Antimicrobials

Preface
Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.
We feel delighted to present you Agam pharmacology notes prepared by Agam Divide and
Rule 2019 Team to guide our fellow medicos to prepare for university examinations.
This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.
Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement
On behalf of the team, Agam would like to thank all the doctors who taught us Pharmacology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Kareeshmaa H C, who took the responsibility of leading
the team. The following are the name list of the team who worked together, to bring out the
material in good form.
 Amritesh K Purushothaman
 Rajeswar V
 Shreevardhan G M
 Monisha T
 Manigandan A
 Nandhinee A
 Sanjay S
 Ramachandiran N
 Syed Muhammad Humayl
 Jeyabharathi T A
 Bijin K
 Joanna P
 Yokesh Kanna C
 Mustansir Aziz Kitabi
 Taher Hussain
 Riya Kant
 Bala Diwakar T
 Vaanathi Ramu
INDEX
Chapter 1: General Considerations
Short Notes
1. Drug Resistance..………………………………..………… 1
Short Answers
2. Post Antibiotic Effect…………………………………… 3
3. Bacteriostatic Drugs…………………………………….. 3
4. Bactericidal Drugs………………………………………… 3
5. Combinations of Antimicrobials…………………... 4
6. Failures for combination of antimicrobials…… 4
1
1. DRUG RESISTANCE
RESISTANCE:
Unresponsiveness of an organism to the antimicrobial agent
TYPES:
 Natural
 Acquired
NATURAL RESISTANCE:
Some microbes show resistance inherently. This is because they lack the metabolic
process or target site which is affected by the particular drug.
E.g.: Penicillin G – gram negative bacilli
ACQUIRED RESISTANCE:
This refers to development of resistance by an organism due to use of an AMA over a
period of time.
Resistance may be developed by
 Mutation
 Gene transfer
Mutation Gene transfer

Definition Stable and heritable Resistance causing gene
genetic change that is passed from one
occurs spontaneously and organism to other.
randomly among
microorganisms.
Transfer of resistance Vertical Horizontal
Time Slow process Rapid process
Degree of resistance Low High
Resistance acquired by Single step Conjugation
Multi step Transduction
Transformation
Conjugation
Antimicrobials Agam Pharmacology

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The R-factor is transferred from cell-to-cell by direct contact through a sex pilus
or bridge and the process is known as conjugation.
Transduction
Plasmid DNA is transferred through the bacteriophage, i.e. virus which infects
bacteria.
Transformation
Resistant bacteria may release genetic material into the medium which is taken
up by other bacteria.
Resistant organisms can broadly be of following three types:
 Drug tolerant – the microorganism loses affinity for a particular AMA

 Drug destroying – the resistance microbe elaborates an enzyme which
inactivates the drug
 Drug impermeable – loss of porins
CROSS RESISTANCE:
 Resistance seen among chemically related drugs
 Development of resistance to one drug is also resistant to other chemically
related drugs.
 E.g.: Tetracyclines
PREVENTION OF DRUG RESISTANCE

 No inadequate or unduly use of AMAs.
 Use narrow spectrum AMAs whenever possible
 Use combination

3
2. POST ANTIBIOTIC EFFECT
 Bactericidal effect is present even when the serum concentration falls

below minimal inhibiting concentration.
 After a brief exposure if the organism is placed in an antibiotic free
medium. The organism starts multiplying again after a lag period.
 This lag period is referred as post antibiotic effect.
3. BACTERIOSTATIC DRUGS
 They inhibit the growth and multiplication of microorganisms.

 Examples: sulphonamides, tetracyclines, erythromycin, chloramphenicol,
etc.
 At high concentration they may produce bactericidal effects
4. BACTERICIDAL DRUGS
 They kill the microorganism

 Examples: penicillins, cephalosporins, aminoglycosides, etc.

4
5. CONDITIONS WHICH ARE TREATED WITH COMBINATION OF

ANTI MICROBIALS
 Rifampin + isoniazid in tuberculosis (to prevent resistance)

 Rifampin + dapsone in leprosy (synergism)
 Drugs sensitive for aerobes and anaerobes in mixed infections like diabetic
foot infection (to broaden the spectrum)
 Penicillin + gentamicin (initial treatment of severe infections)
6. REASONS FOR FAILURE OF COMBINATION ANTI MICROBIAL

THERAPY
 Decreased antibacterial activity due to improper combination

 Noncompliance by the patient
 Poor host defence
 Failure to take necessary adjuvant measures (e.g.: drainage of abscesses,
empyema, etc.)

INDEX
Chapter 2: Sulfonamides, Cotrimoxazole,

Quinolones
Essay
1. Fluoroquinolones...………………..………………………. 5
Short Notes
2. Sulfasalazine……….………………………………..………… 9
3. Cotrimoxazole…….………………...……………………….. 10
Short Answers
4. Topically used Sulfonamides..………………………….. 12
5. four 2nd generation fluoroquinolones………………. 12
5
1. FLUOROQUINOLONES (FQs)
CLASSIFICATION:
CIPROFLOXACIN:
MECHANISM OF ACTION:
 All fluoroquinolones have same mechanism of action.
In gram negative bacteria,

Bacterial DNA gyrase has two subunits: A and B
Subunit A Subunit B
• does nicking • introduces
and resealing negative
of DNA supercoils
CNS Agam Pharmacology

6
FQs bind to bacterial DNA

gyrase
prevents its strand cutting

and
interferes with the resealing

function
In gram positive bacteria
FQ bind to topoisomerase IV
damages DNA
by interferring with nicking of DNA
and seperating of daughter DNA

strands
results in DNA damage
signalling of exonuclease
production
digestion of DNA

7
RESISTANCE:
 Mutation in the target enzyme resulting in decreased affinity for the drug
 Decreased permeability of the organism to the drug
 Increased efflux of drugs
SPECTRUM:
 Gram-negative organism like
Gonococci, Meningococci, H. influenza, E. coli, Salmonella, Shigella,

Enterobacterium
 Gram-positive organism like
Staphylococci
PHARMACOKINETICS:
 Rapidly absorbed
 First pass metabolism occurs
 20% metabolised
 Excreted in urine
 Half-life: 3-5 hours
ADVERSE REACTIONS:
 GI: nausea, vomiting
 CNS: dizziness, headache
 Skin: hypersensitivity, rashes
 Tendonitis

8
USES:
 Urinary tract infection
 Chancroid
 Typhoid
 Respiratory tract infection
 Tuberculosis
 Anthrax
 Diarrhea

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2. SULFASALAZINE
 Sulfasalazine is a sulfonamide.
all sulfonamides have same mechanism of action
sulfonamides competitively inhibit
union of PABA with pteridine residue
prevents formation of dihydropteroic

acid
which conjugates with glutamic acid

to form
dihydrofolic acid ADVERSE EFFECTS:

 Nausea
 Vomiting
PHARMACOKINETICS:  Epigastric pain
 Hypersensitivity
 Rapid and complete oral absorption  Hepatitis
 Widely distributed  Hemolysis
 Metabolised in liver  Kernicterus of
 Excreted in urine newborn
USES:
 First line agents for treatment of mild to moderate active ulcerative colitis.
 Used as disease modifying drug in rheumatoid arthritis.

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3. COTRIMOXAZOLE
 The combination of trimethoprim and sulfamethoxazole is cotrimoxazole.

 Both the drugs approximately have same half-life.
SPECTRUM:
 Gram-positive and gram-negative organisms like Staph. aureus,
Streptococci, Meningococci, C. diphtheriae, E. coli.
 Sulfonamides inhibit the conversion between PABA to di hydro folic acid.

 Trimethoprim inhibits the conversion between Di hydro folic acid and tetra
hydro folic acid.
RESISTANCE:
DHFRase enzyme coding plasmid

11
PHARMACOKINETICS:
Trimethoprim sulfamethoxazole
Absorption Oral - rapid Oral - slow
Distribution Large volume Less volume
Crosses BBB and placenta Yes Poor entry
Protein plasma bound 40% 65%
Metabolized Partly High fraction acetylated
Excretion Urine Urine
Half-life 10 hours 10 hours
ADVERSE EFFECTS:
 Nausea
 Vomiting
 Headache
 Stomatitis
 Rashes
 Megaloblastic anemia
 Renal failure
 Teratogenicity
USES:
 Urinary tract infections
 Respiratory tract infections
 Pneumocystis jirovecii pneumonia
 Chancroid

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4. TOPICALLY USED SULFONAMIDES
Mnemonic: SMS
 Sulfacetamide sodium – eye infections

 Mafenide – burn dressing to prevent infection
 Silver sulfadiazine – preventing infection of burnt surfaces.
5. FOUR 2ND GENERATION FLUOROQUINOLONES
Mnemonic: Prime Minister Loves Second Generation Laptops.
 Prulifloxacin
 Moxifloxacin
 Levofloxacin
 Sparfloxacin
 Gemifloxacin
 Lomefloxacin

INDEX
Chapter 3: Beta-Lactam Antibiotics

Essay
1. Penicillin……………....………………..………………………. 12
2. Cephalosporins……………………………………………….. 14
Short Notes
3. Bacterial Resistance in Penicillin.…………..………… 17
4. Ampicillin…………….………………...……………………….. 17
5. Cefotaxime………………………………………………………. 19
6. Cefriaxone……………………………………………………….. 20
7. 4th Generation Cephalosporins…………………………. 21
Short Answers
8. 2nd Generation Cephalosporins..…….……………….. 22
9. Antipseudomonal Penicillin……………..………………. 22
10. Beta Lactamase Inhibitors………………………………… 22
11. Carbepenems…………………………………………………… 22
12
1. PENICILLIN
CLASSIFICATION:
PENICILLIN G:
ANTIBACTERIAL SPECTRUM:
 Narrow spectrum – limited primarily to Gram-positive bacteria (GPB), few

gram-negative bacteria (GNB) and anaerobes.
 Cocci – streptococcus, pneumococcus (GPB), Neisseria gonorrhea, N.
meningitidis (GNB)
 Bacilli – B. anthracis, C. diphtheriae, Clostridia, listeria, spirochetes
PHARMACOKINETICS:
 Destroyed by gastric acid

 1/3 of oral dose absorbed
 Sod. PnG i.m. – absorption rapid
 Peak plasma level in 30min, t1/2 – 30min
 Distributed extracellularly
 Rapid renal excretion. Tubular secretion of PnG blocked by probenecid.

