Bedside Approach to

Medical Therapeutics with

Diagnostic Clues
 Disclaimer

Note: Medicine is a constantly changing science and not all therapies are clearly established. New
research changes drug and treatment therapies daily. The author and publisher of this book have used
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 Bedside Approach to
Medical Therapeutics with
Diagnostic Clues

Edited by
NK Gami
FRCP (Edinburgh)
PO Darbhanga Medical College
Distt. Darbhanga, Bihar

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Bedside Approach to Medical Therapeutics with Diagnostic Clues

© 2005, NK Gami
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted
in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written
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This book has been published in good faith that the material provided by editor/contributors is original. Every
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only.
First Edition: 2005
ISBN 81-8061-515-4
Typeset at JPBMP typesetting unit
Printed at Gopsons Papers Ltd., A-14, Sector 60, Noida
 Dedicated to My Teacher

Late Dr. SKN Sinha

FRCP (Edinburgh)
Ex Prof. and Head of the Dept. of Medicine
Darbhanga Medical College, Darbhanga, Bihar

Dedicated
to my parents,
wife Aruna,
sons—Nishith and Manoj
and
daughters—Reeta, Kavita and Tanuja
Foreword
Medical therapeutics has made tremendous progress. Every month new drugs and new methods of
treatment are evolving. Many books on therapeutics are available but they are mostly written by
pharmacologists. The book “Bedside Approach to Medical Therapeutics with Diagnostic Clues” written
by Dr. NK Gami, FRCP (Edinburgh) who is himself a clinician active in clinical practice. He has seen
different methods of treatment here and abroad. This book reflects both the world.
The chapters are comprehensive. Brevity reigns supreme in every chapter. Concise and diagnostic
clues are added charms. Flow charts and tables are judiciously placed wherever needed. This book will
be welcome by all sections in Medical Practice.

Dr. DN Jha MD
Prof and Head of the Department of Medicine
Darbhanga Medical College
Darbhanga, Bihar
Preface

“There is no such thing as incurable, there are only things for which man has not
found a cure”.
—Bernard Mannes Baruch
“We have to ask ourselves whether medicine remains humanitarian and respected
profession or a depersonalised science of prolonging life rather than diminishing human
suffering”.
—Elizabeth Kubler-Ross

This book is a bedside approach to medical therapeutics. The purpose is to provide quick and ready
reference to up-to-date management of patients at bedside. The author has taken much pain in
providing in nutshell intricacies of treatment at the same time simplifying to the utmost.

Notable Features
• Includes recent advances up to time of publication.
• Recent data obtained from the Internet wherever possible.
• Extensive coverage of essentials of method of treatment without irrelevant details.
• Brevity, conciseness and quick accessibility of key information in a readable format.

“He who cures a disease may be the skillfullest, but he that prevents it is the safest”.
—Thomas Fuller (1608-1681)

Who will Appreciate the Book

• House officers and medical students both undergraduate and postgraduate.
• Internist, family physician and other specialists.
• General practitioners.

I will be indebted to readers if they will be benefited and help in the management of their patients.
Nagendra Kumar Gami
Acknowledgements
• My gratitude to my teachers, my colleagues and my students from whom I have learned much.
• My sincere thanks to authors of the following books (latest editions) who helped me a lot in preparing
the book:
— Current Medical Diagnosis and Treatment
— Washington Manual of Medical Therapeutics
— Harrison Principal of Internal Medicine
— API Textbook of Medicine
• My sincere thanks to Prof. DN Jha MD for writing a foreword.
• My sincere thanks to the staff of Jaypee Brothers Medical Publishers (P) Ltd., New Delhi for painstaking
efforts to complete this task with precision.
• I wish my thanks to my colleagues and friends here and abroad for helping me in this endeavour.
• I feel indebted to the pharmaceutical houses and editors of prescribers, Handbook for Up-to-date
Information About the Recent Drugs.
• I continue to welcome comments and recommendations for future editions in writing.
Contents
LUNG AND PLEURA
1. Bronchial Asthma.................................................................................................................... 1
2. Lung Abscess ........................................................................................................................... 7
3. Bronchiectasis ........................................................................................................................ 16
4. Diffuse Interstitial Lung Diseases ...................................................................................... 18
5. Pulmonary Thromboembolism (PTE) .................................................................................. 21
6. Pulmonary Atelectasis and Fibrosis .................................................................................... 25
7. Treatment for Eosinophilic Diseases of Lungs .................................................................. 27
8. Treatment of Sarcoidosis ...................................................................................................... 28
9. Bronchogenic Carcinoma ..................................................................................................... 30
10. Pneumonia ............................................................................................................................. 32
11. Treatment of Viral Respiratory Infection
Mycoplasma Pneumoniae and Legionellosis ....................................................................... 36
12. Treatment of Fungal Infection of Lungs ............................................................................ 38
13. Respiratory Failure ............................................................................................................... 40
14. Treatment of Pleural Diseases: Effusion and Empyema .................................................. 46

CENTRAL NERVOUS SYSTEM

15. Ischaemic Cerebrovascular Diseases................................................................................ 116
16. Intracerebral Haemorrhage ............................................................................................... 124
17. Subarachnoid Haemorrhage............................................................................................... 126
18. Epilepsy and Seizures .......................................................................................................... 129
19. Parkinson’s Disease (Paralysis Agitans) .......................................................................... 140
20. Treatment of Other Extrapyramidal Disorders ............................................................... 147
21. Multiple Sclerosis ................................................................................................................ 150
22. Alzheimer’s Disease ............................................................................................................ 154
23. Meningitis (Pyogenic) ......................................................................................................... 156
24. Brain Abscess....................................................................................................................... 162
25. Myasthenia Gravis .............................................................................................................. 163
26. Headache .............................................................................................................................. 168
27. Treatment of Certain Neurological Symptoms and
Diseases Not Already Described ........................................................................................ 178
28. Psychiatric Disorders .......................................................................................................... 186
29. Affective Disorders (Depression) ...................................................................................... 188
30. Grief Reaction ..................................................................................................................... 191
31. Alcohol .................................................................................................................................. 195
32. Drug Abuse and Dependency ............................................................................................. 197
33. Sexual Dysfunction ............................................................................................................. 199
xiv | Bedside Approach to Medical Therapeutics with Diagnostic Clues

HEART
34. Diuretics ............................................................................................................................... 203
35. Digitalis Glycosides ............................................................................................................. 207
36. Beta-adrenoreceptor Blocking Drugs ............................................................................... 212
37. Drugs (Catecholamines and their Synthetic Derivatives) in the
Treatment of Circulatory Failure ...................................................................................... 216
38. Vasodilators .......................................................................................................................... 221
39. Arrhythmias......................................................................................................................... 226
40. Acute Myocardial Infarction .............................................................................................. 249
41. Congestive Cardiac Failure ................................................................................................ 260
42. Hypertension ........................................................................................................................ 269
43. Treatment of Angina ........................................................................................................... 289
44. Valvular Heart Diseases ..................................................................................................... 297
45. Congenital Heart Disease .................................................................................................. 301
46. Rheumatic Fever ................................................................................................................. 306
47. Infective Endocarditis ......................................................................................................... 308
48. Treatment of Cardiomyopathy ........................................................................................... 314
49. Surgical Management of Coronary Artery Disease ........................................................ 316
50. Cor Pulmonale ..................................................................................................................... 319
51. Pericarditis ........................................................................................................................... 322
52. Shock .................................................................................................................................... 325
53. Cardiac Arrest ..................................................................................................................... 330
54. Treatment of Syncope ......................................................................................................... 335

ALIMENTARY SYSTEM
55. Gastro-oesophageal Reflux Disease .................................................................................. 337
56. Gastro-oesophageal Bleeding ............................................................................................. 341
57. Peptic Ulcer Disease ............................................................................................................ 346
58. Gastric Cancer Management ............................................................................................. 352
59. Ulcerative Colitis ................................................................................................................. 354
60. Irritable Bowel Syndrome .................................................................................................. 361
61. Crohn’s Disease ................................................................................................................... 363
62. Malabsorption Syndrome .................................................................................................... 368
63. Intestinal Parasites ............................................................................................................. 375
64. Constipation ......................................................................................................................... 384
65. Diarrhoea ............................................................................................................................. 389

ORAL MEDICINE
66. Oral Medicines ..................................................................................................................... 396

LIVER, GALL BLADDER AND PANCREAS

67. Acute Infective Hepatitis ................................................................................................... 400
68. Cholelithiasis and Cholecystitis ........................................................................................ 410
69. Acute Pancreatitis ............................................................................................................... 417
 ENDOCRINOLOGY
Contents | xv

70. Diseases of Hypothalamus and Anterior Pituitary Gland .............................................. 424

71. Acromegaly and Gigantism ................................................................................................ 430
72. Hyperthyroidism (Thyrotoxicosis) ..................................................................................... 432
73. Hypothyroidism ................................................................................................................... 443
74. Thyroid Enlargement .......................................................................................................... 448
75. Treatment of Hyperparathyroidism .................................................................................. 450
76. Hypoparathyroidism ............................................................................................................ 453
77. Osteomalacia ....................................................................................................................... 456
78. Metabolic Bone Diseases .................................................................................................... 460
79. Diabetes Insipidus ............................................................................................................... 464
80. Diabetes Mellitus ................................................................................................................. 468
81. Phaeochromocytoma ........................................................................................................... 500
82. Hyperaldosteronism ............................................................................................................ 502
83. Cushing’s Syndrome (Hypercortisolism) .......................................................................... 504
84. Addison’s Disease (Adrenocortical Insufficiency) ........................................................... 509

ARTHRITIS AND MUSCULOSKELETAL DISORDERS

85. Arthritis ................................................................................................................................ 514
86. Other Arthritis .................................................................................................................... 525
87. Connective Tissue Disorders ............................................................................................. 533

BLOOD
88. Anaemia ............................................................................................................................... 538
89. Leukaemias ......................................................................................................................... 550
90. Haemorrhagic Disorders .................................................................................................... 557

KIDNEY
91. Glomerular Diseases ........................................................................................................... 565
92. Nephrotic Syndrome............................................................................................................ 569
93. Acute Renal Failure (ARF) ................................................................................................ 573
94. Chronic Renal Failure ........................................................................................................ 582
95. Urinary Tract Infection ....................................................................................................... 592
96. Urinary Incontinence .......................................................................................................... 599
97. Nephrolithiasis ..................................................................................................................... 601
98. Benign Prostatic Hyperplasia (BPH) ................................................................................. 610

INFECTIOUS DISEASES
99. Respiratory Tract Infection ................................................................................................ 623
100. Treatment of Tuberculosis .................................................................................................. 632
101. Infective Endocarditis ......................................................................................................... 641

Index ...................................................................................................................................... 645

 Lung and Pleura
1
Bronchial Asthma
Asthma is a common disease and defined as chronic inflammatory disorder of the airways.

ESSENTIALS OF DIAGNOSIS
Clinical Investigation
Episodic or chronic symptoms of airways obstruction: Pulmonary function tests: (Table 1.1)
• Breathlessness • Limitation of airflow
• Cough • Positive bronchial provocation challenge
• Wheezing • Complete or partial reversibility of airflow
• Chest tightness obstruction, either spontaneously or
• Prolonged expiration, diffuse wheezing and following bronchodilatation therapy
rhonchi on physical examination

Table 1.1: Pulmonary function test in bronchial asthma

Spirometry:
I. a. FEV 1 (Forced expiratory volume in the first second)
b. FVC (Forced vital capacity)
Fall in the ratio of FEV1 to FVC points to airway obstruction due to asthma, COPD,
bronchiectasis and upper airway obstruction
II. Spirometry repeated after use of bronchodilators. In asthma relief is obtained

MANAGEMENT
Antiasthmatic Drugs
Classification:
I. Long-term medications:
1. Corticosteroids:
a. Inhaled corticosteroid:
• Beclomethasone dipropionate • Budesonide
• Fluticasone • Triamcinolone, acetonide
b. Systemic corticosteroids:
• Prednisolone tablet • Methylprednisolone tablet
2. Cromolyn inhaler
3. Long acting B2 agonists:
• Salmeterol inhaler • Salmeterol sustained release tablet
4. Theophylline tablet
5. Leukotriene modifiers tablet (Montair-Cipla 10 mg tablet)
2 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

II. Quick relief medications: 1. Short acting inhaled B2 agonists:

• Terbutaline • Salbutamol • Albuterol
2. Anticholinergics:
• Ipratropium inhaler
3. Systemic corticosteroids:
• Prednisolone tablet • Methylprednisolone tablet

Individual Drugs
See “Properties and Dosages of Antiasthmatic Drugs” (Table 1.5)

TREATMENT OF CHRONIC BRONCHIAL ASTHMA

Table 1.2: Treatment of chronic bronchial asthma
Long-term management Immediate relief medications General advice
Mild intermittent Intermittent use of short acting
bronchial bronchodilators:
asthma • No daily medication needed • Inhaled short acting • Teach about basics
B2 agonists during of asthma (Table 1.3)
exacerbation of symptoms
• Inhaled short acting B2 agonist: • Teach about drugs:
1-2 puffs intermittently a. Inhalant
b. Oral drugs
• Teach about pre-
ventive measures
(Table 1.4)
• Self-monitoring
Mild persistent Regular inhaled bronchodilators
asthma and inhaled corticosteroids on
daily basis:
• Inhaled short acting B2 agonist • Inhaled short acting B2 agonist –Do–
once daily daily as needed for relief of
• Beclomethasone or budesonide symptoms
100-400 microgram b.d. or fluti-
casone 50-200 microgram b.d.
or
• Cromoglycate inhalation
or
• Corticosteroid inhalation daily if
symptoms not controlled
Moderate Mid or low dose inhaled corti- • Inhaled short acting B2 agonist as –Do–
asthma costeroid + long acting inhaled needed for symptoms
B2 agonist and sustained release
theophylline:
• Inhaled mid or low dose corti-
costeroid
or
• Long acting bronchodilator
contd...
contd...
Bronchial Asthma | 3

Long-term management Immediate relief medications General advice

• Long acting inhaled B2 agonist
or B2 agonist (long acting) tab:
Salmetrol
Severe asthma: High dose inhaled corticoste- Inhaled short acting bronchodilator –Do–
roid + regular bronchodilator: on daily basis + inhaled corti-
costeriods
• High dose inhaled corticosteroid • Inhaled short acting B2 agonist as
on daily basis needed for symptoms
• Plus long acting inhaled B2 agonist
plus sustained release theophylline
• Corticosteroid tablet or syrup • Nebulised B2 agonist
(2 mg/kg)
• Leukotriene antagonist recently • Inhaled corticosteroid
introduced
⇓
Review treatment every 3-6 months. If control is achieved stepwise reduction in treatment may
be possible.

TREATMENT OF ACUTE ASTHMA

Immediate treatment

Bronchodilators Anti-inflammatory drugs Supportive treatment

a. Intravenous:
Aminophylline 250 ml diluted with
20 ml 25% dextrose, continued as
infusion (1g in 500 ml of 5% dex-
trose) 0.5 mg per kg per minute
b. Subcutaneous:
Aqueous terbutalin 0.25 mg
repeated 2 to 4 hourly
Or
Epinephrine 0.2 to 0.5 ml 1:1000
tried in patients not complicated by
hypertension, tachycardia, arrhyth-
mia or hypoxia. Epinephrine can be
repeated every 30 minutes up to 3
to 4 times
c. By inhalation:
High dose beta 2 agonist inhalation
Or

In severe cases add hydro- a. Rehydrate with IV fluid
cortisone 200-400 mg or 2 litre 5% dextrose over 12
methylprednisolone 40- to 24 hours
250 mg IV given 2 to b. Humidified oxygen via
6 hourly nasal catheter at highest
Oral prednisolone may be concentration at high flow
added 40 to 60 mg/day rate. CO2 retention does not
when patient improves occur
Or c. Assisted ventilation needed
Beta-2 agonist IV 4 to in impending respiratory
6 hourly failure
d. Antibiotic given for secon-
dary infection
e. Maintain blood pressure


Ipratropium inhalation


Degree of Response
contd...
4 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Degree of Response

Good response Incomplete response Poor response

No wheeze, dysp- Mild wheeze, moderate Severe dyspnoea, chest
noea minimal dyspnoea silent
Heart rate and respi- HR decrease, RR Pulsus paradoxus
ratory rate decrease increase >15 mmHg
Pulsus paradoxus PEFR 40 to 70% PEFR < 40%
< 10 mmHg Oxygen saturation Oxygen < 91%
PEFR >70%, oxygen 91 to 95% ⇓
saturation >95% ⇓ Admit ICU unit
⇓ Add oral or IV steroids Oxygen, nebulisation
Decrease inhalation Mechanical ventilation
Continue oxygen and
of oxygen and bron- beta 2 agonist
chodilators Add ipratropium to
beta agonist inhalation

Table 1.3: Education for asthma patient

• Teach about basics of asthma
• Teach about recognising symptoms-mild, moderate and severe
• Teach about adjusting dose of drugs according to symptoms
• Teach about prevention of asthma

Table 1.4: Prevention

• Stop smoking
• Stop allergens, for example, dust
• Spirometry repeated every 1 to 2 year
• Patient with persistent asthma should receive annual influenzal
vaccine
Properties and Dosages of Antiasthmatic Drugs
Bronchial Asthma | 5

Table 1.5: Properties and dosages of antiasthmatic drugs

Drugs action Dosages and route Indications Side-effects contra- Advantages Disadvantages
of administration indication

Epinephrine: Both 0.3 cc 1/1000 solu- Acute asthma Tremor, palpitation, Tolerance develops
alpha and beta tion SC arrhythmias. Avoid- after repeated use
effects ded in elderly and
IHD
Terbutaline:Selective 2.5 to 5 mg 2 to 3 SC, IM, slow IV in CI: Cardiac cases Rapid onset, longer Tolerance develops.
B2 agonist broncho- times a day. Capsule acute asthma with arrhythmias, duration No anti-inflamma-
dilatation without 5 to 7.5 mg b.i.d. pregnancy, hyperten- More effective with tory effect (always
cardiac side-effects Inhalation 250-500 Nebulising solution sion, hyperthyroi- steroid combine with
mcg 3-4 times a day in severe asthma dism steroid)
SC, IM, IV: 0.25 mg
up to 4 times/day Prophylaxis against
Tab 2.5, 5, 7.5 mg exercise induced
Inj. 0.5 mg/ml asthma: Inhalation.
Salbutamol: 2 to 4 mg 3 to CI: Thyrotoxicosis, Tolerance develops.
Selective B2 agonist 4 times/day hypertension, preg- No anti-inflamma-
Extended release tab nancy tory effects. Hence
4 to 8 mg twice/day combine with
Inhalation: 100 to steroids
200 mcg 3 to
4 times/day For regular use in CI: Thyrotoxicosis, May be combined
Salmeterol: Long 50 mcg inhalation chronic asthma. hypertension, preg- with low dose
acting B2 agonist up to 100 mcg b.d. Prophylactic use nancy, IHD, arrhy- inhaled steroid with
thmia. less side effect
Side-effects: Palpita-
tion, tremor

Prophylactic use. Low side effect. In Less effective than

Sodium chromogly- 2 puffs q.i.d. 2 puffs
Prevents exercise responsive patients inhaled steroids.
cate: Reduces release 15 mts before exer-
induced or cold steroid may be Short acting and
of histamine by inhi- cise or cold exposure
induced asthma. Not reduced or stopped need to be taken
biting mast cell Aerosol inhaler
used in acute asthma 4/day.
degranulation, redu- Aerosol inhaler
More expensive
ces bronchial sensi-
tivity. No broncho-
dilatation or anti-
inflammatory effect
Steroids: Methylprednisolone Status asthmaticus Adrenal and growth
Anti-inflammatory 125 mg IV 6 hourly Prevention suppression, osteo-
action Efcorlin 100 mg IV porosis, cataract,
Inhaled steroid bruises, oral candi-
Oral steroid as main- diasis
tenance dose once in
morning or alternate.
May be added to IV
steroid in acute
asthma
Theophylline Orally 80 to 240 mg Arrhythmia, Only orally twice Drug interaction
t.i.d. tachycardia, tremor daily. Inexpensive less. Well-tolerated
contd...
6 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs action Dosages and route Indications Side-effects contra- Advantages Disadvantages
of administration indication

Bronchodilator and Sustained release

anti-inflammatory tablet 400 mg in 2
action divided dosages—
increased to 800 mg/
day
IM or IV
Deriphyllin 2 ml
amp b.d. or t.d.s. Glaucoma, prostate
Ipratopium: Inhalation enlargement. Side
Anticholinergic effects like atropic
bronchodilator Active orally. Works More expensive than
Leukotriene antago- Zafirlukast: Twice quicker (within first inhaled steroid
nists: Leukotriene daily 24 hr) than steroids
causes bronchocons- Montelukast: Once No tolerance
triction, leukotriene daily Additive effect with
antagonists cause steroid. Effective in
bronchodilatation allergic rhinitis also.
and also anti- Well-tolerated
inflammatory
Effective in allergic
Cetrizine, loratidine: Once daily rhinitis
Antihistaminics
 Lung and Pleura
2
Lung Abscess

PREVENTION
1. Measures to reduce aspiration.
2. Early treatment of pneumonia.
3. Adequate use of antibiotics to reduce relapse.
4. Adequate care of periodontal disease.

MEDICAL MANAGEMENT
A. Antibiotic therapy:
Flow chart:
Determine whether infection is community acquired or hospital acquired.
Community acquired Hospital acquired
a. Penicillin 5 to 40 million units/day till Usually mixed infection with Klebsiella, Pseudo-
defervescence (in 3-6 weeks), followed by monas, Staphylococcus aureus:
oral penicillin G, V, ampicillin in dosages 3rd generation cephalosporin
of 500 to 750 mg 4 hourly +
In case of penicillin resistance: Clindamycin Gentamicin
600 mg IV every 6 to 8 hours until patient is +
afebrile, followed by clindamycin 300 mg Metronidazole for 6 to 8 weeks
4 times a day orally or
b. Alternatively:
Penicillin 10-20 million units/day IV
+
Metronidazole 2 gm orally/day in 2-4 divided dosages
B. Treatment of causes of lung abscess:
Antibiotics according to culture and sensitivity
Aspiration of infected material specially in unconscious patients, alcohol abuse, sedatives, CVA,
head injury and dysphagia (due to achalasia, oesophageal stricture or bulbar palsy).
C. Physiotherapy
a. Postural drainage
b. Steam inhalation
8 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Surgical Treatment
Surgical resection is indicated in:
a. Inadequately treated chronic abscess with persistent symptoms and persistent signs in X-ray.
b. Uncontrollable or life-threatening haemorrhage, bronchogenic neoplasm, bronchiostenosis or a
lung abscess refractory to medical treatment.

EMPYEMA
Medical Management
A. Antibacterial therapy: Important pathogens responsible for empyema
Community acquired Hospital acquired Rare
• Anaerobes: Peptostreptococcus, Enteric gram-negative bacteria • Actinomycosis
fusobacteria, bacteroids • Nocardial infection
• Tuberculosis
• Pneumococcus
• Streptococcus
Antibiotic of choice:
a. Based on culture and sensitivity:
Gram-negative infection ... ... 3rd generation cephalosporin
+
Aminoglycoside
Anaerobes ... ... Benzyl penicillin
+
Metronidazole
Community acquired Staphylococcus aureus, ... ... Cloxacillin or vancomycin
Haemophilus influenzae ... ... Beta-lactum antibiotics

B. Closed drainage: There are two types of closed drainage:

a. Intermittent needle aspiration intercostal
b. Continuous tube drainage under a water seal. Ultrasonographic guidance is required for loculated
empyema.

Surgical Management
A. Open drainage: Indicated when closed drainage is unsuccessful as in case of bronchopleural
fistula, multiple loculations and thick fluid.
Procedure: Resection of rib, manual disruption of loculi and placement of a wide—bore tube for
continuous drainage—when lung expands, drainage stops and then tube is removed.
B. Decortication: Indicated in fluid too thick to drain, pleural fibrosis and lung is not expandition.
C. Pleuropneumonectomy: Indicated in heavily calcified pleura usually seen in tuberculosis.
PULMONARY TUBERCULOSIS
Lung Abscess | 9

Anti-tuberculosis Drugs
Drugs
I. First-line Drugs
Table 2.1: Anti-tuberculosis drugs
Daily adult dose Adverse effects and Monitoring Other considerations
contraindications

Isoniazid 300 mg Peripheral neuritis, increa- Pyridoxin antagonises

Isokin tab 100 mg Doubled in military and ses effect of phenytoin, INH effect (Toxic)
Isokin liquid meningeal form carbamazepine; predni-
100 mg/5 ml (Warner) Child: 5-10 mg/kg solone increases INH
Isonex (Pfizer) 100 mg, Preventive: 300 mg for 6- level, hepatitis rare, hepa-
300 mg 12 month titis enhanced by rifampi-
cin; nausea, vomiting, rash
Rifampicin: 450-600 mg Hypersensitivity, jaundice, Liver function tests In empty stomach
Ribavin Lupin: 150, 300, Child: 10-20 mg daily severe hepatitis if com-
450, 600 mg cap, bined with isonex, GI
Rimpin (Lyka) 450 mg disturbance, influenza-like
Rimpacin (Cadila) 150, symptoms, headache,
300, 450 mg cap ataxia, visual disturbance,
Rimactane (Novartis) 150, urine and tears become
300, 450 mg cap reddish. Blood level dec-
reased by phenobarbitone,
phenytoin
Pyrazinamide: Body wt. Daily Thrice Twice Hepatotoxicity, anorexia, LFT
Civizide (Tata)-500, weekly weekly nausea, vomiting, arthra-
750 mg tab Under 50 kg 1.5 gm 2 gm 3 gm algia, fever, photosensiti-
P-zyde (Cadila): 500, 750, Over 50 kg 2 gm 2.5 gm 3.5 gm vity, rashes, affects control
1 gm tab Child: 15-30 mg/kg as a of diabetes
Pyzina (Lupin)-500, 750, single dose Contraindications:
1 gm tab, Hypersensitivity, preg-
Dis-tab 300 mg nancy, existing liver dise-
ase, gout

Streptomycin:
Ambistryn-S (Sarabhai) IM 0.75-1gm, Anaphylactic shock, Blood urea, creatinine Avoid concurrent adminis-
0.75, 1 gm vial Child: 15-20 mg/kg/day aplastic anaemia, tration of aminoglycoside,
agranulocytosis, vertigo, frusemide
tinnitus, ataxia, hyper-
sensitivity, ototoxicity,
nephrotoxi city. Nephro-
toxicity increased with
aminoglycosides
II. Second-line Drugs
Ethionamide: 500-1000 mg p.o. in divi- GI intolerance, hepatitis, Liver function tests Anti-emetic
Ethide (Lupin) 250 mg tab ded dosages 250 mg b.d. hypersensitivity, endo- Bedtime dose
Ethiocid (Themis) crine disturbance
Cycloserine: 250-700 mg/day or Neurological or psychia- Serum level of cyclosporin Give pyridoxin
Cyclorin (Lupin) 250 mg 250 mg b.d. or t.d.s. tric disturbances LFT
cap
contd...
10 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Daily adult dose Adverse effects Monitoring Other considerations

contraindications
Dose adjusted for renal CI: Severe psychiatric Blood urea
impairment disturbance, severe renal
impairment
Capreomycin: Kapocin 15 mg/kg IM 5 days a Hearing loss, renal toxi- Audiogram, vestibular
(Mac) 0.5 gm, 0.75 gm, week city, electrolyte distur- function, BUN, creatinine
1 gm vial bances
Kanamycin: –Do– –Do– –Do–
Kanamycin (Biochem)
500 mg vial;
Kancin (Alembic) 500 mg,
1 gm vial
Amikacin: –Do– –Do– –Do–
Amicin (Biochem)
100.250, 500 mg vial
IM/IV Mikacin (Aristo)
PAS 10-20 gm p.o. in divided GI intolerance, hepatitis, LFT Give antacids bedtime
dosages: 3 mg q.d.s. hypersensitivity dosage
Ciprofloxacin: 500-1000 mg q.d.s. GI intolerance, headache, Avoid antacid, iron, zinc
p.o. (750 mg b.d.) restlessness, hypersensiti- which decrease absorption
vity
Ofloxacin 400-800 mg q.d.s. (400 –Do– –Do–
mg b.d.)
Clofazimine: 100-300 mg q.d.s. p.o. Abdominal pain, skin dis- Dosing at meal time, avoid
Clafozine (Astra) 50, colouration, photosensiti- sunlight. Efficacy unpro-
100 mg cap vity. ven.

TREATMENT REGIMENS ACCORDING TO DURATION AND FREQUENCY

Table 2.2: Treatment regimens according to duration and frequency
Daily long-term regimens Intermittent long-term regimens Short-term regimens

Initial phase: Advantages: Daily regimens Intermittent regimens

First drug H a. Less drug toxicity than daily Initial intensive a. EHRZ 3 times
+ regimens phase: EHR daily a week for 6 months
Second drug E b. Cheaper than daily regimen for 2 months b. SHRZ 3 times
or R or PAS or T because total quantity of drug ↓ a week for 2 months
+ is smaller than daily regimen Continuation ↓
Third drug S or R c. Suitable for alcoholics and phase: Followed by HR
All the three drugs vagrants who are unreliable HR daily for 3 times a week for
given for 1 to 3 months in taking self-administered 9 months or 6 months
↓ medications. Suitable also ↓ c. SHRZ 3 times a
Continuation phase:
for developing countries due Initial phase: week for 4 months
First drug H
+
to cheapness. SHR daily for ↓
d. Can be supervised conveni- 2 months SHZ twice a week
Second drug E or
R or PAS or T
ently ↓ for 8 months
contd...
 Lung Abscess | 11

Daily long-term regimens Intermittent long-term Short-term regimens

regimens
All drugs given for Continuous ↓
9-15 months Initial daily → twice weekly Continuous phase:
regimens regimens HR daily or 9 months
SHE or SHP or H (15 mg/kg) or
SHT or SHR + S for 18 months SHR daily for 2 months
→
for 3 months ↓
or HR daily for 9 months
SHE or SHP H (15 mg/kg) + or
→
for 3 months E (45 mg/kg) SHRZ daily or 2 months
or for 18 months ↓
SHR for 2 H (15 mg/kg) + Continuation phase:
→ HR daily or 6 months
weeks R (600-900 mg)
for 2 months or
SHRZ daily for 2 months
↓
Continuation phase:
HT daily for 8 months

Key: H = Isoniazid; R = Rifampicin; E = Ethambutol; PAS = Para-aminosalicylic acid;

T = Thiacetazone; S = Streptomycin
In twice weekly regimens, dosages of isoniazid, rifampicin and ethambutol are higher than
daily dosages. These higher dosages are given in brackets.

