Rapid tests, 336 Rosenthal method, 261
Pleomorphic adenoma, 217 Prodrug, 370, 371, 372 Rauvolfia serpentina, 488 Rouge, 44, 46
Pneumococcal infections, 296 Progesterone, 437 Raynaud’s disease, 110 Rough casting, 33
Poisoning, 390 Prokinetic agents, 515 Reactive oxygen species Rough surface, 33
of barbiturates, 458 Prokinetic drugs, 516 (ROS), 125 Roundworm, 348
Poisson’s ratio, 11 Promethazine, 407, 516 Receptors, 375–376 Routes, 181
Polishing, 30, 31, 49 Promoter carcinogens, 176 Recovery of casting, 36 and dose, 417
abrasives, 44 Properties of alginate Rectal route, 362 of administration, 373, 399
agents, 44 hydrocolloid, 14, 15, 20 Red (haemorrhagic) infarcts, 152 of infection, 268
amalgam, 76 Prophylactic use, 532 Red blood cell transfusion, 199 of drug administration,
restorations, 6, 7 Prophylaxis of tetanus, 307 Red hot metallic iron, 262 361, 365, 366
Polyacrylic acid, 49 Proportional limit, 11 Reducing agents, 38 Rubber base impression
Polycarboxylate cement, 57, Propranolol, 402, 403, 487 Reduction reactions, 8, 369 materials, 23
64, 68 Propylthiouracil, 421 Refractive index, 53 Rubbery stage, 94
Polyether, 23t, 24t Prostaglandins, 381, 407 Refractory rickets, 188 Russell’s viper snake
Polymer, 12 Prothrombin time, 213 Reiter’s protein complement venom, 504
Polymerase chain reaction Proton pump inhibitors, 513 fixation (RPCF) test, 315
(PCR), 266, 334 Psychological dependence, 382 Relining material, 18
Polymerization, 11, 12, 93 Pulmonary amoebiasis, 341 Remodelling of callus, 137 S
shrinkage, 90 Pulmonary hydrostatic Renal excretion (urine), 368 Sabin’s vaccine, 327
Porosity, 33, 43, 89, 95 pressure, 158 Renal oedema, 143, 158 Sabouraud’s dextrose, 352
Positive rake angle, 46 Pulmonary oedema, 144, 158 Renal osteodystrophy, 189 Sago spleen, 166, 169
Posterior pituitary Pulmonary tuberculosis, 304 Renal rickets, 189 Salbutamol, 417, 418, 419
extract, 571 Pulp-capping agents, 13 Renal syndromes, 175 Salicylate poisoning, 414
Postmortem thrombi, 147 Pulp-protective agent, 13 Replacement therapy, 431, Salicylates (acetyl salicylic
Postmyocardial infarction, 415 Pumice, 44 433–434 acid or aspirin), 411–412
Postnatal infection, 325 Purgatives, 517, 518 Reserpine, 488 Salicylism, 413
Potassium permanganate, 251 Purine antagonists, 562 Residual compressive Salk’s polio vaccine, 326
Potassium sparing Purulent or suppurative stresses, 86 Salmonellosis, 194
diuretics, 493 exudate, 128 Resilient denture liners, 92 Sandblasting, 36
Potato starch, 25 Pus, 525 Resin-modified glass Sandwich technique, 49, 68
Potentiation, 378 Putty, 24 ionomers, 65 Sarcomas, 171
Index 685
Schizogony, 341, 344 Skeletal muscle relaxants, 442, Status asthmaticus, 419–420 Synergism, 521
Scopolamine, 391, 393 443, 444, 445 Steel burs, 45 Synthetic corticosteroids, 433
Scorbutic rosary, 191 Skin and soft tissue Sterilization, 248 Synthetic reactions, 369
Screening tests, 14, 230, 334 infections, 288 control, 255 Synthetic sources, 364
Scurvy, 190, 191, 499 Skin test, 350, 352 time, 259 Synthetic waxes, 31
Second set response, 298 Skip metastasis, 172 Sticky stage, 94 Synthetic/defined media, 258
Secondary healing, 139t Slime layer, 246 Stiff stage, 94 Syphilis, 126, 134, 135, 316
Secondary mediators, 305 Smallpox, 324 Stimulant effects, 472 Systemic (generalized) haemo-
Secondary syphilis, 126 Smith-Noguchi medium, 261 Stimulation, 376 siderosis, 115
Secondary union, 138 Sodium alginate solution, 94 Stool findings of amoebic Systemic agents, 499t,
Secretion or degranulation Sodium bicarbonate NAHCO3, dysentery, 341 500–503
stage, 123, 224 509–510 Storage of alginate Systemic anaphylaxis, 281
Secretory immunoglobulin, 274 Sodium cromoglycate, 419 impression, 17 Systemic antacids, 509, 511
Sedatives, 463 Sodium valproate, 466, 467 Strain, 9 Systemic candidiasis, 336
Seitz filters, 255 Soft liners, 92, 94 Strength, 11, 17, 26 Systemic miliary