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ADR:
 Local irritancy
 Pain at i.m. site
 thrombophlebitis on i.v.
 nausea on oral ingestion
 Brain toxicity
 Confusion
 Muscle twitching
 Convulsions
 Coma
 Rash
 Itching
 Urticaria
 Fever
 Wheezing
 Angioneurotic edema
 Serum sickness
 Anaphylaxis
USES:
 Streptococcal infections – pharyngitis, otitis media, scarlet fever, rheumatic

fever (strep. Pyogenes), Subacute bacterial endocarditis (Strep. Viridians or
faecalis)
 Pneumococcal infection- lobar pneumonia, meningitis
 Meningococcal infection – meningitis
 Syphilis – PnG is DOC. Early & latent syphilis treated by procaine penicillin, late
syphilis by benzathine penicillin
 Leptospirosis
 Diphtheria- procaine penicillin to prevent carrier state
 Tetanus and gas gangrene
 Prophylaxis of rheumatic fever and bacterial Endocarditis

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2. CEPHALOSPORINS
 They are bactericidal
CLASSIFICATION:
 A rigid cell wall protects the bacterial cell wall from lysis.
 Bacterial Cell Wall has peptidoglycan.
 Peptidoglycan is the chief compound which is responsible for the
synthesis of cell wall.
 Peptidoglycan = peptide chain + glycan chain and they are both cross-
linked;
 glycan chain is composed of alternating amino sugars, NAM (N-
acetyl-muramic acid) and NAG (N-acetyl-glucosamine).
 This cross linking gives the cell Wall its strength:
 pentapeptide (five amino acids), linked to NAM, has a
pentaglycine, attached to it.

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 This pentaglycine is cross linked with a pentapeptide of adjacent

strand.
 The synthesis of peptidoglycan cell wall requires an enzyme
Transpeptidase, which is responsible for linking the peptide & glycan
chains.
 Transpeptidase (penicillin binding protein) causes cross linking between
the pentaglycine residue of one strand and fourth amino acid (d-alanine)
of adjacent pentapeptide, by cleavage of the terminal d-alanine (fifth
amino acid residue)
 The cross linking makes the cell wall rigid and stable.
cephalosporins inhibit
transpeptidase enzyme
leading to inhibiton of
peptidoglycan
cell wall deficient forms are formed
interior of bacterium become

hyperosmotic
bacterial lysis occur
USES:
 As alternatives to penicillins for ENT, upper respiratory and cutaneous

infection
 Respiratory, urinary and soft tissue infection caused by gram-negative
organisms
 Penicillinase producing staphylococcal infections and infection due to MRSA
 Septicemias produced by gram-negative bacteria

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 Surgical prophylaxis
 Meningitis
 Gonorrhea by penicillinase producing enzymes
 Typhoid
 Mixed aerobic-anaerobic infection in cancer patients, etc.
 Hospital acquired infection
 Prophylaxis and treatment of infection in neutropenic patients
ADR:
 Hypersensitivity reactions like skin rashes, fever, serum sickness and rarely
anaphylaxis are seen.
 Nephrotoxicity
 Diarrhoea
 Bleeding is due to hypoprothrombinemia
 Low WBC count (rarely)
 Pain at the injection site.

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3. BACTERIAL RESISTANCE IN PENICILLIN
Bacteria develop resistance
 by producing β-lactamases, which destroy the β-lactam ring, e.g. S.

aureus, E. coli, gonococci, H. influenzae, etc.,
 due to altered PBPs which have less affinity for β-lactams, e.g. S.
pneumoniae,
 due to decreased ability of the drug to penetrate to its site of action.
4. AMPICILLIN
a. Not resistance to penicillinase and beta lactamase.

b. It is active against all organisms sensitive to PnG
c. It also inhibits many gram-negative bacilli, e.g. H. influenzae, E. coli,
Proteus, Salmonella and Shigella.
d. It is more active than PnG for STREP. VIRIDANS and ENTEROCOCCI
e. Equally active for pneumococci, gonococci and meningococci (penicillin
resistant strains are resistant to ampicillin as well)
f. Less active against other gram-positive cocci. Penicillinase producing Staph.
are not affected, as are other gram-negative bacilli, such as Pseudomonas,
Klebsiella, indole positive Proteus and anaerobes like Bacteroides fragilis.
PHARMACOKINETICS:
g. Ampicillin is not degraded by gastric acid
h. Oral absorption is incomplete but adequate
i. Food interferes with absorption.
j. It is partly excreted in bile and reabsorbed—enterohepatic circulation
occurs
k. However, primary channel of excretion is kidney, but tubular secretion is
slower than for PnG
l. plasma t½ is 1 hr

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USES:
 Urinary tract infection
 Respiratory tract infection
 Meningitis
 Gonorrhea
 Cholecystitis
 SABE
ADR:
 Diarrhoea
 Rashes
INTERACTIONS:
 Hydrocortisone inactivates ampicillin
 Probenecid retards renal excretion of ampicillin

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5. CEFOTAXIME
a. Prototype of 3rd generation cephalosporins.

b. Highly active Against gram-positive organism (except enterococci and
MRSA)
PHARMACOKINETICS:
c. Administered i.m. or i.v.
d. Cross BBB
e. Deacetylated in the body
USES:
 Meningitis
 Hospital acquired infection
 Septicemias
 Alternative in typhoid
 PPNG urethritis

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6. CEFTRIAXONE
a. 3rd generation
b. Given i.m. or i.v.
c. Long acting cephalosporin.
d. Cross BBB and seen in CSF
e. No dosage adjustment reqd. In renal failure.
USES:
 Meningitis
 Multi-resistant typhoid fever
 Complicated UTI
 Septicemias
ADR:
 Hypoproteinemia
 Bleeding
 Hemolysis

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7. FOURTH GENERATION CEPHALOSPORINS
Cefepime
Cefpirome
a. Active against many gram-positive & gram-negative organism
PHARMACOKINETICS:
b. Parenterally administered
c. Excretion completely through kidneys
d. Cefepime can attain high concentration in CSF
e. Excreted by kidney
USES:
 Hospital-acquired pneumonia
 Febrile neutropenia
 Septicemia

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8. FOUR SECOND GENERATION CEPHALOSPORINS
 Cefuroxime
 Cefoxitin
 Cefaclor
 Cefprozil
9. FOUR ANTIPSEUDOMONAL PENICILLIN
 Carbenicillin
 Ticarcillin
 Piperacillin
 Mezlocillin
10. TWO BETA LACTAMASE INHIBITORS AND USES
 Clavulanic acid – re-establishes the activity of amoxicillin against Beta

lactamase producing resistant staph. aureus, H. influenzae, N.
gonorrhea, E. coli, proteus, Klebsiella, salmonella, shigella.
 Sulbactam – N. gonorrhea, mixed aerobic- anaerobic infections. Intra-

abdominal, gynecological, surgical, skin infection.
11. FOUR CARBEPENEMS
 Imipenem
 Meropenem
 Faropenem
 Doripenem

INDEX
Chapter 4: broad-spectrum Antibiotics

Essay
1. Tetracycline…..……....………………..………………………. 23
Short Notes
2. Doxycycline……………………………….…………..………… 26
3. Chloramphenicol….………………...……………………….. 28
23
1. TETRACYCLINE
 They are bacteriostatic antibiotics.
 Has broad spectrum of activity.
Tetracycline binds
30S ribosme of susceptible

organisms
blocks attachment of aminoacyl

tRNA
to acceptor(A) site
peptide chain doesnt grow
SPECTRUM:
 More active against gram-positive than gram-negative bacteria.
 Cocci: Active against Streptococcus pyogenes, streptococcus

pneumoniae, etc.
 Most gram-positive bacilli: like clostridia
 Anaerobes: listeria, cornybacteria, etc.
 Gram-negative bacilli: H. ducreyi, V. cholerae, etc.
 Spirochetes, rickettsiae, protozoa.

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RESISTANCE:
Mechanism:
 Resistant bacteria acquire capacity to pump tetracyclines out
 Plasmid mediated synthesis of protection protein which protect the ribosomal
binding site from tetracyclines.
 Elaboration of tetracycline inactivating enzyme.
Partial cross resistance between tetracyclines and chloramphenicol is noted.
PHARMACOKINETICS:
 Poor oral absorption.
 i.m. injection should not be given.
 Widely distributed
 Plasma T1/2 - 6-12 hours.
 Peak plasma concentration- 2-4 hrs.
 Tetracycline crosses placenta and enters fetal circulation and amniotic fluid.
USES:
 Empirical therapy – mixed infection

 As 1st choice of drugs in
 Venereal disease – chlamydial non-specific urethritis, endocervicitis
 Atypical pneumonia
 Cholera
 Brucellosis
 nd
As 2 choice of drugs in
 Tetanus
 Anthrax
 Gonorrhea
 Urinary tract infections
 Community-acquired pneumonia
 Amoebiasis

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ADVERSE EFFECTS:
 Epigastric pain
 Nausea
 Vomiting
 Diarrhea
 Phototoxicity
 Hepatic toxicity
 Renal toxicity
 Brown discoloration of the teeth.
CONTRAINDICATIONS:
 Pregnancy
 Lactating mothers
 In children

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2. DOXYCYCLINE
 It is the semisynthetic member of tetracyclines and is similar to Minocycline.
Similar to tetracycline
Doxycycline binds
30S ribosme of susceptible

organisms
blocks attachment of aminoacyl

tRNA
to acceptor(A) site
peptide chain doesnt grow
RESISTANCE:
 Doxycycline is not effectively effluxed.

 Some organisms not responding to other tetracyclines may be inhibited by
therapeutic concentration of doxycycline.
PHARMACOKINETICS:
 It has high potency than any other tetracyclines but less than Minocycline.
 95-100% absorbed in intestines.
 No interference by food
 High plasma protein binding

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 Excreted in faeces as conjugates.

 Plasma half-life: 18-24 hour.
ADVERSE EFFECTS:
 It has least effects on intestinal flora.
 Low incidence of diarrhoea
 High photo toxic effect
 Low renal toxicity.
USES:
 Chlamydial non-specific urethritis /endocervicitis.