WHO TREATMENT REGIMENS: (MODIFIED)

New initial cases Chronic cases

Smear positive: Smear negative Relapse after cure or Remain smear positive
Short-term regimen: A.Long-term regimen: treatment failure who after completing retreat-
Initial phase: a. Least toxic regi- is smear positive after ment regimen under
HRZS or HRZE daily men: 5 months of chemo- supervision points to
for 2-3 months Isonex + ethambu- therapy: multi-drug-resistance
tol for 12-18 months (MDR) see below.
↓
Followed by HR b. Least expensive Initial phase:
HR daily or but effective regi- SHRZE daily for
alternate day men: 3 months except strepto-
INH + thiocetazine mycin only for initial
150 mg/day for 12- 2 months
18 months ↓

contd...
12 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

New initial cases Chronic cases

for 4 months Usual regimen: If still smear positive after

INH + Rifampicin 3 months of treatment:
for 9-12 months HRZE daily for another
1 month
B. Short-term regimens: ↓
Initial phase: HRZ Continuation phase:
daily or 3 times HRE daily for 5 months
weekly for 2 months or 3 times a week under
↓ supervision for
Continuation phase: HR 5 months
daily or 3 times weekly
for 2 months.
↓
INH alone daily for
another 4 months if
parenchymal involve-
ment exceeds total of
10 sq. cm. on chest X-ray

TREATMENT OF MDR TUBERCULOSIS

Basic Principles
1. Drugs should be given in adequate dosages and for adequate duration.
2. Drugs selected for the treatment should have not been used in the past or used regularly for shorter
duration.
3. Use of the first-line drugs to be preferred because they are effective and less toxic.
4. New drugs used for MDR tuberculosis:
a. Rifampicin derivatives: Rifabutin
b. Quinolones: Ciprofloxacin, ofloxacin, pefloxacin, lomofloxacin, sparfloxacin
c. Clofazinamine: Sulphone derivatives
d. Macrolides: Roxithromycin, clarithromycin, azithromycin
e. Betalactum antibiotics with clavulanic acid
f. Cephalosporins
g. Folate antagonists: Trimethoprim derivatives
h. Immunomodulators: Interferon Y, interlukin-2
5. INH should be used in all regimens because of its effectiveness, least toxic and less cost.
6. Cross resistant drugs should be avoided as they are not effective and increase toxicity:
Drugs with one way cross resistance:
Vancomycin and capreomycin
Kanamycin and streptomycin
Thiacetazine and PAS (Thiacetazine usually not used today Udani, 1991)
 Lung Abscess

7. Preferably three new drugs should be given along with the first-line drugs. If the second-line drugs
| 13

or new drugs are prescribed, then at least 4-5 drugs to be given.

8. Addition of a single drug in failing regimens is contraindicated.
9. Considering the toxicity of reserve drugs, dosages should be increased in with optimal tolerance of
the patient to acheive best results.
10. Retreatment should always be given preferably in hospital under strict supervision for monitoring
adverse reactions of reserved drugs.
11. Intermittent chemotherapy is normally not effective and should not been given in MDR cases.
12. An early surgical treatment can be planned if disease is limited and patients’ general condition
permits.
13. Bactericidal drugs should be used.
14. Minimum 4 and preferably 6 drugs should be used.
15. Parenteral drugs should be used for 3-6 months and others for 24 months after sputum negativity.

DRUGS USED IN MDR-TB: DOSAGES AND ADVERSE EFFECTS

Table 2.3: Drugs used in MDR-TB: Dosages and adverse effects
Drugs Adult daily dose Dose Adverse drug reaction
(Maximum Dose) mg/kg
Ofloxacin 400 mg b.d. 8-10 Abdominal distress
Ciprofloxacin 750 mg b.d. 15-20 Headache, anxiety
Sparfloxacin 400 mg b.d. 8-10 Tremulousness
Kanamycin 1 gm-0.75 gm 15 Vestibular side effect
Capreomycin 1 gm-0.75 gm 15 Vestibular side effect
Amikacin 1 gm-0.75 gm 15 Auditory
Cycloserine 250 mg b.i.d. or t.i.d. 15 Seizure, psychosis, impaired cognition
Ethionamide 250 mg b.i.d. or t.i.d. 15 Abdominal distress, diarrhoea
Prothionamide 250 mg b.i.d. 15 Anorexia, metalic taste
Roxythromycin — 9-10 Gastrointestinal
PAS 10-12 gm 200 Gastrointestinal
Azithromycin — 9-10 Gastrointestinal
Clarithromycin — 15-16 Gastrointestinal
Clofazimine 100-200 4-5 GIT and skin
Rifabutin 450 — —

Suggested Regimens for MDR-TB

Table 2.4: Suggested regimens for MDR-TB
Resistance pattern Suggested regimens Duration
H+R Z, E, Quinolone aminoglycoside 18-24 months
H+S R, Z, E, Amikacin or capreomycin 6-9 months
H+E R, Z, Quinolone aminoglycoside 6-12 months
H+R+Z E, Quinolone, aminoglycoside, 24 months after
plus ethionamide conversion
H+R+Z+E Quinolone, aminoglycoside, Conversion
ethionamide, cycloserine
14 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Treatment of Pregnant Women

Table 2.5: Treatment of pregnant women
Drugs Avoided with reasons Suitable
Ethionamide Avoided because of its tetragenic potential —
Streptomycin Avoided because of 8th nerve damage —
Cycloserine Avoided because of psycosis and seizure —
PZA Avoided because of hepatitis and other —
side effects
Rifampicin Used with caution and only with strong Only used in dissimi-
indication because crosses placental nated and extensive
barrier easily lesions
Isonex + Ethambutol Most suitable

Patients with Renal Failure

Isoniazid : Not necessary to reduce the dose but give pyridoxin and monitor the patient for hepatitis
and peripheral neuropathy.
Streptomycin : Dose must be reduced, serum level checked and monitored for deafness.
Ethambutol : Dose should be reduced, serum level checked and visual acuity monitored.
PZA, PZA : Dose to be reduced because they are excreted by kidney.

Treatment of Children
Most suitable combination: INH 10 mg/kg daily maximum 300 mg + RMP 15 mg/kg daily (maximum
450 mg). A third drug (SM, EMB or PAS) may be added in resistant cases. EMB not recommended in
children under 13 year of age.

Patients’ Default
The major problem in TB treatment program today is the patients’ default in taking drugs. The default
rate goes up to 40 to 60%, the highest in developing countries. Default in taking drugs lead to:
i. Treatment failure.
ii. Emergence of resistant organisms to existing drugs.
The short course chemotherapy specially twice weekly completely supervised may eliminate these
risks.

TIME OF IMPROVEMENT
Types of Improvement Time
Symptomatic improvement Within first 2-3 weeks
Radiological clearance and stability In 4-6 months
Sputum conversion Within first 2 months

PREVENTION
INH Prophylaxis
Large clinical trials have proved that 1 year of INH therapy is effective in reducing the incidence of
tuberculosis in tuberculin positive individuals specially children. Dose will be 300 mg/day for 12 months.
 Indications of INH prophylaxis:
Lung Abscess | 15

i. All persons younger than age 35 with positive tuberculin test.

ii. Older persons with remote tuberculosis, either known historically or evident radiographically, who
have never received adequate chemotherapy.
iii. Tuberculin positive persons who have AIDS, Hodgkin’s disease, silicosis, renal failure or who are
receiving steroids chronically or immunosuppressive drugs, regardless of age.

BCG Vaccination
It is safe, but its efficacy regarded by some as controversial. In large study carried out in South India, no
protection was observed, but in the UK and the USA it was found to offer greater than 80% protection.

CLINICAL NOTES
Isonex
Inexpensive. Can also be given parenterally. Widely distributed including CNS and reaches bacilli in
cells. Peripheral neuropathy results from interference with the metabolism of pyridoxin, which can be
prevented by giving 25 mg of pyridoxin daily, and is not likely to occur when ordinary dose in INH is
given in non-alcoholic non-diabetic, well-nourished and young individual. Risk of hepatitis is more with
advancing year. Rare untoward effects such as encephalopathy, loss of memory, optic atrophy, convulsion,
purpura hypersensitivity reaction (fever, rash, can produce lupus like syndrome).

Rifampicin
More expensive than INH. Penetrates CNS when meninges are inflamed. Allergic reactions (chills,
fever, rarely renal failure, massive haemoptysis) occasionally occur in those patients who take drug
irregularly or in those who are given intermittent therapy. Excreted mainly by liver, hence must be given
with caution in liver failure.

Pyrazinamide
It has excellent tissue sterilizing ability. Penetrates well into CNS. Excreted mainly by kidney, hence
dose adjustment necessary when renal function is reduced hepatitis.

Classification of Anti-TB Drugs Based on their Tissue Penetration:

TB bacilli exists

In metabolically active In relatively metabolic In necrotic casium pool

extracellular pool inactive intracellular pool
RMP : Bactericidal Bactericidal Bactericidal
INH : Bactericidal Bactericidal —
SM : Bactericidal Inactive —
PZA : — Bactericidal —
 Lung and Pleura
3
Bronchiectasis

PREVENTION
Prevention depends upon treatable precipitating causes:
Precipitating factors Prevention
1. Foreign body inhalation aspiration of Early and adequate management
gastric content
2. Empyema –Do–
3. Childhood respiratory infection Prompt treatment
(pneumonia, bronchopneumonia,
whooping cough)
4. Sinus infection –Do–
Infection of oral cavity
5. Recurrent infection Influenzal vaccine

MEDICAL MANAGEMENT
A. Management of bronchial secretion:
a. Postural drainage
b. Expectorants such as potassium iodide. They are of questionable value.
c. Mucolytic agents such as bromhexine.
d. Bronchodilators for bronchospasm.
e. Regular physical therapy.
B. Antibiotics for infection (characterised by cough, blood streaked sputum, purulent sputum,
progressive dyspnoea and weight loss):
a. Usual antibiotics: Ampicillin, cephalosporin, tetracycline, chloramphenicol, cotrimoxazole.
Tetracycline, chloramphenicol and cotrimoxazole given if patient is allergic to penicillin.
b. For anaerobes producing foul-smelling sputum: Metronidazole.
c. Remember culture may be sterile.
Duration of antibiotic therapy: Usually 1-3 weeks or after sputum becomes less purulent. In cystic
fibrosis long-term course of antibiotics is needed.
C. General:
a. Attention to general health and nutrition is essential.
b. Hydration is effective like expectorants.
c. Cessation of smoking.
D. Oxygen for hypoxia during acute exacerbation.
SURGICAL TREATMENT
Bronchiectasis| 17

A. Surgical resection or lobectomy:

Indications:
i. Bronchiectasis with complication such as recurrent large haemoptysis
ii. Empyema
iii. Bronchopleural fistula
iv. Localised disease not responding to medical management specially in adults.
Remarks: Usually now less frequently employed because successful medical management is
available in most cases, and many patients have generalised disorder.
B. Selective bronchial artery embolisation specially in large haemoptysis with poor lung function and
patient not fit for surgery.
C. Fiberoptics bronchoscopy permits removal of retained secretion.
 Lung and Pleura
4
Diffuse Interstitial Lung Disease

CLASSIFICATION
There are hundreds of causes of interstitial lung disease (ILD) but only clinically important diseases are
mentioned in the following table:
Table 4.1: Causes of interstitial lung disease (ILD)
I. Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)
II. Disorders associated with ILD:
1. ILD associated with collagen vascular disorders:
• Rheumatoid arthritis
• Systemic lupus erythromatosus (SLE)
• Progressive systemic sclerosis
• Polymyositis
2. Occupational lung diseases: (pneumoconiosis)
• Silicosis
• Asbestosis
• Siderosis
• Berylliosis
• Talcosis
3. ILD associated with pulmonary vascular diseases:
• Wegner’s granulomatosus
• Goodpasture’s syndrome
• Pulmonary vasculitis
4. Inherited disorders:
• Familial idiopathic pulmonary fibrosis
• Neurofibromatosis
• Tuberous sclerosis
• Neimann-Pick disease
• Gaucher’s disease
5. Infection:
• Miliary tuberculosis
• Disseminated histoplasmosis
• Pneumocystis carinii pneumonia
6. Physical and chemical agents:
• Radiation injury
• Inhalation of toxic gases
contd...
contd...
Diffuse Interstitial Lung Disease | 19

7. Disorders of unknown aetiology:

• Sarcoidosis
• Idiopathic pulmonary haemosiderosis
• Pulmonary alveolar proteinosis
• Histocytosis-X
• Pulmonary microlithiosis
8. Miscellaneous conditions:
• Allergic alveolitis
• Farmer’s lung
• Tropical pulmonary eosinophilia
• Carcinomatous lymphangiectasis

TREATMENT
Divided under following headings:
1. Medical treatment
2. Surgical treatment
3. Treatment of special conditions

DRUG TREATMENT
Table 4.2: Drug treatment
Drugs Dosages and duration Monitoring Advantages Disadvantages
of treatment
Corticosteroids 1.5-2 mg/kg/day for 2- Monitor for adverse Subjective improvement Improvement in lung
3 months effects function and radiological
↓ features occur in a mino-
Tapered to lowest point rity
and maintained for 3-
6 months
Cyclophosphamide 2 mg/kg/day for 9- Regular blood count Acts by depleting lymph- Second-line drug
12 months. May be com- ocytes.
bined with low dose of More effective than aza-
steroid (0.25 mg/kg/day) thioprine
Azathioprine 200 mg/day for 3- Regular blood count and Less effective than cyclo-
6 months liver function test phosphamide

Oxygen
Oxygen given long-term for respiratory failure and advanced disease.

Surgery
Lung transplantation offers hope to patients with chronic respiratory failure.

SPECIAL CONDITIONS
Rheumatoid arthritis If lung disease is asymptomatic, treatment not required. If pulmonary disease
is active, corticosteroid is indicated.
20 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Systemic lupus erythmatosus High dose of steroids and cytotoxic drugs.

Progressive systemic sclerosis Treatment is disappointing. Corticosteroid and D-penicillamine are
worth a trial.

CLINICAL NOTES
Diffuse interstitial lung disease:
1. Drugs have limited value. Exercise: Walk every morning, stationary bicycle exercise or treadmil
exercise. Nutritious diet. Proper rest. No smoking. Supplemental oxygen for 18 hours a day.
Emotional support.
2. Potential therapeutic interventions: Adapted from Internet:
a. Pirfenidone: An anti-fibrotic agent, less toxic
b. Interferon gamma: Regulates macrophages and fibroblast function
c. Interferon beta: Anti-inflammatory
d. Suramen: Healer of wound
e. Relaxin
f. Prostaglandin PGE 2: Inhibits fibroblasts
g. Captopril: Inhibits fibroblasts
h. Thalidomide
All the above drugs are claimed to reduce lung fibrosis which is the basis of Diffuse Interstitial Lung
Disease.
 Lung and Pleura
5
Pulmonary Thromboembolism
(PTE)

DIAGNOSTIC APPROACH
It includes two parts:
A. Diagnosis of deep vein thrombosis in legs.
B. Diagnosis of pulmonary thromboembolism.

Diagnosis of Deep Vein Thrombosis (DVT)

In 95% cases PTE is complication of DVT of lower extremities:
i. Look for predisposing factors of DVT: Hip fracture, recent major surgery, past history of
thrombophlebitis, bedrest for more than a few days in medical conditions such a CCF, acute
myocardial infarction, pregnancy, pelvic disease, malignancy, oral contraceptives.
ii. Look for signs: Local pain, redness, heat and oedema in legs.
iii. Investigate for DVT

Doppler studies Impedence plethysmography

↓ ↓
Too subjective Best choice Non-investive, safe and easily
hence not very available
specific
Normal: Abnormal:
a. Rules out DVT in Confirms DVT
95% cases
b. If recurrent DVT:
Dynamic ascending
venography (gold
standard test) for
DVT
22 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Diagnosis of Pulmonary Thromboembolism (PTE)

Clinical features Investigations

a. Symptoms: Sudden death during prolonged
illness, acute myocardial infarction like
substernal pain, pleural pain, unexplained
dyspnoea, cough, haemoptysis, occasionally
symptomless.
b. Signs: Tachycardia, tachypnoea (respiratory
rate; greater than 16 breaths per minute),
gallop rhythm, accentuated P2 raised JVP,
pleural rub.
a.. X-ray chest: May be normal, pleural opacities
(wedgeshaped, linear), pleural effusion,
elevated hemidiaphragm.
b. ECG: Normal in 70 to 80% cases, acute right
ventricular strain, right axis deviation,
clockwise rotation, deep S in lead I, Q in lead
III, inverted T in lead III, prominent P in lead
II and V1, right bundle branch block, sinus
tachycardia, auricular fibrillation.
c. ECHO: Right atrial dilatation, tricuspid
regurgitation.
d. Radioisotope scan:
i. Lung perfusion scan: Negative scan
excludes PTE, positive scan suggests PTE.
ii. Ventilation/perfusion scan

Abnormal If normal
in PTE ↓
Arrange for
pulmonary angiography
e. Arterial blood gas analysis: Low PaO 2 +
Respiratory alkalosis supports clinical
suspicion of PTE.

TREATMENT OF PULMONARY THROMBOEMBOLISM (PTE)

In the USA, PTE is the third most common cardiovascular disorder. The overall mortality is estimated at
38%. Massive PTE causes sudden death.
Goals of therapy:
a. To prevent recurrence of thromboembolism.
b. To reduce morbidity of acute episode.
c. To prevent chronic pulmonary hypertension.
Unstable patients with hypotension need supportive measures such as oxygenation, mechanical
ventilation, volume resuscitation and vasoactive drugs. Fluid should be given cautiously in the presence
of marked increase of pulmonary vascular resistance and right ventricular failure. Best vasoactive drugs
are dobutamine and norepinephrine. Dopamine produces tachycardia. If the patient is stable with or
without supportive measures, prompt institution of anticoagulation therapy is highly effective in decreasing
recurrence rate of pulmonary embolism and can reduce mortality from 30% or higher to 8% or less.
Other three groups of specific therapy are thrombolytic therapy, embolectomy and mechanical interruption
of inferior vena cava.
TYPES OF SPECIFIC THERAPY OF PULMONARY EMBOLISM
Pulmonary Thromboembolism (PTE) | 23

Table 5.1: Types of specific therapy of pulmonary embolism

Anticoagulation Thrombolysis Embolectomy Interrupting vena cava
Prevent further embolisation Dissolves pulmonary emboli and Surgical removal of emboli Placement of mechanical filters
thrombi in deep vein and elimi- in inferior vena cava to obstruct
nates source of further emboli emboli
Drugs and dosages: Drugs and dosages: Procedure: Procedure:
Heparin and warfarin: a. Streptokinase: 250000 U/IV a. Embolectomy a. Ligation or clipping under
a. Heparin more immediately (loading dose over 30 minu- b. Catheter embolectomy: general anaesthesia
effective and potent than tes) followed by 10000 U/ i. Catheter embolectomy b. Use of umbrella or filter
warfarin. Heparin started hr for 24 hr with suction inserted percutaneously
5000 to 10000 units conti- b. Urokinase: 4400 U/IV ii. Catheter fragmentation through jugular or femoral
nuous IV bolus followed by (loading dose over 20 min), and angioplasty veins under local anaes-
1000 U per hour adjusted to followed by 4400 U/kg/hr c. Direct intraembolic low thesia.
partial thromboplastin time for 12 hours. dose thrombolytic infusion
to twice normal for 5-7 days. c. Tissue-type plasminogen combined within mecha-
b. IV heparin + oral warfarin activator: 100 mg (56 nical disruption of emboli.
adjusting prothrombin time million U) IV over 2 hours
to 1.2 to 1.5 times, control Streptokinase is cheaper than
for 5-7 days urokinase but can produce febrile
c. Only oral anticoagulant for and allergic reaction.
1 month and half. Tissue type plasminogen acti-
vator is more effective than strep-
tokinase and urokinase.
Indications: Indications: Indications: Indications:
Recommended in stable patients Strongly recommended in un- • Contraindications to • Recurrent PTE despite anti-
without hypotension. stable patients with hypotension. thrombolytic therapy coagulation
Reduced the need for embo- • Refractory hypotension • A large free-floating
lectomy. despite thrombolytic therapy thrombus in iliofemoral
• Trapped emboli within right veins.
atrium or right ventricle • Immediately followed surgical
• For removal of chronic emboli: catheter embolectomy.
To improve function, to reduce • High-risk patient where anti-
pulmonary artery pressure, coagulant and thrombolytics
normalise pulse artery per- contraindicated.
fusion and arterial oxyge-
nation.
Contraindications: Contraindications: —
Intracranial bleeding, active Internal active bleeding, recent
internal bleeding. stroke, neurological or ophthal-
mological surgery, head injury,
pregnancy, severe hypertension
Complications: Complications: Complications: —
Bleeding, thrombocytopenia, Bleeding. a. Emergency embolectomy:
warfarin teratogenic and hence mortality 25%
not used in pregnancy. b. Elective embolectomy for
symptomatic unresolved
pulmonary emboli in large
branches of pulmonary
artery is safer and effective.
24 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

ALGORITHM OF TREATMENT OF PULMONARY THROMBOEMBOLISM

Algorithm of treatment of pulmonary thromboembolism

Haemodynamically stable patients Haemodynamically unstable patients with

hypotension
Institute following measures:
Anticoagulants Anticoagulant not a. Ventilation
contraindicated contraindicated b. Oxygenation
↓ c. Mechanical ventilation
Give heparin d. Vasoactive drugs: Dobutamine, norepi-
↓ nephrine, dopamine
Arrange for ECHO e. Volume resuscitation, amrinone

Normal Abnormal:
↓ Right ventricle, If becomes stable If remains unstable
Continue enlarged, ↓ ↓
heparin pulmonary Anticoagulation with Thrombolytics with
hypertension, heparin (Prophylactic) streptokinase, etc.
tricuspid ↓
regurgitation a. If refractory hypo-
↓ tension despite of
Thrombolytic thrombolytics
therapy b. Trapped embolus
within right atrium
or ventricle
↓
Embolectomy
U

In high-risk patients if thrombolytics and anticoagulants contra-

indicated or fail and recurrent PTE despite anticoagulation
↓
Placement of inferior vena cava filters

Prevention of PTE
In 95% cases, PTE is complication of deep venous thrombosis (DVT) of lower extremities.
Measures to prevent PTE by reducing incidence of DVT

Low dose subcutaneous
Heparin (5000 U 8-12 hourly)
started preoperatively in general
surgical cases in many medical
cases and in patients in ICU
Low dose low molecular Dextran Miscellaneous regimes
weight heparin Effective a. Intermittent pneumatic compression
Prevents PE for patients b. Graduated compression stackings
undergoing elective hip c. Mixed:
surgery i. Heparin + Stackings
ii. Intermittent pneumatic
compression + stackings
 Lung and Pleura
6
Pulmonary Atelectasis and Fibrosis

PULMONARY ATELECTASIS
For treatment purpose causes of atelectasis must be known for rational therapy. Causes are summarised
below:
Congenital causes Premature birth, neonatal hyaline membrane disease.
Acquired causes
A. Compression collapse due to external compression by pleural effusion, haemothorax, pneumothorax,
enlarged gland and aortic aneurysm.
B. Absorption collapse due to bronchial obstruction:
Intraluminal causes: Bronchial wall causes:
Foreign body, Bronchial stricture often due to TB and tumour
inspissated mucus,
tumour and aspiration of
gastric content during
anaesthesia or in comatosed
state

Diagnostic Clues
Clinical Manifestations
A. Slowly developing atelectasis: Asymptomatic
B. Acute, sudden and rapidly developing atelectasis: Cough, dyspnoea. Usually occurs in obstructive
collapse due to FB or during operation.
C. Massive collapse: Cynosis, restlessness, tachycardia, occasionally circulatory collapse.
Signs on affected side Limited chest excursion, shift of trachea and heart to the same side, resonance
diminished, breath sound and vocal resonance markedly diminished, bronchial breathing, whispering
pectoriloquy and acute respiratory failure in massive collapse.

Investigations
A. X-ray chest: Shrunken lung, lobe or segment, displaced fissures, elevated diaphragm and mediastinal
shift.
26 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

B. Bronchoscopy and cytology of bronchoscopic aspirate for knowing the aetiology.

C. CT scan: For knowing the location of tumour and enlarged lymphgland.
D. Pulmonary function test: Restrictive defect.

Management
1. Prevention: Preoperative or postoperative deep breathing exercise, steam inhalation and
encouragement to cough in patients undergoing chest or major abdominal surgery.
2. Specific therapy: Causes should be treated. For example, aspiration of effusion or pneumothorax,
gastroscopic removal of aspirated gastric content, mucus and FB.
3. Surgical excision of affected segment if atelectasis is complicated with lung abscess, bronchiectasis
and severe chest infected.
Chest physiotherapy This is the mainstay of all therapeutic regimes. Postural drainage and vibration
are additional measures. Bronchospasm should be removed by ultrasonic nebulisation with albutrol,
salbutamol or terbutaline. Steam inhalation and coughing should be encouraged for clearing the secretion.

PULMONARY FIBROSIS
Many pulmonary diseases heal by fibrosis. Important ones are pulmonary tuberculosis, occupational
pneumoconeosis, sarcoidosis, radiation, collagen diseases and idiopathic pulmonary fibrosis (Hamman-
Rich syndrome).

Diagnostic Clues
Clinical manifestations Productive cough with large mucopurulent sputum and dyspnoea.
Signs On affected side: Retracted flat chest, drooping shoulder, scoliosis, shifting of trachea and
heart to the same side, resonance impaired, breathe sound diminished, expiration prolonged and rales.

Investigations
a. X-ray chest: Mediastinal shift, affected side shrunken
b. Pulmonary function test: Restrictive defect
c. Repeated examination of sputum for AFB
d. CT scan and bronchoscopy for finding the cause.

Management
Usually symptomatic.
Treatment of the cause.
Surgery indicated if pulmonary function test show good pulmonary reserve and disease is localised.
 Lung and Pleura
7
Treatment for Eosinophilic
Diseases of Lungs

DOSAGES AND INDICATIONS

Corticosteroids
1. Simple pulmonary eosinophilia (Loeffler’s syndrome): Resolves spontaneously in one month.
Prednisolone rarely required.
2. Chronic eosinophilic pneumonia: Prednisolone 30-40 mg/day—reduces symptoms within 24-
48 hours. If corticosteroids are discontinued in the first 6 months, relapse may occur. Most patients
do not relapse after 6 months treatment.
3. Acute eosinophilic pneumonia: Methylprednisolone 60-125 mg every 6 hour until respiratory
failure resolves usually within 1-3 days and then 40-60 mg per day for 2-4 weeks and then tapered
over the next 2-4 weeks.
4. Idiopathic hypereosinophilic syndrome: Prednisolone 60 mg/day for a week, and then 60 mg
every other day for 3 months. Fifty per cent show good response.
5. Tropical pulmonary eosinophilia: Steroids significantly reduces the lower respiratory tract
inflammation.
6. Drug induced pulmonary eosinophilia: Withdraw the drug. In severe and persistent cases need
short course of steroids.

Diethylcarbamazine (DEC)
Tropical pulmonary eosinophilia: DEC 6-12 mg/kg body weight/day. Relapse occurs even with steroids
in 20% cases and hence repeat monthly course of DEC at 2-3 monthly intervals for a period of 1-2 years.

Cytotoxic Drugs

Busulfan, hydroxyurea, cyclophosphamide, interferon, cyclosporine-A etoposide and vincristine. They

are used in idiopathic hypereosinophilic syndrome and Langerhan’s cell granuloma of the lung.

Radiation Therapy
Langerhan’s cell granulomatosis: Granulomatosus masses compressing the chest wall and adjacent
lung may resolve with radiation therapy.
 Lung and Pleura
8
Treatment of Sarcoidosis

TREATMENT OF SARCOIDOSIS
It is essentially symptomatic.
I. Corticosteroids
Indications
a. Depends upon clinical,
radiological and functional
findings.
b. Absolute indications:
i. Involvement of CNS, eye,
heart or any other vital
organs
ii.Acute symptoms with hyper-
calcaemia and breathlessness
with hypoxaemia
Dosages and preparations Remarks and prognosis
Prednisolone : Start a. In West, remission rate
0.5-1 mg/kg body wt 80-90% and may last for
↓ lifetime. In India, relapses
Gradually tapered to 10-15 mg are common.
/day in 3-6 months and conti- b.Severe cases do not remit.
nued for a year or two c. Terminal complications
↓ are respiratory failure,
Followed carefully, if signs renal failure, cardiac
of recurrence observed, failure, corpulmonale or
treatment started again. massive haemoptysis.

II. Patients who contact tuberculosis: If tuberculin test is positive, prophylactic and curative treatment
should be given.
III. Ophthalmic and skin lesions: Topical steroids, chloroquine, methotrexate.
IV. Arthritis occurring in Loefgren’s syndrome: Indomethacin, NSAID.
V. Hypercalcaemia and hypercalciuria: Stop milk and cheese, avoid sun bathing, stop vitamin D.
↓
If fails
↓
start corticosteroids
VI. Other drugs:
1. Chloroquine: Have some suppressive effect on labile sarcoid infiltration of lung and skin.
Dose: 200 mg twice daily. Should not be continued for more than 6 months.
2. Cytotoxic and immunosuppressive drugs. They have suppressive effect on sarcoid granuloma
resistant to steroids.
Examples: Methotrexate
Azathioprine
CLINICAL NOTES
|
Treatment of Sarcoidosis 29

Half of the patients need no treatment. In many patients symptoms are not disabling. In some patients
symptoms disappear spontaneously.
Steroid induced osteoporosis is treated with calcitonin (salmon).
Etanercept therapy (a specific TNF antagonist) is used in recent research.
To stop scar formation steroids, methotrexate, cyclophosphamide and chlorambucil are used.
Spontaneous remission occurs in 80-90% patients in west with hilar lymphadenopathy and mediastinal
lymphadenopathy or Loefgren’s syndrome. Once the disease remits recurrences are rare.
Bilateral hilar lymphadenopathy in itself requires no treatment.
 Lung and Pleura
9
Bronchogenic Carcinoma

TREATMENT
Treatment depends on a number of factors:
• Type of lung cancer (non-small or small cell lung cancer)
• Size of tumour
• Location of tumour
• Extent of tumour
• General health of patient
Aim is to control lung cancer, and/or improve quality-of-life by reducing symptoms.
Table 9.1: Types of treatment, indications, procedures and prognosis
Types of treatment Indications Procedures Prognosis
Surgery Non-small cell type and stage I Resection of primary tumour and Only 30-35% operated patients
and II regional lymph nodes: survive for 5 years, giving overall
Some tumours are inoperable a. Wedge resection: Only a survival rate of 4%.
because of size and location or small part or segment of
for other medical reasons lung removed.
b. Lobectomy: Whole lobe
removed.
c. Pneumonectomy: Remo-
val of entire lung.
Chemotherapy a. Locally advanced surgi- a. Most drugs given by injec- —
Kill cancer cells throughout the cally resectable disease tion directly into vein.
body. Controls cancer growth and b. Malignant pleural effusion b. Or by catheter into vein.
relieves symptoms c. Superior mediastinal com- c. Some drugs given in the
pression syndrome form of a pill.
Drugs used:
Cisplatin, carboplatin, ifosamide,
—
vinidestine, vinblastine, etopo-
side, mitomycin C.
Radiation therapy a. Treatment of choice in Two types of radiation therapy:
High energy rays kill cancer cells patients who are unfit for a. External radiation from a a. Radiation + chemotherapy
operation. machine increases survival rate.
b. Used before surgery to b. Internal radiation comes b. Radiation is as good as
shrink tumour, or after from an implant (a small surgery in slowly growing
surgery to destroy any container of radioactive epidermoid carcinoma.
cancer cells that remain in material) placed directly
the treated area. into or near the tumour.
contd...
contd...
Bronchogenic Carcinoma | 31

Types of treatment Indications Procedures Prognosis

Photodynamic therapy
c. Used with chemotherapy
as primary treatment ins-
tead of surgery.
d. Used to relieve symptoms
such as shortness of breath.
Used to reduce symptoms, i.e. to
control bleeding or dyspnoea due
to blocked airways when cancer
cannot be removed by surgery.
Also used to treat very small
tumours in patients for whom the
usual treatment of lung are not
appropriate.
—
—
Special chemicals injected into
blood stream and absorbed by
—
cells all over the body. Chemical
rapidly leaves normal cells but
remains in cancer cells for a
longer time. A laser light aimed
at the cancer activates the chemi-
cal, which then kills the cancer
cells that have absorbed it.