Selective cox-2 inhibitors, 412 Solar keratosis, 227 Streptococcal infections, 296 tuberculosis, 128
Selective media, 258, 259 Solder joints, 6 Streptococcus mutans, 350 Systemic route, 366–367
Self-cured resins, 93 Solid crystalline phase, 13 Streptococcus pyogenes, 290, Systemic toxicity, 14
Semicontinuous cell strains Solid solutions, 13 293, 295
(diploid cell strains), 323 Soluble plaster, 25 Streptokinase, 505, 506
Semisynthetic penicillins, 535 Sore throat, 293, 296 Streptomycin, 544, 547–548 T
Semple vaccine, 229, 329 Sources of drugs, 364 Streptozyme test, 291 T and B cells in immune
Senile keratosis, 227 Space lattice, 5 Stress corrosion, 7, 8 response, 279
Separating medium, 94 Specific gravity, 230 Stress, 9, 11 Tachyphylaxis, 377
Septic infarcts, 152 Specific tests, 334 Stretch or elongate, 10 Taenia solium, 349
Septic shock, 145, 154, 159 Specific toxicity, 561–562 Structure of a bacterial Tannic acid, 565
Septicaemia, 321, 529 Specific Treponema pallidum spore, 247 Tartaric acid, 56
Septicaemic malaria, 343 tests, 315, 318 Structure of matter, 4–5 T-cell-mediated (type-IV)
Sequestrum, 225, 226 Spectrum of activity, 554 Struma ovarii, 222 hypersensitivity, 163
Serological reactions, 276 Spectrum penicillins, 529 Study casts, 29 Tear strength, 17
Serological tests, 290, 313, Spherical amalgam alloy, 75 Study models, 15 Temporary cementation, 61
315, 316, 317, 328 Spironolactone, 489, 490, 493 Styptics, 501, 505 Temporary soft liners, 92
Serotonin, 124, 281 Spirochetes, 315 Subcutaneous test, 214, 298 Tensile strength, 29
Serratia marcescens, 261 Spores of bacteria, 247 Sublingual route, 362, 365 Tensile stress, 10
Serum amyloid associated Sporozoites, 342 Subunit vaccine, 230, 330 Teratogenic infections, 267
(SAA) protein, 164 Spray anaerobic dish, 260 Succinylcholine, 443, 444 Teratogenicity, 380, 382
Serum sickness, 167, 284 Spread of malignant Suck back porosity, 43 Teratoma, 179, 222
Setting reaction, 28 tumours, 171 Sucralfate, 513 Tertiary amines, 391
Setting time, 27, 28 Spread via CSF, 173 Sugar media, 258 Tertiary syphilis, 126
Shear strength, 11 Sprue, 35 Sulphamethoxazole, 526 Tetanus, 305, 307, 308, 571
Shelf life and storage, 20 Sprue former, 42, 45 Sulphate conjugation, 369 Tetracyclines, 537, 539–540
Shock, 141, 145, 146, 154 Sprue-casting junction, 34 Sulphides, 5, 7 Thalassaemia, 207
in burns, 159 Spuma virinae, 332 Sulphonamides, 524, 535 Therapeutic uses, 524–525
Shock kidney, 146 Squamous cell carcinoma, 183, Sulphonylureas, 423–424 Thermal conductivity, 8, 31, 32
Shock lung, 146 184, 227 Sulphur granules, 319 Thermal expansion, 35–36, 39
Shock lung syndrome, 214 Squamous metaplasia, 113, Superficial lesions, 336 Thermal properties, 32, 90
Shore hardness test, 9, 10 119 Superficial mycosis, 338 Thiamin deficiency, 569
Shrinkage, 35 Stages in healing of a Superinfection, 522 Thiazides, 488, 489–491, 494
Shrink-spot porosity, 34, 42 fracture, 137 Suppurative infections, 293 Thiazide diuretics, 484–485
Shwartzman reaction, 285 Stains, 5 Surface anaesthetics, 450 Thiazolidine diones, 424
Sialagogues, 575 Standard tests for syphilis, 316 Surface films, 5 Thioglycollate medium, 257
Sickle cell anaemia, 151 Staphylococcal diseases, 295 Surface roughness, 33 Thiopentone sodium, 457
Silica particles, 16, 37 Staphylococcal food Suture tracks, 138 Thixotropic materials, 17
Silicate cements, 59 poisoning, 295 Swab, 352 Thoracic actinomycosis, 131
Silicate, 59 Staphylococcal Sweetening agents, 574 Thrombin, 501, 503
Single-composition infections, 533, 545 Sympathetic stimulation, 396 Thrombocytopenia, 201, 204
alloys, 72, 77 Staphylococcus aureus, 291, Sympatholytic drugs, Thrombocytopenic
Sintering, 88 295, 320, 521 485–486 purpura, 213
Skeletal lesions, 190 Stationary phase, 245 Sympathomimetic drugs, 394 Thromboembolism, 156
Thrombosis, 141, 150 Trophozoite, 339, 342 Vascular changes, 130 W