 Along with quinine it is used to treat Falciparum malaria and vivax malaria.
 Leptospirosis
 Brucellosis

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3. CHLORAMPHENICOL
 Primarily bacteriostatic
chloramphenicol attaches to
50S ribosome near acceptor(A) site
prevents peptide bond formation
between newly attached amino

acid
and nascent peptide chain
peptide synthesis is terminated

prematurely
RESISTANCE:
Being orally active, broad spectrum and relatively cheap, it was extensively and
often indiscriminately used, resulting in high resistance among many bacteria.
Mechanism:
 Transfer of R factor by conjugation
 Acquisition of R plasmid encoded for an acetyl transferase which inactivates
chloramphenicol
 Decreased permeability into the resistant bacterial cells
 Lowered affinity of bacterial ribosome for chloramphenicol

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PHARMACOKINETICS:
 Rapidly and completely absorbed after oral ingestion.
 50-60% bound to plasma proteins.
 It crosses placenta and is secreted in bile.
 Conjugation with glucuronic acid occur in liver.
 Excreted unchanged in urine.
 Plasma half-life: 3-5 hours.
ADVERSE EFFECT:
 Bone marrow depression – aplastic anaemia, agranulocytosis
 Hypersensitivity reactions – rashes, fever, etc.
 Irritative effects – nausea, vomiting, diarrhoea
 Super infections
 Gray baby syndrome
USES:
 Pyogenic meningitis
 Anaerobic infections
 Intraocular infections
 Enteric fever
 As second choice of drug – brucellosis and rickettsial infection
 Topically – conjunctivitis

INDEX
Chapter 5: Aminoglycoside Antibiotics

Essay
1. Aminoglycoside…...………………..………………………. 30
Short Notes
2. Streptomycin……...………………………………..………… 32
3. Amikacin……………..………………...……………………….. 34
30
1. AMINOGLYCOSIDES
CLASSIFICATION:
The aminoglycosides are bactericidal antibiotics. Its action is described in 2 main

steps:
1. Transport of the aminoglycoside through the bacterial cell wall and cytoplasmic
membrane
 It is a multistep process.
Aminoglycosides
|
| diffuse across the outer coat of
↓ gram-negative bacteria through porin channels
periplasmic space
|energy dependent phase
↓
cytoplasmic membrane

31
 Thus, penetration is dependent upon maintenance of a polarized membrane

and on oxygen dependent active processes (EDP1 entry).
 Therefore, anaerobes are not sensitive and facultative anaerobes are more
resistant.
2. Binding to ribosomes resulting in inhibition of protein synthesis
aminoglycosides binds to
30S ribosome
freeze protein synthesis

initiation
prevents polysome formation
promote their disaggregation
to non-functional monomers
distortion of mRNA codon

recognition
misreading of codon
ADVERSE EFFECTS:
THERAPEUTIC USES OF GENTAMYCIN:
 Ototoxicity
 Cochlear damage.  Respiratory infections
 Vestibular damage  Pseudomonas, proteus or Klebsiella
 Nephrotoxicity infections
 Neuromuscular  Meningitis by gram-negative bacilli
blockade  Subacute bacterial endocarditis (SABE)

32
2. STREPTOMYCIN
 It is the oldest aminoglycoside antibiotic obtained from Streptomyces

griseus
 It is less potent (MICs are higher) than many other aminoglycosides.
 The antimicrobial spectrum streptomycin is relatively narrow primarily
covers aerobic gram-negative bacilli.
Refer above answer
PHARMACOKINETICS:
 Neither absorbed nor destroyed in g.i.t.

 Absorption from injection site in muscles are rapid
 Large volume of distribution
 Crosses placenta
 Not metabolised
 Excreted unchanged in urine

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ADVERSE EFFECTS:
 Vestibular disturbances
 Lowest nephrotoxicity
USES:
 Tuberculosis
 Subacute bacterial endocarditis
 Plague
 Tularemia

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3. AMIKACIN
 It is a semisynthetic derivative of kanamycin.

 Amikacin is resistant to bacterial aminoglycoside inactivating enzymes.
 Thus, it has the widest spectrum of activity, including many organisms resistant
to other aminoglycosides.
 Cross resistance between Kanamycin and Amikacin is very common.
ADVERSE EFFECTS:
 Ototoxicity
 Nephrotoxicity
 Neuromuscular blockade
 Contraindicated in pregnancy
USES:
 Reserve drug for empirical treatment of hospital acquired gram-negative

bacillary infection when gentamycin or tobramycin resistance is high.
 MDR TB

INDEX
Chapter 6: Macrolide, Lincosamide,

Glycopeptide and other Antibiotics, Urinary
Antiseptics
Essay
1. Macrolide……………..………………..………………………. 35
Short Notes
2. Clarithromycin…….………………………………..………… 39
3. Azythrumycin……..………………...……………………….. 40
4. Vancomycin……………………………………………………. 41
5. Clindamycin……………………………………………………. 42
6. Treatment for UTI…………………………………………… 43
35
1. MACROLIDE ANTIBIOTICS
CLASSIFICATION:
MACROLIDE ANTIBIOTICS OLD ERYTHROMYCIN
CLARITHROMYCIN
AZITHROMYCIN
NEW ROXITHROMYCIN
TELITHROMYCIN
SPIRAMYCIN
ERYTHROMYCIN:
 Isolated from Streptomyces erythreus.
 Slightly water soluble.
 Solution remains stable when kept in cold.
 Low doses: Bacteriostatic
 High doses: Bactericidal
 Acts by inhibiting bacterial protein synthesis.

36
Erythromycin combines with
50S ribosomal subunit
prevents the availability of Acceptor (A)

site
for next aminoacyl tRNA attachment
failure of ribosome to move to next

codon
premature termination of peptide chain
suppression of protein synthesis
SPECTRUM:
 Narrow.
 Mostly Gram-positive bacteria and some gram-negative bacteria.
 Overlaps with Penicillin G.
 Highly active against: Str. Pyogenes, Str. pneumoniae, N. gonorrhoeae,
Clostridia, C. diphtheriae, Listeria.
 Staphylococci was previously sensitive but now have become resistant.
 Also, Campylobacters, Legionella, Gardnerella vaginalis, Mycoplasma are highly
sensitive.
 N. Meningitis, Rickettsiae are moderately sensitive.
 Enterobacteriaceae - Gram negative.
RESISTANCE:
 All cocci develop resistance readily
 Resistant Enterobacteriaceae found to produce erythromycin esterase.
 Alteration in the ribosomal binding site for erythromycin by plasmid encoded
methylase enzyme.
 Either plasmid mediated or chromosomal mutation as in 50s ribosome.
 Cross resistance is also observed with clindamycin and chloramphenicol.

37
PHARMACOKINETICS:
 Erythromycin base is acid labile.
 Food delays absorption.
 Cross serous membranes, placenta and not blood brain barrier.
 Metabolised and excreted through bile.
 Minimal renal excretion.
 t½: 1.5 hr.
ADVERSE EFFECTS:
 GASTRO INTESTINAL:
 Anorexia
 Nausea
 Vomiting
 Diarrhoea
 LIVER TOXICITY
 Acute cholestatic hepatitis
 Hepatitis occur on re-administration of drug.
DRUG INTERACTIONS:
 Inhibit cytochrome p450 enzyme
 Increase in serum concentration of other drugs: theophylline, oral anti-
coagulants, cyclosporine, methyl prednisolone.
 Increase serum conc. Of oral digoxin.
USES:
 ALTERNATE TO PENICILLIN:
 Streptococcal pharyngitis, tonsillitis, mastoiditis, Resp. Infections by
pneumococci, H. Influenza.
 Alternate drug for prophylaxis of rheumatic fever and SABE.
 Diphtheria.
 Tetanus
 Syphilis and gonorrhoea.

38
 FIRST CHOICE OF DRUG

 Atypical pneumonia caused by mycoplasma pneumoniae.
 Legionnaire's pneumonia
 Whooping cough: 2-week course. Most effective.
Prophylactic: during 10 days incubation period.

Catarrhal stage: lasts for a week, may abort next stage or reduce
its duration and severity.
Paroxysmal stage: 2-4 weeks, no effect on duration and severity
of disease despite eradication of organisms.
Convalescent stage: whoop gradually resolves. (4-12 weeks)
 AS SECOND CHOICE DRUG

 Campylobacter enteritis
 Chancroid
 Chlamydia trachomatis.
 Penicillin resistant Staphylococcal infection. Not for MRSA.

39
2. CLARITHROMYCIN
 Semisynthetic macrolide
SPECTRUM:
 similar to erythromycin (G+ and few G- bacteria) + MAC (Mycobacterium
avium complex), M. leprae, other atypical mycobacteria.
PHARMACOKINETICS:
 Oral bioavailability- 50% due to 1st pass metabolism
 T1/2 - 4-6 hrs (lower doses), 16-9 hrs (higher doses)
USES:
 Respiratory tract infections
 Sinusitis
 Otitis media
 Whooping cough
 Atypical pneumonia
 Skin infections- Streptococcus pyogenes & Staph. aureus
 Anti H. pylori regimen
 MAC infections in AIDS patients
 M. avium complex- second line drug
ADVERSE EFFECTS:
 GI disturbances
 Reversible hearing impairment
 Pseudomembranous enterocolitis
 Hepatic dysfunction
 Rhabdomyolysis (rare)
DRUG INTERACTIONS
 Inhibits CYP3A4

40
3. AZITHROMYCIN
 Azalide congener of erythromycin
 Extended spectrum, improved pharmacokinetics, better tolerability.
PHARMACOKINETICS:
 Acid stable
 Rapid oral absorption
 Larger tissue distribution and intracellular penetration
 T1/2 >50 hrs
 Excreted unchanged in bile, renal excretion<10%
USES:
 FIRST CHOICE DRUG IN,
 Legionnaire’s pneumonia
 Chlamydia trachomatis
 Donovanosis
 Chancroid, PPNG urethritis
 OTHER INDICATIONS:
 Pharyngitis
 Tonsillitis
 Sinusitis
 Otitis media
 Community acquired pneumonia (CAP)
 MAC prophylaxis in AIDS patients
 Toxoplasmosis
ADVERSE EFFECTS:
 Mild gastric upset
 Abdominal pain
 Headache
 Dizziness

41
4. VANCOMYCIN
vancomycin binds to
D-Ala-D-Ala sequence
prevents its release from
the bactoprenol lipid

carrier
failure of assembling and

cross linking of cell wall
PHARMACOKINETICS:
 Route of administration: Oral, i.v.
 T1/2: 6 hours
 Widely distributed USES:
 Excreted unchanged in urine  MRSA
 Antibiotic associated
ADR: pseudomembranous
 Toxicity: ototoxic and nephrotoxic enterocolitis
 Clostridium difficle –
Mnemonic: Vancomycin is NOT Recommended bacteriostatic effect.
 N- Nephrotoxic
 O- Ototoxic
 T- thrombophlebitis
 R – Red man syndrome (in rapid i.v. chills, fever, urticaria, intense
flushing)

42
5. CLINDAMYCIN
Mechanism of action ad spectrum similar to erythromycin
SPECTRUM:
 Most gram-positive cocci and anaerobes
 Bacterial action – gram positive cocci, C. diphtheriae, Nocardia,
Actinomycetes, Toxoplasma, Anaerobes – Bacteroides fragilis.
PHARMACOKINETICS:
 Route of administration: oral, i.v.
 Large volume of distribution
 Largely metabolised
 Metabolites are excreted in urine and bile
 T1/2 – 3 hr.
ADR:
 Rashes
 Urticaria
 Abdominal pain
 Pseudomembranous enterocolitis
 Thrombophlebitis.
USES:
 Anaerobic infections above the diaphragm
 In patients allergic to penicillin.
 Prophylaxis of endocarditis.
 In AIDS, combined with pyrimethamine for toxoplasmosis.
 In multidrug resistant falciparum infection- alternative to doxycycline.
 Drug of choice for Toxic shock syndrome.