SIDE EFFECTS OF TREATMENT

Table 9.2: Side effects of treatment
Surgery Chemotherapy Radiation therapy Photodynamic therapy
a. Air and fluid collect Nausea, vomiting, hairloss, Dry, sore throat; dysphasia, Makes skin and eye sensitive to
in chest: Needs mouth sore, fatigue fatigue, local skin changes, light for 6 weeks or more after
help turning over, anorexia. treatment. Patients are advised to
coughing and breathing Radiation to brain produces avoid direct sunlight and bright
b. Chest pain headache, skin changes, nausea, indoor light for at least 6 weeks. For
c. Weakness in arm vomiting, hairloss and problem going outdoors, they should wear
d. Dyspnoea with memory and thought pro- protective clothings and sunglasses.
cess. Other side-effects include cough-
ing, trouble in swallowing and
painful breathing. Skin blistered,
red or swollen.

CLINICAL NOTES
Treatment of Non-small Cell Lung Cancer
Table 9.3: Treatment of non-small cell lung cancer
Surgery Cryosurgery Radiation and chemotherapy
Most common treatment Freezes and destroys cancer cells. Used to May also be used to slow the progress
control symptoms in later stages of of the disease and to manage symptoms
non-small cell tumour

Treatment of Small Cell Lung Cancer

Table 9.4: Treatment of small cell lung cancer
Chemotherapy Radiation therapy Surgery
Treatment of choice because a. Radiation therapy to brain or lung. Only indicated in small number of
this cancer spreads rapidly Some patients have radiation to brain even though no patients with small cell lung tumour.
cancer is found there—this is called prophylactic cranial
irradiation (PCI), is given to prevent tumours from forming
in the brain.
 Lung and Pleura
10
Pneumonia

PREVENTION
Prevention usually revolves round the precipitating factors for pneumonia:

Precipitating factors Prevention

Immunosuppression (diabetes, HIV infection,
immunosuppressive drugs
Coexisting disease such as pulmonary, cardiac,
renal and liver diseases
IV drugs abuse
Aspiration of oropharyngeal contents
(unconscious patients, oesophageal obstruction
Alcohol, smoking
Mechanical ventilation
Legionellosis pneumonia precipitated by
a. Contaminated cooling towers, airconditio-
ners, evaporative condensers, humidifiers
b. Potable water
Pneumococcal vaccine
Pneumococcal vaccine
Pneumococcal vaccine
Head up position (30 degree) during nasogastric
tube feeding, prevention feeding tube dislodgement,
suction, frequent position change, chest physio-
therapy. Removal of nasogastric and endotracheal
tubes early.
Discontinuance of smoking and alcohol.
Disinfection of respiratory equipment should be
done between patients and change of respiratory
tube every 48 hours. Cleaning and drying nebulisers.
Turning off the equipments.
Raising the temperature of hot water to above
55 degree C or by hyperchlorination

ANTIBIOTIC THERAPY
Antibiotic therapy is based on organisms involved and types of pneumonia. (Table 10.1)
Table 10.1: Types and organisms of pneumonia
I. Primary pneumonia (community acquired)
Organisms : S. pneumoniae, S. aureus, M. pneumoniae, Legionellosis pneumoniae, H. influenzae,
Klebsiella, S. pyogenes, Coxiella, Chlamydia, Actinomyces, Viruses (measles,
varicella, cytomegalovirus)
contd...
contd...
|
Pneumonia 33

Clinical Types: Types of primary pneumonia:

a. Pneumococcal pneumoniae
b. Mycoplasma pneumoniae (Primary atypical pneumonia)
c. Legionella pneumoniae
d. Staphylococcal aureus pneumoniae
e. Fungal pneumoniae
II. Secondary pneumonia: (Weak host defence mechanisms or pre-existing abnormalities of respiratory system)
Organisms: Gram-negative organisms, Pneumocystis carinii, Mycobacterium avium—intracellular,
Cytomegalovirus, S. aureus, anaerobes S. pneumoniae.
Conditions associated with secondary pneumonia:
a. Nosocomial (hospital acquired) pneumoniae
b. Aspiration pneumonia: Aspiration of infection from nasal sinuses, during dental extraction and
due to gastro-oesophageal reflux; common during sleep, general anaesthesia or following surgery.
c. Necrotising pneumonia: Common in elderly and immunocompromised male.
Common organisms: Klebsiella, Pseudomonas, staphylococci, anaerobes, fungi
d. Acute bronchopneumonia: Common in extremes of ages, patchy widespread diffuse inflammation
in X-ray.
e. Pneumocystis carinii: Common in HIV infected cases.

DRUGS AND DOSAGES

Table 10.2: Drugs and dosages
Pathogens Drugs Dose Remarks
I. Gram-positive cocci:
S. pneumoniae (Pne- Penicillin G, erythromycin,
umococcal pneumonia) azithromycin, ciprofloxacin, — —
and other gram-positive clarithromycin and sparflo-
cocci, Legionella, Myco- xacin
plasma, Chlamydia and
H. influenzae
A. S. pneumoniae and Penicillin G ***10 lac units IV 4 hourly
other gram-positive or 300,000-600,000 U IM every —
cocci Procain penicillin G 12 hour

Penicillin V 500 mg po 4 times/day Patient with mild symptoms

Cefazolin 0.5G IM/IV every 8 hours If patient is allergic to peni-
cillin
Erythromycin 250-500 mg IV or po every If patient is allergic to peni-
6 hours cillin or cephalosporin
***Penicillin G 3-4 million U
IV every 4 hours for 7-10
days, if associated with
meningitis and 2-4 weeks if
associated with pericarditis or
endocarditis.
See above —
B. All the above + Legio- Erythromycin
contd...
34 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Pathogens Drugs Dose Remarks

nella, Mycoplasma and Azithromycin 500 mg po/day for 3 days —
Chlamydia Clarithromycin 250 mg po 12 hourly for
10 days
C. All the above + H. Ciprofloxacin 400 mg IV 12 hourly (750 mg
influenzae po 12 hourly) —
D. S. aureus, aerobes Cephotaxime 1 G 12 hourly
II. Gram-negative bacilli:
Gentamicin 5 mg/kg IV 8 hourly in 3
or divided dosages —
Gentamicin, tobramycin or
amikacin
+
Cephotaxime, cefotriaxone or
Aztreonam
III. Mixed infection as in Penicillin G IV
— —
aspiration pneumonia: +
Strep. pneumoniae, Gentamicin IV
Staph. pneumoniae, H. or
influenzae Cefotaxime

SUPPORTIVE TREATMENT
• Bedrest
• Analgesic: Codeine, parenteral meperidine every 3 to 6 hours 50 to 100 mg dose in severe pain.
Intercostal nerve block for severe pleuritic pain.
• Cough suppressant for unproductive cough.
• Oxygen to moderately or severely ill patient.
• Intubation and mechanical ventilation for respiratory failure.
• Adequate hydration.
• Nutrition to be maintained.
• Management of fluid and electrolyte specially in L. pneumoniae.

DRUGS AND DOSAGES

Duration of antibiotic therapy
a. 2 weeks only : For usual pneumonias
b. 6 weeks : Immunocompromised necrotising pneumonias
Drugs Dosages Organisms Remarks
Penicillin G 10 lac units IV 4 hourly S. pneumoniae, other Pneumococcal pneumonia,
or gram-positive cocci. aspiration pneumonia (com-
Mixed anaerobes munity acquired)
Procaine 3000,000-600,000 units IM
Penicillin G every 12 hour
Penicillin V 500 mg po 4 times/day Patients with mild symptoms
CLINICAL NOTES
Pneumonia | 35

Seventy-five per cent of pneumonias are due to pneumococci, the majority will respond to penicillin G
(or erythromycin, vancomycin or cephalosporins if the patient is allergic to penicillin). If gram-negative
rod pneumonia are excluded on gram staining of sputum but the cause is uncertain, erythromycin is the
treatment of choice, it will control Mycoplasma pneumoniae and L. organisms.
 Lung and Pleura
11
Treatment of Viral Respiratory Infection
Mycoplasma Pneumoniae
and Legionellosis

Treatment of Viral Respiratory Infection Mycoplasma Pneumoniae and Legionellosis

Table 11.1: Diseases, symptomatic treatment, specific treatment and prevention
Diseases Symptomatic treatment Specific treatment Prevention
Personal hygiene. Hand
Viral upper respiratory tract a. Nasal congestion: Nasal
washing. Avoid contact
infection decongestant—Avoid
prolonged use to prevent
rebound congestion.
Drugs: Nasevion drop
(Merk), Otrivin nasal
drop (Novartis)
b. Sore throat aspirin (con-
traindicated in children
below 16 year to prevent
Reye’s syndrome).
Acetaminophen
Xylocaine viscous 2% as
gargle, warm saline
gargle. Tantum oral rinse
(elder)
c. Cough: Codeine linctus
indon.
Dextromethorphan—15-
30 mg 8 hourly—Glycodeine
(Alembic), eltuss (Elder),
grilinctus (Francho India)

Respiratory syncytial virus Ribavirin (see table 11.2) Same as above

Influenzal virus Amantadine Same as above
Rimantadine Influenzal vaccine specially
contd...
contd...
Treatment of Viral Respiratory Infection Mycoplasma Pneumoniae and Legionellosis | 37

Diseases Symptomatic treatment Specific treatment Prevention

above 65 year age
Viral pneumonia Good hydration, rest, relief of (See table 11.2 below)
fever with aspirin in adult and Amantadine
acetaminophen in children
Mycoplasma pneumoniae Erythromycin 500 mg
6 hourly for 7-10 days
Terramycin 500 mg twice
daily
Legionellosis
Erythromycin 1 gm IV
6 hourly—after response
If erythromycin fails, rifam-
picin 600 mg twice daily
Or
Oral erythromycin 2-4
gm per day for 14-21 days

ANTIVIRAL DRUGS
Table 11.2: Antiviral drugs
Drugs Dosages and preparations Remarks and side-effects
Amantadine Amantrel (protec) 100 mg cap Indications: Influenzal viral pneumonia
100-200 mg/day for 2-5 days Contraindications: Pregnancy, lactation,
hypersensitivity, gastrointestinal side
effects, severe renal failure.
For prophylaxis: 200 mg/day for Side-effects: Acute confusion, heart
10 days 4 weeks failure, depression, blood dyscrasia
Ribavirin Ribavin (lupin) 100, 200 mg cap Indication: Respiratory syncytial virus
Syrup: 50 mg/5 ml Contraindications: Pregnancy, lactation,
hypersensitivity
200 mg t.d.s. or q.d.s. Side-effects: Gastrointestinal upset,
headache, abdominal cramps, insomnia
 Lung and Pleura
12
Treatment of Fungal
Infection of Lungs

TREATMENT OF FUNGAL INFECTION OF LUNGS

The treatment includes medical (antifungal drugs), surgical and preventive therapy.
Table 12.1: Diseases, antifungal therapy, surgical therapy and prevention
Diseases Antifungal therapy Surgical therapy Prevention

Localised Disseminated and

disease invasive disease
↓ ↓
Candidiasis Local amphotericin-B Flucytosine 100 mg per
or nystatin kg per day orally in
4 divided dosages
+
Amphotericin-B pare- — —
nteral
Or
Ketoconazole
+
Fluconazole (oral or
IV) also effective
Cryptococcosis Fluconazole oral Progressive form, — Hydrated lime and sodi-
(Tolurosis) meningitis: um hydroxide kill fungi
a. Amphotericin-B in droppings of pet
total dose 1-3 gm pigeon.
b. Amphotericin-B
intrathecally in
meningitis
c. Amphotericin-B
0.4 mg/kg +
5-Flucytosine
150 mg/kg in
divided dosages.
Side effects:
Venous thrombosis
contd...
contd...
Treatment of Fungal Infection of Lungs |
39

Diseases Antifungal therapy Surgical therapy Prevention

at the site of infu-
sion. Renal dam-
age. GI intolerance.
Leukopenia. Plate-
let count reduced.
Aspergillosis a. Ketoconazole and a. Amphotericin-B IV Recalcitant or relapsing —
intraconazole useful + disease: Thoracotomy
in some patients Rifampicin with wedge resection
b. Aspergilloma (my- + when lesion is localised
cetoma) of bronchi: Steroids
Intrabronchial or +
intracavitary instal- Cytotoxic drugs
lation of antifungal
drugs like amphote- b. Granulocytic infu-
ricin-B, nystatin and sion in neutropenic
sodium iodide patients.
Mucormycosis Invasive form: a. Aggressive debri-
a. IV Amphotericin-B dgement of necrotic
b. Control of keto- tissue
—
acidosis b. Surgical resection
Histoplasmosis a. Benign and epi- Disseminated form with a. Fibrosing mediasti-
demic form: No respiratory failure: nitis: Early surgery,
treatment required a. A m p h o t e r i c i n - B antifungal therapy
with steroid not needed
b. Ketoconazole 200- b. Tumour: Surgical
400 mg/day for removal
6 months
Sporotrichosis a. Lymphocutaneous
disease: Saturated
solution of potas-
sium iodide (SSKI) — — —
10 drops TDS
+
Itraconazole 100 mg
/day for 6 months.
b. Localised pulmo- — — —
nary disease: Amph-
otericin-B, SSKI,
itraconazole and
ketoconazole
Coccidioidomycosis Early infection self a. Meningitis: Intra- Surgery for cavities and
limited, needs no thecal amphotericin pyopneumothorax
therapy B
b. Extensive pulmo-
— —
nary lesions: Amph-
otericin or itracona-
zole or fluconazole
 Lung and Pleura
Respiratory Failure
ACUTE RESPIRATORY FAILURE
Diagnosis
History
Dyspnoea, cough, sputum, fever.
History of fume inhalation, trauma
to chest and central nervous
system.
Management
Goals of treatment:
A. Maintenance of airway
B. Administration of oxygen
C. Treatment of infection
D. Treatment of underlying conditions and specific therapy
13
Physical Examination Investigations
Altered sensorium, confusion i. Arterial blood gas: PaO2 less
open mouth panting, jaw tug, than 60 mmHg, PaCO 2
tightening and pursing of lips, above 49 mmHg.
hypercapnia, flaring of ala nasi, ii. Arterial pH below 7.3 with
sweating, central cyanosis in hypercapnia.
mucosa of lips and tongue, muscle iii. Chest radiograph: Look for
twitching, tremor. pneumonia, fluffy shadows
of adult respiratory distress
syndrome, hyperinflation of
chronic obstructive lung
disease, cystic shadow of
bronchiectasis pleural effu-
sion, pneumothorax, infiltra-
tion and chest cage defor-
mity.
iv. Bacteriological examination
of secretion.
v. Examination of blood and
urine.
vi. Investigations for evaluation
of CNS and CVS.
Maintenance of airway
Respiratory Failure| 41

I. Management of respiratory arrest:

Clear all materials (saliva, vomitus and other secretions) from oropharynx by sweeping finger and
suction apparatus.
Place the victim on his or her back with head tilted backwards and jaw extended forward.
If breathing is not assumed, start mouth to mouth breathing or by Ambu bag or mask device.
II. Establishment of airway:
There are three different methods: Oropharyngeal tube, endotracheal tube and tracheostomy:

Technique Indications Remarks

Oropharyngeal tube: Unconscious patient who A temporary measure
are breathing. until tracheal tube inser-
ted.
Endotracheal tube: Can be passed through Should be used in all
nose or mouth by an expe- patients.
rienced person. Tube is Emergency tracheostomy
used both for ventilation is contraindicated except
and removal of secretion. in acute obstruction of
Oxygen and air is admi- upper airway due to
nistered fully saturated foreign body, trauma or
with water vapour inflammation.
through a T-tube connec-
ted to endotracheal or
tracheostomy tube.
Tracheostomy: See above. Elective tracheostomy if
needed can be done in
operation theatre with
minimum complications.

Administration of Oxygen
Goals of oxygen therapy The goal is to raise arterial PO2 to between 60 to 80 mmHg. During
emergency the higher concentration of oxygen is better. After the patient is stabilised, oxygen is given in
lowest possible concentration required to correct hypoxia especially in hypercapnic patient.
Disadvantages of oxygen therapy Excess of oxygen than required to raise PO2 to a safe level,
exposes the patient to direct toxicity of oxygen on lung parenchyma and reduces mucociliary clearance.
In chronic obstructive pulmonary disease with chronic hypercapnia excess oxygen administration may
worsen the CO2 retention. This is due to suppression of pre-existing hypoxic ventilatory drive. In these
patients “Low-flow” oxygen is given.
42 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Ways of giving supplemental oxygen:

Methods Technique Remarks

Nasal route: By nasal cannula, tongs and catheter.
Venturi mask: Fixed proportion of air mixed with
constant inspired concentration of
oxygen that is 24-40% concentration; in
hypercapnic patient low concentration of
oxygen is given, to prevent CO 2
narcosis.
Reservoir mask:
Mechanical ventilator Connected to endotracheal or tracheo-
stomy tube. Regulates oxygen concen-
tration from 21% to 100%.
Two types:
a. Pressure ventilator: Adjustable
pressure is reached by machine
during each breathing cycle.
b. Volume ventilator: Adjustable
constant tidal volume is delivered
to patient with each breath. More
versatile and reliable.
Two modes:
a. Intermittent positive pressure
ventilation (IPPV): Indicated in
patients who have no spontaneous
ventilation.
b. Intermittent mandatory ventilation
(IMV): Indicated in patients who
have some respiratory drive.
Dries nasal mucosa. Hence if above 3-
5 litres of oxygen/min is required other
methods are used.
a. Venturi mask is uncomfortable.
b. Must be removed for eating and
drinking.
c. High cost.
a. For delivery of high concentration
of oxygen.
b. Tight fitting of mask produces
discomfort and cannot be used for
long period.
a. Best way to achieve delivery of
high concentration of oxygen.
b. Indications:
i. Elevated and rising PCO2, low
PO2 that cannot be raised with-
out excess oxygen.
ii. Head injury.
iii. Traumatic injury of chest.

TREATMENT OF INFECTION
• Ampicillin 500 mg 6 hourly
or
• Trimethoprim + sulfamethoxazole every 12 hour
or
• Tetracycline 500 mg every 6 hour
or
• Ciprofloxacin 500 mg twice daily.
TREATMENT OF UNDERLYING CONDITIONS AND SPECIFIC THERAPY
|
Respiratory Failure 43

Find out the causes of acute respiratory failure and treat them accordingly.

Conditions Therapy
Respiratory centre depression from Naloxone
narcotic overdose
Primary alveolar hypoventilation Respiratory centre stimulant such as
progesterone
Diaphragmatic paralysis Diaphragmatic pacemaker
Asthma Bronchodilator and corticosteroids
ARDS Reversing shock, sepsis and other causes
of ARDS
COPD and cystic fibrosis Bronchodilator and antibiotics

CHRONIC RESPIRATORY FAILURE

Diagnosis
Apart from chronic dyspnoea and cough the following parameters are suggestive of chronic respiratory
failure:
• PO2 30 mmHg
• PCO2 70 mmHg
• pH 7.3

Important causes
Chronic bronchitis and emphysema.
Asthma.

Precipitating Factors for Acute Episode

• Acute bronchopulmonary infection
• Pneumothorax
• Pulmonary embolism
• Surgical procedure
• Misuse of sedatives.

MANAGEMENT
Oxygen
Initially, oxygen given in low concentration (2 litre/min) to prevent CO2 narcosis and later elevated to
maintain PO2 to 40-60 mmHg.
44 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

BRONCHODILATORS
i. In acute exacerbation aminophyline IV 250 mg or 500 mg bolus given slowly and if prolonged
treatment is needed constant infusion of 0.9 mg/kg wt per hour. This dose is reduced if the patient
who has been taking aminophylline, elderly or in liver and heart failure.
ii. Corticosteroids: In acute exacerbation methylprednisolone 60 mg or hydrocortisone 100 mg IV
6 hourly.
iii. Salbutamol or bricanyl by inhalation, initially more frequently at 2 hour interval for first12 to
24 hours.

ANTIBIOTICS
Ampicillin 500 mg 6 hourly or trimethoprim-sulfamethoxazole 12 hourly or terramycin 500 mg 6 hourly.

MANAGEMENT OF SECRETIONS
i. Hydration (but not excessive) by IV fluid.
ii. Intermittent nasotracheal suction for troublesome sputum retention.
iii. Manual or mechanical percussion and respiratory physiotherapy by a skilled therapist.

HEART FAILURE
• Rest
• Oxygen
• Oral diuretic in low dosages
• ACE inhibitor
• Nitrate
• Digoxin in left heart failure.

RESPIRATORY STIMULANT
Drugs Remarks
Nickethamide Obsolete.
Doxapram Works by stimulating carotid chemoreceptor. Much safer.
Minimises depression of ventilation.
Almitrine Stimulates carotid chemoreceptors, can be given orally and
widely used in Europe to improve arterial PO2 in outpatient
with chronic respiratory failure.

TREATMENT OF ADULT RESPIRATORY DISTRESS SYNDROME

Goals of Treatment
Correction of tissue hypoxia by oxygen administration is the cornerstone in the management of ARDS.
Control of sepsis, accurate fluid management, haemodynamic monitoring and support, protection of
pulmonary capillary endothelium, reduction of catabolism and treatment of initiating causes are important
supportive measures.
OXYGEN
Respiratory Failure| 45

Oxygen delivery is maintained by continuous positive airway pressure (CPAP) in spontaneously breathing
patient and PO2 is maintained above 60 mmHg. If PO2 is maintained above 60 mmHg, mechanical
ventilator is required. Two types of mechanical ventilator is used:
a. Controlled mandatory ventilator (CMV).
b. Synchronised intermittent mandatory ventilator (SIMV).
The above two ventilators may be combined with end-expiratory pressure (PEEP). It prevents alveolar
collapse at the end of expiration due to lack of surfactant.
Cardiotonic agents Digoxin, dobutamine or amrinone are used if cardiac function is compromised.
Nutritional balance Patients are hypermetabolic and quickly become malnourished and needs early
enteral feeding.
Treatment of underlying causes The following causes should be attended:
Shock (volume replacement and blood transfusion), sepsis and infection, haemorrhage, anaphylaxis,
aspiration of gastric content, inhalation of toxic gases and fumes, drugs and poisons (antidote and neutra-
lisation of drug overdose), pancreatitis, disseminated intravascular coagulation, eclampsia, amniotic
fluid emboli, high alttitude and lymphoma (Radiotherapy).
 Lung and Pleura
14
Treatment of Pleural Disease:
Effusion and Empyema

DIAGNOSIS
Clinical Manifestations
Pain aggravated by respiration, fever, dyspnoea.
Chest movement reduced, stony dullness, vocal fremitus and breath sound reduced.

Investigations
a. X-ray chest (PA view)—dense opacity shadow in hemithorax; Lateral view—for small and encysted
effusion.
b. Ultrasound for small effusion.
c. CT scan for detecting hilar lymph nodes or tumour as the cause of effusion.
d. Fibroptic bronchoscopy and pleuroscopy for establishing the aetiology in some cases.
e. Pleural biopsy, scalene biopsy for the cause in some cases.

DIAGNOSTIC FLOW CHART

First differentiate different types of pleural fluid.

Exudate Transudate Chylus Bloody

Protein: 3 gm/dl or more Low protein, low LDH, Milky, no cell, chylomic- Evidence of pleural, lung
LDH: Above 0.6 low sp. gravity rons. and mediastinal malig-
Sp. gravity: 1016 Evidence of cancer lung nancy
Cells: Acute infection→ and lymph gland with
polymorph excess, chro- mediastinal spread
nic infection→lympho-
cytes excess
Causes:
CCF, cirrhosis, myxo-
edema, Meigs’ synd-
rome, sarcoidosis
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema| 47

Common causes of pleural effusion:

Causes: Pleural fluid Other features

Tuberculosis Pleural fluid serous, Other features: Positive
straw coloured, Mantoux test, raised
lympho++ ESR, X-ray findings
present

Pneumonia Poly++ X-ray diagnostic

Malignancy Blood stained, lympho- Other features: Pleural

++, malignant cells biopsy +, evidence of
cancer lung or elsewhere

Pulmonary infarct Pleural fluid serous or Other features: Signs of

blood stained, RBC+, DVT or other sources of
eosinophil+ emboli

Rheumatoid disease Pleural fluid serous, Other features: Rheuma-

lympho + high choleste- toid factor +
rol, low glucose
Effusion usually bilateral

Acute pancreatitis Pleural fluid serous or

blood stained, raised
amylase.
Common on left side

SLE Pleural fluid serous, Other features: ANA or

lympho + anti-DNA + LE cell
Often bilateral

MANAGEMENT
Depends upon causes.
Tuberculosis Malignancy Pneumonia Other causes
First 2 months: a. Systemic chemothe- Aspiration is important to Treatment of causes
Isonex + rifampicin + rapy. prevent empyema and helps in resolving effu-
pyrazinamide + etham- b. When chemotherapy pleural thickening sion as in CCF, pulmo-
butol fails, pleurodesis nary embolism. Effusion
(obliteration of resolves also in pulmo-
contd...
48 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Tuberculosis Malignancy Pneumonia Other causes

Followed by: 4 months of pleural space) by nary embolism with anti-
treatment: Isonex + rifa- intrapleural instil- coagulant therapy.
mpicin lation of tetracycline
In some cases predniso- HCl to prevent
lone 20 mg/day for recurrence by
4 weeks for rapid adhering pleural
absorption of fluid surfaces
c. For pain: Analgesic
and instillation of
intrapleural lidocaine
TREATMENT OF EMPYEMA
Empyema usually accompanies or follows pneumonia, lung abscess, thoracic surgery, trauma and chest
tube insertion.

Organisms Responsible
a. Gram +ve: Staph. aureus, Streptococcus, H. influenzae in child.
b. Gram –ve: Organisms originating from below diaphragm (hepatic abscess or pancreatitis causing
subdiaphragmatic abscess leading to empyema).
c. Other infections: Tuberculosis, amoebic liver abscess, actinomyces.

Diagnostic Clues
Clinical manifestations: Fever with chill, pleuritic chest pain, cough with purulent sputum. Oedema and
tenderness of chest wall. Clubbing. Signs of pleural effusion. Chest deformity in chronic empyema.

Investigations
a. X-ray chest: Signs of fluid in hemithorax, loculated fluid, air-fluid level due to pyopneumothorax as
a result of bronchopleural fistula.
b. Ultrasound: Fibrin strands.
c. Pleural fluid: pH higher than 7.2, LDH above 1000 IU/L, low glucose (less than 60 mg/dl). Gram
staining done, smear and culture for AFB.

MANAGEMENT
Antibiotics:
A. Culture and sensitivity not available: Penicillin + aminoglycoside + metronidazole for 6 weeks.
B. Culture and sensitivity available:
a. Staph. aureus: Cloxacillin or vancomycin
b. Anaerobes: Benzyl penicillin + metronidazole
c. H. influenzae: Beta-lactum antibiotic
C. Other infections such as tuberculosis, amoebiasis, actinomyces—treated with appropriate agents.
DRAINAGE
Treatment of Pleural Disease: Effusion and Empyema | 49

A. Closed drainage: Intermittent needle aspiration or continuous intercostals tube drainage under a
water seal.
B. Open drainage:
Indication: If closed tube drainage is ineffective due to bronchopleural fistula or multiple loculation
of fluid or pus is too thick.
Procedure: Resection of ribs, manual disruption of loculi and placement of a wide bore tube for
continuous drainage.
C. Decortication: If fluid too thick to drain, evidence of pleural fibrosis or lung is not expanding.

TREATMENT OF PNEUMOTHORAX
Diagnostic Clues
Clinical manifestations: Sudden onset of chest pain and dyspnoea. Fullness of intercostal spaces, dimi-
nished movement and hyper-resonance on the affected side:
A. Closed pneumothorax: Breathlessness mild; breath sound, vocal fremitus and vocal resonance
diminished. Air gets absorbed within a few weeks and patient recovers.
B. Tension pneumothorax: Amphoric breath sound, whispering pectoriloquy at localised place and
diminished breath sound in other places. Severely dysponoeic and cyanosed.
C. Open pneumothorax: Amphoric breath sound with increased vocal resonance and vocal fremitus
and whispering pectoriloquy. Patient more dysponoeic. Pleural infection common.

Investigations
X-ray Chest
Translucent shadow of air with sharply defined edge of deflated lung. Mediastinal shift to opposite side.
In tuberculosis hydropneumothorax and underlying lung disease seen.

Management
A. Closed pneumothorax:
a. Small pneumothorax: No treatment required.
b. Large pneumothorax with breathlessness: Drained under water seal.
c. If hydropneumothorax with tuberculosis: Antituberculous treatment and if required pleural
aspiration should be done to relieve dyspnoea.
B. Open pneumothorax: Pleural cavity is usually infected due to bronchopleural fistula. Requires
pleural aspiration of fluid and air and appropriate antibiotics and antituberculous drugs if required.
C. Tension pneumothorax: A medical emergency. Intercostal catheter or wide bore plastic cannula
inserted immediately under water seal with antibiotic cover or antituberculous treatment.
D. Recurrent pneumothorax: Pleurodesis (obliteration of pleural space) by instilling an irritant substance,
e.g. kaolin or by pleural abrasion or in some cases by parietal pleurectomy.
50 |
ANAEMIA
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Classification
I. Diminished production
A. Microcytic
1. Iron deficiency
Causes
• Deficient diet
• Decreased absorption
• Increased requirement in pregnancy and lactation
• Blood loss: Gastrointestinal, menstrual
2. Thalassaemia • Haemoglobinuria
a. Alpha thalassaemia Hereditary
b. Beta thalassaemia
3. Anaemia of chronic infection
• Chronic infection or inflammation
• Cancer
B. Macrocytic • Liver disease
1. Megaloblastic
a. Vitamin B12 deficiency
• Pernicious anaemia
• Gastrectomy
• Blind loop syndrome, surgical resection of ilium
• Fish tapeworm
• Pancreatic insufficiency
• Crohn’s disease
b. Folic acid deficiency • Dietetic insufficiency
• Decreased absorption in tropical sprue, drugs
(phenytoin, sulfasalazine, septran)
• Increased requirement in pregnancy and chronic
haemolytic anaemia
2. Nonmegaloblastic • Myelodysplasia, chemotherapy, liver disease
myxoedema
C. Normocytic • Chronic alcoholism
a. Sideroblastic anaemia • Drug toxicity (anti-TB drugs, chloramphenicol
• Lead poisoning
b. Aplastic anaemia: Pancytopenia • Idiopathic
• Acquired:
— SLE
— Chemotherapy, radiotherapy
— Toxins: Benzene, toulene, insecticides
— Drugs: Chloramphenicol, phenylbutazone,
gold salt, sulphonamides, phenytoin, carba-
mazepine, tolbutamide
contd...
 Treatment of Pleural Disease: Effusion and Empyema

— Pregnancy
| 51

— Paroxysmal nocturnal haemoglobinuria.