Thrombus, 147 stages, 344 Vascular permeability, W/P ratio, 33
Thrush, 338 Tubercular bacilli, 303 120–121 Waiting period, 280
Thyrotoxicosis, 224 Tuberculin reaction, 284 Vascular syndrome, 175 Warfarin sodium, 502, 507
Timolol, 403 Tuberculin test, 303 Vasoactive amines, 124 Warthin’s tumour, 220
Tin oxide, 44 Tuberculoid granuloma, 135 Vasoconstriction, 120 Wassermann reaction, 316
Tissue anoxia, 145 Tuberculoid leprosy, 136 Vasoconstrictors, 501, 504 Water/powder ratio, 16
Tissue conditioners, 92, 95 Tuberculosis, 127, 546, 548 Vasodilator, 485 Wax distortion, 32
Tissue cultures, 322 Tuberculous caseous Vasogenic oedema, 144 Wax elimination, 35–36
test, 214, 298 pneumonia, 128 Vaso-occlusive phenomena, 21 Wax pattern, 29, 32, 35–36
vaccines, 230 Tuberculous lesions, 302 VDRL test, 276, 318 Wear and tear pigment, 113
Titanium, 96 Tuberculous osteomyelitis, 225 Venous emboli, 157t Westergren’s method, 207
TNM staging, 178 Tubular reabsorption, 370 Venous thrombi, 147 Western blot test, 334
Tolbutamide, 429, 429t Tubular secretion, 370 Verapamil, 479 Wet calcinations, 26
Tolerance, 374 Tumour embolism, 150 Vertical transmission, 267 Wet corrosion or aqueous
Tooth angle, 47 Tumour markers, 182, 185 Vibrio cholerae, 268, 312 corrosion, 6
Tooth/teeth preparation, 35 Tumour necrosis factor, 147 Vicat needle, 28 Wet field technique, 18
Topical local Tumours, 171 Vickers hardness test, 10 Wet gangrene, 110–111
anaesthetics, 449 Tungsten carbide burs, 45 Vinblastine, 562 Wet–Sandy stage, 94
Toxic complex disease, 283 Tungsten halogen bulb, 12 Vinca alkaloids, 561, 563 Wettability, 4
Toxic effects, 379, 476, 561 Tyndalization, 249, 254 Vincent’s angina, 217, 318 Wetting agent, 5, 35
Toxic evaluation, 14 Type I hypersensitive Vincent’s bacilli, 318, 351 White (anaemic) infarcts, 152
Toxic manifestations of reaction, 284 Vincristine, 562 White blood cells, 201, 204
streptomycin, 547 Tzanck cell, 326 Vinyl polysiloxane, 22t, 24t Whooping cough, 314
Toxic shock syndrome, 289 Tzanck smears, 326 Viral DNA polymerase, 331 Widal reaction, 312
Toxic food poisoning, 295 Virchow’s lymph node, 172 Widal test, 193, 276, 312
Toxicity of, 14, 562 Virchow’s triad, 150, 156 Wilson-Blair’s medium, 310
U
aspirin, 411 Viridans streptococci, 295 Window period, 335
Ultimate tensile strength, 11
anticancer, 562 Virkon, 251 Wintrobe’s and Landsberg’s
Undercut areas, 25
lignocaine, 449 Virulence, 268 method, 207
Unicompositional alloys, 72, 75
Toxins, 293, 296 Virulence tests, 298 Working casts, 15
Urease test, 264
Tranquilizers, 463 Virus isolation, 334 Wound healing, 136, 139
Urinary tract infections, 523
Transcoelomic spread, 173 Virus-related human Wound infections, 523
Urine, 230
Transdermal drug delivery tumours, 182
Urine culture, 192, 310
systems, 368 Visceral leishmaniasis, 343
Uses, 455 X
Transdermal patches, 362 Visceral lesions, 325
of diazepam, 444 Xylocaine, 399, 446, 449
Transmission of HIV, 169 Visible light-activated resins, 12
of GICs, 67
of infection, 287 Vitamin A, 570
Transport media, 258, 259
UV light cured composites, 52
deficiency, 189 Y
UV light-activated Yeasts, 337
Transthyretin, 164 Vitamin B12 deficiency, 203,
systems, 12 Young’s formula, 373
Transudate, 131, 144 496–497
and exudate, 158 Vitamin B12, 191, 505, 570 Young’s modulus, 10
Tray compound, 21 V Vitamin B6, 570
Treponema pallidum Vaccine, 241, 327 Vitamin C deficiency, 190 Z
haemagglutination bath, 253 Vitamin C, 191, 499, 569 Zero or radial rake angle, 46
(TPHA) test, 317 for polio, 326 Vitamin D, 187, 440–441 Zidovudine, 556
Treponemal tests, 316–17 for immunization, 329 Vitamin D deficiency, 191 Zinc oxide, 19t, 59
Triamterene, 491 Vacuum desiccators, 260 Vitamin E, 191 Zinc oxide eugenol (ZOE), 24
Trimethoprim, 526 Valdecoxib, 413 Vitamin K deficiency, 505 Zinc oxide eugenol
Trimming and carving, 73 Varicella zoster or V-Z Vitamin K, 500, 501–503 cement, 61
Triple antigen, 307 virus, 325 Vitamins, 187 Zinc phosphate cement, 66, 69
Triple vaccine, 300 Variola major, 324 Voges-Proskauer test, 264 Zinc polycarboxylate
Trituration, 73 Variola minor, 324 Vomiting, 515 cement, 58
of dental amalgam, 75 Variola virus, 324 Von Willebrand’s disease, 206 ZN staining, 247