43
6. TREATMENT OF UTI
lower UTI
upper UTI
LOWER UTI UPPER UTI

INFECTION Localised to urethra Kidney is involved
and bladder
DURATION OF ANTI- Short course Prolonged therapy
MICROBIAL THERAPY
TREATMENT SCHEDULES (EMPIRICAL THERAPY):

Acute cystitis:
 Ciprofloxacin 250-500mg bd oral for 3 days (or)
 Norfloxacin 400mg bd oral for 3 days (or)
 Ofloxacin 200mg bd oral for 3 days (or)
 Cotrimoxazole ds bd oral for 3 days
Acute pyelonephritis:
 Ampicillin 1g for every 6 hrs i.v. and gentamicin 1 mg/kg every 8 hrs i.v. for 3
weeks (or)
 Ciprofloxacin 750mg bd oral for 3 weeks (or)
 Ofloxacin 200mg bd oral for 3 weeks (or)
 Cotrimoxazole DS bd oral for 3 weeks.
Chronic pyelonephritis:
 Drug regimen same as acute pyelonephritis but duration is 3-6 months.

INDEX
Chapter 7: Antitubercular Drugs

Essay
1. Antitubercular Drugs……………..………………………. 44
Short Notes
2. Rifampin……………..………………………………..………… 47
3. Pyrazinamide………………………...……………………….. 49
Short Answers
4. Drug Regimen in Drug Sensitive TB………………….. 51
5. 2nd line Antitubercular Drugs……………………………. 51
6. MAC Infection………………………………………………….. 51
44
1. ANTI TUBERCULAR DRUGS
CLASSIFICATION:

45
ISONIAZID
INTRODUCTION:
 Isoniazid is an excellent antitubercular drug
 It is primarily tuberculocidal.
 Fast multiplying organisms are rapidly killed, but quiescent ones are only
inhibited.
 It acts on extracellular as well as on intracellular TB (bacilli present within
macrophages), and is equally active in acidic or alkaline medium.
 Isoniazid (INH) enters sensitive bacteria.
catalase
Isoniazid --------------> active metabolite ----------> adducts with NAD and NADP
peroxidase
NAD adduct NADP adduct
inhibits 'InhA' and inhibits mycobacterial

'KasA' gene DHFRase
mycolic acid DNA synthesis is

synthesis is interrupted
interfered

46
RESISTANCE:
The most common mutation is
 KatG gene which produces catalase peroxidase
Other mutations are
 InhA gene and KasA gene
PHARMACOKINETICS:
 INH is completely absorbed orally
 Penetrates all body tissues, tubercular cavities, placenta and BBB.
 It is extensively metabolized in liver - most important pathway being N-
acetylation by NAT2.
 The acetylated metabolite is excreted in urine
INTERACTIONS:
 Aluminium hydroxide inhibits INH absorption.
 INH retards phenytoin, carbamazepine, diazepam, theophylline and
warfarin metabolism by inhibiting CYP2C19 and CYP3A4, and may raise
their blood levels.
ADVERSE EFFECTS:
 Peripheral neuritis
 Neurological manifestations.
INH neurotoxicity is treated by pyridoxine 100 mg/day.
 Hepatitis
Other side effects:

 Lethargy
 Rashes
 Fever
 Acne
 Arthralgia

47
2. RIFAMPIN (RIFAMPICIN, R)
 Semisynthetic derivative of rifamycin

 First line antituberculous drug
 It kills both intracellular and extracellular bacilli
 It also has resistance preventing actions
rifampin binds to β subunit

of
mycobacterial DNA
dependent RNA polymerase
interrupts DNA synthesis
PHARMACOKINETICS:
 Orally well absorbed from GIT
 Presence of food reduces its absorption
 Distributed widely across body
 Metabolized in liver
 Active deacylated form undergoes enterohepatic circulation
 Excreted in urine and bile
INTERACTION:
 Microsomal enzyme inducer – CYP450, CYP3A4, etc.

48
USES:
 Tuberculosis
 Leprosy
 Prophylaxis of meningococcal and H. influenzae meningitis
 2nd or 3rd choice of drug for MRSA, diphtheroids and legionella infections.
 In combination with doxycycline used in brucellosis as first line therapy
ADVERSE EFFECTS:
 Hepatitis
 Flushing
 Rashes
 Headache
 Malaise
 Nausea
 Vomiting
 Diarrhoea
 Orange-red urine

49
3. PYRAZINAMIDE (Z)
 It is weakly tuberculocidal
 First line drug
 Active in acidic medium
 It is more lethal to intracellular bacilli
pyrazinamidase acts on
pyrazinamide to form
pyrazinoic acid which gets
accumulated in acidic pH
inhibits mycolic acid

synthesis
Other actions:
 Disrupts mycobacterial cell wall
 Disrupts transport function

50
PHARMACOKINETICS:
 Well absorbed orally
 Good penetration in CSF -highly useful in meningeal TB
 Metabolized in liver
 Safe In pregnancy
ADVERSE EFFECTS:
 Hepatotoxicity
 Hyperuricemia
 Abdominal distress
 Arthralgia
 Flushing
 Rashes

51
4. DRUG REGIMEN IN DRUG SENSITIVE TB
TYPE OF INTENSIVE PHASE CONTINOUS TOTAL

PATIENT PHASE DURATION
NEW HRZE – 2months HRE – 4 months 6 months
PREVIOUSLY HRZES – 2 months HRE – 5 months 8 months
TREATED + HRZE – 1 month
H – isoniazid
R – rifampin
Z – pyrazinamide
E – ethambutol
S – streptomycin
5. FOUR 2ND LINE ANTITUBERCULAR DRUGS
 Kanamycin
 Capreomycin
 Ethionamide
 Fluoroquinolones
6. DRUG REGIMEN IN MAC INFECTION

INDEX
Chapter 8: Antileprotic Drugs

Essay
1. Antileprotic Drugs……………..…………………………… 52
Short Notes
2. Clofazimine.………..………………………………..………… 55
3. MDT of Leprosy..…………………...……………………….. 57
4. Lepra Reaction………………………………………………… 59
52
1. ANTILEPROTIC DRUGS
CLASSIFICATION:
DAPSONE
 Mechanism of action similar to sulfonamides.
 Dapsone act by the inhibition of PABA incorporation into folic acid by folate
synthase, cause the antibacterial action of dapsone is antagonized by PABA.
 It is leprostatic at very low concentrations, while the growth of many other
bacteria sensitive to sulphonamides is arrested at higher concentrations.
RESISTANCE:
 Primary – when dapsone resistance is encountered in an untreated patient
and it indicates that the infection was contacted from a patient harbouring
resistant bacilli.
 Secondary – resistance which develops during monotherapy with dapsone.
 Persisters – the drug sensitive bacilli which become dormant, hide in some
tissues and are not affected by any drug and relapse occurs when the drug is
withdrawn.

53
PHARMACOKINETICS:
 Completely absorbed after oral administration
 Widely distributed in the body
 Penetration in CSF is poor.
 70% plasma protein bound
 Concentrated in the skin, muscle, liver and kidney.
 Acetylated as well as glucuronide and sulphate conjugated in liver.
 Metabolites are excreted in bile and reabsorbed from intestine.
 Ultimate excretion occurs mostly in urine.
 Elimination take 1-2 weeks or long.
ADVERSE EFFECTS:
 Mild haemolytic anaemia is common.
 GIT intolerance
 Nausea
 Anorexia
 Other side effects

 Methemoglobinemia
 Headache
 Paraesthesia
 Mental symptoms
 Drug fever
 Cutaneous side effects

 Itching
 Allergic reactions
 Hypermelanosis
 Phototoxicity

54
 Sulfone syndrome
 develops 4-6 weeks after starting dapsone treatment, generally seen
in malnourished patients.
 Manifestations are
 Fever
 Malaise
 Lymph node enlargement
 Desquamation of skin
 Jaundice
 Anaemia
 Treatment includes withdrawal of dapsone and instituting
corticosteroid therapy along with supportive measures.
CONTRAINDICATIONS:
 Severe anemia
 In those showing hypersensitivity reactions.
USES:
 Leprosy
 Dapsone + pyrimethamine is used in chloroquine resistant malaria,
toxoplasmosis and P. jirovecii infection.

55
2. CLOFAZIMINE
 Phenazine derivative group of anti-leprotic drug

 Dye with lepro static and anti-inflammatory properties
Interference with template function

of DNA in M. leprae
Alteration of membrane structure

and its transport function
Disruption of Mitochondrial
electron transport chain
PHARMACOKINETICS:
 Oral route
 40-70% absorbed
 Accumulates in macrophages and deposits as needle shaped crystals in
many tissues including subcutaneous fat
 Entry into CSF is poor
USES:
 For Dapsone resistant M. leprae
 Component of Multi drug therapy of Leprosy
 Used in Lepra reaction for its anti-inflammatory property
 Occasionally used in combined regimen for XDR-TB

56
ADVERSE DRUG REACTIONS:

 Reddish black discoloration of skin
 dryness of skin
 Itching
 scaling
 Nausea
 Anorexia
 abdominal pain
 weight loss
 enteritis with loose stools
 GI symptoms
CONTRAINDICATIONS:
 Early pregnancy
 Patients with liver and Kidney disease

57
3. MULTI DRUG THERAPY (MDT) OF LEPROSY
 Introduced in 1981 by WHO and implemented by NLEP
OBJECTIVES:
 To deal with Dapsone resistant strains
 Shorten the duration of treatment
 To eliminate microbial persisters
ADVANTAGES:
 Effective in cases of primary dapsone resistance
 Prevents emergence of Dapsone resistance
 Affords quick symptom relief, stops progression, prevents further
complications and renders MBL cases noncontagious within few days
 Reduces total duration of therapy and chances of relapse < 1%
 Efficacy, safety, acceptability of MDT for both PBL and MBL is excellent
 No resistance to rifampicin has developed after use of MDT
 Relapse cases have been successfully treated with the same MDT
CLASSIFICATION:
PAUCIBACILLARY LEPROSY (PBL) MULTIBACILLARY LEPROSY (MBL)

1-5 skin lesions 6 or more skin lesions
No or one nerve involvement, ± 1-5 skin >1 nerve involved irrespective of number
lesions. of skin lesions.
Skin smear negative at all sites Skin smear positive at any one site.
DRUGS:
 Rifampicin
 Dapsone
 Clofazimine

58
OLD REGIMEN:
 PBL – Dapsone + Rifampicin for 6 months
 MBL – Dapsone + Rifampicin + Clofazimine for 2 years
NEW REGIMEN:
DRUGS MBL PBL
RIFAMPIN 600 mg once a month 600 mg once a month
supervised supervised
DAPSONE 100 mg daily self- 100 mg daily self-
administered administered
CLOFAZIMINE 300 mg once a month -
supervised + 50 mg daily
self-administered
DURATION 12 months 6 months
CHILD DOSE
RIFAMPIN 10 mg/kg once monthly
CLOFAZIMINE 1 mg/kg daily + 6 mg/kg once monthly
DAPSONE 2 mg/kg daily
 Relapse of Leprosy  Same MDT

 Leprosy and TB coinfection  MDT is continued but rifampicin is given daily
for TB
 Leprosy in HIV patients  MDT can be given safely

59
4. LEPRA REACTION
 Occurs in lepromatous leprosy.