II. Increased destruction: Haemolytic anaemia:
Morphologic changes in RBC Other abnormalities Suggestive of types of haemolytic
anaemia
• Microspherocytes RBC osmotic fragility increased Hereditary spherocytosis
• Elliptocytes — Hereditary elliptocytosis
• Sickel cells Haemoglobin S Sickel cell anaemia
• Target cell Haemoglobin C Haemoglobin C disease
• Fragmented RBC — Macroangiopathy (Disseminated
intravascular coagulation, haemo-
lytic-uremic syndrome, thrombo-
tic thrombocytopenic purpura)
• Spherocytes, reticulocytosis, Positive Coombs’ test Autoimmune haemolytic anaemia:
agglutinated RBC • Idiopathic
• Acquired: SLE, chronic lymph-
atic leukaemia, lymphoma,
drugs (methyldopa, penicillin,
quinidine)
• Basophil stippling Lead poisoning

DIAGNOSTIC CLUES FOR ANAEMIA

I. Microcytic Anaemia
Iron deficiency anaemia Anaemia of chronic Anaemia with haemoglo-
infection bin defect (Thalassaemia)
Clinical • Usually caused by Known chronic disease • Geography: Alpha tha-
bleeding from GI tract— lassaemia in southern
ulcer, cancer Asia and China. Beta
• Responds to iron ther- thalassaemia in Medi-
apy terranean area (Greek,
• Smooth pale bald ton- Italian)
gue, angular stomatitis • Splenomegaly, growth
• Plummer-Vinson synd- failure, bony deformities
rome: Dysphagia due to (frontal bossing and
oesophageal web + koi- prominent cheek bones)
lonychia + spleno- Positive family history
megaly
• Thin and brittle nail
• Pica
Peripheral blood Microcytic hypochromia Acanthocytes, target cell
contd...
52 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Iron deficiency anaemia Anaemia of chronic Anaemia with haemoglo-

infection bin defect (Thalassemia)
tear drop cells, nucleated
RBC abundant
Bone marrow Absent bone marrow iron Normal or increased iron Hypercellular marrow
store store
Specific lab findings and • Serum ferritin less than • Normal or elevated • In beta thalassaemia Hb
other findings 12 microgram/L serum ferritin A or Hb F elevated
• Elevated TIBC • TIBC normal or low • RBC survival dimi-
• Low transferrin satura- nished
tion • X-ray skull: Hot-cross
bun appearance, wide-
ned diploic space and
hair-on-end appearance.

II. Macrocytic Anaemia

Megaloblastic Non-megaloblastic
Vit. B12 deficiency Folic acid deficiency characteristic:
Clinical Glossitis, peripheral neu- Similar to vit. B12 defi- • Alcoholics (target cell
ritis, posterior column ciency except neurolo- present)
signs, mild icterus gical signs absent • Hypothyroidism: Also
associated with perni-
Peripheral blood Macro-ovalocytes, cious anaemia
hyper segmented • HIV treated with zido-
neutrophils, megalo- vudine
blasts seen • Myelodysplasia (blee-
Bone marrow Hypercellular megabla- Similar to B12 deficiency ding, splenomegaly).
sts, giant metamyelocytes Cytopenia, hypercel-
lular marrow, promy-
elocyte and blast cell in
peripheral blood
Biochemical abnormali- • Elevated LDH
ties • Ser. Vit. B12 less than • Reduced folate level in • Liver disease
100 pg/ml RBC or serum • Haemolytic anaemia
• Serum bilirubin inc- • Cytotoxic drugs
• Specific for PA: reased • Multiple myeloma
Histamine fast achlor- • Pregnancy
hydria, anti-intrinsic
factor and anti-parietal
cell antibodies present,
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema| 53

Megaloblastic Non-Megaloblastic
Vit B12 deficiency Folic acid deficiency
gastric atrophy (sto-
mach biopsy)
• Increased unconju-
gated bilirubin
• Schilling test (see table
14.1)

III. Haemolytic Anaemia

Congenital haemolytic anaemia Acquired haemolytic
Sickel cell disease anaemia
Clinical: Growth failure. Acute crisis (acute pain A. Autoimmune:
in chest, abdomen and long bones). Veno-occlusion i. Warm antibody type:
leading to splenic infarct, acute myocardial Above age 40 year;
infarction, stroke, organ failure (cardiac, kidney) mild jaundice. Posi-
Investigations: Features of haemolytic anaemia. tive direct antiglo-
Sickel cells: 5-50% of RBC. Howel-Jolly bodies bulin test
target cells. Leukocytosis, thrombocytosis. Haemo- ii. Cold antibody type:
globin S 85-95% 1. Cold haemagglu-
tinin disease
Summary of abnormalities of RBC in (CHAD):
haemolytic anaemia Raynaud’s phe-
Abnormalities Congenital haemolytic Acquired haemolytic nomenon; RBC
anaemia anaemia agglutination
Sickel cells Sickel cell anaemia Microangiopathy occurs while col-
Schistocytes lecting blood as
the temperature
is lowered in the
syringe. IgM
antibody present.
2. Paroxysmal cold
Acanthocytosis Abetalipoproteinaemia Severe liver disease haemoglobinuria
Spherocytes Hereditary spherocytosis Immune warm body type (PCH): Children;
acute episode pre-
cipitated by expo-
sure to cold with
haemoglobinuria
and jaundice
Target cells Thalassaemia B. Non-immune: Secon-
Haemo-globinopathy dary to infection,
(HbC)
contd...
54 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Congenital haemolytic anaemia Acquired haemolytic

sickel cell disease anaemia
drugs (penicillin, cep-
halosporin, quinine,
rifampicin, PAS, met-
hyldopa), Pb, burn
injury
C. Paroxysmal nocturnal
haemoglobinuria
(PNH): Adult; noc-
turnal episode of red
urine related to sleep;
mild jaundice, sple-
nomegaly; venous
thrombosis, haemo-
lytic anaemia, throm-
bocytopenia, leuko-
openia, decreased
leukocyte alkaline
phosphatase, aplastic
marrow; positive acid
HAM test
Table 14.1: Schilling test
Done by giving IM B12 and radio labelled B12
Conditions causing megaloblastic anaemia
1. Pernicious anaemia: Giving concurrently B12 + Intrinsic factor, corrects vitamin B12 deficiency.
2. Bacterial overgrowth in blind loop: Giving antibiotic corrects B12 deficiency.
3. Pancreatic insufficiency: Giving pancreatic enzymes corrects B12 deficiency.
4. Fish tapeworm: Giving antihelmintic corrects vitamin B12 deficiency.

IV. Normocytic Anaemia

Sideroblastic anaemia
Clinical: Refractory anaemia:
a. Hereditary: Child, young
adult
b. Acquired: Middle-aged and
elderly. Associated with
myeloproliferative dis-
orders, rheumatoid arthritis
and due to drugs (isoni-
azid, cycloserine, chlora-
mphenicol, lead). Bleeding
Haemolytic anaemia Aplastic anaemia
Pallor, icterus, splenomegaly, a. Pancytopenia without
haemolytic faces, ankle ulcer, aplastic marrow: Due to
pigment gallstones aleukaemic leukaemia,
a. Without reticulocytosis: myelodysplasia, hyper-
Due to haemolytic anaemia splenism (Tropical, cir-
associated with other dis- rhotic), bone marrow
orders: Infection, folate infiltration by cancer,
deficiency lymphoma, multiple
myeloma, myelofibrosis,
b. With reticulocytosis:
osteopetrosis, SLE.
↓
contd...
contd.../
Investigations:
Hereditary spherocytosis G-6-PD deficiency
Clinical: Jaundice, spleno- Acute haemolytic crisis due to
megaly, pigment gallstone. drug, favabeans or infection
Inherited as autosomal domi-
nant disorder.
Investigations: Microsphero-
cytes (small dense cell), RBC
osmotic fragility increased,
Coombs’ test negative
Treatment of Pleural Disease: Effusion and Empyema | 55
Sideroblastic anaemia Haemolytic anaemia Aplastic anaemia
↓ ↓ b. Pancytopenia with aplas-
• Hypochromic + micro- i. Evidence of excessive RBC tic bone marrow:
cytosis destruction: Raised indirect i. RBC indices: Normo-
• Ring sideroblasts, a few bilirubin, urinary urobilino- chromic normocytic
target cells, stippled RBC, gen increased, serum hap- ii. Peripheral blood: Reti-
siderocytes in peripheral toglobin decreased, serum culocytopenia; pancy-
blood. LDH rasied. topenia, thrombocyto-
• Bone marrow: Hyper- ii. Features of increased RBC penia
plastic with predominant production: Reticulocyto- iii. Bone marrow: Marke-
macronormoblasts sis, erythroid hyperplasia dly hypocellular, meg-
of bone marrow, basophilic akaryocytes, iron store
stippling in Pb, thalas- normal
saemia, Heinz bodies in G-
Certain other aplastic
6-PD deficiency.
anaemias
iii. Change in RBC: Sickel cell
a. Fanconi’s anaemia:
in sickel cell disease, target
Abnormalities:
cell in thalassaemia,
• Skeletal-hypoplastic or
spherocytes in hereditary
absent thumb)
spherocytosis, elliptocytes
• Neurological (micro-
in hereditary elliptocytosis,
cephaly, microphthalmia
schistocytes (fragmented
and mental retardation).
RBC) in microangiopathic
• Renal malformation
disease.
• Patchy hyperpigmen-
iv.Features of intravascular
tation of skin
haemolysis: Haemoglo-
b. Red cell aplasia:
binaemia, haemosideri-
• Congenital
nuria, methemalbumi-
• Acquired: Associated
naemia.
with thymoma
⇓
Specific Haemolytic Anaemias
Sickel cell disease Acquired haemolytic anaemia
Investigation
• Heinz bodies
• Enzyme G-6-PD deficiency
⇒
See pages 53 and 54
56 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
TREATMENT OF INDIVIDUAL ANAEMIAS
Iron Deficiency Anaemia
Correction of iron deficiency and replenishing body iron store:
Iron Preparations
Oral
Indications: Majority of cases respond to oral iron
therapy
Forms: Ferrous form (ferrous sulphate, ferrous
gluconate, ferrous fumarate) better than
ferric form. Iron in the form of haemo-
globin is not more advantageous and
more expensive.
Dose: Ferrous sulphate 325 mg t.d.s. given at
bedtime better in a single dose after food.
Better absorbed if given with vitamin C
and fructose but vitamin C is expensive.
Duration of therapy: Haemoglobin
normalises in about 6-8 weeks. To
replenish body iron store, therapy has to
be continued for 6 months.
Advantage: Oral iron safer and cheaper
Disadvantages: Nausea, vomiting, epigastric discomfort,
Side-effects constipation, diarrhoea, anaphylaxis rare.
Parenteral
Very few indications for parenteral
therapy:
i. Patient not tolerating oral iron
ii. Refractory to oral iron.
iii. Patient’s needing repeated periodic
parenteral iron due to excess chronic
blood loss not preventable by oral iron
therapy.
iv. Patients with GI diseases (PU,
ulcerative colitis) which may be
aggravated by oral iron.
Iron dextran (Imferon)
a. IM: Given by “Z” track technique to
prevent staining of skin at injection
site. Before giving IM a test dose
(small dose) should be given. Imferon
(50 mg/ml) 2.5 ml injected IM into
each buttock (Total 5 ml = 250 mg of
iron) daily.
b. IV: IV iron dextran 1:20 dilution in
saline (not in dextrose), total dose
given 20 drops/minute after 5 minutes
if no side-effect, then the rate is
increased to 40-60 drops per minute.
Calculation of total dose:
Iron to be injected (mg) = (15 × 3 –
patient’s weight in gm/dl)
Parenteral iron has more side-effects and
costlier.
Anaphylaxis (rare), fever, joint pain,
nausea, vomiting, diarrhoea, abdominal
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema | 57

Oral Parenteral
GI side-effects lessened by starting with pain, backache, skin rash,
smaller dose with gradual increase in the lymphadenopathy
dose or given after meals
Failure of response Causes:
to oral iron i. Non-compliance
ii. Non-absorption of iron (rare)
iii. Prolonged GI bleed exceeding rate
of new erythropoiesis
Treatment of underlying causes:
Hookworm infestation, PU, pile and
other causes of occult blood should be
treated.
Prevention
i. Fortification of food item such as
salt with iron
ii. Mass treatment of hookworm
infestation in endemic areas.
iii. Iron supplement is essential for
first 3 year of life and during
pregnancy

Aplastic Anaemia: Treatment

I. Specific Treatment
A. Mild to moderate cases with slow progression
• RBC transfusion and platelet transfusion
given as necessary
• Antibiotic for infection
• Identification and removal of causative agent
• Androgen (oxymetholone, fluoxymesterone),
nandrolone decanoate): Oxymetholone (2-4
mg/kg per day orally. Injectable form of
testerone enanthate (5-8 mg/kg once weekly).
Disadvantages
Side effects Advantages
Masculinisation with hir- • Improves haematocrit
sutism, acne, fluid reten- • Lessens transfusion
tion, hepatocellular carci- requirement
noma and clitoral enlarge- • Stimulates bone
ment. Oral agent can cause marrow within 3-6
cholestatic jaundice also. months
B. Severe cases with rapid progression
(Neutrophil : Less than 500
Platelets : Less than 20000
Reticulocyte : Less than 1%
Bone marrow cellularity : Less than 20%)
1. When compatible donor (HLA mediated sibling)
not available and patient is above 50 year:
a. IV antithymocytic globulin (ATG) 15 mg/
kg/day for 8-10 days + cyclosporin A 5-
10 mg per kg per day orally. ATG must be
used in combination with corticosteroid
(prednisolone 1-2 mg/kg/day initially with
rapid tapering).
b. Antilymphocytic globulin (ALG) with or
without androgen or high dose of corticoste-
roid (Methylprednisolone 100 mg/kg per day
over one or two week period).
contd...
58 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

c. Granulocyte-macrophage colony stimulating

factor or granulocyte colony stimulating
factor given as continuous infusion for two
weeks in aplasia due to myelotoxic drugs or
aplastic anaemia in children or with predomi-
nant neutropenia.
d. Aplastic anaemia due to SLE: Prednisolone
+ plasmapheresis
2. When compatible donor is available and the
patient is young adult:
a. Allogenic bone marrow transplant
b. Blood transfusion
c. ALG
II. General Measures
• Suppression of menses by drugs
• Avoidance of aspirin and anti-platelet drugs
• Low dose prednisolone (10-15 mg) decreases capillary bleeding in severely thrombocytopenic patients
• Strictly follow aseptic technique in IV infusion. Avoidance of IM injection.

TREATMENT OF HAEMOLYTIC ANAEMIA

Congenital: Acquired:
• Hereditary spherocytosis • Autoimmune haemolytic anaemia
• Hereditary elliptocytosis • Cold agglutinin disease
• Paroxysmal nocturnal haemoglobinuria • Paroxysmal cold haemoglobinuria
• G-6-PD deficiency • Immune haemolysis due to drugs
• Sickel cell disease. • Microangiopathic haemolytic disease.
Hereditary spherocytosis
Moderate to severe cases: Very mild cases
• Splenectomy: Eliminates site of haemolysis Splenectomy not necessary
• Unsplenectomised patient should receive folic
acid 1 mg/day for sustain erythropoesis
• Pneumococcal vaccine given prior to splenectomy
and oral penicillin prophylaxis given postsplenectomy
to avoid sepsis due to encapsulated organisms.
Hereditary elliptocytosis
• No treatment required
• Occasionally splenectomy required.
Paroxysmal nocturnal haemoglobinurea
Mild to moderate cases Severe case
a. Erythropoesis enhanced by: • Allogenic bone marrow transplant
• Iron • Saline washed RBC given through leukocyte filter
 • Folic acid
Treatment of Pleural Disease: Effusion and Empyema

• Folic acid supplement and iron replacement

| 59

Androgen: Oral fluoxymesterone • Androgen, steroid and antithrombotic drugs

5-50 mg or IM nandralone are occasionally used.
deconate 25-200 mg once weekly.
b. Prednisolone alternate day reduces
haemolysis. Prolonged administration
with low dose required.
G-6-PD deficiency
No specific treatment available.
• Stoppage of offending drugs specially sulpha, primaquine, nalidixic acid, chloramphenicol,
nitrofurantoin, dapsone, etc.
• Maintenance of high urine output and, if required haemodialysis.
• Jaundice in neonatal patient if severe may need phototherapy and exchange transfusion.

Treatment of Sickel Cell Disease

No specific treatment available.
A. Management of specific complications:
Infection Transfusion Pain management Management of crisis
• Prophylactic penicillin • Used to treat all compli- • Analgesic Acute painful crisis Acute vasospastic crisis
• Immunisation: Against cations • Ensure fluid supplement • Elimination of precipi- • Exchange transfusion
pneumococci, H. influ- • Suppresses HbS • Identify aetiology espe- tating factor • Cytotoxic drug hydro-
enzae and hepatitis B • Disadvantages: cially infection • Infection treated. xyurea (500-700 mg/
recommended a. Transmission of • Ensure hydration day). Increases HbF by
• Proper management of viral disease • Oxygen: For hypoxia stimulating erythropoe-
febrile patient. b. Iron overload (due to chronic pulmo- sis (HbF milder than
c. Allo-immunisation. nary disease). Moni- HbS)
Hence give with advice of tored by arterial PO2
a haematologist

B. General Management:
• Treatment of pain
• Prevention of dehydration
• Treatment of fever and infection
• Supplements: Adequate calori intake, folic acid, vitamin C and vitamin E, zinc.
C. New therapies:
• Hydroxyurea: Induces HbF synthesis which is a milder form of sickel disease. Decreases
frequency of vaso-occlusive episodes
• Benefitted by erythropoetin or butyric acid
• Bone marrow transplant
• Gene therapy
D. Prevention:
a. Genetic counselling: Can alert the couple at risk about the possibility of having affected offspring.
b. Prenatal diagnosis: Alert the couple for pregnancies at risk.
60 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Treatment of Acquired Haemolytic Anaemia

A. With warm antibody:
Initial treatment: Prednisolone 1-2 mg/kg/day in divided dosages. Monitored by haematocrit (raised).
Haemoglobin (raised) and reticulocyte count (decreased) and if satisfactory taper the dose 5-
15 mg/day or 10-30 mg alternate day.
If prednisolone ineffective: Splenectomy advised if reduced RBC survival found in spleen.
If ineffective: Refractory cases:
a. Azathioprine 50-200 mg/day or cyclophosphamide 60-150 mg/day or
b. IV gamma globulin 500 mg/kg/day for 1-4 days
Advantage Disadvantage
Highly effective in • Benefit is short lived
controlling haemolysis • Very expensive
c. Or Danazol
d. Blood transfusion: Reserved for life-threatening anaemia or significant hypoxia.
Difficulties:
• Transfused RBC may be rapidly destroyed
• Both grouping and cross matching difficult due to presence of antibodies
slow administration of least incompatible blood is advised.
B. Cold agglutinin disease:
Severe cases Mild cases
a. Steroids and splenectomy often ineffective Avoidance of cold exposure.
b. Chlorambucil is effective: 2-4 mg/day Protective clothing in cold weather,
use of leather gloves and stocking or moving
to a temperate climate is advised.
c. High dose immunoglobulin (2 g/kg may be
effective temporarily.
d. Interferon may be effective for some patients
e. Blood transfusion: Rarely necessary.
Indicated in critically ill patients with
tachycardia, angina, CCF, cerebral hypoxia
with confusion and responding to bed rest
and oxygen
C. Paroxysmal cold haemoglobinuria:
• Avoid cold exposure
• If chronic: Steroid and cyclophosphamide may benefit.
D. Microangiopathy:
• Withdraw offending drugs
• Treat infection with antibiotics
• RBC transfusion or platelet pack needed
• Vigorous plasma exchange induces dramatic remission
TREATMENT OF THALASSAEMIA
Treatment of Pleural Disease: Effusion and Empyema
Hb H Severe case
• Folate supplement a. Regular blood trans-
• Avoid oxidative drug fusion to maintain
such as sulpha and Hb at 10-14 gm/dl
iron b. Iron chelation for
iron overload
⇓ nectomy
Iron chelation:
Desferrioxamine:
Advantages Disadvantages
• Free of serious side- • Must be given perman-
effects, cardiac disease ently
delayed, reversal of CCF • Very short half-life
c. Folate
d. Splenectomy in hyper-
splenaemia
TREATMENT OF MEGALOBLASTIC ANAEMIA
Vitamin B12 deficiency
General management: Severe anaemia (less than 4 gm/dl)
treated by packed RBC given slowly (15
drops to 30 drops/minute). Before
transfusion collect sample for vitamin
B12 and folic acid estimation
Preparations and dose: a. IM or deep subcutaneous:
Vit B 12 100 microgram/day: 1st
week
100 microgram weekly for first
month
100 microgram monthly for life.
Indicated if patient not wanting
parenteral.
b. Oral cobalamine: 1000 microgram
per day and continued indefinitely.
Response to therapy: i. Haematological improvement
occurs.
ii. Neurological features of short
duration (6 months) also improve.
Neurological features do not improve if
persist for beyond 12 months.
| 61
Thalassaemia inter- Mild case
media (Alpha thalassaemia,
Most difficult to treat. trait, beta thalassaemia
Needs careful judgement minor) requires no
regarding transfusion, treatment
iron chelation and sple-
Dose
• Subcutaneously: By using
an infusion pump over 8-
10 hrs/day, 5 days a week.
Forms standard chelation
therapy.
• IM: 1.5-2 gm b.d. or t.d.s.
• IV in CCF
Folic acid deficiency
Same as vitamin B12
Folic acid 1 mg/day for 2 months.
Large dose (5 mg t.d.s.) in severe mala-
bsorption
Indications for long-term folic acid
therapy:
i. Severe haemolytic anaemia (Sickel
cell, thalassaemia major)
ii. Myelosclerosis
iii. Glutein induced enteropathy when
glutein free diet not effective.
Haematological improvement occurs.
Response delayed if there is infection
or the patient has already received
blood transfusion.
contd...
62 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Vitamin B12 deficiency Folic acid deficiency

Treatment of cause: i. Expulsion of tapeworm
ii. Improvement of vegan diet
iii. Surgical correction of intestinal
stagnant loop
Prophylaxis: Vitamin B12 given from time of opera- i. To all pregnant women: Folic acid
tion after total gastrectomy or after ileal + iron
resection if B12 absorption test post- ii. Patient undergoing regular haemo-
operatively point to malabsorption of dialysis
vitamin B12. iii. Premature infants (less than 1.5 kg)
iv. Parenteral nutrition
Precautions: In severe anaemia in whom there is no Folic acid should not be given alone in
clear indication as to which deficiency megaloblastic anaemia until vitamin
present, it is better to give both B12 and B 12 excluded since folic acid
folic acid. precipitates neurological change by
aggravating methionine deficiency in
Treatment of other defi- i. If iron deficiency present, should be the brain.
ciency: treated.
ii. Potassium needed occasionally if
hypokalaemia occurs due to initial
therapy with vitamin B12 (there is
sudden requirement of potassium
for young RBC due to enhanced
erythropoesis)
Unresponsive cases: Megaloblastic anaemia unresponsive to
vitamin B12 and folic acid
Causes Treatment
i. Drugs: i. Discontinue offending drug
• 6-mercaptopurine ii. Pyridoxin
• Azathioprine iii. Thiamine
• Methotrexate
• Hydroxyurea
ii. Inborn error of metabolism: Rare
iii. Unexplained disorders:
• Pyridoxine responsive
• Thiamine responsive
LEUKAEMIAS
Treatment of Pleural Disease: Effusion and Empyema | 63

Diagnostic Clues

Clinical Laboratory findings

Acute leukaemia Symptoms: Short duration of symptoms including Cytopenia or pancytopenia, more than
fatigue, fever, and bleeding (from skin, mucosa, 30% blast cells in bone marrow and blast
epistaxis or menorrhagia) and infection in peripheral blood is 90%.
Signs: Purpura, petechiae, variable enlargement of
liver, spleen and lymph nodes. Sternal tenderness.
Chronic myelogenous Symptoms: Fatigue, night sweats and low grade fever • Strikingly elevated WBC above
leukaemia: Signs: Splenomegaly (often markedly so, sternal 150,000/L
tenderness) • Markedly left-shifted myeloid series
but a low percentage of promyelocytes
and blast cell (less than 5%)
• Leukocyte-alkaline phosphatase low
(in leukocytosis due to infection
leukocyte-alkaline phosphatase
increased)
• Presence of Philadelphia chromosome
• bcr-abl gene found in peripheral blood
by molecular technique.
• Lymphocytes above 5000/L
Chronic lymphocytic Symptoms:
• Elevated WBC
leukaemia: • Older patients • Bone marrow infilterated with small
• Fatigue lymphocytes
Signs: • Immunophenotype of CLL is unique
• Lymphadenopathy in that it co-expresses B lymphocyte
lineage markers such as CD19 with
T lymphocyte marker CD5.

Hairy cell leukaemia: Clinical symptoms: • Pancytopenia

• Middle-aged men • Hairy cell present on blood smear and
• Fatigue bone marrow biopsy
Signs: Splenomegaly (often massive)

TREATMENT OF LEUKAEMIA
Chronic Myeloid Leukaemia
Treatment is based on the three phases of the natural history of disease:
1. Chronic phase with leukocytosis
2. Accelerated phase (Leukocyte count resistant to control with busulphan and hydroxyurea; more
than 5% blast cells in peripheral blood, more than 20% blast cells plus promyelocytes in marrow;
persistent or increasing splenomegaly and unexplained fever).
3. Blastic or terminal phase (Blast cells more than 30% in peripheral blood and marrow).
64 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Chronic Phase
a. Drugs:
Single drug therapy

Drugs Dose Monitoring Response Side effects and Comment

Hydroxyurea: Started at 2 gm/daily p.o., Adjusted to keep WBC WBC count decreases,
usual maintenance dose count near 5000/L
1.0-1.5 gm daily
Given without interruption
because WBC count rises
within days after disconti-
nuation.
Busulphan: 4 mg/day. In the early stage
give allopurinol 400-600
mg daily with copious
fluid to avoid hyperuricae-
mia
Recombinant alpha 5 million units/m2
interferon:
Side-effects rare but inclu-
spleen becomes smaller, des rashes, mouth ulcer, GI
symptoms, disappear symptoms. Does not eradi-
cate cells with Ph chromo-
some. Also useful in
patients who cannot tole-
rate interferon alia.
WBC count monitored Clinical improvement, Hb • Pancytopenia, if treat-
weekly and never allow to rises, WBC count falls ment not stopped, bone
fall below 15 × 109/L and within a few weeks of irreversibly damaged
maintain near normal starting treatment • Pigmentation in patients
count by giving 1-2 mg on on busulphan more than
alternate day two years
• Amenorrhoea
• Interstitial pulmonary
fibrosis, reversible if
recognised early and
steroids help.
Normalisation of blood Early side-effect: Influ-
count and marrow in 35- enza-like febrile reaction
85% of patients suppressed by paraceta-
mol.
Late side-effects: Ano-
rexia, weight loss, neuroto-
xicity, Parkinsonian synd-
rome and immune throm-
bocytopenia occurs in
10% cases.

b. Combination therapy:
i. Combination of interferon with low dose cytarabine may be more effective than interferon
alone.
ii. Many haematologists start with hydroxyurea, then switch to interferon alfa once symptoms
relieved and WBC count restored.
iii. Intensive combination therapy: It has been used in an attempt to induce Ph-negative haemopoiesis
and in the hope of eradicating the Ph-positive clone which has been achieved in about one-third
of patients by using cycles of combination chemotherapy similar to those used in acute leukaemia.
However, the effect is usually transient and intensive therapy delay blast transformation or
prolong survival.
c. Leukopheresis: It has been used in reduction of leukocyte count, symptomatic improvement and
reduction in splenomegaly. But this treatment has not been shown to have any effect on long-term
survival.
d. Splenic irradiation or splenectomy:
Indications: Refractory cases or terminally ill patients with marked splenomegaly.
Disadvantages: No significant effect on survival, nor the quality-of-life.
e. Bone marrow transplant: The only available curative therapy is allogenic bone marrow
transplantation.
Requirement
Treatment of Pleural Disease: Effusion and Empyema | 65

Allogeneic HLA matched donor

HLA matched sibling HLA matched unrelated donor
Young adult (under 60 year) Young adult (under 60 year)
60% have long-term disease free survival Results are inferior to those achieved in
following BMT sibling transplant

Beneficial response
• Cures by initial cytoreduction followed by long-term immunologic control mediated by donor’s
immune system.
• The chronic phase disease which has recurred after allogeneic transplantation can usually be reversed
without additional chemotherapy by the infusion of T-lymphocytes from the initial donor (“Donor
lymphocyte infusion”).
• Probability of 3 year survival is 50% for recipient is in chronic phase.
f. Recent drug: Experimental oral agent: STI 571 has recently been reported to produce remarkable
results in chronic myeloid leukaemia. It inhibits the tyrosine kinase activity of the bcr-abl oncogene.
It has excellent tolerability, low toxicity and excellent control of the disease even in advanced form.

Accelerated Phase
• Responds temporarily to oral hydroxyurea or busulphan.
• Splenectomy only facilitates treatment in patients with thrombocytopenia and progressive
myelofibrosis.
• The result of BMT is poor.

Blastic or Terminal Phase

Highly resistant to treatment and usually fatal.
The result of acute myeloid leukaemia is poor. Response rate ranges from 10-30%.