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Foreword vii Topic 3 Tissue Repair: Regeneration,

Topic 6 Identification of Bacteria Topic 30 Herpes Viruses 324

Topic 10 5-Hydroxytryptamine, Its Antagonists Topic 29 CNS Stimulants and Cognition

Topic 50 Antifungal Drugs 553 Topic 61 Dental Pharmacology 572

Structure of Matter and Principles of Adhesion

Q. 2. Wetting agent l A space lattice can be defined as any arrangement of

Physical Properties of Dental Materials

phide or ammonium sulphide corrode silver, copper,

following: oxygen and chloride have been said to be responsible

If more than 12% Cr is added to iron or cobalt, we get

surface of the amalgam restoration. However, the

l Discolouration of surfaces of castings caused by oxidation Examples:

the metallic grains with the lower electrode potential are

TABLE 3.1 Differences between Tarnish and Corrosion

2. An electrolytic cell is as follows: M1 1 e2 n M0

electrolyte, the stressed metal will become the anode of Ans.

Mechanical Properties of Dental Materials

HARDNESS ROCKWELL HARDNESS TEST

1. Brinell hardness test cording to particular indenter and load employed.

3. Vickers hardness test test is suitable for brittle materials.

l Hardness is defined as the resistance of a material to tation.

The projected area is divided into the load to give the

Knoop hardness number (KHN).

being the second. Platinum ranks third in ductility. Q. 4. Resilience

MALLEABILITY of energy a material can absorb without undergoing

Q. 2. Brinell hardness number Q. 5. Compressive and tensile stress

l The Brinell hardness test is one of the oldest tests

determining the hardness of metals and metallic materi-

l It describes the relative stiffness or rigidity of a material. 4. Flexural strength

Q. 7. Proportional limit Shear Strength

Chemically Activated Resins 1. Induction or Initiation Period

Visible Light-Activated Resins 2. Propagation

Solid Solutions Phases in Cast Alloys

Biocompatibility of Dental Materials

BIOCOMPATIBILITY rials to protect the pulp against various types of injuries

cium hydroxide suspension in an aqueous or resin

Bases: In contrast to liners, bases are applied in much

thicker layers (. 0.75 mm) under restorations to pro-

l preweighed packets for single impression

Only after the supply of the retarder is over does calcium

calcium sulphate reacts with sodium alginate to form

the tray is achieved by mechanical locking features in the l Undermixing results in

l Gelation time is best controlled by adding retarders

use, so as to minimize moisture contamination.

l For fast-set alginate: 45 s

extracted from certain types of seaweed. It is a sulphuric

The irreversible hydrocolloids may be disinfected by 10 min. Alkylbenzoates 0.1

of saliva. borates, thereby ensures proper setting of the cast

ica, clay, rubber, etc.

l Because of the above drawbacks, it is not recommended patient comfort.

crown and bridge, etc.

Q. 2. Classify hydrocolloid impression materials. De-

results in swelling of the impression. Storage in 100%

Wet Field Technique

Black tray compound is used as it is not affected in the l Type II or soft

COMPOSITION OF ZINC OXIDE EUGENOL SETTING TIME

Zinc oxide should be finely divided and should contain

slight amount of water.

Rigidity and Strength

hanced by zinc acetate dehydrate (accelerator), which is

ADVANTAGES l Minor defects can be corrected locally without discard-

Taste and Odour Biological Properties

Topic 6 Identification of Bacteria Topic 30 Herpes Viruses 324

Topic 50 Antifungal Drugs 553 Topic 61 Dental Pharmacology 572

CaSO 4 .2H 2 O 110 130°C