 Usually coincides with the administration of chemotherapy and / or
intercurrent infection.
 It is a Jarish Herxheimer type of reaction due to release of antigens from the
killed bacilli and may be mild, severe or life threatening, i.e. erythema
nodosum leprosum (ENL).
 Lepra reaction is of abrupt onset
 Existing lesions enlarge, become red, swollen and painful.
 Discontinuation of dapsone is recommended only in severe cases.
 Clofazimine is effective in controlling the reaction, probably because of its
anti-inflammatory property.
 In severe reactions, prednisolone 40 – 60 mg/day is started immediately
and continued till the reaction subsides.
 Thalidomide – an anti-inflammatory, cytokine modulating drug is used in
ENL as an alternative to prednisolone.

INDEX
Chapter 9: Antifungal Drugs

Essay
1. Antifungal Drugs....………………..………………………. 60
Short Notes
2. Caspofungin………..………………………………..………… 65
3. Griseofulvin………………………......……………………….. 67
4. Ketoconazole..…………………………………………………. 69
5. Fluconazole……………………………………………………… 71
6. Terbinafine………………………………………………………. 72
Short Answers
7. Amphotericin B Preparation…………………………….. 73
8. Uses of Itraconazole…………………………………………. 74
9. ADR Of Flucytosine…………………………………………… 74
10. Topical Antifungal Agents…………………………………. 74
60
1. ANTI FUNGAL DRUGS
 Drugs that are used for deep and superficial fungal infections.
CLASSIFICATION:

61
AMPHOTERICIN B (AMB)
Amphotericin B is a polyene antibiotic molecule
AMB has ↑ affinity for ergosterol
AMB combines with it andget inserted into the membrane
several polyene molecules orient themselves to form

micropore
the hydrophilic side forms interior of the pore
through which water soluble substances move out
sterols fill up the outer surface and stabilise the outer

membrane (lipophilic)
cell permeability is markedly ↑
AMB enhance immunity thus help in immunocompromised individuals of fungal

infections.

62
SPECTRUM: broad spectrum

 Active against wide range of yeasts and fungi: Candida albicans, Histoplasma
capsulatum, Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides
immitis, Torulopsis, Aspergillus, Rhodotorula, Spirothrix, etc.
 Dermatophytes are inhibited in vitro.
 Fungicidal at high concentration and static at low concentration.
 Resistance is rare (Among Candida)
 Also active on various species of Leishmania.
PHARMACOKINETICS:
 Not absorbed orally but can be given for intestinal candidiasis without
systemic toxicity.
 Administered i.v. as a suspension made with the help of DOC (Deoxy cholate).
 Penetration in CSF is poor.
 Binds to sterol in tissues and to Lipoproteins in plasma and stays in body for
long periods.
 T½: 15 days.
 Metabolised in liver (60%).
 Excreted slowly in urine and bile.

63
ADVERSE EFFECTS: High toxicity

ACUTE REACTION:
 Chills
 Fever
 Body ache
 Pain
 Nausea
 Vomiting
 Dyspnoea for 2-5 hours
 thrombophlebitis
Probably due to loss of cytokines (IL, TNF-alpha). Dose to be increased based on

intensity of the reaction, intensity decreases on continued medication.
Hydrocortisone injection 0.6 mg/kg along with AMB infusion decreases
reaction.
LONG TERM TOXICITY:
 Nephrotoxicity: dose related, reduced on discontinuing therapy.
Manifestations:
 Azotemia
 Reduced GFR acidosis
 Hypokalaemia
 Inability to concentrate urine
 Anemia: Progressive. Due to bone marrow depression, reversible.
 CNS toxicity: (Only on intrathecal injection)
 Headache
 Vomiting
 Nerve palsies

64
USES:
Applied topically for oral, vaginal, cutaneous candidiasis, fungal corneal ulcer and
Otomycosis. GOLD STANDARD FOR ANTIFUNGAL THERAPY.
 It is the most effective for systemic mycosis.
1st choice in
 Candidiasis
 Cryptococcosis
 Histoplasmosis
 Coccidioidomycosis
 Blastomycosis
 Disseminated sporotrichosis
 Aspergillosis
 Mucormycosis
2nd choice of drugs in

 Paracoccidiodomycosis
 In initial induction of therapy in immunocompromised patients.

 Febrile neutropenia
 Leishmaniasis
INTERACTIONS:
 Flucytosine has supra additive with AMB
 Aminoglycosides, vancomycin, cyclosporine increase renal impairment along
with AMB.

65
2. CASPOFUNGIN
 It is the first and the prototype member of the class

 Active mainly against Candida and Aspergillus.
 Strains of candida that have become resistant to azoles are susceptible to
caspofungin.
Caspofungin inhibits
β-glucan synthase enzyme
which is needed for synthesis of β-1,3-

glucan
cross linking between chitin and β-1,3-

glucan doesnt occur
weakening of cell wall
fungal cell succumbs to osmotic

susceptibility
PHARMACOKINETICS:
 Caspofungin is not absorbed orally
 Has to be infused through i.v.
 It is distributed into tissues, but does not enter CSF.
 Metabolism is extensive and metabolites are excreted in urine as well as
faeces
 Plasma t1⁄2: 10 hours.

66
USES:
 Deep and invasive candidiasis
 Oesophageal candidiasis
 Salvage therapy of nonresponsive invasive aspergillosis.
Because of good tolerability, it is now increasingly used in neutropenic

immunocompromised patients whose fever is not responding to antibacterial
antibiotics.
ADVERSE EFFECTS:
 An acute febrile reaction
 Thrombophlebitis of the injected vein
 Rash
 Vomiting
 Dyspnoea
 Hypokalemia
 Joint pain

67
3. GRISEOFULVIN
 Insoluble fungistatic drug

 Derived from penicillium griseofulvum
 Used in systemic dermatophytosis but not against fungi causing deep mycosis.
Griseofulvin
interacts with polymerised

microtubules
distrupts the mitotic spindles
daughter nuclei fails to move or move

short distance
inhibits mitosis - fungistatic action
PHARMACOKINETICS:
 Absorption - incomplete oral absorption
 Absorption can be improved along with fatty foods
 Metabolism - methylation in liver
 Excretion - kidneys
 Plasma t½ - 24 hrs

68
USES:
 Dermatophytosis (dose-125-250 mg QID)
 For scalp - 4 weeks
 Palms, soles - 6 to 8 weeks
 Finger nails - 6 to 8 months
 Toe nails - 10 to 12 months
 Effective in athletes’ foot

 Onychomycosis
 Tinea capitis
ADVERSE EFFECTS:
 Headache
 g.i.t disturbances
 CNS symptoms
 Peripheral neuritis
INTERACTIONS:
 Hastens warfarin metabolism
 Efficacy of oral contraceptives maybe lost

69
4. KETOCONAZOLE (KTZ)
 First oral azole to be produced.

 Broad spectrum antifungal drug.
Azoles inhibit
fungal CYP450 enzyme -

lanosterol 14-methylase
impairs ergosterol synthesis
leads to cascade of
membrane abnormalities
increases the susceptibility of

fungus
PHARMACOKINETICS:
 Well absorbed from the gut
 Food and low pH enhance absorption
 Extensive hepatic metabolism
 Metabolites are excreted in urine and faeces
USES:
 Mucocutaneous candidiasis and dermatophysis
 Cushing’s syndrome
 Cutaneous leishmaniasis
 Monilial vaginitis

70
ADVERSE REACTION:
 Nausea
 Vomiting
 Headache
 Loss of appetite
 Gynaecomastia
 Infertility
 Decreased Libido
 Azoospermia
 Hypertension
INTERACTIONS:
 Rifampicin induce the metabolism
 Inhibition of CYP450 enzymes and increases the plasma level of several drugs
like sulfonylureas
 Proton pump inhibitors ↓ oral absorption of KTZ

71
5. FLUCONAZOLE
 Water soluble triazole

 Has wide range of activity than KTZ.
Azoles inhibit
fungal CYP450 enzyme -

lanosterol 14-methylase
impairs ergosterol synthesis
leads to cascade of
membrane abnormalities
increases the susceptibility of

fungus
PHARMACOKINETICS:
 Absorbed from the gut – 94%
 Penetrates brain
 Eliminated by kidneys
 Half-life - 25 hrs.
USES:
 Cryptococcaal meningitis
 Coccidioidal meningitis
 Candidiasis

72
ADVERSE EFFECTS:
 GI disturbances
 Headache
 Rashes
NOT RECOMMENDED IN PREGNANT AND LACTATING MOTHERS
6. TERBINAFINE
 Fungicidal
Terbinafine acts as a non-competitive inhibitor of squalene epoxidase
Squalene epoxidase <---x----- terbinafine

↓
Squalene epoxide
↓
Lanosterol
↓
Ergosterol
PHARMACOKINETICS:
 Well absorbed
 Extensive first pass metabolism
 99% bound to plasma proteins
 Excreted in urine and faeces

73
ADVERSE EFFECTS:
 Rashes
 Headache
 GI disturbances
USES:
 Tinea pedis/ cruris/ corporis/ capitis
 Onychomycosis
7. AMPHOTERICIN B PREPRATION
 Conventional (deoxycholate)
Used in Systemic mycosis
 Liposomal
Used in
 Kala azar
 Deep mycosis
 As empirical therapy in febrile neutropenic patients not
responding to antibacterial antibiotics