PROGNOSIS
Therapies Survival rate
Past treatment : 3-4 year
Interferon based : 5-6 year
STI 571 Further increase in survival rate

TREATMENT OF CHRONIC LYMPHOCYTIC LEUKAEMIA

Asymptomatic patients warrant therapeutic interference. Complete remission is rare and aim is to control
symptoms and improve the quality-of-life rather than cure the disease.
Indications for treatment:
Symptoms Signs Investigation Complications
Systemic symptoms Increasing Marrow failure Haemolytic anaemia
Progressive fatigue lymphadenopathy and immune thrombo-
cytopenia
66 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

I. Early indolent asymptomatic stage: Treatment not needed.

II. Late stage I, II, III, IV (Progressive and symptomatic stage):

Drugs
Drugs Dose Monitoring Advantages Disadvantages Comment
Chlorambucil 0.6-1mg/kg p.o. every Regular blood count Convenient, effective 80% respond less well May be combined
3 weeks for 6 months every 2-3 week and well tolerated. Immunosuppression with steroid.
Stopped temporarily In 20% good result: Intermittent treatment
if low platelet count Lymph node impalp- produces less immu-
and reintroduced at a able and blood count nosuppression: Given
lower rate normal 0.2 mg/kg/day in
cycles of 10-14 days,
followed by a two
Higher response No improvement in week interval
Fludarabine: IV 5 days a week which is long lasting survival. Second line
every month for 4- therapy.
6 months Long lasting immu-
nosuppression

Chemotherapy + anti- New experimental

body directed against treatment
antigen expressed by
CLL.

Bone marrow transplant

The rare young patient with aggressive CLL may require allogeneic bone marrow transplant.

Splenectomy
Indications:
i. Autoimmune haemolytic anaemia and immune thrombocytopenia resistant to steroid
ii. For controlling resistant symptoms
iii. Gross splenomegaly may be dominant feature of the disease.

Radiotherapy
It may be useful to control localised lymphadenopathy which has not responded to chemotherapy.

Treatment of complications
Autoimmune haemolytic anaemia and Infusion
immune thrombocytopenia
• Steroid: If needed prolonged steroid treatment • Should be treated promptly
for control, splenectomy should be considered, • Regular intravenous infusion of normal human
if the general condition is fit for operation. immunoglobulin (400 mg/kg 3 weekly for one year)
• RBC and platelet transfusion has been shown to reduce minor bacterial infection.
 Treatment of Pleural Disease: Effusion and Empyema

Hairy Cell Leukaemia (Indolent Cancer of B lymphocytes):

| 67

Diagnostic clues:
Clinical Laboratory investigations
• Splenomegaly, often massive • Pancytopenia
• Liver enlargement in 50% cases • Hairy cells present on blood smear and bone
marrow biopsy
• Middle-aged men
• Recurrent infection

TREATMENT OF HAIRY CELL LEUKAEMIA

Older treatment Efficacy
• Alpha interferon In 20-30% cases response rate 70-80% with 5 year
disease-free survival. Rarely used now.
• Splenectomy Rarely done now.

New Agents
Drugs Advantages Dose Side-effects
Cladribine (2-chloro- • Benefits 90% patients Administered fort- • Leukopenia
deoxy-adenosine- • Relatively non-toxic nightly for 5-7 months
CDA) • Complete remission in • Neutropenia
above 80% cases • Infection

Lymphomas (Cancer of lymphocytes)

Diagnostic clues Clinical Laboratory investigations

Hodgkin’s disease: • Age: 2 peaks-20 year, over 50 year • Lymph node biopsy
• Painless lymphadenopathy: Isolated or • Tissue biopsy
widespread, commonly in neck. Pain • Chest X-ray for mediastinal lymphade-
in lymph node following alcohol nopathy
ingestion • CT scan of abdomen and pelvis for
• Constitutional symptoms: Fever, dren- lymph gland enlargement
ching night sweat, weight loss, genera-
lised pruritus
Non-Hodgkin’s lym- • Lymphadenopathy –Do–
phomas: • Fever, night sweat, weight loss
• In Burkit’s lymphoma pain in abdo-
men and abdominal fullness.

TREATMENT OF HODGKIN’S DISEASE

Depends upon the staging of the disease.
68 |
Staging
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Treatment
Stage I and II: Radiation therapy
(Stage I: One lymph node region involved;
Stage II: Two lymph node areas on one side of
diaphragm involved)
Stage III and IV: Best treated with combination therapy :
(Stage III: Lymph node regions involved on both
sides of diaphragm; Regimen Comments
Stage IV: Disseminated disease with bone marrow a. Doxorubicin 9 (Adria- More effective and
and liver involvement) mycin) + Bleomycin less toxic than MOPP
+ Vincristine + Dac- regimen
arbazine (ABVD)
Or
b. Mechlorethamine +
Vincristine + Procar-
bazine + Predniso-
lone (MOPP)

TREATMENT OF NON-HODGKIN’S LYMPHOMAS

I. Depends upon the stage of the disease.
Chemotherapy staging and severity
A. Low grade lymphomas:
a. With limited disease with only one abnor- chemotherapy, treatment can be delayed until the
mal lymph node
b. With disseminated disease:
i. Asymptomatic and disease not bulky
ii. Symptomatic patient
Treatment
Because this disease is not curable with standard
patient is symptomatic (“watch and wait”).
Localised radiation is preferred.
No initial therapy is required. Some patients have
spontaneous remission and treatment may be
deferred for 1-3 years
Chlorambucil, 0.6-1 mg/kg every 3 weeks
or
Cyclophosphamide + Vincristine + Prednisolone
(CVP)
or
Fludarabine
or
Chlorambucil + Monoclonal antibody (Rituximab)
directed against the B cell surface antigen. This
combination is very effective in relapsed cases.
contd...
 Treatment of Pleural Disease: Effusion and Empyema

B. Intermediate grade: (diffuse large cell lympho-

| 69

mas)
a. With localised disease: Treated with short course chemotherapy: Three
courses of cyclophosphamide, adriamycin, vinc-
ristine and prednisolone (CHOP)
+
Localised radiation
b. With more advanced disease: Treated with 6-8 cycles of CHOP
C. High grade lymphomas: (Burkitt’s lymphoma): Combination chemotherapy with CNS prophylaxis
with CNS and bone involvement if CSF is free of tumour cells
II. Allogeneic transplantation:
Indications:
i. Occasionally young patients with clinically aggressive low grade lymphomas
ii. Some patients with high-risk lymphomas are treated early in their course.

MULTIPLE MYELOMA (MALIGNANCY OF PLASMA CELLS)

Diagnostic Clues
Disease of older adults.

Clinical Features and Laboratory Features

Mechanism Effects
A. Replacement of bone marrow with plasma
cells:
a. Causing bone destruction: Bone pain and tenderness especially in ribs and back
(detected by skeletal survey of skull, chest, thora-
columbar vertebrae and pelvic bone), osteoporosis,
pathological fracture and hypercalcaemia (mani-
fested by thirst, diuresis, somnolence, renal failure)
b. Bone marrow failure: Anaemia
B. Malignant plasma cell tumour (Plasmacytoma): Causes spinal cord compression, soft tissue tumour
C. Secretion of paraprotein by malignant plasma • High paraprotein level (either IgG or IgA) or
cells: Bence-Jones protein on serum protein electro-
phores is causing hyperviscosity (manifested by
bleeding, vertigo, visual disturbances, alteration
in mental status and high ESR).
• Light chain component of immunoglobulin
(Bence-Jones protein):
i. May lead renal failure due to tubular damage
(osmotic diuresis and amyloidosis are other
causes of renal failure)
contd...
70 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

ii. May be deposited as amyloid (manifested by

enlarged tongue, neuropathy, CCF, hepato-
megaly)
D. Failure of antibody production in response Recurrent infection
to antigen challenge and neutropenia

LABORATORY DIAGNOSTIC CRITERIA FOR MULTIPLE MYELOMA

Major criteria Minor criteria Other investigations
• Tissue biopsy: Plasmacytoma • Bone marrow: Plasmacytosis • 24 hour urine for total protein
• Bone marrow: Plasmacytosis with 10-30% plasma cells and electrophoresis
with 30% plasma cells • Monoclonal globulin spikes • Serum creatinine
• Serum electrophoresis: Mono- present but less than major • Serum uric acid
clonal globulin spikes criteria • Liver function test
• Lytic lesions in bone

TREATMENT OF MULTIPLE MYELOMA

I. Patients with minimum disease without symptoms: No treatment required.
II. Patient with bone pain and other symptoms:

Chemotherapy

Regimen Indications Monitoring Comment

a. Melphalan p.o. 8 Low-risk disease age Early aggressive treat-
mg/m2 on days 1-4 over 70 year or major — ment prolongs duration
+ prednisolone 100 medical problem of survival and remission
mg p.o. on days 1-4
b. VAD: Vincristine High-risk patients, renal
0.4 mg/day IV + failure, or hypercalcae-
adriamycin 9 mg/ mia, young patient and
— —
m 2 /day IV (both who do not respond to
drugs by continuous standard chemotherapy
infusion) + dexa- (Melphalan + steroid)
methasone 40 mg/
day p.o. on days 1-
4, 9-12 and 17-20
Radiotherapy
c. D e x a m e t h a s o n e With spine involvement
40 mg/day: or resistant to melphalan
— —
+ prednisolone.

contd...
 d. Myeloablative
Treatment of Pleural Disease: Effusion and Empyema

Resistant to dexametha-
| 71

therapy + blood or sone and VAD

marrow stem cell
transplant
— A promising new agent
e. Thalidomide: Patients who respond or
do not respond to
chemotherapy

Transplantation
a. Allogeneic bone marrow transplantation:
Patient’s status Regimen Advantages Disadvantages
Young patient with high Intensive chemotherapy • No need of tumour cell • Allogeneic BMT is
tumour burden followed by bone mar- infusion however possessing
row or blood stem cell • 40% response with only 5-10% patients.
transplantation longer survival • Early mortality is high
• Early disease and remi- (35%)
ssion cases have better
outcome.
b. Autologous bone marrow transplantation:
• Younger patients (under • Early aggressive treat- • Contamination of clo-
60 year) ment prolongs remis- genic myeloma cells
• Patients with relapsed sion and survival
disease if the disease is • HLA matching not
still chemotherapy-sen- required
sitive • Early mortality less
• No contraindication to than 10%
older patients • Avoidance of severe
and prolonged post-
transplant immunosup-
pressive drugs
• 70-80% response rate

Ancillary measures
Bone pain
Localised radiotherapy
Hypercalcaemia Pathological fracture
• Immobilisation • Localised radiotherapy for eradi-
• Avoidance of dehydration cating at the site of pathological
fracture
• Biphosphonate pamidrone 90
mg IV monthly reduces patho-
logical fracture.
72 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

APPROACH FOR MANAGEMENT OF SYMPTOMATIC MULTIPLE MYELOMA

Start with Melphalan + Prednisolone
↓
If initial resistance observed switch to:
VAD regimen
Or
High dose dexamethasone
↓
If relapse occurs after initial response:
Administer initial chemotherapy

50% responds but 40% requires VAD regimen

with short remission for remission

HAEMORRHAGIC DISORDERS
Classification
I. Platelet disorders:
1. Thrombocytopenia:
a. Decreased platelet production:
• Marrow infiltration by malignant cells, myelofibrosis
• Marrow hypoplasia by radiation, drugs, viruses, alcohol
b. Increased destruction:
• Idiopathic thrombocytopenic purpura (ITP)
• Drug induced thrombocytopenic purpura (DTP)
• Post transfusion purpura
• HIV infection
c. Increased consumption:
• Thrombotic thrombocytopenic purpura (TTP)
• Disseminated intravascular coagulation (DIC)
• Haemolytic-uremic syndrome
• Cardiopulmonary bypass
2. Thrombocytosis:
a. Essential thrombocythaemia
3. Qualitative platelet disorders:
a. Drugs: Aspirin, ethanol, NSAIDs, ticlopidine,
b. Uraemia
II. Coagulation disorders:
a. Inherited: Haemophilia
von-Willebrand’s disease
b. Acquired:
• Vitamin K deficiency
• Liver disease
• DIC
THROMBOCYTOPENIA
Treatment of Pleural Disease: Effusion and Empyema | 73

Diagnostic Clues: Clinical Approach

Thrombocytopenia (Below 100000/microlitre, in severe case below 20000/microlitre) with or without
bleeding (epistaxis, oral bleeding, menorrhagia, renal bleeding, purpura, petechiae, ecchymoses) +
prolonged bleeding and poor to absent clot retraction + anaemia.

With spleen enlarged Spleen not enlarged

↓ ↓
Bone marrow aspi- Bone marrow aspirates and
ration and biopsy biopsy

Normal marrow Abnormal marrow Abnormal marrow Normal marrow

Causing • Leukaemia With decreased megaka- With accelerated destruction of platelets
sequestration • Lymphoma ryocytes due to defective ↓
of platelets: production of platelets: With microangiopathic haemolytic
↓ ↓ anaemia (reticulocytosis, fragmented
Causes: • Aplasia RBC, bilirubin +, Coomb’s test negative)
• Congestive splenome- • Myelofibrosis
galy • Malignant cell infiltra- With coagulation Without coagu-
• Portal hypertension tion disorders lation disorders
• Splenic tumour • Storage disease (Mac- ↓ ↓
rophage infiltration) Disseminated • Haemolytic ure-
• Drugs (myelosuppres- intravascular mic syndrome
sive drugs, ethanol, coagulation (DIC) (renal failure)
estrogen) (Hypofibrinogenae- • TTP (acutely ill
• Virus infection-HIV mia, prolonged with fever, renal
• Radiotherapy prothrombin time, failure, confu-
fibrin degradation sion, aphasia
products). coma, elevated
DIC: (Underlying LDH)
serious illness • ITP
especially sepsis, Acute in child and
severe tissue chronic in adult;
injury, head in pregnancy and
injury, burn, obs- neonates; antipla-
tetric complica- telet antibody in
tion, cancer and 75% cases but not
major haemolytic done routinely
transfusion reac- • Virus infection
tion; bleeding; • Drugs: Novo-
thrombosis-digital biocin, PAS, qui-
ischaemia and nine, anticonvul-
gangrene) sant methyldopa,
heparin.
• Prosthetic cardiac
valve
74 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

TREATMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

Chronic ITP of Adult: Flow Chart
Initial treatment with prednisolone:
Dose Response Monitoring
High dose 1-2 mg/kg/d Bleeding stops on day 1, By platelet count
continued until platelet platelet count rises within
count normal—then tapered a week. Eighty percent respond.
and keep on maintainance
dose to avoid splenectomy ⇓
If prednisolone fails:
Splenectomy (most definitive treatment) is advised:
Other indications Preoperative Postoperative Response Relapse
• Risk of intracranial Pneumococcal, menin- Soon after surgery 80% respond. Restart prednisolone
bleeding as indicated gococcal and H. influ- platelet count shoot up
by haemorrhagic bleb enzae vaccine given causing thrombotic epi-
in mucosa, retinal 2 weeks before splenec- sode needing antiplate-
haemorrhage and very tomy let drugs and heparin. In
low platelet count some cases small dosa-
• Side effects of steroid ges of steroid may be
• High dose of steroid required
needed for mainte-
nance
• Pregnancy with ITP
where steroid and
immunosuppressive
treatment unsuccess-
ful.
⇓
Patients who do not respond to steroid and splenectomy:
Danazol is prescribed:
Dose Response
100-300 mg/d. After control of acute Improves 50% cases
episode, danazol may be given as a mainte-
nance dose for 2-3 months.
May be combined with steroid.
⇓
Refractory cases
1. Anti-Rh-D immunoglobulin 25 microgram/kg IV on 2 consecutive days effective especially in
Rh-D positive individuals.
2. Immunosuppressive drugs:
Vincristine, vinblastine infusion, azathioprine, cyclosporine and cyclophosphamide. May be
combined with steroid. They contraindicated in pregnancy.
 Treatment of Pleural Disease: Effusion and Empyema

Life-threatening Haemorrhage or Severe Thrombocytopenia (Below 10000/microlitre)

| 75

Hospitalisation is essential.
Emergency measures:
• Methylprednisolone IV 1-2 gm q.d. for 3 days
• High dose IV immunoglobulin:
↓
Dose Indication Advantages Disadvantages
400 mg/kg/d for 3-5 days • Bleeding emergencies • Benefits 90% cases • Expensive
• Platelet transfusion • Preparing a severely • Platelet count rises • Benefit lasts only 1-2
reserved only for life- thrombocytopenic within 1-5 days weeks
threatening bleeding patient for surgery
since exogenous plate-
lets will survive no
better than the patients’
own and will survive
less than a few hours
• Platelet transfusion reserved only for life-threatening bleeding since exogenous platelets will survive
no better than the patient’s own and will survive less than a few hours.

Treatment of ITP under special circumstances

Pregnancy Neonatal thrombocytopenia Drug induced thrombocytopenia
• IV immunoglobulin given Has benign course in 90% cases • Withdrawal of offending drug
during last trimester to prevent and spontaneous recovery is the • Platelet transfusion in severe
neonatal thrombocytopenia rule cases
• IV methylprednisolone 1 gm/day • Corticosteroid arrests platelet
given for 3 days effective in destruction
many cases • IV immunoglobulin given if
⇓ thrombocytopenia is life threat-
If medical therapy fails: Emer- ening.
gency splenectomy may have to
be carried out and caesarean
section may also have to be taken
simultaneously
THROMBOTIC TREATMENT OF THROMBOCYTOPENIC PURPURA
A medical emergency and admitted in ICU for: Emergency plasmapheresis:
Dose Duration Additional treatment Response
60-80 ml/kg of plasma Continued for at least 5 days i. M e t h y l p r e d n i s o l o n e • 90% recover completely.
removed and replaced with or for 2 days after normali- 200 mg IV Neurologic abnormalities
fresh-frozen plasma sation of platelet count and ii. Antiplatelet agents: completely reversed.
LDH and resolution of neuro- Aspirin 325 mg/day and • 20% cases relapse and
logical signs and impro- dipyridamole 100 mg become chronic.
vement in microangiopathy 6 hourly but benefit is not
convulsive
76 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Patients not responding to plasmapheresis and have rapid recurrence.

• Splenectomy
• Or combined splenectomy + Glucocorticoid + Dextran

TREATMENT OF OTHER CAUSES OF THROMBOCYTOPENIA

Haemolytic = Uremic Syndrome
Children Adult
• Self limited Treatment of choice is large volume plasmapheresis
• Conservative management of acute renal failure with fresh frozen replacement (exchange of up to
80 ml/kg), repeated daily until remission is achieved
Prognosis:
Without effective therapy:
• Death occurs in 40% cases
• Eighty percent develop chronic renal insufficiency

Hypersplenism
a. Treat underlying conditions
b. Indications of splenectomy:
• If cause of splenomegaly is not remediable
• If splenomegaly is symptomatic
• For diagnosis in idiopathic splenomegaly

Thrombocytosis
Platelet count rises above 500000/microlitre.

Causes: Reactive thrombocytosis

Due to:
Essential thrombocythaemia
• Splenectomy
Diagnosed by
• Iron deficiency
• Excluding causes of reactive thrombocytosis
• Chronic infection
• Absence of Philadelphia chromosomes in bone
• Chronic inflammation
marrow
• Malignancy
Slightly predisposes to bleeding and thrombosis
No risk of bleeding and thrombosis

Management
Clinical situations Treatment
• Usual cases: a. Daily aspirin (81-325 mg/d)
b.Anagrilide or hydroxyurea
reduces platelet count
• Pregnancy or child bearing years: Interferon-alpha
 Treatment of Pleural Disease: Effusion and Empyema

• Age above 60 year + prior Cytoreduction by anagrilide or

| 77

thrombotic episode: hydroxyurea

• Age less than 60 year + no prior Kept under observation
thrombosis + no cardiovascular
risk factors + platelet count less
than 1.5 million per microlitre
• Asymptomatic patients + platelet Kept under observation
count above 1.5 million/micro-
litre + no cardiovascular risk-
factors
• Acute thrombosis: Platelet pheresis + Aspirin
Platelet transfusion in life-threate-
ning haemorrhage

Coagulation Disorders
Classification:
Inherited disorders
• Haemophilia A (Classical Haemophilia)
• Haemophilia B (Christmas disease)
• von Willebrands’ disease
Acquired disorders:
• Vitamin K deficiency
• Liver disease
• DIC

Diagnostic Clues for Inherited Coagulation Disorders

Inheritance and sex Bleeding pattern Laboratory investiga-
tions
Haemophilia A X-linked recessive pat- • Spontaneous haemar- • Prolonged partial thro-
(Classic haemophilia): tern with only males throsis is diagnostic, mboplastin time (PTT)
affected. Affected boy bleeding in knee, ankle • Normal bleeding time
acquires it from carrier below, into muscles and and prothrombin time
mother. Female children from GI tract, traumatic • Low coagulation factor
of haemophilic father and and postoperative blee- VIII and normal factor
normal mother will ding VIII antigen
always be carriers though
sons are unaffected.
Haemophilia B: X-linked recessive inheri- –Do– • Low level of coagu-
tance with males affected lation factor IX
• Other investigations
same as haemophilia A
contd...
78 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

von Willebrand’s disease: Family history with auto- Most bleeding mucosal
somal dominant pattern (epistaxis, gingival blee-
of inheritance ding, menorrhagia. Blee-
Both men and women ding exacerbated by aspi-
affected rin and decreases during
pregnancy or estrogen
use
• Reduced level of von
Willebrand’s factor
(vWF)
• Prolonged PTT
• Prolonged bleeding
time.

TREATMENT OF HAEMOPHILIA A
I. Infusion of factor VIII concentrate (Standard treatment)
Dose Advantages Disadvantages

Depending on severity of bleeding:

Severity of bleeding: Raising of factor VIII (%) Units of factor VIII • Heat treated reduces Expensive
likelihood of transmis-
Minor bleeding: To 25% 1000 units-one infusion sion of HIV
Moderate bleeding: To 50% and maintain at 2000 U followed by repea-
25% with repeated infu- ted infusion of 1000 U for • Safe
sion for 2-3 days 2-3 days • Effective

Severe bleeding: To 100% and then main- 4000 U initially followed

tain the factor at above by 2000 U every 12 hour
50% continuously for
10-14 days

II. Desmopressin:
Acetate: Mechanism
Releases factor VIII: C
and raises its level two to
three-fold for several
hours
Indication Dose
• Mild haemophilics 0.3 microgram/kg every
• Useful in preparing for 24 hour
minor surgical proce-
dure

III. Ancillary Measures

Mechanism Indication Dose Contraindication
A. E p s i l o n - a m i n o - Transiently raises factor Minor haemorrhage in 4 gm p.o. every 4 hour • Aspirin
caproic acid VIII level mild haemophilics for several days 12 • Genitourinary blee-
B. DDAVP: hourly ding because of the
–Do– –Do–
risk of ureteral
occlusion

IV. Management of Inhibitors

IgG antibodies to factor VIII develo p in haemophilic patients treated with factor VIII concentrate. They
inhibit (called inhibitors) the efficacy of therapy by accelerating the clearance of infused factor:
Depletion of factor VIII due to inhibitors is measured by Bethesda unit (BU). Treatment depends on
severity of bleeding:
Life-threatening severe bleeding
Treatment of Pleural Disease: Effusion and Empyema

Less severe bleeding Minor bleeding

| 79

100 units/kg of porcine factor 100 U, IV bolus of human If Bethesda unit (BU) is less than
VIII, IV bolus followed by 4 U VIII followed by infusion of 5, then DDAVP 0.3 microgram/
per kg per hour IV 10 U per kg per hour kg IV given
If do not improve, 100-200 U
bolus of porcine factor VIII given
followed by infusion of 10 U/kg
per hour
If still no response, prothrombin
complex concentrates (PCC) at
100 units/kg IV 12 hourly
If still fails, plasmapheresis is done
followed by repeated infusion of
human or porcine factor VIII

TREATMENT OF HAEMOPHILIA B
I. Infusion of factor IX concentrate: Standard therapy:
Dose Comments
100 units/kg IV followed by 50 u/kg IV 24 hourly • Desmopressin acetate is not useful
• Inhibitors develop less frequently in haemophilia
B and are managed with prothrombin complex
concentrate
• Aspirin should be avoided

Treatment of von Willebrand’s Disease

Aim: To raise vWF: RCO and factor VIII to normal
I. Treatment according to clinical types:
Types Clinical and laboratory Management
features
Type 1 vWD: Quantitative • Minor bleeding • DDAVP: Releases stored vWF from endothelial cell
decrease in vWD. 70-80% • vWF: Ag and vWF: RCO Dose: 0.3 microgram/kg 24 hourly
cases proportionately low • Patient undergoing minor surgical procedure can receive
• Moderate bleeding DDAVP 1 hour before surgery and 12-24 hourly for 2-3 days
Type 2 vWD: Qualitative
• VIII: C normal postoperatively
deficiency in vWD
• vWF: RCO decreased out
Some patients benefit with DDAVP
Type 3 vWD: Severe of proportion to vWF: Ag
quantitative deficiency of • Major bleeding • DDAVP not useful
vWD • Level of vWF: Ag absent • For extensive surgery: Plasma products infusion 8-12 hourly
to raise vWF: RCO level to 100% initially and then above 50%
for 5-10 days
80 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

II. Factor VIII concentrate:

Indicated in patients who require factor VIII. Factor VIII concentrate also contains functional vWF and
do not transmit HIV or hepatitis.
Dose: 20-50 U/kg depending upon the severity of disease.

INFECTIOUS DISEASES
Antimicrobial Therapy
Penicillins
Classification and antimicrobial activity
Natural Penicillin Extended spect- Penicillin combi- Anti-pseudomo- Penicillinase-
rum penicillin ned with beta nas resistant penici-
lactum inhibitor llin

Penicillin G Parenteral Oral • Ampicillin Augmentine • Carboxy-peni- (Anti-staphylo-

• Aqueous Phenoxymethyl • Amoxicillin (Amoxicillin + cillin: carbeni- coccal)
crystalline penicillin (Peni- Gram–bacilli Clavulanic acid) cillin, ticarcillin • Methicillin
• Procaine cillin V) (notably entero- • S. aureus Ureidopenicillin: • Nafcillin
• Benzathine bacteria and • H. influenzae Aziocillin, mezlo- • Cloxacillin
Spectrum of Gram + bacilli haemophilus). • Bacteroides cillin, piperacillin • Dicloxacillin
activity: Gram-negative Gram + cocci. fragilis Pseudomonas • Oxacillin
cocci Destroyed by Other gram– Staphylococcus,
Spirochaetes staphylococcal bacteria other gram+ cocci
Actinomyces beta-lactamases
Anaerobes L.
monocystogenes

Mode of Action and Resistance

Bactericidal by inhibition of cell. Inactivated by beta lactamase and pencillanase
Preparation, dose and clinical uses and adverse effects
Preparation Dose and clinical uses Adverse effects
Aqueous penicillin G a. 5-10 lac U/24 hr IM/IV in divi- a. Allergy:
ded doses specially in pneumo- • Anaphylaxis (rare)
cocci, streptococci, non-beta- • Serum sickness (urticaria,
lactamase producer staphylo- fever, joint swelling, angio-
coccus, actinomycosis neurotic oedema 7-12 days
b. For severe life-threatening after exposure)
infection (meningitis, endo-
carditis) 18-24 million U by IV
infusion every 4-6 hr
a. Beta haemolytic streptococcal
Benzathine penicillin G pharyngitis: Single injection of b. Toxicity:
LA 12 • Excessive dose produces
seizure
contd...
contd.../
Treatment of Pleural Disease: Effusion and Empyema | 81

Preparation Dose and clinical uses Adverse effects

Penidure LA 6, 12, 24 lacs per vial b. Prophylaxis for rheumatic • Local pain and induration at
(Wayeth) fever: LA 12 or 24 IM every injection site
3-4 weeks
c. Syphilis: c. Haematological: Thrombo-
i. Early: LA 24 only once IM cytopenia, haemolytic anaemia,
ii. Latent: LA 24 IM once a platelet functional defect (car-
week for 3 weeks benicillin)
iii. Neurosyphilis: Aqueous d. Interstitial nephritis (methi-
penicillin G 12-24 million cillin)
U/day IV for 10-14 days
Penicillin V Mild respiratory tract infection, e. Pseudomembranous colitis
pharyngitis and skin and soft (extended spectrum penicillin)
tissue infection.
250-500 mg q.d.s. orally f. Hepatitis (oxacillin, nafcillin)
Ampicillin 250-500 mg 6 hourly, oral/injec- g. Bleeding (Ticarcillin)
tion
Amoxicillin 250-500 mg 8 hourly
Both ampicillin and amoxicillin
indicated in uncomplicated sinu-
sitis, pharyngitis, otitis media and
UTI, acute exacerbation of chro-
nic bronchitis, pneumonia, menin-
gitis and endocarditis
Cloxacillin Oral/Injection: 0.5-1 gm 6 hourly-
maintenance dose 250 mg
6 hourly in penicillin resistant
staphylococci.
Carbenicillin: Injection: 2 gm 4-6 hourly
Effective in pseudomonas.
Ticarcillin: Injection: 15-20 gm/day diluted
IV/IM 4-6 gm 6 hourly
Ureidopenicillins: Effective in pseudomonas. In
severe pseudomonas infection
with an aminoglycoside or a
quinolone
Also as empirical therapy in
febrile neutropenia
contd...
82 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Preparation Dose and clinical uses Adverse effect

Augmentine 250-500 mg t.d.s.
(Amoxicillin + clavulanic acid) 200-300 mg/kg/day in Pseudo-
monas
Effective in S. aureus, H. influen-
zae, and bacteroides fragilis which
produce beta-lactamase
Ampicillin + sulbactum IV 0.5-3 gm 6 hourly in Staph.
aureus, anaerobes, gram-negative
respiratory tract infection, genito-
urinary and soft tissue infection
Oxacillin 250-500 mg orally q.d.s. Staph.
Cloxacillin aureus
Nafcillin Serious systemic Staph. infection
2 gm IV 4-6 hourly

CEPHALOSPORINS
I. Antibacterial spectrum
Effective against
Ist generation:
Cephalexin • Gram+ cocci
Cephadroxil • Gram-negative bacteria
Cephradine (E. coli, K. pneumoniae,
Cephazolin P. mirabilis) and several
Cephalothin gram positive bacteria
Cephaprin including coagulase
positive and coagulase
negative strains
• Beta-lactamase stable
• Penicillinase producing
staph.
2nd generation: • Anaerobic cocci
Cefuroxime
• Same as 1st generation
Cefaclor
cephalosporin but exten-
Cefuroxime axetil
Cefamandole ded activity against
Gram-negative orga-
Cefonicid
nisms
Cefoxitin
Cefotetan • Indole + proteus and K.
pneumoniae
Ceforanide
• Moraxella catarrhalis,
neisseria
Ineffective against Clinical uses Advantages/Disadvantages
• Enterococci • RTI, UTI, bone and • Cephalexin, cephadroxil,
• Methicillin resistant joint, soft tissue and cephadrin orally effective
staph. biliary tract infection • Cephazoline less neph-
• Gram negative: P. aeru- • Due to poor CSF pene- rotoxic than cephalexin
genosa, enterobacter, H. tration not used in meni- but has to be given pare-
influenzae, Cytobacter, ngitis nterally.
B. fragilis, Indole + • Minor staph. infection
proteus • Cellulitis, abscess
• Parenteral cephalosporin
for surgical prophylaxis
Poor CSF penetration hence
P. aeruginosa, or entero- • Cefuroxime, cefuroxime not used in CNS infection,
cocci axetil, ceforanide, active but cefuroxime has good
against beta-lactamase penetration
producer H. influenzae,
hence used in sinusitis
and otitis media if not
responding to amoxy-
cillin but not against B.
fragilis
• Cefoxitin and cefotetan
active against B. fragilis
hence used in anaerobic
infection of peritonitis
and diverticulitis, but
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema | 83