74
8. FOUR USES OF ITRACONAZOLE
 Systemic mycosis
 Vaginal candidiasis
 Onychomycosis
 Pityriasis versicolor
9. ADVERSE EFFECTS OF FLUCYTOSINE
 Bone marrow depression

 Gastrointestinal disturbances – enteritis and diarrhoea
 Liver dysfunction is mild and reversible
10. FOUR TOPICAL ANTIFUNGAL AGENTS
 Tolnaftate
 Ciclopirox olamine
 Butenafine
 Benzoic acid

INDEX
Chapter 10: Antiviral Drugs (Non-Retroviral)
Short Notes
1. Acyclovir……………..………………………………..…………. 74
2. Interferon α………………………......……………………….. 76
Short Answers
3. Anti Herpes Virus Drugs……………………………………. 78
4. Anti Influenza Virus Drugs………………………………… 78
5. ADR of Ribavirin……………………………………………….. 78
6. Drugs for CMV………………………………………………….. 78
74
1. ACYCLOVIR
 It is an Anti-Herpes virus drug
 This Deoxiguanosine analogue requires a virus specific enzyme for
conversion into active metabolite that inhibits DNA synthesis and viral
replication
Acyclovir ----- Acyclovir monophosphate ----- Acyclovir triphosphate

1 2
i. Inhibits Herpes virus

DNA polymerase
completely
ii. Gets incorporated in

1  herpes virus specific thymidine kinase
viral DNA and stops
2  cellular kinases lengthening of DNA
 Acyclovir is preferentially taken up by the virus infected cells because of

selective generation of active inhibitor in the virus infected cell.
 It is active only against herpes group of viruses

HSV-1 > HSV-2 > VZV=EBV
 HSV and VZV develop resistance mainly due to mutants deficient in

Thymidine Kinase and change in in specificity of virus directed enzyme
PHARMACOKINECTICS:
 20% orally absorbed

 Wide distribution
 CSF concentration is 50% of that of Plasma’s
 Penetrates Cornea well
 Excreted in urine via glomerular filtration and tubular secretion

75
USES:
 Genital Herpes simplex
 Generally caused by Type 2 virus
 Primary disease: 5% ointment is applied locally 6 times a day for 10
days in early and mild cases. Late or severe cases local + oral therapy
(800 mg TDS for 10 days) is given.
 Recurrent disease: parenteral – 5 mg/kg i.v. infused over 1 hour,
repeated 8 hourly for 10 days. suppressive oral therapy with 400 mg BD
prevent recurrences as long as given.
 Mucocutaneous H. simplex
 Type 1 virus
 10-day oral acyclovir is given
 H. simplex encephalitis
 10-20mg/kg/8 hr IV for 10 days is Drug of choice
 H. simplex keratitis (type 1 virus)

 Better than idoxuridine because causes less blindness
 Administered 5 times daily till 3 days after healing
 Herpes zoster
 High doses needed to be used
 Chickenpox
 Only in immunodeficient and neonates
 15 mg/kg/day i.v. for 7 days (d.o.c.)
ADR:
 Tropical
 Stinging and burning sensation
 Oral
 Headache
 Nausea
 Malaise

76
 Intravenous
 Rashes
 Sweating
 Emesis
 Fall in BP
 Dose-dependent decrease in GFR
2. INTERFERON α
 Low molecular weight glycoprotein cytokines produced by host cells in

response to viral infections, TNFα, IL-1
 Interferon receptors are JAK-STAT tyrosine protein kinase receptors.
activation of JAK-STAT
phosphorylate cellular
proteins
induce transcription of
Interferon induced proteins
exert anti-viral effects

77
 Very Host specific

 Human Anti-viral IFNs are α, β, γ out of which IFNα2A and IFNα2B are produced
by recombinant technology and clinically used.
PHARMACOKINETICS:
 Given as i.m. or s.c. (Pegylated forms)
 Destroyed in Kidney and remain in plasma for <24 hrs
 Peginterferon is absorbed more slowly and produce long lasting effects
permitting weekly administration.
USES:
 Chronic Hepatitis B
 Chronic Hepatitis C
 AIDS related Kaposi sarcoma
 Condyloma acuminata
 H.simplex, VZV, CMV
 CML, follicular lymphoma, cutaneous T-cell lymphoma and multiple myeloma
ADR:
 Flu-like symptoms (fatigue, fever, pain, nausea, anorexia, taste and visual
disturbances
 Neurotoxicity (numbness, neuropathy, depression, tremor)
 Myelosuppression
 Thyroid dysfunction
 Hypotension and arrythmias
 Alopecia
 Liver dysfunction (reversible)

78
3. 4 ANTI HERPES VIRUS DRUGS
 Idoxuridine
 Acyclovir
 Valacyclovir
 Famciclovir
4. 4 ANTI INFLUENZA VIRUS DRUGS
 Amantadine
 Rimantadine
 Zanamivir
 Peramivir
5. ADR OF RIBAVIRIN
 Dose dependent Haemolytic anaemia

 Bone marrow depression
 CNS and G.i. symptoms
 Teratogenic (contraception is need during and 3 months after treatment)
 Aerosol form can cause mucosal irritation and bronchospasm
6. FOUR DRUGS FOR CYTOMEGALOVIRUS (CMV)
 Ganciclovir
 Valganciclovir
 Cidofovir
 Foscarnet

INDEX
Chapter 11: Antiviral Drugs (Anti-retrovirus)

Essay
1. Anti Retroviral Drugs……………..………………………. 79
Short Notes
2. Principles and Guidelines in Treatment of HIV… 81
3. Prophylaxis of HIV Infection.....……………………….. 83
4. Fusion Inhibitors..……………………………………………. 86
Short Answers
5. Protease Inhibitors………………………………………….. 87
6. Nevirapine – MOA…………………………………………… 87
79
1. ANTI RETROVIRAL DRUGS
CLASSIFICATION:
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)

Zidovudine is the prototype drug
zidovudine is
phosphorylated
to zidovudine
triphosphate
selectively inhibits
viral reverse
transcriptase
terminates proviral DNA

80
NRTIs ADR USES

ZIDOVUDINE (AZT) Anaemia, neutropenia, A component of
nausea, anorexia, alternative regimen.
abdominal pain, etc.
DIDANOSINE (ddl) Peripheral neuropathy, Infrequently used due to
diarrhoea, nausea, etc. high toxicity
STAVUDINE (d4T) Metabolic complications No longer used
like lactic acidosis,
peripheral neuropathy,
etc.
LAMIVUDINE (3TC) Headache, fatigue, Triple line drug in WHO
nausea, anorexia, etc. and NACO regimen.
Chronic hepatitis B
ABACAVIR (ABC) Hypersensitivity 1st line WHO regimen for
reactions. Flu-like children
respiratory and
constitutional symptoms
EMTRICITABINE (FTC) Fatigue, headache, 1st line anti-HIV drugs.
nausea, diarrhoea, etc. Pre-exposure prophylaxis
of HIV in high risk adults.
TENOFOVIR (TDF) Renal toxicity 1st line WHO regimen for
adults and adolescents.

81
2. PRINCIPLES AND GUIDELINES IN TREATMENT OF HIV
The treatment of HIV infection and its complications is complex, prolonged, needs
expertise, strong motivation and commitment of the patient, resources and is
expensive.
INITIATING ANTIRETROVIRAL THERAPY:
The WHO (2016) guideline has recommended that ART should be started in all adults
including
 Pregnant and breast-feeding women
 Adolescents as well as children
as soon as possible after diagnosis of HIV infection is confirmed irrespective of
 CD4 cell count
 the HIV-RNA load
 the clinical stage of the disease.
THERAPEUTIC REGIMENS:
NACO selects first line regimens for untreated patients on the following principles:
 All regimens should have 2 NRTI+1NNRTI.
 Include lamivudine in all regimens.
 The other NRTI can be zidovudine or stavudine.
 Choose one NNRTI from nevirapine or efavirenz.
 Choose efavirenz in patients with hepatic dysfunction and in those
concurrently receiving rifampin.
 Do not use efavirenz in pregnant women or in those likely to get pregnant.

82
CHANGING OF FAILING REGIMEN:
An ART regimen is considered to have failed when:

 Plasma HIV-RNA count is not rendered undetectable (<50 copies/μl) within 6
months therapy.
 Repeated detection of virus in plasma after initial suppression to undetectable
levels despite continuation of the drug regimen.
 Clinical deterioration, fall in CD4 cell count, serious opportunistic infection
while continuing drug therapy.

83
PROPHYLAXIS OF HIV INFECTION:
 Pre-exposure prophylaxis (PrEP)

 Post-exposure prophylaxis (PEP)
 Prophylaxis after sexual exposure
 Perinatal HIV prophylaxis
3. PROPHYLAXIS OF HIV INFECTION
PRE-EXPOSURE PROPHYLAXIS
 This serves to protect people at high risk of contracting HIV infection
POST-EXPOSURE PROPHYLAXIS
 Health care workers and others who get accidentally exposed to the risk of HIV
infection by needlestick or other sharp injury or contact with blood/ biological
fluid of HIV patients or blood transfusion should be considered for PEP.
 The aim of PEP is to suppress local viral replication prior to dissemination, so
that the infection is aborted.

84
PROPHYLAXIS AFTER SEXUAL EXPOSURE:
 Though there is no data to evaluate the value of prophylaxis after sexual

exposure, the same regimen as for needle stick may be used.
PERINATAL HIV PROPHYLAXIS:
 HIV may be transmitted from the mother to the child either through the
placenta, or during delivery, or by breastfeeding.

85
 The highest risk (>2/3rd) if transmission is during the birth process. As per
current recommendation, all HIV positive women, who are not on ART, should
be put on the standard 3 drug ART.
 This should be continued through delivery and into the postnatal period and
has been shown to prevent vertical transmission of HIV to the neonate, as well
as benefit the mother’s own health.
 The first line NACO regimen for pregnant women is:
Tenofovir 300mg + Lamivudine 300mg + Efavirenz 600mg
 In addition, the neonate should be given syrup nevirapine for 6 weeks

86
4. FUSION IHIBITORS
 Also known as Entry inhibitors
ENFUVIRTIDE:
enfuvirtide binds to
HIV-1 envelope transmembrane

glycoprotein
prevents fusion of
viral and cellular membranes
entry of virus into cell is blocked
 It is not active against HIV-2.

 No cross resistance with other classes of ARV drugs occurs.
 Administered s.c. twice daily, it is used as an add on drug to an optimized
regimen in selected patients who have failed many earlier regimens and for
whom there is no other treatment option.
 The injections are painful and cause local nodules/cysts.