Effective against Ineffective against Clinical uses Advantage/

Disadvantages
15% of B. fragilitis is
resistant to them hence
in severe infection
metronidazole + amino-
glycoside or 3rd gene-
ration cephalosporin
are used.
• Cefoxitin and cefo-
tetan used as surgical
prophylaxis in colo-
rectal surgery, vaginal
and abdominal hyste-
rectomy and appendi-
cectomy because of
their activity against
3rd generation: B. fragilis • Good penetration in CSF
Cefotaxime Listeria, enterococci (except cefoperazone)
Ceftizoxime • Meningitis due to good. • Ceftriaxone has once
Ceftriaxone • Gram +ve and negative penetration in CSF. In daily dose and hence
Ceftazidime organisms elderly add ampicillin more convenient.
Cefoperazone • Active against beta- Ceftazidime used in pse-
Cefsulodine lactamase producer udomonal meningitis.
organism • Enterobacter and cyto-
• Strep. pyogenes bacter sinusitis
• Extended gram-negative • Febrile neutropenic pati-
coverage. ent
• Haemophilus, • Ceftriaxone used in go-
Neisseria, providencia nococci, chancroid and
• Parenteral cephalosporin serious form of Lyme
against Pseudomonas, disease
Enterobacter, Morga-
4th generation: nella Febrile neutropenia (emp-
Cefepime irically)
Enterobacter, Cytobacter,
P. aeruginosa

DOSES AND SIDE-EFFECTS OF CEPHALOSPORINS

Side-effects
Allergy reaction Adverse effects Superinfection
• Hypersensitivity: Anaphylaxis, • Local pain after IM injection 3rd and 4th generation cephalo-
fever, skin rash, nephritis, hae- • Thrombophlebitis on IV injec- sporins have very low activity
molytic anaemia, patient allergic tion against Gram +ve organisms and
to penicillin should not receive • Long use of ceftriaxone causes super infection with these orga-
cephalosporin biliary sludging and gallstone nisms—as well as with fungi may
• GI tract side-effects occur specially pseudomemb-
ranous colitis
84

Dose
| Bedside Approach to Medical Therapeutics with Diagnostic Clues

1st generation a. Oral: • Cephalexin 250-500 mg 6 hourly

• Cephadroxil 1-2 gm 12 horuly
b. IV: • Cephradine 1-2 gm 4-6 hourly
• Cephazoline 0.5-2 gm 8 hourly
• Cephalothin 1-2 gm 4-6 hourly
• Cepharin 1-2 gm 4-6 hourly
c. IV/oral: • Cephradine 1-2 gm 4-6 hourly
2nd generation a. Oral: • Cefaclor 150-500 mg 8 hourly
• Cefuroxime 250 mg 12 hourly
b. IM/IV: • Cefonicid 1-2 gm 4-6 hourly
• Cefoxin 1-2 gm 4-8 hourly
• Cefotetan 1-3 gm 12 hourly
• Ceforanide 1-3 gm 12 hourly
c. IV: • Cefuroxime 0.7-1.5 gm 8 hourly
3rd generation a. IM/IV • Cefotaxime 102 gm 4-6 hourly
b. IV; • Ceftizoxime 1-2 gm 6-8 hourly
• Ceftriaxone 1-2 gm 12-24 hourly
• Ceftazidime 1-2 gm 8 hourly
• Cefoperazone 1-2 gm 8 hourly
• Cefsulodine 1-2 gm 8 hourly

Macrolides
Classification
1. Erythromycin group
2. Azalides:
• Azithromycin
• Clarithromycin
Antimicrobial activity Clinical Use Dose Adverse Effects
Sensitivity: Azalide used for strep. a. Erythromycin: Oral i. Oral dose: Nausea,
• Bacteriostatic pharyngitis, skin infec- 250-500 mg q.d.s. IV vomiting, diarrhoea,
• Gram + cocci: Pneumo- tion and acute exacerba- (erythromycin lacto- cholestatic jaundice
cocci, streptococci, tion of chronic bronchi- bionate) 250-500 mg ii. IV dose: Prolonga-
corynebacteria tis, canchroid, chlamydial every 6 hour tion of QT, torsade de
• Chlamydia infection, gonococcal b. Azithromycin: 500 pointes
• Mycoplasma infection, dysentery due mg/day for one day, iii. Large dose: (4 gm/
• Legionella to multiresistant Shigella. then 250 mg/day on day or more). Oto-
• Campylobacter Clarithromycin for H. days 2 to 5 toxicity particularly
• Bartonella pylori (with amoxicillin Single dose 1gm for with renal and
or metronidazole and chlamydial genital infec- hepatic dysfunction
omeprazole). Azalides tion and non-gonococcal
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema | 85

more acid resistant, urethritis.

penetrates tissue well than
erythromycin but more
expensive.
Prophylaxis:
i. Weekly 1200 mg for
preventing M. avium
in HIV
ii. 250 mg/day for
malaria
c. Clarithromycin: 250-
500 mg b.d. 500 mg
b.d. for 6 month for
disseminated M. che-
lonei.

ANTIVIRAL AGENTS
There are two ways to control viral infection: Drugs and vaccines
Drugs Viruses inhibited Dose Clinical uses Adverse effects
comments
Amantadine: Influenzal A Oral 200 mg/day Both prophylaxis and Insomnia, ataxia
during influenzal sea- therapy for influenza A
son for 6-8 weeks for
highly susceptible pati-
ents
Rimantadine: –Do– –Do– –Do– Less CNS side-effects
Analogue of amanta- but more expensive
dine than amantadine
Acyclovir Herpes simplex, Vari- i. Oral 400 mg t.d.s. • Herpes simplex Non-toxic
cella zoster for genital herpes • Varicella zoster
and prevents recu- • Herpes encephalitis
rrent Herpes labi- • Herpetic keratitis
alis • Herpetic whitlow
ii. IV 15 mg/kg/day • Herpes proctitis
in three divided (400 mg 5 times daily
doses for muco- for 10 days)
cutaneous Herpes • Erythema multiforme
simplex
IV 30 mg/kg/day
in three divided
dosage in Varicella
zoster and Herpes
encephalitis
iii. Topical 5% oint-
ment for Herpes
simplex
Ribavirin Respiratory syncytial
virus
contd...
86 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Viruses inhibited Dose Clinical uses Adverse effects

comments
• Lassa fever
• Hanta virus pneumo-
IV. Ribavirin
nia
Broad antiviral activity
Ganciclovir including CMV
HIV
Lamivudine Hepatitis B
Orally once daily
Antiviral, antitumour • Chronic hepatitis B,
(100 mg) for a year
Human interferons: and immunoregulatory C and D Influenza like fever
properties • Hairy cell leukaemia, arthralgia, myalgia
Kaposi’s sarcoma, Bone marrow suppres-
chronic myelogenous sion
leukaemia, multiple
myeloma, renal cell
carcinoma
• Relapsing multiple
sclerosis
• Leishmaniasis, toxo-
plasmosis, leprosy

ANTIVIRAL THERAPY (CONTINUED)

Drugs
Drugs used in HIV infection:
Zidovudine (AZT)
Zalcitabine (DDC)
Didanosine (DDI)
Dose Clinical uses Adverse effects
500-1500 mg/day HIV encephalopathy, Nausea, myalgia, anae-
myelopathy mia insomnia, head-
Better to use in combi- ache, neutropenia
nation to prevent drug
resistance
0.75 mg every 8 hour Advanced HIV infection • Painful peripheral neu-
May be combined with ropathy
200 mg of zidovudine • Pancreatitis
• Hepatic failure
• Lactic acidosis
• Stomatitis
• Skin rash
Adult: 200 mg b.d. Advanced HIV patients • Peripheral neuropathy
who do not respond or • Pancreatitis
cannot tolerate zidovu- • Retinal depigmentation
dine • Diarrhoea
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema | 87

Stavudine 40 mg b.d. Advanced HIV • Peripheral neuropathy

• Nausea, vomiting abdo-
minal pain
• Skin rash

CLINICAL APPROACH TO ANTIMICROBIAL THERAPY

First guess clinically based on organ involved, the organisms causing infection and empirical treatment
should be started especially in acutely ill patients after sending laboratory specimens for culture and
sensitivity:
Empirical therapy for acutely ill patients pending
identification of causative organisms

Suspected diagnosis based on organs Likely organisms Treatment of choice

involved
1. Meningitis, bacterial Pneumococci, meningococci i. Cefotaxime 2-3 gm IV 6 hourly
(ceftriaxone, ceftazidime, cefti-
zoxime can be used)
or
ii. Ceftriaxone 2 gm IV 12 hourly +
vancomycin 10 mg/kg every 8 hours
2. Bacterial meningitis in above age Pneumococci, meningococci, listeria i. Ampicillin 2 gm IV every 4 hours,
50 year monocytogenes, gram-negative bacilli plus cefotaxime or ceftriaxone and
vancomycin as in 1
ii. TPM-SMZ can be used to treat
Listeria monocytogene in patients
allergic to penicillin
3. Brain abscess Mixed aerobes, pneumococci, strepto- i. Penicillin G, 4 million IV every
cocci 4 hours
or
ii. Metronidazole 500 mg IV every 8
hours plus cefotaxime or ceftriaxone
as in i
4. Acute pneumonia, severe, com- Pneumococcus, M. pneumoniae, legio- i. Erythromycin (other macrolides
munity acquired nella, C. pneumoniae such as azithromycin or clarithro-
mycin can be used) 0.5 gm orally
or IV four times daily
or
ii. Doxycycline 100 mg IV or orally
12 hourly
5. Acute endocarditis S. aureus, E. faecalis, gram-negative Vancomycin 15 mg/kg every 12 hours
anaerobic bacteria, viridans, strepto- plus gentamicin, 2 mg every 8 hours
cocci
6. Osteomyelitis S. aureus i. Nafcillin, 2 gm IV every 4 hours
contd...
88 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Suspected diagnosis Likely organisms Treatment of choice

based on organs involved

ii. Orcefazolin 2 gm IV every 8 hours

7. Septic arthritis S. aureus, N. gonorrhoea Ceftriaxone 1-2 gm IV every 4 hours
8. Acute pyelonephritis (Recurrent E. coli, Klebsiella, Enterobacter, Pseu- i. Ciprofloxacin 400 mg IV every
UTI) domonas 12 hours
ii. Levofloxacin 500 mg IV once daily
9. Intra-abdominal sepsis (e.g. post- Gram-negative bacteria, bacteroides, i. Ampicillin 1-2 gm every 8 hours
operative, peritonitis, cholecystitis anaerobic bacteria, streptococci, clostri- or
dia ii. Gentamicin 2 mg/kg every 8 hours
plus metronidazole 500 mg IV
every 8 hours
or
iii. Piperacillin
10. Suspected sepsis in neutropenic S. aureus, pseudomonas, Klebsiella, i. Ceftazidime 2 gm IV every 8 hours
patient receiving cancer chemo- E. coli ii. Cefepime 2 gm IV every 8 hours
therapy

Suspected diagnosis Likely organisms Drug of choice Alternative drug

based on organs
involved
11. Erysipelas, impetigo, Group A streptococci
cellulitis
12. Furuncle with surroun- Staph. aureus
ding cellulitis
13. Otitis media
14. Acute sinusitis
Strep. pneumoniae, H. influ-
enzae, Moraxella catarrhalis
ii. TMP-SMZ
S. pneumoniae, H. influenzae, i. Amoxicillin 0.5 gm
M. catarrhalis
Phenoxymethyl penicillin, i. Erythromycin 0.5 gm
9.5 gm orally 4 times daily orally 4 times daily
or
ii. Cephalexin 0.5 gm orally
4 times daily for 7-10
days
or
iii. Azithromycin 500 mg on
day 1, 250 mg on days
2-5.
Dicloxacillin 0.5 gm orally
4 times daily for 7-10 days Cephalexin 0.5 gm orally 4
times daily for 7-10 days
i. Amoxicillin 0.5 gm
orally 3 times daily i. Augmentin 0.5 3 times
or day
(double ii. Cefuroxime 0.5 gm
strength) b.d. for 10 days orally b.d.
or
iii. Doxycycline 100 mg b.d.
orally 3 times daily
or –Do–
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema | 89

Suspected diagnosis Likely organisms Drug of choice Alternative drug

based on organs
involved
ii. TPM-SMZ (double
strength) b.d. for 10
15. Aspiration pneumonia Mixed oropharyngeal flora Clindamycin, 0.3 gm orally Phenoxymethyl penicillin
including anaerobes 4 times daily for 10-14 days 0.5 gm orally 4 times daily for
10-14 days
16. Pneumonia S. pneumoniae, Mycoplasma i. Doxycycline 100 mg b.d. i. Amoxicillin 0.5 gm
pneumoniae, Legionella or 4 times a day
pneumoniae, Chlamydia pne- ii. Erythromycin 0.5 gm or
umoniae 4 times a day ii. Fluoroquinolone.
or
iii. Clarithromycin 0.5 gm Levofloxacin 500 mg/day,
b.d. for 10-14 days gatifloxacin 400 mg per day,
or sparfloxacin 400 mg on day
iv. Azithromycin 0.5 gm on 1, and then 200 mg once daily
day 1, 0.25 gm on days
2-5
17. Cystitis E. coli, Klebsiella, proteus, i. Fluoroquinolones i. TMP-SMZ (double
Staph. saprophyticus ii. Nitrofurantoin strength) b.d. for 3 days
or
ii. Cephalexin 0.5 gm orally
4 times daily for 7 days
18. Pyelonephritis E. coli, K. pneumoniae, pro- Fluoroquinolones: TMP-SMZ (double strength
teus, Staph. saprophyticus • Ciprofloxacin 500 mg orally tab) b.d.
b.d.
or
Ofloxacin 400 mg
b.d. orally
or
Levofloxacin 500 mg/day
or
Sparfloxacin 500 mg
loading dose and then
200 mg/day
19. Gastroenteritis Salmonella, Shigella, Cam- i. For Salmonella: Do not
pylobacter, E. histolytica need treatment
ii. Shigella: TPM-SMZ
(double strength) b.d. for
5 days
or
Ampicillin 0.5 gm
4 times daily for 5 days
or
contd...
90 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Suspected diagnosis Likely organisms Drug of choice Alternative drug

based on organs
involved
Ciprofloxacin 500 mg
b.d. × 5 days
iii. Campylobacter: Ery-
thromycin 0.5 gm orally
4 times daily for 5 days.
or
Ciprofloxacin
iv. E. Histolytica: Metro-
nidazole 750 mg orally
t.d.s. for 5-10 days follo-
wed by diiodohydroxy-
quin 600 mg t.d.s. for
3 weeks
20. Urethritis, epididymitis: N. gonorrhoeae, Chlamydia
i. Cefixime 400 mg orally Ceftriaxone 250 mg IM once
trachomatis
once + doxycycline 100 mg b.d. for
Or 10 days for N. gonorrhoeae
Ciprofloxacin 500 mg
orally once
ii. N. gonorrhoeae: Doxy-
cycline 100 mg b.d. for
10 days
iii. C. trachomatis: Oflo-
xacin 300 mg orally b.d.
for 10 days
21. Pelvic inflammatory N. gonorrhoeae, C. tracho-
i. Ceftriaxone 250 mg IM Cefoxitin 2 gm IM with pro-
disease matis, anerobes, gram-nega-
once followed by doxy- benecid, 1 gm orally, follo-
tive rods
cycline 100 mg orally wed by doxycycline 100 mg
b.d. for 14 days orally b.d. for 14 days.
22. Syphilis:
a. Early syphilis (Pri- Treponema pallidum
Benzathine penicillin G, 2.4 Doxycycline 100 mg b.d. for
mary, secondary or
million units IM once 2 weeks
latent of less than
1 year duration)
b. Latent syphilis of –Do–
Benzathine penicillin G, 2.4 Doxycycline 100 mg orally
more than 1 year
million units IM once a week b.d. for 4 weeks
duration or cardio-
for 3 weeks (total: 7.2 million
vascular syphilis)
units)
c. Neurosyphilis –Do–
Aqueous penicillin G, 12-24 Procaine penicillin G, 2-4
million units/day IV for 10- million units/day IM plus
24 days probenecid 500 mg orally
4 times daily both for 10-14
⇓ days.
contd...
 Treatment of Pleural Disease: Effusion and Empyema

Next, find out the proved microbial pathogens and modify the treatment accordingly:
| 91

Specific treatment of proved microbial pathogens:

Proved microbial pathogens Drugs of first choice Alternative drugs

Gram-positive:
a. Cocci
i. Streptococcus pneumoniae Parenteral penicillin Erythromycin, cephalosporin,
(Pneumococcus) vancomycin, TMP-SMZ, clinda-
mycin, azithromycin, clarithro-
mycin, tetracycline, imipenem,
fluoroquinolones
ii. Strep. haemolyticus A, B, C, Parenteral penicillin Erythromycin, cephalosporin,
G vancomycin, clindamycin,
azithromycin, clarithromycin
iii. Streptococcus viridans Penicillin ± gentamicin Cephalosporin, vancomycin
iv. Staphylococcus:
a. Methicillin resistant Vancomycin ± gentamicin ± TMP-SMZ, minocyclin, fluoro-
rifampin quinolone
b. Non-penicillinase produ- Parenteral penicillin Cephalosporin, vancomycin, imi-
cing penem, fluoroquinolone, clinda-
mycin
c. Penicillinase producing Parenteral nafcillin, cloxacillin Vancomycin, cephalosporin, clin-
damycin, amoxicillin + clavulanic
acid, ampicillin + sulbactam,
imipenem, fluoroquinolone,
TPM-SMZ
Vancomycin
v. Enterococcus Ampicillin
Severe enterococcal infection Ampicillin + gentamicin Vancomycin + gentamicin

b. Gram-positive rods:
• Tetracycline
i. Actinomyces Penicillin
• Clindamycin
Erythromycin, tetracycline,
ii. Anthrax Penicillin
fluoroquinolone
Metronidazole, chloramphenicol,
iii. Clostridium (gas gangrene, Penicillin
clindamycin, imipenem,
tetanus)
Penicillin
iv. C. diphtheriae Erythromycin
TPM-SMZ
v. Listeria Ampicillin + aminoglycoside

contd...
92 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Proved microbial pathogens Drugs of first choice Alternative drugs

Gram-negative:
a. Cocci:
Cefuroxime, ceftriaxone, erythro-
i. Moraxella catarrhalis TPM-SMZ
mycin, tetracycline, azithromycin,
amoxicillin + clavulanic acid,
clarithromycin, fluoroquinolones
ii. N. gonorrhoeae Cefixime, ciprofloxacin, oflo- Ceftriaxone, spectinomycin
xacin
iii. N. meningitidis Penicillin Cefotaxime, ceftriaxone, ampi-
cillin, chloramphenicol
b. Gram-negative rods
i. Acinetobacter Imipenem Minocycline, TPM-SMZ, doxy-
cyclic aminoglycoside, fluoroqui-
nolone
ii. Bacteroids (gastro-intestinal Metronidazole Chloramphenicol, clindamycin,
strains) cefmetazole, ampicillin + sul-
bactum
iii. Brucella Tetracycline + gentamicin
TMP-SMZ ± Gentamicin,
chloramphenicol ± gentamicin,
doxycycline + rifampin
iv. Campylobacter jejuni Fluoroquinolone
Tetracycline, erythromycin,
azithromycin
v. Enterobacter TPM-SMZ, imipenem
Aminoglycoside, fluoroquinolone
vi. E. coli (sepsis) Cefotaxime, cefuroxime
Imipenem, aminoglycoside, flu-
oroquinolone
vii. E.coli (uncomplicated UTI) Fluoroquinolone, nitrofurantoin
TPM-SMZ, oral cephalosporin
viii. Haemophilus (meningitis) Cefotaxime, ceftriaxone
Chloramphenicol
ix. Haemophilus (respiratory TPM-SMZ
infection, otitis) Ampicillin, amoxicillin, doxy-
cycline, azithromycin, clarithro-
mycin, cefotaxime, ampicillin +
clavulanate
x. H. pylori Amoxicillin + clarithromycin +
omeprazole Clarithromycin + omeprazole +
metronidazole + tetracycline
xi. Klebsiella Cephalosporin
TMP-SMZ, aminoglycoside, imi-
penem, fluoroquinolone
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema| 93

Improved microbial pathogens Drugs of first choice Alternative drugs

xii. Legionella (Pneumonia) Erythromycin or azithromycin or TPM-SMZ, doxycycline ±
clarithromycin, or ciprofloxacin rifampin
xiii. Proteus mirabilis Ampicillin Aminoglycoside, TPM-SMZ,
fluoroquinolone, cephalosporin
xiv. Proteus vulgaris Cefotaxime, ceftriaxone Aminoglycoside, imipenem,
TPM-SMZ, fluoroquinolone
xv. Pseudomonas
aeruginosa Aminoglycoside, antipseudo- Ceftazidime, ± aminoglycoside,
monal penicillin (Piperacillin, imipenem ± aminoglycoside,
ticarcillin) ciprofloxacin ± piperacillin, cipro-
floxacin ± ceftazidime
• Pseudomallei (melioi- Ceftazidime Chloramphenicol, tetracycline,
dosis) TPM-SMZ, amoxicillin + clavula-
nic acid, imipenem
• Mallei (glanders) Streptomycin + tetracycline Chloramphenicol + streptomycin
xvi. Salmonella Ceftriaxone, fluoroquinolone TPM-SMZ, ampicillin, chloram-
phenicol
xvii. Shigella Fluoroquinolone Ampicillin, TMP-SMZ, ceftria-
xone
xviii. Vibrio (cholera) Tetracycline TPM-SMZ, fluoroquinolone
xix. Yersinia pestis (plague, tula- Streptomycin ± tetracycline Chloramphenicol, TPM-SMZ
raemia)
Spirochaetes:
a. Borrelia burgdorferi (Lyme dis- Doxycycline Amoxicillin, ceftriaxone, penicil-
ease) lin
Borrelia recurrentis (relapsing Tetracycline Penicillin
fever)
b. Leptospira Penicillin Tetracycline
Mycoplasmas Erythromycin, or tetracycline Clarithromycin, azithromycin,
Chlamydiae: fluoroquinolone
• C. psittaci (psittacosis) Tetracycline Chloramphenicol
• C. trachomatis (urethritis, pelvic Doxycycline, erythromycin Ofloxacin
inflammatory disease)
• C. pneumoniae Tetracycline Erythromycin, clarithromycin,
azithromycin, fluoroquinolone
Rickettsiae Tetracycline Chloramphenicol, fluoroquino-
lone
⇓
94 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

⇓
Find out other characteristics of antimicrobial therapy for devising rational treatment:
Characteristics Examples
A. Bacteriostatic or bactericidal drugs: In infective endocarditis and meningitis bactericidal drugs
Bactericidal antibiotics, such as penicil- are used.
lin, cephalosporins and aminoglyco-
sides, kill bacteria and bacteriostatic
drugs, such as macrolides and tetra-
cycline, merely inhibit their growth.
B. Broad spectrum and narrow spectrum Narrow spectrum drug, such as benzyl penicillin, should be
therapy: Broad spectrum drugs also used for pneumococcal pneumonia
encourage proliferation of resistant
species of gram-negative bacteria in the
gut—examples are ampicillin and
cephalosporin. Hence, narrow spectrum
drugs such as penicillin should be used
to treat specific infection
C. Patient’s condition:
In pregnancy certain antibiotics are Antimicrobial therapy in pregnancy
avoided. Dosage modification is needed Relatively safe drug Avoided in first tri- Avoided in all sta-
in impaired hepatic and renal function. • Cephalosporin mester ges pregnancy
• Erythromycin • Chloramphe • Aminoglyco-
• Ethambutol nicol side
• Metronidazole • Ethionamide • Amphotericin B
• Penicillin • Nalidixic acid • Chloroquine
• Rifampicin • Griseofulvin
• Isoniazid
• NFT
• Primaquine
• Quinine
• Tetracycline
• TMP-SMZ
• Vancomycin
Antimicrobial therapy in impaired renal function
Normal dose Modified dose Drugs avoided
• Chloramphenicol • Aminoglycoside • Cycloserine
• Cloxacillin • Ethambutol • Nalidixic acid
• Doxycycline • NFT
• Erythromycin • Tetracycline
• Rifampin • Vancomycin
• Amphotericin B
contd...
 Treatment of Pleural Disease: Effusion and Empyema

• Ampicillin
| 95

• Amoxicillin
• Penicillin
• Clindamycin
Antimicrobial therapy in impaired liver function
Use with caution Avoided
Clindamycin • Chloramphenicol
Fusidic acid • Erythromycin
TMP-SMZ estolate
• Rifampin
• Isoniazid if fast
acetylators
• Tetracycline
D. Duration of therapy:
Decided by type of infection, site of a. Type of infection: Bacterial infection can be cured rapidly
infection and immunocompetence of than fungal or microbacterial ones.
patients.
b. Site of infection: Endocarditis and osteomyelitis require
prolonged therapy.
c. Immunocompromised patients need prolonged therapy.

RESPIRATORY TRACT INFECTION

Upper Respiratory Tract Infection
Etiology Clinical Laboratory Treatment
investigations
Pharyngitis: a. Infectious: Viral • Fever, sore a. Indications for A. Therapy for GABHS:
and bacterial throat, dysphagia throat culture: • Penicillin V 250 mg p.o. q.d.s. or
(responsible for History of rheu- 500 mg p.o. b.d. for 10 days
rheumatic fever matic fever, symp- • Benzathine penicillin G, 1.2 mil-
and pyogenic tomatic patients lion units IM as single dose
complications (fever, pharyngeal • Penicillin allergy: Erythromycin
due to Group A exudate and cer- 250 mg p.o. q.i.d. for 10 days
beta-haemolytic vical adenopathy) or
streptococci- and failure to Azithromycin 500 mg/day for
GABHS) resolve with 3 days
b. Non-infectious: symptomatic • Cefuroxime for 5 days
Pemphigus, SLE therapy B. Therapy for non-GABHS:
Symptomatic measures: Analgesic,
b. Antigen detection
NSAID, benzocaine lozenges,
test for GABHS
saline gargle
Prophylaxis against GABHS:
Indications for prophylaxis:
• Patients at high-risk (children,
parents of young children, school
contd...
96 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

teachers, medical or military

personnel, patients living in
crowded living condition
• Those who have had rheumatic
fever within last 5 years
Prophylactic regimens
Benzathine penicillin G, 1.2 million
units IM every 4 weeks (regimen of
choice)
or
Penicillin V, 125-250 mg p.o. b.i.d.
or
Sulfadiazine, 1g p.o. q.d. (for adults
with normal renal function)
or
Erythromycin 250 mg p.o. b.i.d. indefi-
a. Lateral soft tissue nitely for those at high-risk.
Epiglottitis H. influenzae Fever X-ray of neck to a. Ampicillin sensitive: Ampicillin
(Severe sore throat assess airway b. Ampicillin resistant:
dysphagia) obstruction Ceftriaxone (1-2 gm IV/day)
b. Throat and blood Cefotaxime (1-2 gm 6-8 hourly)
culture or
Cefuroxime (0.75-1 gm IV 8 hourly)

Acute sinusitis • S. pneumoniae Cough, purulent a. Antimicrobial treatment: Amoxi-

• H. influenzae postnasal discharge, cillin/ clavulanate for 10 days
• Rhinovirus fever in 50% cases, or
• Aerobes pain over affected TMP/SMX one double strength tab
sinus b.d.
or
Cefuroxime axetil
b. Adjunctive measures: Topical decon-
gestants (phenylephrine or oxymeta-
zoline) only for 3-5 days; nasal
irrigation with saline spray

Chronic sinusitis: S. pneumoniae, Nasal congestion, CT of sinus with • Antimicrobial therapy, nasal steroid
H. influenzae, obstruction, pain, bone window. Nasal spray, some chronic cases require
rhinovirus, S. pressure, postnasal endoscopy endoscopic surgery
aureus, C.dipthe- discharge, fatigue
riae, bacteroids

FLOW CHART FOR MANAGEMENT OF CHRONIC SINUSITIS

Medical Management
Antibiotics Adjunctive Measures
• Amoxicillin (500 mg t.d.s.) possibly with clavu- • Analgesic
lanate (125 mg t.d.s.) • Decongestants
 Or
Treatment of Pleural Disease: Effusion and Empyema

• Nasal steroid spray

| 97

TMP/SMZ b.d. • Saline nasal spray

Or
Cephalexin (250-500 mg p.o. q.d.s.)
Or
Cefuroxime (250 mg p.o. b.d.)
Or
Cefaclor (250 mg p.o. t.d.s.)
Or
Cefixime (400 mg p.o. daily)
Or
Quinolone: Ciprofloxacin (500 mg b.d.)
Levofloxacin
(500 mg/daily), Sparfloxacin (200 mg/day after
initial dose of 400 mg)
Or
Macrolides: Azithromycin (500 mg/day for 3 days)
Or
Clarithromycin (500 mg p.o. b.d. for 14 days) Resolves
Resolves, but recurs in a few weeks
Another course of medical therapy:
i. IV antibiotic
Or
ii. Extended antibiotic regimen for 3-4 weeks
Resolves
Does not resolve or recurs shortly
a. CT scan or MRI of sinuses confirming the diagnosis of sinusitis (soft tissue density without bone
destruction) or showing bone destruction (points to neoplasm) or identifying anatomic blockage of
osteomeatal complex (may help guide endoscopic sinus surgery) referred to otorhinolaryngologist.
b. Investigate for suspected underlying allergy and if found, treated by:
i. Environmental control
ii. Drugs
iii. Immunotherapy
c. Investigate for suspected immune deficiency by analysing immunoglobulins and, pre-and post-
pneumococcal titre and if found positive, treated by: Supplementary IVIG

LOWER RESPIRATORY TRACT INFECTION

Aetiology Clinical Laboratory investi- Treatment
gations
Acute bronchitis: • Usual causes: Viruses Acute productive cough • Symptomatic: Cough
such as corona virus, with or without fever, by dextromethorphan
rhinovirus, influenza symptoms of upper res- 15 mg p.o. 6 hourly;
or parainfluenza piratory tract infection for persistent cough
• Rare causes: Myco- erythromycin or
plasma pneumoniae, doxycycline used
contd...
98 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

chlamydia pneumo- • Antimicrobial is

niae and Bordetella controversial
pertussis • For pertussis: TMP/
SMX, ampicillin,
chloramphenicol
Acute exacerbation of a. H. influenzae, S. pne- Productive cough, dys- • Antimicrobial: TMP/
chronic bronchitis: umoniae pnoea SMX, doxycycline,
b. Precipitating factors: amoxicillin/clavu-
Smoking, air pollu- lanate, third genera-
tion, viral infection, tion fluoroquinolone
allergy, occupational
exposure
Pneumonia: Fever, productive a. Chest X-ray: New See Flow chart
A. Community acqui- cough, dyspnoea, pulmonary infilt-
red: signs of pleurishy, rates, effusion and
consolidation and consolidation
crepts b. Sputum for gram-
stain and culture
c. Fiberoptic broncho-
scopy
d. Examination of pleu-
ral fluid
B. Hospital acquired • Gram-negative Occurs in hospitalised –Do– –Do–
or nosocomial pne- • S. aureus patient more than
umonia 48 hours after admis-
sion. Fever with or
without cough
C. Lung abscess: • Follows aspiration of Fever, weight loss, foul • Sputum culture a. A n t i m i c r o b i a l :
oropharyngeal con- smelling sputum points • Bronchoscopy if obs- Aqueous penicillin G
tent, extensive and to anaerobic infection truction or foreign 1.5-2 million units
dental diseases pre- body suspected IV 4 hourly
dispose, tuberculosis, • X-ray chest: Cavi- Or
cancer, fungal disease, tation, air filled Clindamycin
pneumonia, lymph- cavity, infiltrates b. Surgical: Resection
oma, septic emboli, pleural effusion, or percutaneous drai-
pulmonary embolism empyema nage of lung abscess
rarely required.
Indications for sur-
gery:
Bronchopleural fis-
tula, empyema, per-
sistent haemoptysis,
enlarged cavity

contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema | 99

c. Penicillin resistant
organisms:
Clindamycin (600
mg IV every 8 hours
until improvement,
then 300 mg orally
6 hourly or amoxi-
cillin-clavulanate
12 hourly

D. Empyema: Signs of effusion, fever, • X-ray chest: a. Antibiotics

weight loss • Pleural fluid: Pus- b. Large tube drainage
cells, pH less than c. Intrapleural throm-
7.3, glucose less than bolytic therapy: Stre-
40 mg often very low ptokinase 250,000
• WBC 25000-100000 units in 100 ml in
Poly high 0.9% saline daily via
RBC low chest tube may acce-
• LDH above lerate drainage
1000 U/L d. Surgery: Decorti-
cation, thoracoscopy
and open surgical
drainage may be
required.

PNEUMONIA
Introduction
Precipitating factors Prevention
Immunosuppression (diabetes, HIV infection, Pneumococcal vaccine
immunosuppressive drugs)
Coexisting diseases such as pulmonary, Pneumococcal vaccine
cardiac, renal and liver disease
IV drug abuse Pneumococcal vaccine
Aspiration of oropharyngeal contents (uncon- Head up position (30 degree) during nasogastric tube
scious patients, oesophageal obstruction) feeding, prevention feeding tube dislodgement,
suction, frequent position change, chest physio-
therapy. Removal of nasogastric and endotracheal
tubes early.
Alcohol, smoking Discontinuance of smoking and alcohol
Mechanical ventilation Disinfection of respiratory equipment should be
done between patients and change of respiratory
tube every 48 hours. Cleaning and drying nebulisers.
Legionellosis pneumoniae precipitated by: Turning off the equipments.
100 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

a. Contaminated cooling towers, airconditioners,

evaporative condensers, humidifiers
b. Potable water Raising the temperature of hot water to above
55 degree C or by hyperchlorination

Organisms: Aetiology
Antibiotic therapy is based on organisms involved and type of pneumonia. (Table 14.2)

Table 14.2: Types and organisms of pneumonia

I. Primary pneumonia (Community acquired)
Organisms: S. pneumoniae, S. aureus, M. pneumoniae, Legionellosis pneumoniae, H. influenzae,
Klebsiella, S. pyogenes, Coxiella, Chlamydia, Actinomyces, Viruses (measles,
varicella, cytomegalovirus)
Clinical types: Types of primary pneumonias:
a. Pneumococcal pneumonia
b. Mycoplasma pneumoniae (Primary atypical pneumonia)
c. Legionella pneumoniae
d. Staphylococcal aureus pneumoniae
e. Fungal pneumonia
II. Secondary pneumonia: (Weak host defence mechanisms or pre-existing abnormalities of respiratory system).
Organisms: Gram-negative organisms, Pneumocystis carinii, Mycobacterium avium—intracellular,
Cytomegalovirus, S. aureus, anaerobes, S. pneumoniae.
Clinical types:
a. Nosocomial (hospital acquired) pneumoniae
b. Aspiration pneumonia: Aspiration of infection from nasal sinuses, during dental extraction and due to
gastro-oesophageal reflux; common during sleep, general anaesthesia or following surgery.
c. Necrotising pneumonia: Common in elderly and immunocompromised male. Common organisms: Klebsiella,
Pseudomonas, staphylococci, anaerobes, fungi.
d. Acute bronchopneumonia: Common in extremes of ages, patchy widespread diffuse inflammation in X-ray.
e. Pneumocystis carinii: Common in HIV infected cases.

FLOW CHART FOR THE MANAGEMENT OF PNEUMONIA

Essential diagnostic clues and complications

Clinical Investigations Complications

Symptoms: a. Chest X-ray: Consolidation, patchy • Bacteremia
Fever or hypothermia, cough (dry or infiltration, pleural effusion, cavita- • Meningitis
productive), dyspnoea, chest discom- tion • Pericarditis
fort, sweats or rigor b. Gram stain and culture of sputum • Endocarditis
Signs: c. Culture of blood and pleural fluid • Lung abscess
Bronchial breathsound and crepts d. Serology: For HIV, Legionella,
(signs of consolidation) Mycoplasma pneumoniae, Chla-
mydia pneumoniae
 Treatment of Pleural Disease: Effusion and Empyema | 101

First start antimicrobial therapy as early as possible on empirical basis. Differentiate whether primary
community-acquired pneumonia (begins outside the hospital or is diagnosed within 48 hours after
admission to hospital) or hospital-acquired or Nosocomial pneumonia (occurs more than 48 hours after
admission to the hospital especially common in patients requiring intensive care and mechanical
ventilation) exist:
Empirical
Antibiotic therapy of community-acquired pneu-
monia:
A. Patients who do not need hospitalisation and B. Patients who can be treated in general medical
treated as outpatients. ward: Ceftriaxone or cefotaxime with or
1. Macrolides: Clarithromycin 500 mg p.o. without clarithromycin or azithromycin
b.d., or azithromycin 500 mg p.o. as a first Or
dose and then 250 mg/day for 4 days Levofloxacin or gatifloxacin
2. Doxycycline 100 mg b.d. C. Patients who need intensive care:
3. Fluoroquinolones: Levofloxacin 500 mg/ Erythromycin, azithromycin or levofloxacin
day, gatifloxacin 400 mg/day or moxiflo- with ceftriaxone or cefotaxime
xacin 400 mg/day D. Other subsets of patients:
4. Alternatives especially for suspected • Penicillin allergy: Levofloxacin or gati-
aspiration pneumonia: Amoxicillin- floxacin with or without clindamycin
potassium clavulanate 500 mg p.o. t.d.s. + • Suspected aspiration pneumonia: Levo-
second and third generation cephalo- floxacin or gatifloxacin plus clindamycin
sporins (cefuroxime axeteil 250-500 mg • Patients with pre-existing structural
p.o. b.d.) disease of lungs such as bronchiectasis or
Duration of treatment: cystic fibrosis: Antipseudomonal peni-
a. For S. pneumoniae: Therapy until the patient cillin, carbapenem, or cefepime plus a
is afebrile for at least for 72 hours macrolide
b. For M. pneumoniae, C. pneumoniae or Or
Legionella pneumoniae: A minimum 2 weeks Fluoroquinolone plus aminoglycoside
of therapy is needed. A 5 days of therapy is
usually sufficient if azithromycin is used.

Empirical Therapy of Hospital-Acquired Pneumonia

Differentiate two categories of patients:
Mild to moderate cases without unusual risk factors Severe, late cases needing mechanical ventilation
and early onset: and ICU
Second generation cephalosporin Antibiotics against most virulent organisms,
Or particularly P. aeruginosa, acinetobacter species
Nonantipseudomonal third generation cephalo- and enterobacter species:
sporin a. Aminoglycoside or fluoroquinolone + Anti-
Or pseudomonal penicillin or an antipseudo-
Combination of a beta-lactam and beta-lactamase monal cephalosporin or imipenem. Vanco-
inhibitor mycin is added if infection with methicillin
resistant S. aureus is present
102 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. For anaerobic infection: Clindamycin or beta-

lactam/beta-lactamase inhibitor combination
c. For legionella infection: A macrolide is added
to the above regimen
⇓
When culture and sensitivity is known, treat accordingly :
Organisms Clinical settings Antimicrobial therapy
Streptococcus pneumo- Chronic cardiovascular disease, Preferred Penicillin G or V, amoxicillin
niae: follows upper respiratory infection Or
Macrolides, cephalosporins, doxycycline, fluoroqui-
nolones, vancomycin
H. influenzae: – Do – Preferred: Cefotaxime, ceftriaxone or cefuroxime,
doxycycline
Or
Azithromycin, TMP-SMZ, fluoroquinolones
Staphylococcus aureus: Hospital-acquired, influenza epi- a. For methicillin sensitive strains:
demics, cystic fibrosis, bronchi- Preferred; Penicillinase resistant penicillin vancomycin
ectasis, injection drug users Or
Cephalosporins, clindamycin, fluoroquinolone, TMP/
SMZ, vancomycin
b. For methicillin resistant strains: Vancomycin with or
without gentamicin with or without rifampin
Klebsiella pneumoniae: Diabetes, alcohol abuse, noso- Preferred: Third generation cephalosporin. For severe
comial infection add an aminoglycoside
Or
Imipenem or beta lactam/beta lactamase inhibitor or
fluoroquinolone
E.coli Nosocomial Same as for Klebsiella pneumoniae
Pseudomonas aeruginosa: Nosocomial, cystic fibrosis, bron- Preferred: Antipseudomonal beta lactam + aminoglycoside
chiectasis Or
Ciprofloxacin + aminoglycoside

Anaerobes: Aspiration pneumonia, poor Preferred: Clindamycin, penicillin + metronidazole, beta

dental hygiene lactam/beta lactamase inhibitor
Mycoplasma pneumoniae: Young adult, summer skin rashes, Preferred : Erythromycin
bullous myringitis, haemolytic Or
anaemia, PMNs and no bacteria on Doxycycline, clarithromycin, azithromycin, fluoro-
Gram stain, extensive patchy quinolones
infiltrates in chest X-ray, comple-
ment fixation titre four-fold rise
Legionella species: Summer, exposure to water Preferred; Macrolide with or without rifampin, fluoro-
source, air conditioner, both quinolone
community acquired or noso- Or
comial. Few PMNs and no bac- TMP/SMZ or doxycycline with or without rifampin

contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema |
103

teria on Gram stain. Direct

immunofluorescent examina-
tion of sputum or tissue and
four-fold rise in immuno-
fluorescent titre
Chlamydia pseudomoniae Similar to Mycoplasma pneu- Preferred: Doxycycline
moniae. Heart failure Or
Erythromycin, clarithromycin, azithromycin or fluoro-
quinolone
AIDS, cancer, cytotoxic drug Preferred: TMP/SMZ or pentamidine isothionate +
Pneumocystis carinii: therapy, pneumothorax, respi- prednisone
ratory failure Or
Dapsone + trimethoprim or clindamycin + primaquine
Supportive Therapy:
a. Patient frequently dehydrated and needs dehydration therapy (5% dextrose with half normal saline).
b. Some patients require mechanical ventilation, intensive care and oxygen.
c. If patient is confused, do a LP to exclude meningitis.
d. Pleural effusion should be aspirated to exclude empyema needing chest tube drainage.
e. Adequate analgesia: Codeine, parenteral meperidine 50-100 mg every 3-6 hour, intercostal nerve
block to relieve pleuritic pain.
f. Cough suppressant.

PREVENTIVE THERAPY

Polyvalent pneumococcal vaccine Influenzal vaccine

Advantage:
It has the potential to prevent or lessen the severity
of pneumococcal infections in immunocompetent
patients.
Indications:
• Age above or equal to 65 years
• Any chronic illness that increases the risk of
community-acquired pneumonia
Regimen:
a. Immunocompromised patients : Should
receive a single revaccination 5 or more years
after the first vaccination
b. Immunocompetent persons: Aged 65 years or
older should receive a second dose of vaccine
if the patient received the vaccine 5 or more
years previously and was under 65 years old
at the time of vaccination.
Advantage:
Effective in preventing severe disease due to
influenza virus responsible for both primary
influenzal pneumonia and secondary bacterial
pneumonia
Indications:
• Administered annually to persons at risk for
complications of influenzal infection (age 65 years
older), patient with pulmonary and cardiovascular
disorders, patients recently hospitalised with
chronic metabolic disorders, residents of chronic
care facilities.
104 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

TREATMENT OF TUBERCULOSIS
Anti-Tuberculous Drugs
I. First Line Oral Drugs:

Dose Common side-effects Tests for side-effects Drug interactions Remarks

Isoniazid: Adult: 300 mg doub- Hepatitis with rifam- AST and ALT, neuro- Increases effect and Bactericidal. Pyri-
led in meningitis. picin; nausea, vomi- logical examination toxicity of phenytoin doxin 10 mg per day
Child: 6-10 mg/kg/ ting, epigastric pain, and carbamazepine. as prophylaxis for
day peripheral neuritis Steroid decreases neuritis; 50-100 mg/
Prophylaxis: INH level day as treatment
Adult: 300 mg/day for
6-12 months
Child: 5-10 mg/kg for
6 months

Rifampicin: 450-600 mg/day Hepatitis, fever, GI AST and ALT Inhibits the effect of Bactericidal
Child: 10-20 mg per disturbance, influenza oral contraceptive,
kg per day like symptoms, quinidine, steroid,
headache, urine and digoxin, oral hypogly-
tears reddish coloured cemic agents

Pyrazinamide: Adult: 20-35 mg/kg/ Hyperuricaemia, hepa- Uric acid, AST, ALT Affects control of dia- Bactericidal
day daily max. 3 gm totoxicity, anorexia, betes
Child: 15-30 mg per nausea, vomiting,
kg per day arthralgia, fever
Intermittent therapy: C/I Pregnancy
a. Under 50 kg 2 gm
thrice weekly or
3 gm twice weekly
b. Over 50 kg: 2.5 gm
thrice weekly or 3.5
gm twice weekly
Ethambutol: 15-25 mg/kg/day • Optic neuritis: Reve- Red-green colour Bactericidal
Intermittent therapy: rsed with disconti- discrimination and
50 mg/kg 2-3 times a nuance of drug; rare visual acuity
week at 15 mg/kg
• Rash

II. First Line Injectable Drugs

Streptomycin: 15 mg/kg 8th nerve damage, Vestibular function N e u r o m u s c u l a r Bactericidal use with
nephrotoxicity (audiogram), BUN, blocking agent and caution in elderly and
creatinine may cause paralysis those with renal dis-
ease
III. Second Line Antituberculous Drugs
Daily dose Common side-effects Monitoring Remarks

Ethionamide: 500-1000 mg p.o. (in GI disturbances, hepatitis Liver function tests Consider antiemetics or
divided doses if necessary bedtime dosing
for tolerance)

Cycloserine: 250-750 mg p.o. (in Neurological and psycho- Serum levels Give pyridoxin
divided doses). Adjust for logical disturbances
renal impairment
contd...
contd...
Treatment of Pleural Disease: Effusion and Empyema | 105

Daily dose Common side-effects Monitoring Remarks

Capreomycin 15 mg/kg IM 5 days a
week adjust for renal
Amikacin Kanamycin
impairment
Para-amino-salicylic 10-20 gm p.o. in divided
acid (PAS) doses
Hearing loss vestibular Audiogram, vestibular
damage, renal toxicity, examination, BUN, crea-
electrolyte disturbance tenine
GI intolerance, hepatitis, Liver function tests Prolonged use causes
hypersensitivity hypothyroidism. Consider
antacids or dosing at meal
time.
Cheap.

Ciprofloxacin 500-1000 mg q.d.s. for GI intolerance, headache, Avoid antacids, iron, zinc,
Ofloxacin: ciprofloxacin; Ofloxacin: restlessness, hypersensi- and sucralfate which dec-
400-800 mg q.d.s. p.o. tivity rease absorption

Clofazimine 100-300 mg q.d.s. p.o. Abdominal pain, skin dis- Consider dosing at meal
colouration, photosensi- time, avoid sunlight
tivity

List of drugs for multi-drug-resistant (MDR) TB

I. First line, if not used previously:
• Streptomycin
• Ethambutol
• Isoniazid
• Rifampicin
• Pyrazinamide
II. Second line drugs:
• Kanamycin
• Viomycin
• Capreomycin
• Amikacin
• Cycloserine
• Ethionamide
• Prothionamide
• Para-amino-salicylic acid (PAS)
Variation of dosages according to weight of the patient
Weight Dose (daily)
Rifampicin • Less than 50 kg 450 mg
• 50 kg or more 600 mg
Streptomycin • Less than 50 kg 750 mg
• 50 kg or more 1gm (750 mg if over 40 years of age)
Pyrazinamide • Less than 50 kg 1.5 gm
• 50 kg or more 2.0 gm
Ethionamide and • Less than 50 kg 750 mg
Prothionamide • 50 kg or more 1 gm
106 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Principles and scientific basis of chemotherapy

a. Frequency and number of drugs: At least three drugs should be used to reduce bacterial resistance.
Drugs can be given daily or intermittently (twice or thrice a week). All drugs except PAS and
thiocetazone inhibit M. tuberculosis growth for 3-4 days after a single dose. This is the principle
behind using anti-TB drugs intermittently. Most popular short-course treatment programmes consist
of two phases. An initial 2 months intensive phase of daily therapy includes isoniazid, rifampicin,
pyrazinamide and either streptomycin or ethambutol. After that a consolidation phase with isoniazid
+ rifampicin (or any other effective drug) should be given at least for 4 months, and preferably
6 months. But many clinicians recommend four drugs for 6 months in India due to high level of
primary resistance and where sputum culture is rarely performed.
b. Bactericidal versus bacteriostatic drugs: Tubercle bacilli occur in the patient in three pools:
Metabolically-active Relatively-inactive Necrotic caseous pool
extracellular pool intracellular pool
Rifampicin: Bactericidal (killer drug) Bactericidal Bactericidal
Isoniazid and strepto- Bactericidal
mycin:
Isoniazid and pyrazi- Bactericidal
namide:
Ethambutol is only bacterostatic.
c. Patient’s default in taking drugs is the major problem. Default causes treatment failure and also
produces drug resistance. Since most patients default occurs within the first 6 months, short course
therapy has been recommended. Directly observed therapy (DOT) is highly successful for non-
compliant (alcoholic) patients and prevent multi-drug-resistant tuberculosis.
d. Follow-up for improvement:
Period of drug therapy:
• Symptomatic improvement Occurs within 2-3 weeks of drug therapy
• Clearing of lung infiltrates on X-ray: Between 2nd and 4th months
• Sputum conversion: Within 2 months
e. Drug toxicity: If drug is discontinued promptly with the onset of jaundice, drug hepatitis can be
resolved without untoward incident. Pyridoxin prevents isoniazid neuropathy.
f. Drugs of pregnancy: Isoniazid and ethambutol are safe in pregnancy. Rifampicin should be used in
disseminated tuberculosis. Streptomycin should not be used because of foetal ototoxicity.
g. Drug resistance: In one-third of patients who relapse after adequate drug therapy, the relapse is
caused by drug-resistant organisms. Therapy of drug resistant tuberculosis should be instituted
with two drugs which the patient has not taken previously. When resistance studies become available,
the regimen should be modified appropriately. It is beneficial to continue isoniazid even when
laboratory studies indicate drug resistance.
Hemotherapeutic Regimens for Pulmonary Tuberculosis
|
Treatment of Pleural Disease: Effusion and Empyema 107

Daily Long-term Regimens

Initiation phase for 1-3 months Continuation phase for 12-18 months
Daily isoniazid + ethambutol or rifampicin or Isoniazid + ethambutol or rifampicin in developed
streptomycin or PAS or thiocetazone countries and PAS or thiocetazone in developing
countries

Disadvantages if Daily Long-Term Therapy

• Patient terminates treatment prematurely or takes irregularly
• The infection is drug resistant to start with
Not highly successful is revealed by controlled trial
To obviate the disadvantages of long-term daily regimen, two ways have been developed for impro-
ving patient’s compliance:
1. Intermittent supervised chemotherapy
2. Short course chemotherapy daily.

Intermittent Supervised Chemotherapy

Advantages: Regular treatment possible due to full supervision
Less chronic drug toxicity than long-term daily regimen
Cheaper than long-term daily regimen
Highly effective regimen as revealed by controlled clinical trial.
Regimen:
Initial daily regimen Continuation intermittent twice weekly regimen
a. For 3 months: a. For 18 months:
Streptomycin (less than 50 kg weight: 750 mg/ Isoniazid (15 mg/kg twice weekly)
day and 50 kg or more: 1gm/day) +
+ Streptomycin (1gm twice weekly)
Isoniazid (300 mg/day) Or
+ Isoniazid (300 mg biweekly)
Ethambutol (25 mg/kg for 2 months and then +
15 mg per kg for 1 month) Ethambutol (30 mg/kg twice a week or 25 mg/
Or kg thrice a week)
Streptomycin + Isoniazid + Thiocetazone b. For 12 months: Isoniazid (300 mg biweekly)
(150 mg/day) +
Or Rifampicin (600-900 mg twice weekly)
Streptomycin + Isoniazid + Rifampicin (Less than
50 kg: 450 mg/day and 50 kg or more:
600 mg/day)
Or
Streptomycin + Isoniazid + PAS (10-15 gm/day)
b. For 2 weeks:
Streptomycin + Isoniazid + Rifampicin
108 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Short Course Chemotherapy

Advantages:
• Rapidly reduces bacillary load and thus prevents relapse.
• Controlled clinical trials have revealed that isoniazid, rifampicin and pyrazinamide combined has
proved to be particularly effective in short course chemotherapy: Isoniazid kills rapidly multiplying
bacilli, rifampicin and pyrazinamide kill those bacilli relatively unaffected by other drugs,
streptomycin kills actively dividing bacilli and bacteriostatic drugs such as ethambutol and
thiocetazone probably help to prevent the emergence of drug resistance.
• Controlled clinical trials have revealed that the short course chemotherapy is highly effective for
patients even extensive disease with strains initially resistant to isoniazid and streptomycin.
• The short course is acceptible to patients without disturbing daily life much.
• Relapse if occurs, usually does so soon after the end of treatment and can be identified rapidly and
early and retreated successfully with the drugs of primary regimen.
Regimen:
Initial intensive phase Duration Continuation phase Duration
A. Daily regimen:
E + H + R daily 2 months H + R daily 9 months
Or
S + H + R daily 2 months H + R daily 9 months
Or
S + H + R + Z daily 2 months H + R daily 6 months
Or
S + H + R + Z daily 2 months
B. Intermittent regimen:
E+H+R+Z 3 times a week 6 months
Or for 6 months
S+H+R+Z 3 times a week for 6 months
Or 6 months
S+H+R+Z 3 times a week for H + R thrice a week 6 months
Or 2 months
S+R+Z 3 times a week for S + H + Z twice a week 8 months
4 months

Choice of Regimens
A. Choice of Regimens in Developed Countries
Medical services are plentiful bacillary resistance low and incidence of disease is low.
Regimens:
Usual regimen In alcoholics where self-medication is not reliable
Daily regimen of isoniazid and rifampicin for Fully supervised twice weekly regimen
9 months with ethambutol or streptomycin as Or
well for first 2 months Fully supervised short course intermittent regimen
 B. Choice of Regimen in Developing Countries
Treatment of Pleural Disease: Effusion and Empyema | 109

Usual regimen Urban areas where medical Rural areas

facilities better than rural areas
Daily isoniazid plus thioceta- Short course fully supervised Short course daily regimen
zone for 12 months or longer intermittent regimen
with up to 3 months of daily Or
streptomycin Isoniazid + ethambutol + rifam-
Or picin + pyrazinamide 3 times a
Isoniazid + rifampicin + pyra- week for 6 months
zinamide + ethambutol or strepto-
mycin daily for 2 months
followed by isoniazid + rifam-
picin daily for 6 months
C. Choice of Drugs in Special Circumstances
Pregnancy Renal failure
Streptomycin should never be given in any stage of • Drugs such as isoniazid, rifampicin, pyrazinamide,
pregnancy and should be withdrawn immediately if ethionamide and prothionamide are not excreted
pregnancy occurs during its administration because through kidney and hence should be given in
of foetal toxicity. normal dosage
No anti-TB drug is teratogenic and not at all if preg- Aminoglycosides and ethambutol are excreted by
•
nancy has advanced beyond 12 weeks kidney. Hence ethambutol (25 mg/kg 3 times a
week) and streptomycin (0.75 gm at long interval)
should be given in reduced dosage in renal
impairment.

CHEMOTHERAPY OF MULTI-DRUG-RESISTANT TUBERCULOSIS

Basic Principles and Guidelines
Drugs
i. First line drugs should be preferred.
ii. Previously unused drugs should be preferred.
iii. INH should be included in all regimens.
iv. Bactericidal drugs (INH, rifampicin, pyrazinamide, streptomycin) should be used.
v. Bacteriostatic drugs (ethambutol, capreomycin, vancomycin) should be avoided.
vi. Minimum four drugs and preferably six drugs should be used.
vii. Drugs should be administered in adequate dosages; adequate duration; adequate parenteral drugs
for 3-6 drugs and other for 24 months after sputum negatively.
viii. Cross resistant drugs should be avoided as they are not effective and increase toxicity.
Drug with one-day cross resistance;
Vancomycin and capreomycin
Vancomycin and kanamycin
Kanamycin and streptomycin
Thiocetazone and PAS (Thiocetazone used rarely now)
110 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

ix. Preferably their drugs should be given along with first-line drugs, if second-line or newer drugs are
prescribed, then at least 4 to 6 drugs should be given.
x. Addition of single drug in falling regimen is contraindicated.
xi. Retreatment regimens should be supervised.
xii. Intermittent regimens should be avoided.
xiii. If result of susceptibility tests are not available for two months or more, it is prudent to add several
new drugs.
xiv. Serum level of drugs may become necessary to optimise therapy and ensure bioavailability.

Hospitalisation
Patients require hospitalisation to monitor adverse drug reactions and drug initiation.

Surgery
Surgical intervention should be done early, if required, when disease is limited.

List of drugs for MDR-Drugs

First-line drugs if not used previously:
• Streptomycin (S) • Ethambutol (E)
• Isoniazid (H) • Rifampicin (R)
• Pyrazinamide (Z)
Second-line drugs:
• Rifampicin—rifampicin • Kanamycin (K)
derivatives—Rifabuti, Rifapentin
• Viomycin (V) • Capreomycin (C)
• Amikacin (A) • Cycloserine (CYCL)
• Ethionamide (ETH) • Prothionamide (PTH)
• Para-amino-salicylic acid (PAS) • Ciprofloxacin, ofloxacin, pefloxacin,
lomfloxacin, sparfloxacin
• Clofazinamine-sulphone derivatives • Macrolides-Roxithromycin,
clarithromycin, azithromycin.