87
5. FOUR PROTEASE INHIBITORS
 Atazanavir (ATV)
 Indinavir (IDV)
 Nelfinavir (NFV)
 Saquinavir (SQV)
 Ritonavir (RTV)
6. NEVIRAPINE – MECHANISM OF ACTION
 Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV.

 Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-
dependent and DNA-dependent DNA polymerase activities by causing a
disruption of the enzyme's catalytic site.

INDEX
Chapter 12: Antimalarial Drugs
Essay
1. Antimalarial Drugs……………..………………………….. 88
Short Notes
2. Treatment of Chloroquine Resistant Malaria..… 91
3. Mefloquine………………………......……………………….. 92
4. Primaquine………..……………………………………………. 94
5. Artemisinin Based Combination Therapy………… 95
Short Answers
6. Management of Cerebral Malaria.………………….. 97
7. Erythrocytic Schizonticidal Agents…………………… 97
8. Artemisinin Derivatives of Malaria………………….. 97
88
1. ANTIMALARIAL DRUGS
CLASSIFICATION:
CHLOROQUINE (CQ):
 Rapidly acting erythrocytic schizontocide against all species of plasmodia
 Controls most clinical attacks in 1-2 days with disappearance of parasites in
peripheral blood
 Does not prevent relapse of vivax and ovale malaria.
 No gametocidal activity
 It’s a basic drug

89
MECHANISM OF ACTION: Not exactly known
CQ (a weak base) is taken up by
acidic vacuoles of parasite
where it is concentrated
it prevents formation of
hemozoin
by forming a drug-haeme
complex
damages plasmodial membrane
PHARMACOKINETICS:
 Oral
 50% binds to plasma
 Increased affinity for melanin and nuclear chromatin
 Selective accumulation in retina  ocular toxicity
 T1/2: 3- days, since tightly bound, persist for 1-2 months.
ADR:
 Nausea LONG TERM USE
 Vomiting
 Loss of hearing
 Anorexia
 Rashes
 Uncontrollable itching
 Photoallergy
 Epigastric pain
 Myopathy
 Headache
 Graying of hair

90
USES:
 D.O.C. for P. vivax, ovale, malaria
 Extraintestinal amoebiasis
 Rheumatoid arthritis
 Lepra reaction
 Discoid lupus erythematous (very effective)
 Photogenic reaction
 Infectious mononucleosis – symptomatic relief

91
2. TREATMENT OF CHLOROQUINE RESISTANT MALARIA

92
3. MEFLOQUINE
 Synthetic quinoline methanol
 Effective against chloroquine resistant P. falciparum malaria
 Fast acting erythrocytic schizontocide but slower than chloroquine/quinine due
to very slow and variable rate of absorption
 No effects as gametocidal; doesn’t kill vivax hypnozoites
 Efficacious suppressive prophylaxis for multi resistant P. falciparum and other
types of malaria
Not known but morphological changes in intra erythrocytic parasite resemble quinine
and chloroquine.
CQ (a weak base) is taken up by
acidic vacuoles of parasite
where it is concentrated
it prevents formation of
hemozoin
by forming a drug-haeme
complex
damages plasmodial membrane
However, recent evidences suggest that the site of action of mefloquine is in parasitic
cytosol rather than in the acidic vacuole.

93
PHARMACOKINETICS:
 Orally administered
 Highly plasma bound
 Concentrated in liver, lung, intestines etc.
 Long t1/2 – 2-3 weeks due to considerable enterohepatic circulation and its
tissue binding capacity
 Extensive metabolism in liver
 Primarily secreted in bile
ADR:
 Bitter in taste
 Dizziness
 Nausea, Vomiting, Diarrhea
 Abdominal pain
 Sinus bradycardia
 QT prolongation
 Neuropsychiatric reaction
CONTRINDICATION:
 Anxiety
 Depression
 Psychosis
 Cardiac conduction defects
INTERACTIONS:
 Halofantrine / quinine / CQ + mefloquine  QT lengthening
Not administered < 12hrs of MQ administration
USES:
 Prophylaxis of chloroquine resistant P. falciparum and P. vivax malaria
 Combination with artesunate for multi-drug resistant P. falciparum malaria

94
4. PRIMAQUINE
 It is a synthetic 8- aminoquinoline
 More active against pre-erythrocytic stage of P. falciparum
 Highly active against gametocytes and hypnozoites
 Poor erythrocytic schizontocide
 Primaquine differs from all other available anti-malarial in having marked
effect in primary as well as secondary hepatic phase of malarial parasite
Not known but reactive metabolites of primaquine  generate intraparasitic toxic
oxidative species  disrupt electron transport in plasmodial mitochondrion
PHARMACOKINETICS:
 Oral ingestion
 Plasma t1/2 6-8 hours
 Oxidised in liver
 Excreted in urine within 2-4 hours
ADR:
 Abdominal pain
 GI upset
 Weakness
 Uneasiness in chest
 Leucopenia  large doses
Important toxic potential is dose related: due to oxidant property
 Hemolysis
 Methemoglobinemia
USES:
 Tachypnoea
 Cyanosis  Vivax malaria
 Falciparum malaria

95
5. ARTEMISININ BASED COMBINATION THERAPY
ADVANTAGES:
 Rapid clinical and parasitological cure.
 Low recrudescence.
 Absence of parasite resistance
 Good tolerance.
Uncomplicated malaria - oral drugs.

Complicated malaria - Parenteral drugs
DRUGS:
 ARTESUNATE – SULFADOXINE + PYRIMETHAMINE:

 First line drug for uncomplicated falciparum malaria.
 Can be used in 2nd & 3rd trimester.
 ARTESUNATE – MEFLOQUINE:
 Standard and most extensively used.
 Effective for uncomplicated falciparum malaria
 ARTESUNATE – LUMEFANTRINE:
 Nucleic acid and protein synthesis of parasite affected.
 Vivax hypnozoites not affected.
 Long acting.
 Effective in multidrug or chloroquine resistant malaria.
 Must be administered with fatty food or milk to enhance lumefantrine
absorption
 DIHYDROARTEMISININ(DHA) – PIPERAQUINE:
 Piperaquine is high efficacy
 Long acting erythrocytic schizontocide
 Active against Chloroquine resistant P. falciparum.

96
 ARTESUNATE – AMODIAQUINE(AS/AQ):
 AQ short t ½.
 Its metabolite – long t ½.
 Active against uncomplicated falciparum malaria.
 ARTEROLANE – PIPERAQUINE:
 Arterolane is an orally active synthetic trioxolane congener.
 Acts rapidly at all stages of asexual schizogony.
 Accumulates in food vacuole of parasite. Peak conc at 3-5 hrs.
 ADR: headache, postural dizziness, vomiting, abdominal pain, diarrhoea
 ARTESUNATE – PYRONARIDINE:
 Pyronaridine – erythrocytic schizontocide
 MOA similar to CQ.
 Active against CQ resistant and sensitive P. falciparum.

97
6. MANAGEMENT OF CEREBRAL MALARIA
7. FOUR ERYTHROCYTIC SCHIZONTICIDAL AGENTS

 Mefloquine
 Atovaquone
 Chloroquine
 Halofantrine
8. FOUR ARTEMISININ DERVIATIVES OF MALARIA

 Dihydroartemisnin
 Artesunate
 Artemether
 α/β arteether

INDEX
Chapter 12: Antiprotozoal Drugs
Essay
1. AntiAmoebic Drugs……………..………………………….. 98
Short Answers
2. Intravaginal Preparations for Tichomoniasis...… 101
3. Uses of Diloxanide Furoate......……………………….. 101
4. Drugs for Giardiasis…………………………………………. 101
98
1. ANTIAMOEBIC DRUGS
CLASSIFICATION:
METRONIDAZOLE - MECHANISM OF ACTION:

99
PHARMACOKINETICS:
 Metronidazole is available for oral, i.v. and topical administration.
 Well absorbed after oral administration
 Poorly bound to plasma proteins.
 Diffuses well into the tissues including brain
 Therapeutic levels are achieved in various body fluids—saliva, semen, vaginal
secretion, bile, breast milk and CSF.
 Metronidazole is metabolized in liver {by Oxidation & glucuronide
conjugation}
 The metabolites are excreted mainly in urine.
 Half-life: 8hours
ADR:
 Gastrointestinal: Anorexia, nausea, metallic taste, dry mouth, epigastric
distress, abdominal cramps and occasionally vomiting.
 Allergic reactions: These include skin rashes, Urticaria, itching and flushing.
 CNS: Dizziness, vertigo, confusion, irritability, headache, rarely convulsions and
ataxia may occur. Polyneuropathy may occur on prolonged therapy.
 Thrombophlebitis
INTERACTIONS:
 Disulfiram-like reaction (nausea, vomiting, abdominal cramps, headache,
flushing, etc.) may occur if taken with alcohol; hence patient should be
warned to avoid alcohol during treatment with metronidazole.
 Cimetidine ↓ metronidazole metabolism.
 Metronidazole enhances warfarin action.
CONTRAINDICATIONS:
 Neurological disease
 Blood dyscrasias
 Should be avoided in pregnant women in 1st trimester
 Cautious use needed in chronic alcoholics.

100
USES:
 Amoebiasis:
 Dose: (400–800 mg TDS for 7–10 days)
 first-line agent for the treatment of both intestinal and extraintestinal
amoebiasis except in asymptomatic carriers.
 Trichomonas vaginitis:
 Metronidazole (400 mg TDS orally for 7 days) is the drug of choice.
 Both sexual partners should be treated simultaneously.
 Giardiasis:
 Metronidazole is very effective and is given orally (200 mg TDS for 7
days).
 Anaerobic infections:
 Metronidazole is highly effective in most of the anaerobic infection.
 15 mg/kg infused over 1 hour followed by 7.5 mg/kg every 6 hours till
oral therapy can be instituted with 400-800 mg TDS.
 H. pylori infections:
 Treatment done with a combination of Metronidazole (400 mg TDS) /
tinidazole (500 mg BD) with amoxicillin / clarithromycin and a proton
pump inhibitor (omeprazole)
 Pseudomembranous colitis
 250- 500mg TDS or 7-14 days.

101
2. INTRAVAGINAL PREPARATIONS FOR TRICHOMONIASIS.
 Diiodohydroxyquin 200 mg inserted intravaginally at bed time for 1–2

weeks; FLORAQUIN 100 mg vaginal pessaries.
 Quiniodochlor 200 mg inserted in the vagina every night for 1–3 weeks;
GYNOSAN 200 mg vaginal tab.
 Clotrimazole 100 mg inserted high up in vagina every night for 6–12 days;
SURFAZ 100 mg vaginal tab.
 Hamycin 4–8 lac U intravaginally daily for 15 days; HAMYCIN VAGINAL 4 lac
U ovules.
 Natamycin 25 mg nightly intravaginal application for 10 days; NATAMYCIN
25 mg vaginal tab.
 Povidone-iodine 400 mg inserted in the vagina daily at night for 2 weeks;
BETADINE VAGINAL 200 mg pessaries.
3. USES OF DILOXANIDE FUROATE

a. It is a highly effective luminal amoebicide: directly kills trophozoites
responsible for production of cysts.
b. It is used alone in mild intestinal amoebiasis & asymptomatic cyst
passers
c. It is used with Nitroimidazole against amoebiasis.
4. FOUR DRUGS FOR GIARDIASIS
 Metronidazole / tinidazole / secnidazole

 Nitazoxanide
 Quiniodochlor
 Furazolidone

INDEX
Chapter 14: Anthelmintic Drugs
Short Notes
1. Mebendazole……..………………………………..………… 102
2. Treatment of Tapeworm Infection………………….. 104
3. Pyrantel Pamoate……………………………………………. 105
4. Praziquantel……………………………………………………. 106
5. Ivermectin……………………………………………………….. 108
Short Answers
6. COD for Hookworm Infestation.……………………….. 110
7. Uses of Albendazole…………………………………………. 110
8. Rationale of Albendazole in Neurocysticercosis.. 110
102
1. MEBENDAZOLE
 Mebendazole is a broad-spectrum antibiotic

 It has produced nearly 100% cure rate / reduction in egg count in
roundworm, hookworm, enterobius and Trichuris infestations.
 It is much less active on strongyloides.
mebendazole binds to β-
tubulin.
inhibits its polymerisation
intracellular microtubules
are gradually lost
In addition,
 It blocks glucose uptake in the parasite, and depletes its glycogen stores.
 Hatching of nematode eggs and their larvae are also inhibited.
 Ascaris ova are killed.
PHARMACOKINETICS:
 Absorption from intestines is minimal.
 75-90% of an oral dose is passed in faeces.
 The fraction absorbed is excreted mainly as inactive metabolites in
urine/faeces.

103
USES:
 Mebendazole is one of the preferred drugs for multiple infestations. It is more
effective than albendazole in Trichuriasis.
 The dose and duration are same for children above 2 year as for adults, ½ dose
for children between 1-2 yrs.
 Round worm, hookworm, whipworm: 100mg BD for 3days.
 In heavy Trichuriasis upto 7days treatment may be needed
 Pin worm: 100mg OD, repeated after every 2-3weeks
 Trichinosis: 200 mg BD for 4 days
 Hydatid disease: 200-400mg BD or TDS for 3-4 weeks (less efficient than
albendazole)
ADVERSE EFFECTS:
 Diarrhea
 Nausea
 Abdominal pain
 Alopecia and granulocytopenia have been reported with high doses.

104
2. TREATMENT OF TAPEWORM INFECTION
T. saginata and T. solium

 Praziquantel – 10 mg/kg single dose in morning.
 Niclosamide – 2 g per day in divided doses
 Albendazole – 400 mg twice daily for 3 consecutive days.
H. nana and D. latum

 Praziquantel – 15-25 mg/kg single dose in the morning.
 Niclosamide – 2 g dose is repeated daily for 5 days. (H. nana)
Neurocysticercosis
 Cysts do not cause any problem unless larval products induce an intense focal
reaction- increased intracranial pressure, seizures, neurologic phenomenon
 Albendazole is preferred
 Albendazole – 400 mg BD for 8-15 days + corticosteroids – prednisolone 40-60
mg/day or dexamethasone 8-12 mg/day
 Praziquantel – 50 mg/kg daily in 3 divided doses for 15-30 days.

105
3. PYRANTEL PAMOATE
 Pyrantel pamoate is anthelmintic drug specifically effective against

roundworm and hookworm.
 Efficacy against Ascaris, Enterobius and Ancyclostoma is high and comparable
to mebendazole.
pyrantel activates
nicotinic cholinergic receptors in

worms
persistent depolarisation
causes contracture and spastic

paralysis
worms are then expelled
PHARMACOKINETICS:
 Only 10-15% of an oral dose is absorbed
 Partly metabolized
 Excreted in urine
ADVERSE EFFECTS:
Free of side effects
Occasionally, G.i. symptoms, headache and dizziness

106
USES:
For Ascaris, Enterobius and Ancyclostoma 11 mg/kg single dose, strongyloides and
necator requires three Day course.
4. PRAZIQUANTEL
 Wide ranging activity against schistosomes, other trematodes, cestodes and

their larvae forms but not nematodes.
Praziquantel
rapidly taken by susceptible worms
causes leakage of intracellular Ca2+
from the membranes
produces contracture and paralysis of

worms

107
At relatively high doses,

It causes vacuolization of the tegument and release of the contents of tapeworms
and flukes followed by their destruction by immune mechanisms of the host.
PHARMACOKINETICS:
 Rapidly absorbed from intestines
 Absorption is enhanced by ingestion with food.
 High first pass metabolism in liver limits systemic bioavailability.
 Phenytoin, carbamazepine and dexamethasone induce praziquantel
metabolism and further decrease its bioavailability.
 It crossed blood-brain barrier and attains therapeutic concentrations in the
brain and CSF.
 Plasma t½ is short (1.5 hrs)
 Metabolites excreted in urine.
USES:
 Tapeworms
 Neurocysticercosis
 Schistosomes
 Other flukes except Fasciola hepatica.
ADVERSE EFFECTS:
 Bitter taste
 Nausea
 Abdominal pain
 Headache
 Dizziness
 Malaise

108
When used for schistosomes and visceral flukes, symptoms like

 Itching
 Urticaria
 Rashes
 Fever
 Body ache
 Destruction of cysticerci in brain cause neurological complications.
5. IVERMECTIN
 It is an extremely potent semisynthetic derivative of the antinematodal

principle
 Obtained from Streptomyces avermitilis.
 Nematodes develop tonic paralysis when exposed to ivermectin.
 It acts through special glutamate gated Cl channel found only in invertebrates.
 Potentiation of GABAergic transmission in the worm has also been observed.
PHARMACOKINETICS:
 Well absorbed orally
 Widely distributed in body but does not enter CNS, liver and fat.
 Has long terminal t½ of 48-60 hrs.
 Metabolized by CYP3A4 in liver.
 No drug interactions.

109
USES:
 Drug of choice for single dose treatment of onchocerciasis and
strongyloidiosis
 It is comparable to DEC for bancroftian and brugian filaria.
 It is microfilaricidal but not macrofilaricidal
 Ivermectin (0.2 mg/kg single dose) is also highly effective in cutaneous larva
migrans and ascariasis, while efficacy against Enterobius and Trichuris is
moderate.
 Add-on drug to albendazole/Mebendazole in heavy Trichuriasis.
ADVERSE EFFECTS:
 Mild pruritis
 Giddiness
 Nausea
 Abdominal pain
 Constipation
 Lethargy
 Transient ECG changes
Reactions due to degeneration products of the Microfilariae are

 Fever
 Urticaria
 Myalgia
 Edema
 Tender lymph nodes

110
6. 1ST CHOICE OF DRUGS FOR HOOKWORM INFESTATION.

 Mebendazole
 Albendazole
 Pyrantel pamoate
7. FOUR USES OF ALBENDAZOLE

 Round worm
 Pin worm
 Neurocysticercosis
 Hydatid disease
8. RATIONALE OF ALBENDAZOLE IN NEUROCYSTICERCOSIS

 Course of treatment is shorter
 Cure rates are higher
 Corticosteroids enhance the absorption of albendazole
 Cheaper

Antimicrobials

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Antimicrobials

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Preface

Chapter 1: General Considerations

Mutation Gene transfer

Antimicrobials Agam Pharmacology

Resistant organisms can broadly be of following three types:

 Drug tolerant – the microorganism loses affinity for a particular AMA

PREVENTION OF DRUG RESISTANCE

Antimicrobials Agam Pharmacology

2. POST ANTIBIOTIC EFFECT

 Bactericidal effect is present even when the serum concentration falls

 They inhibit the growth and multiplication of microorganisms.

 They kill the microorganism

Antimicrobials Agam Pharmacology

5. CONDITIONS WHICH ARE TREATED WITH COMBINATION OF

 Rifampin + isoniazid in tuberculosis (to prevent resistance)

6. REASONS FOR FAILURE OF COMBINATION ANTI MICROBIAL

 Decreased antibacterial activity due to improper combination

Antimicrobials Agam Pharmacology

Chapter 2: Sulfonamides, Cotrimoxazole,

In gram negative bacteria,

CNS Agam Pharmacology

FQs bind to bacterial DNA

prevents its strand cutting

interferes with the resealing

In gram positive bacteria

by interferring with nicking of DNA

and seperating of daughter DNA

results in DNA damage

CNS Agam Pharmacology

Gonococci, Meningococci, H. influenza, E. coli, Salmonella, Shigella,

CNS Agam Pharmacology

CNS Agam Pharmacology

sulfonamides competitively inhibit

union of PABA with pteridine residue

prevents formation of dihydropteroic

which conjugates with glutamic acid

dihydrofolic acid ADVERSE EFFECTS:

CNS Agam Pharmacology

 The combination of trimethoprim and sulfamethoxazole is cotrimoxazole.

 Sulfonamides inhibit the conversion between PABA to di hydro folic acid.

CNS Agam Pharmacology

CNS Agam Pharmacology

4. TOPICALLY USED SULFONAMIDES

 Sulfacetamide sodium – eye infections

5. FOUR 2ND GENERATION FLUOROQUINOLONES

Mnemonic: Prime Minister Loves Second Generation Laptops.

CNS Agam Pharmacology

Chapter 3: Beta-Lactam Antibiotics

 Narrow spectrum – limited primarily to Gram-positive bacteria (GPB), few

 Destroyed by gastric acid

Antimicrobials Agam Pharmacology

 Streptococcal infections – pharyngitis, otitis media, scarlet fever, rheumatic

Antimicrobials Agam Pharmacology

 They are bactericidal

Antimicrobials Agam Pharmacology

 This pentaglycine is cross linked with a pentapeptide of adjacent

cell wall deficient forms are formed

interior of bacterium become

bacterial lysis occur

 As alternatives to penicillins for ENT, upper respiratory and cutaneous

Antimicrobials Agam Pharmacology

Antimicrobials Agam Pharmacology

3. BACTERIAL RESISTANCE IN PENICILLIN

Bacteria develop resistance