Drugs and Doses for MDR-TB

Drug Dose mg/kg Daily adult dose Adverse effects
max. dose
Ofloxacin 8-10 400 mg b.i.d. Abdominal distress
Ciprofloxacin 15-20 750 mg b.i.d. Headache, anxiety
Sparfloxacin 8-10 400 mg b.i.d. Tremulousness
Kanamycin 15 0.75 gm-1gm Vestibular
Capreomycin 15 0.75-1gm Vestibular
Amikacin 15 0.75-1gm Auditory
Cycloserine 15 250 mg b.i.d. or t.i.d. Seizure, psychosis
contd...
Ethionamide 15
Treatment of Pleural Disease: Effusion and Empyema

250 mg b.i.d. or t.i.d.

| 111

Abdominal distress, diarrhoea

Prothionamide 15 250 mg b.i.d. Anorexia, metallic taste
Azithromycin 9-10 Gastrointestinal
Roxithromycin 9-10 Gastrointestinal
PAS 200 10-12 gm Gastrointestinal
Clarithromycin 15-16 Gastrointestinal
Rifabutin — 450 —
Clofazimine 4-5 100-200 GIT, skin

Suggested Regimens for MDR-TB

Resistance pattern Suggested Regimens Duration

H+R Z + E + Quinolone + Amino- 18-24 months
glycoside
H+S R + Z + E + Amikacin 6-9 months

H+E R + Z + Quinolone + Amino- 6-12 months

glycoside

H+R+Z E + Quinolone + Aminoglycoside 24 months after conversion

plus 2 of Ethionamide, Cyclo-
serine and PAS

H+R+Z+E
Quinolone + Aminoglycoside + – Do –
Ethionamide + Cycloserine + PAS

Key: H = Isoniazid; R = Rifampicin; Z = Pyrazinamide; E = Ethambutol; S = Streptomycin

SUMMARY OF DRUG REGIMENS FOR TUBERCULOSIS

I. Daily long-term regimen:
Isoniazid + Other companion drugs

Plus or Plus or Plus or Plus

R or S E PAS for Thiacetazone daily (T)
daily for for 12-18 12-18 months for 12-18 months
9-12 months months

Usual regimen Least toxic Least expensive

useful in developing
countries
112 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

II. Daily-intermittent (mixed) regimens:

Isoniazid + S Plus other companion drugs daily

Plus or Plus or Plus or Plus

E T R P
Daily for Daily for Daily for Daily for
3 months 3 months 2 weeks 3 months

Followed by twice weekly regimen: Isoniazid 15 mg/kg biweekly + Companion drugs

Plus or Plus or Plus

S E R
1gm twice 30 mg/kg 600-900 mg
weekly for biweekly for biweekly for
18 months 18 months 12 months

III. Short course regimen:

A. Daily regimen:
Isoniazid + R Plus other companion drugs

Plus or Plus or Plus

E S Z+S or E
Daily for Daily for Daily for
2 months 2 months 2 months most popular

Followed by Followed by Followed by

H+R daily H+R daily HH+R daily
for 9 months for 9 months for 6 months
B. Intermittent regimen:
Isoniazid + R + Z Plus other companion drugs

Plus or Plus or Plus or Plus

E S S S
3 times/week 3 times/week 3 times/week 3 times/week
for 6 months for 6 months for 2 months for 4 months

followed by H+R followed by S+H+Z

3 times/week for twice a week for
6 months 8 months
Ethambutol can be substituted for streptomycin with all combinations
Key: H = Isoniazid; R = Rifampicin; Z = Pyrazinamide; E = Ethambutol; S = Streptomycin
INFECTIVE ENDOCARDITIS
Treatment of Pleural Disease: Effusion and Empyema | 113

Clinical Approach to Treatment of Subacute and Acute Bacterial Endocarditis

Diagnostic clues

a. Fatigue, weight loss, low grade fever, nephritis, Laboratory findings

arthralgia and emboli (renal, splenic and a. Blood culture positive in 90% cases
cerebral infarct, petechiae, Osler’s nodes) b. Echocardiography: Vegetation, but normal
b. Presence of damaged heart valve, new or echocardiogram does not exclude the diagnosis
changing heart murmur of IE
c. Chest X-ray shows underlying cardiac abnor-
malities
⇓
Next, find out the type of infective endocarditis

Subacute bacterial endocarditis Prosthetic valve endo- Acute bacterial endo-

carditis carditis
a. Caused most often by streptococci. Strepto- caused by S.aureus, a. Most likely patho-
coccus bovis, group B and G streptococci is S.epidermidis, gram- genes: S.aureus
associated with lower GI disease, including negative and gram-negative
neoplasm bacilli.
b. For Strep. viridans: Regimen of choice: b. Empiric therapy
• Penicillin sensitive: Penicillin G IV Vancomycin for should be started
4 million units 6 hourly for 4 weeks 6 weeks pending culture
Or + report:
Penicillin G 2 million units IV 4 hourly + Rifampin 300 mg every
Aminoglycoside for 2 weeks only to 8 hour for 6 weeks Empiric therapy inclu-
prevent ototoxicity and nephrotoxicity des anti-staphylococcal
+
• Penicillin allergy: Vancomycin agents till culture
Gentamicin 1 mg/kg
c. Group A beta-haemolytic streptococci and every 8 hours for the reports are available:
S. pneumoniae: a. Ampicillin IV 2 gm
first 2 weeks
• Penicillin sensitive: 4 hourly
Penicillin G 2-4 million units +
IV 4 hourly for 4-6 weeks Nafcillin sodium IV
• Penicillin resistant: Ceftriaxone daily for 4- 2 gm 4 hourly
6 weeks +
d. Enterococcus species: Gentamicin IV 1 mg
• Ampicillin, 2 gm IV 4 hourly per kg 8 hourly
Or Or
Penicillin G, 3-5 million units I.V. 4 hourly b. Vancomycin IV
+ gentamicin for 4-6 weeks 30 mg/kg/day in
2 divided doses (for
contd...
114 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

• Penicillin allergic or with beta-lactamase- penicillin allergic

producing strains: Vancomycin + Amino- patients)
glycoside +
e. S. aureus: Gentamicin 1 mg/kg
• Penicillin sensitive: 8 hourly
Nafcillin sodium 2 gm IV 4 hourly + Gentamicin
for first 3-5 days
• Penicillin allergy: Cefazolin IV 2 gm 8 hourly
+ Gentamicin for first 3-5 days
• Penicillin and cephalosporin allergy: Vancomycin
IV 30 mg/kg/day in 2 divided doses
f. HACK organisms: Fastidious slow growing gram-
negative bacteria (Haemophilus, Actinobacillus,
cardiobacterium, Eikenella, Kingella species)
• Penicillin sensitive: Ampicillin IV 2 gm 4 hourly
+
Gentamicin 1 mg/kg 8 hourly
• Penicillin allergy: Ceftriaxone 2 gm OD IV/IM
g. Enterobacteriacae: Cefotaxime IV 8 gm/day in
4 divided doses
h. Pseudomonas aeruginosa: Piperacillin IV 18 g/day
in 6 divided doses
Or
Ceftazidime IV 6 gm/day in 3 divided doses
i. Fungal infection: Amphotericin B IV 1 mg/kg per
day
j. When IE suspected but routine culture are negative:
Penicillin G, 2-3 million units IV 4 hourly or
ampicillin 2 gm IV 4 hourly + aminoglycoside for
4-6 weeks

⇓
Surgery
Indications for urgent cardiac surgery

Cardiac complications Antimicrobial refractory IE

• Refractory heart failure
• An unstable prosthetic valve
• Prosthetic valve obstruction
• Systemic emboli which is recurrent
• Mycotic aneurysm, persistent conduction
defect, chordae tendinae or papillary muscle
rupture
• Fungal endocarditis refractory to medical
therapy
• IE due to refractory gram-negative bacilli
• Uncontrolled infection as manifested by
sustained bacteremia

Indications
a. High-risk patients: Patients
with prosthetic cardiac
valves, history of IE or comp-
lex cynotic heart disease
b. Moderate-risk patients:
Congenital cardiac malfor-
mations, rheumatic valvular
disease, hypertrophic cardiac
myopathy, mitral valve pro-
lapse with valvular regur-
gitation or thickened leaflets
Clinical Situations
I. Prophylaxis for dental, oral, respiratory tract or oesophageal procedures:
a. Standard prophylaxis:
b. Unable to take orally:
c. Penicillin allergy:
d. Penicillin allergy and
unable to take orally:
II. Prophylaxis for GI and genitourinary procedures:
a. High-risk patients:
i. Without penicillin allergy:
ii. Penicillin allergy:
b. Moderate risk patients:
i. Without penicillin allergy:
ii. Penicillin allergy:
Prophylaxis
|
Treatment of Pleural Disease: Effusion and Empyema 115
⇓
Surgical procedures that Procedures which do not
warrant prophylaxis warrant prophylaxis
a. Dental procedures: Dental a. Dental: Filling cavities
extraction, peridontal or b. Gastrointestinal: Routine
endodontal procedures, pro- endoscopy, trans-
fessional teeth cleaning oesophageal
b. GI procedure: oesophageal echocardiography
sclerotherapy, oesophageal c. Endotracheal intubation
stricture dilatation and d. Bronchoscopy
endoscopic retrograde cho- e. Caesarean section
langiography with biliary f. Cardiac catheterisation,
obstruction pacemaker transplantation
Prophylactic Drugs
Drug and Dosage
Amoxicillin 2 gm p.o. 1 hour before procedure
Ampicillin 2 gm IM/IV within 30 minutes before procedure
Clindamycin 600 mg p.o. 1 hour before procedure
Or
Cephalexin or cefadroxil 2 gm p.o. 1 hour before procedure
Or
Erythromycin p.o. 1 gm 2 hour prior to procedure and 0.5 gm
6 hour after first dose
Clindamycin 600 mg IV within 30 minutes before procedure
Or
Cefazolin 1 gm IV within 30 minutes before procedure
Ampicillin 2 gm IM/IV + Gentamicin 1.5 mg/kg (maximum
120 mg) within 30 minutes before procedure and 6 hour later,
ampicillin 1 gm IM/IV
Vancomy cin 1gm + Gentamicin 1.5 mg/kg (max. 120 mg) within
30 minutes before procedure
Amoxicillin 2 gm p.o. 1 hour before procedure
Or
Ampicillin 2 gm IM/IV within 30 minutes before procedure
Vancomycin 1 gm IV within 30 minutes before procedure
 Central Nervous System
15
Ischaemic Cerebrovascular
Diseases

Ischaemic cerebrovascular diseases include cerebral infarction, cerebral haemorrhage cerebral embolism
and TIA (transient ischaemic attack).

CAUSES
A. Cerebral infarction:
1. Cerebral thrombosis with or without atherosclerosis
2. Cerebral embolism due to:
• Congenital heart disease • Acquired valvular disease
• Cardiomyopathy • Myocardial infarct
• Endocarditis • Mitral valve prolapse
3. Cerebral venous thrombosis and cortical thrombophlebitis.
4. Aortitis due to syphilis, tuberculosis, rheumatic, Takayasu disease.
5. Bleeding disorders.
6. Dissecting aneurysm of bracheo-cephalic vessels.
B. Cerebral ischaemia:
1. TIA
2. Arterial hypotension
3. Cardiac arrhythmia
4. Rare causes: Oral contraceptives, disseminated intravascular clotting, cerebral malaria.
C. Cerebral haemorrhage: See chapter 16
Causes of stroke in young: Valvular lesion, mitral valve prolapse, arteritis, arterial anomalies.
Diagnostic clues:
Three clinical syndromes:
A. Cerebral thrombosis B. Intermediate syndrome: C. TIA (Transient ischaemic
Neurological deficit lasts more than Neurological deficit attack):
24 hours resulting from occlusion clearing in 1-3 weeks. Neurological deficit
of major vessels, minor vessels as clears in less than 24
in hypertension or in lacunar infarct. hours. See Table 15.1
See table 15.1 Stroke syndrome. “Stroke syndrome”.
 Table 15.1: Stroke syndrome
Ischaemic Cerebrovascular Diseases | 117

Due to cerebral thrombosis:

Artery occluded:
a. Anterior cerebral artery
b. Middle cerebral artery
Clinical features:
Sensory motor paralysis of opposite
lower limb—leg weaker than arm, in
continence, apraxia, and grasp and
sucking reflex present.
Contralateral hemiplegia. Arm weaker
than leg, hemianaesthesia.
Due to TIA:
a. Middle cerebral artery TIA: Dys-
phasia, weakness and numbness in
right hand.
b. Vertebro-basilar TIA:Ataxia,
slurred speech and diplopia.

c. Internal carotid artery Warning symptoms (brief-episode of

confusion, speech disturbance, sensory
paresthesia with or without motor
weakness, transient monocular blind-
ness) contralateral hemiplegia or
— sensory disturbance like middle.
— cerebral artery occlusion. Feeble.
— internal carotid pulsation, cervical
bruit.

d. Posterior cerebral artery Contralateral homonymous-hemiopia,

thalamic syndrome.

e. Vertebro-basilar artery Vertigo, diplopia, speech disturbances,

incoordination, bilateral sensory motor,
deficit, ipsilateral cranial nerve palsy
and contralateral hemiplegia.

Abnormalities
Fluid and electrolyte balance:
a. Cerebral oedema: Ischaemic tissue and
broken blood-brain barrier retains fluid
producing cerebral oedema.
b. Haemoconcentration, hyponatraemia and
acidosis damage neurons.
c. Hyperglycaemia increases lactic acid pro-
duction in ischaemic tissue.
Position:
a. Due to loss of cerebral autoregulation the
regional blood flow is reduced in head up
position.
b. Early contracture formation due to develop-
ment of abnormal tone producing internal
rotation of upper limb and flexion of wrist;
external rotation of lower limb and foot
drop.
Management
Judicious restriction of fluid intake (oral or paren-
teral) during 48-96 hours.
Must be corrected
Corrected with insulin
Head low or flat position is preferred.
Upper limb positioned with shoulder abducted and
externally rotated and a rolled washcloth in hand to
prevent flexion of fingers. Lower limb is positioned
by placing sandbags around the limb to prevent
external rotation of hip and use of footboard to
118 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

prevent footdrop.
Movement:
Hypostatic congestion causes bedsore. Frequent changing of position from side to side.
Prevents bedsore. Passive movement should be
started early.
Hyperviscosity:
Hyperviscosity reduces cerebral blood flow. Should be treated by isovolemic haemodilution for
72 hours to 5 to 7 days with help of low molecular
weight dextran or hydroxyethyl starch or 5%
albumin infusion.
Increased intracranial pressure and cerebral
oedema:
Resulting in neuronal damage. i. Head should be elevated by 30 degrees.
ii. Reduce high blood pressure (above 240/140)
by sodium nitroprusside or parenteral beta
blocker plus IV atropine and frusemide or
sublingual calcium channel blocker.
iii. IV mannitol. Contraindicated in incipient left
ventricular failure when pulmonary oedema
may be precipitated.
iv. IV dexamethasone may reduce cerebral
oedema but it is controversial.
Dysphagia:
Risk of aspiration due to dysphagia. Nutritional Safe diet is prescribed. Physiotherapist may teach
deficiency proper technique of swallowing.
Bowel and bladder movement:
a. Patient incontinent without retention a. External condom device advised.
b. Retention of urine b. Intermittent catheterisation.
c. Bowel movement c. Daily stool softener and alternate day use of
bisacodyl (dulcolax) suppositories.
Table 15.2: Specific drugs for stroke
Drugs Mechanism Dosages Remarks
Antiplatelet drugs:
a. Aspirin Antiplatelet aggregation 100-325 mg/day Gastric bleeding

b. Sulphinpyrazone or – Do – Not used

dipyridamole

c. Ticlopidine A theophyline derivative. 250 mg twice daily More than 30% reduction in stroke
Inhibits platelet aggrega- mortality as compared to aspirin.
tion, reduces plasma Equally beneficial to men and
fibrinogen women. Diabetic, hypertensive and
patients with high creatinine level
benefit more with ticlopidine than
contd...
Contd...
Ischaemic Cerebrovascular Diseases | 119

aspirin. Drug is expensive.

d. Clopidogrel 75 mg tab Clopidogrel 75 mg/day Toxicity: Reversible neutropenia
25% more risk reduction and diarrhoea.
than aspirin.

Anticoagulants: Prevents extension of a. Parenteral heparin: a. Its benefit in complete stroke

thrombus. IV bolus 100 U/kg is doubtful. Often dangerous.
followed by b. Recommended indications:
continuous • Recurrent TIA
infusion (1000 • Thrombosis-in-evolution
units per hour) for • Cardiac embolisation
24 hours. • Patient no responding to
b. Long-term antico- antiplatelet drugs
agulant coumarin • Patient not fit for carotid
sodium 2-5 mg/day surgery.
(controlled by pro- Exclude arterial haemorrhage by
thrombin time. CT scan and CSF examination.

Nimodipine Voltage dependent cal- Treated within 6-8 hours

cium channel blocker. (maximum 18 hrs) of
Cytoprotective action in ischaemic insult. Oral
ischaemic stroke. 120 mg/day monitoring
blood pressure as nimo-
dipine reduces blood
pressure.

LABORATORY INVESTIGATIONS
A. For TIA: CT scan, ultrasound Doppler flow study.
B. For embolism: To find out the sources of emboli: Ultrasonic Doppler for evaluating both extra and
intracranial vessels, ECHO for cardiac evaluation, X-ray chest, Holter monitoring for arrhythmias.
C. For cerebral thrombosis: CSF examination, X-ray skull, CT scan, MRI, isotope brain scan.

TREATMENT OF ISCHAEMIC CEREBROVASCULAR DISEASES

Treatment involves three stages:
1. Acute stage—Emergency measures.
2. Stage of rehabilitation—Physiotherapy employment.
3. Prevention of recurrence.

TREATMENT OF ACUTE STAGE

1. Temperature: Antibiotics for infection and analgesic such as paracetamol or analgin for
defervescence.
2. Pulse:
a. Premature beats: Diphenylhydantoin 100 mg b.d. or t.d.s.
b. Ventricular or atrial tachycardia: Lidocaine, beta blocker, disopyramide (norpace) and amidarone
(cardaronex).
c. Anticoagulants given to prevent further embolisation.
120 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

d. Bradyarrhythmia: May be responsible for increased intracranial pressure and—cerebral oedema.

Give parenteral frusemide or 100 ml bolus of mannitol.
3. Respiration and ventilation: Cerebral hypoxia predisposes to cerebral-oedema, raised intracranial
pressure and brain-herniation.
a. Keep the airway patent by preventing accidental aspiration and caring for pulmonary secretion
by aspiration by utmost sterile precaution.
b. Oxygen:
i. 4-6 litres per minute preferably through oxygen tent.
ii. Indications of ventilatory support: Oxygen less than 90% or raised PaCO2 or comatosed
patient with signs of cerebral hypoxia.
iii. Use of heat and moisture exchanger with hygroscopic properties + bacteria/viral filter near
face mask.
iv. Tracheostomy needed if long-term ventilatory support is desired.
4. Blood pressure:
Blood pressure should be maintained as the cerebral autoregulation is lost and cerebral blood flow
is solely dependent on mean blood pressure: Before embarking on anticoagulant therapy. High BP
treated sublingual or parenteral beta blocker with atropine and diuretic. Low BP treated by
vasopressor agents or by giving adequate fluid 300 ml of colloid infusion slowly over 2 to 4 hours.

Experimental Controversial Drugs

Naloxone: Opiate receptor antagonist without agonistic action. Limits neuronal injury by its calcium
channel blocking and antioxidant properties.
Prostacycline
Fish oil
IV glycerol. Reduces mortality by decreasing cerebral oedema.
Cytokine inhibitor.

Surgery
For cerebral thrombosis and embolism:

Type of surgery Indications Remarks

Thromboendarterectomy with or
without reconstructive vascular surgery
done a few hours or days after acute
ischaemic insult.
Extracranial to intracranial bypass
surgery.
Percutaneous angioplasty with stent.
Endovascular lesser technique to erode
the plaque.
i. Tight carotid stenosis up to 70 Early perfusion may convert a pale
to 90%. Result encouraging infarct into a haemorrhagic infarct.
ii. Moderately tight carotid stenosis
upto 30 to 60% or asymptomatic
cases with recent (within
20 days) hemispheric or TIA or
non-disabling strokes: Carotid
endarterectomy is under investi-
gation.
Recurrent symptoms related to distal
occlusion of either internal carotid or
middle cerebral artery.
Particularly useful in extracranial
stenosis of vertebral artery.
TIA
Ischaemic Cerebrovascular Diseases | 121

A. Evaluation of TIA by clinical examination and laboratory investigations.

B. Reducing risk factors: Treat hypertension if above 160/90 mmHg, stop smoking, treat coronary
artery disease, CCF and valvular disease, stop alcohol and oral contraceptives, treat hyperlipidaemia,
encourage physical activity.
C. Medical therapy:
a. Antiplatelet agents: Aspirin, sulphinpyrazone, aspirin + dipyradimole but no benefit from adding
dipyradimole to aspirin, ticlopidine in patients who cannot take aspirin due to side effects (dose:
250 mg/day) and who continued to have symptoms inspite of aspirin and clopidogrel (clopidogrel
75 mg/day).
b. Anticoagulants: Not particularly recommended.
Indications:
i. TIA with significant occlusive disease of vertebro-basilar vessels.
ii. Cardioembolic TIA specially with auricular fibrillation.
D. Surgical therapy:
Type of surgery: Carotid endarterectomy for extracranial disease:
Indications:
1. Severe carotid stenosis (above 70%)
2. Hemispheric TIA
3. Ulceration seen in angiogram
4. Repeated TIA in-spite of antiplatelet therapy even stenosis is only 30-60 per cent.

REHABILITATION OF HEMIPLEGIC PATIENTS

After stabilisation of neurological function for 12-24 hours proceed for rehabilitation as follows:
↓
Encourage the patient to sit up and then stand for increasing long period beginning with 5 to
10 minutes several times a day. Also start active and passive exercises of the weakened limbs. For
standing they need firm support by splinting and bracing of knees.
↓
Ambulation: Gait training started after the patient standing comfortably for 15 to 20 minutes without
fatigue. Parallel bars or walker may be needed at first. Foot may be braced to avoid foot drop.
↓
Encourage and retain the patient for activities of daily living such as dressing, undressing, eating and
personal hygiene. Marked recovery is gained usually in 3 to 4 months.
↓
Encourage the patient to speak if dysphasia present. Speech therapist may also help. Passive movement
must be continued indefinitely to prevent contracture.
For painful shoulder:
a. Passive movement
b. Heat
c. Subacromial steroid injection
d. Short course of systemic steroid
122 |
PROPHYLAXIS
Bedside Approach to Medical Therapeutics with Diagnostic Clues

A. Risk factors should be modified to reduce morbidity and mortality.See Table 15.3: Stroke Risk
Factors.
Table 15.3: Stroke risk factors
Lifestyle Diseases Drugs
Smoking a. Cardiac lesions: Hypertension Oral contraceptives
Alcohol Mitral valve lesion with or without auricular fibrillation
Sedentry habit Postmyocardial infarction
Obesity Infective endocarditis
Coronary artery disease
Mitral valve prolapse
Prosthetic valve with attached thrombi
b. Haematological abnormalities:
Increase or decreased Hb
Proteins C and S deficiency
Elevated fibrinogen
Lupus anticoagulants
Polycythaemia
Sickel cell anaemia
Thrombocythaemia
Hyperlipidaemia
c. Diabetes
d. Angiopathies:
Fibromuscular hyperplasia
Dissecting aneurysm
Collagen vascular disease
Giant cell arteritis
Meningovascular syphilis
Vasculitis with homocystinuria
e. Miscellaneous:
Manifest or occult cancer
Postoperative
Homocystinuria

B. Drugs: See above: Drugs for strokes

Antiplatelet drugs
Anticoagulants
C. Surgery: TIA with symptomatic carotid stenosis (70 to 99%), endarterectomy is currently advocated.

What is New in Stroke Therapy?

Short-Term Therapy in Acute Stroke Long-Term Therapy Following Acute Stroke
(Acute ischaemic stroke or TIA) (Secondary Prevention)
Aspirin 150 to 300 mg/day a. Aspirin: 75 to 150 mg/day
b. Alternative to aspirin:
i. Clopidogrel (more expensive)
ii. Clopidogrel + Aspirin
iii. Aspirin + Modified release dipyridamole.
Anticoagulant therapy:
Ischaemic Cerebrovascular Diseases | 123

i. No role in acute stroke because of intracranial Stroke associated with auricular fibrillation:
haemorrhage. i. Warfarin (risk of intracranial bleeding).
ii. Heparin (including low molecular weight ii. If contraindication to warfarin, aspirin should
heparin) does prevent deep vein thrombosis be used.
and fatal pulmonary embolism. In order to minimise cerebral haemorrhage, start
with aspirin until, for example, the majority of stroke
deficit has resolved or in the course of more severe
stroke, more than two weeks have elapsed, then
warfarin used.
Thrombolytic Therapy:
IV thrombolytics (streptokinase or urokinase or
recombinant tissue plasminogen activator (rtPA):
Patients making good recovery by 3 to 6 months,
but increase in cerebral haemorrhage within first
2 weeks. It should be used early (probably within
3 to 6 hours). It should be used in highly selected
patients in a carefully monitored environment.

Role of Carotid Surgery in Stroke:

Carotid endarterectomy has a role in preventing stroke in patients with recent (within 6 months) carotid
territory symptoms in association of severe stenosis of ipsilateral carotid artery, patient is fit for surgery
and patient with higher risk of further stroke (such as those with frequent TIA, cerebral rather ocular
symptoms, ulcerated rather than smooth stenosis) and performed as soon as possible after the initial
event by rapid access to duplex ultrasound, CT and angiography. Carotid angioplasty with or without
stent is a future possibility.
 Central Nervous System
16
Intracerebral Haemorrhage

COMMON CAUSES
Hypertension
Ruptured saccular aneurysm
Ruptured arteriovenous malformation
Bleeding disorders
Ruptured mycotic aneurysm.

DIAGNOSTIC CLUES
Clinical Manifestations
a. Headache, vomiting, nuchal rigidity without prodromal symptoms, followed by flaccid, are flexic
sensory-motor paralysis with lethargy or coma.
b. Common clinical syndromes:
• Putaminal haemorrhage: Haemipaeresis, slurred speech, drowsiness, coma, ipsilateral dilated
pupil and complete third nerve palsy.
• Thalamic haemorrhage: Hemiplegia, hemianaesthesia, eyes displaced downwards and medially
• Pontine haemorrhage: Very rapid coma, pupils miotic but reacting to light, quadriplegia.
• Cerebellar haemorrhage: Recurrent vomiting, truncal ataxia without haemiparesis, occipital
headache, vertigo, forced deviation of eyes to opposite side, bifacial weakness, stupor.

Laboratory Investigations
a. CT scan showing site and size of clot, hydrocephalus, oedema, tissue shift and ruptured blood into
ventricle.
b. MRI more reliable.
c. Arteriography excludes aneurysm, arteritis and angioma.
d. EEG and skull X-ray not very helpful.
e. Platelet count and coagulation studies should be done.

TREATMENT
1. General supportive measures: See treatment of ischaemic cerebrovascular accident.
2. Agents to minimise cerebral oedema resulting in decreased intracranial pressure specially in
supratentorial haematoma 3 cm or above in size or infratentorial haematoma 1 cm or above in size
on CT scan which can raise intracranial pressure to lethal level:
 Intracerebral Haemorrhage | 125

a. IV mannitol (1 gm/kg) 20% as initial bolus followed by 100 mg every 4 to 6 hours to raise the
serum osmolarity above 310 milli osmol per litre.
b. Oral glycerol.
c. Dexamethasone 4 mg IV or orally 4 to 6 hourly. This treatment is controversial.
d. Aminocaproic acid (20 gm IV 8 hourly) is gaining support.
3. Hypertension: Sudden dramatic lowering of blood pressure is harmful. BP above 190 mmHg should
be lowered by diuretics and beta blockers. IV calcium channel blocker or nitroprusside should be
used if haematoma is small. For rapid control of very high blood pressure should be done by
sublingual nifedipine or parenteral hydralazine (25 mg in every 2 to 4 hours).

Surgical Evacuation of Blood Clot

1. Surgical evacuation is not required if haematoma is less than 3 cm in diametre.
2. Surgical evacuation is helpful under the following circumstances:
a. Supratentorial haematoma larger than usual, situated in subcortical white matter without
hemiplegia or aphasia and showing signs of progressive deterioration of level of consciousness.
b. Evacuation of cerebellar clot is a lifesaving measure and gives excellent recovery and prevents
brainstem compression.
3. Contraindications of evacuation: Deeply comatosed moribund patient with deeply placed lesion.
 Central Nervous System
17
Subarachnoid Haemorrhage

FACTS YOU CAN USE FOR THE TREATMENT PURPOSE

Subarachnoid haemorrhage is usually due to bleeding from surface arteries of brain.
Important aetiological facts:
• Ruptured aneurysm: Congenital berry aneurysm (most common) mycotic aneurysm.
• AV malformation.
• Intracerebral haemorrhage with extension to subarachnoid space.
• Vasculitis.
• Infection (TB, syphilis and bacterial).
Incidence:
Eighty-five per cent of congenital cerebral aneurysm are found in the anterior half of the circle of Willis
rupture usually occurs at branches or bifurcation: Anterior communicating anterior junction in 29% and
posterior communicating internal carotid in 28% cases, middle cerebral bifurcation in 18%, intracranial
carotid bifurcation in 8% and vertebro-basilar bifurcation in 3% cases.

DIAGNOSTIC CLUES
Sudden excruating headache with or without vomiting and a brief period of unconsciousness followed
by lucid interval or a restless state with confusion, paucity of focal signs, normal blood pressure and
presence of nuchal rigidity. Occasionally, focal signs occur depending on the vessel involved:

Arteries involved Clinical features

a. Posterior communicating aneurysmal bleed Ipsilateral 3rd nerve palsy (most common)
b. Anterior communicating aneurysm rupture Transient weakness of legs with pyramidal
signs and akinetic mutism
c. Internal carotid and middle cerebral artery bleed Hemiplegia

LABORATORY INVESTIGATIONS
CSF Serial CT scan MRI scan Cerebral angiography
Raised pressure Within first 48 hrs scan can Better than CT scan Outlines aneurysm
and blood stained shows subarachnoid bleed and shows vasospasm or
and in 75% cases contrast subdural clot
CT shows aneurysm
TREATMENT
Subarachnoid Haemorrhage | 127

Position and activity: Absolute bed rest with head slightly elevated for 6 weeks is essential. Physical
strain such as coughing, sneezing or straining during defaecation must be avoided.
General medical and nursing care: See: Ischaemic cerebrovascular disease.
Blood pressure: Should be maintained to normal.
Headache and restlessness: Mild sedative such as phenobarbitone should be prescribed. Heavy sedation
should be avoided. Analgesic such as paracetamol should be prescribed for headache. Aspirin is
contraindicated.
Nausea and vomiting: Chlorpromazine not only sedates but also checks vomiting.
Convulsion: Prophylactic phenytoin may be prescribed.
Prevention and treatment of vasospasm: Nimodipine, a calcium channel blocker 0.7 mg/kg followed by
0.35 mg/kg every 4 hours for 24 days may be prescribed.
To augment cerebral blood flow: Hypervolemic therapy. See: Ischaemic cerebrovascular disease.
To prevent rebleeding: Gamaaminocaproic acid (inhibitor of fibrinolysis) or tranexamic acid 20 to
40 gm IV 8 hourly is beneficial as shown in a recent studies, but risk of cerebral infarction is predicted.

Surgery
A. Indications for urgent surgery:
• Accessible aneurysm should be operated as early as possible.
• A patient deteriorates from haematoma or hydrocephalus needs urgent surgery.
B. Contraindications to surgery:
• Inaccessible aneurysm
• Non-visualised aneurysm
• Other systemic disease present
• Defer surgery if severe vasospasm present
C. Types of surgery:
• Surgically placing a small clip or ligature across the neck of the aneurysm.
• If the aneurysm cannot be directly obliterated, surgical ligature of a proximal vessel reduces the
chance of rebleeding.

Prevention
a. Hypertension is not a significant risk factor. Aneurysms have been known to rupture after sudden
rise of blood pressure. After an episode of SAH blood pressure should be maintained normal.
b. Severe emotional excitement and severe physical exertion such as atheletic competition or coitus
should be avoided after an episode SAH.
c. Certain medical conditions (coarctation of aorta, polycystic disease of kidney, Marfan’s syndrome
and collagen vascular disease) should be attended to.
d. Septic emboli from subacute bacterial endocarditis is a risk factor.
e. Bleeding disorders are risk factors.
128 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

CLINICAL NOTES
Involvement of cranial nerves in aneurysmal rupture:
Most cranial nerve palsies result from bleeding and not from compression of the nerves by aneurysm.

Site of rupture of aneurysm Cranial nerve involved

• Rupture of aneurysm related
to posterior communicating artery
• Rupture of basilar artery aneurysm
• Rupture of ophthalmic artery aneurysm
• Rupture of carotid aneurysm in cavernous sinus
Ipsilateral 3rd nerve palsy (common)
Ipsilateral 3rd nerve palsy (less common)
Optic nerve palsy
3rd, 4th and 6th nerve palsy.

Sequalae of Aneurysmal Rupture

Bleeding in subarachnoid space, rarely haematoma is formed
↓
Raised intracranial pressure—papilloedema with coma may occur
↓
Cerebral vasospasm with arterial narrowing, often excessive, occurs with ischaemic cerebral infarction
↓
Late sequalae: Hydrocephalus
 Central Nervous System
18
Epilepsy and Seizures

FACTS YOU CAN USE FOR TREATMENT OF EPILEPSY

Precipitating Factors of Seizures
I. Disease: Hyperpyrexia, infection (encephalitis, meningitis, cerebral malaria, toxoplasmosis,
cysticercosis, AIDS), brain abscess, intracranial SOL, CVA, metabolic and electrolytic disturbances,
hyponatraemia, hypoglycaemia, hyperglycaemia, hypocalcaemia (less than 7 mg/dl), hepatic failure,
uremia, hypertensive encephalopathy, toxaemia of pregnancy.
II. Drugs: Isoniazid, chloroquine, strychnine, lead, alcohol, withdrawal of antiepileptic drugs.
III. Others: Emotional stress, physical and mental exhaustion sleep deprivation, visual stimulation
(flickering of light, television viewing), hot water, loud noise, music.

Aetiology of Epilepsy Depending on Age

Injury Congenital Metabolic Infection Toxin Others
abnormalities abnormalities
Newborn Birth trauma Microcephaly, Hypocalcaemia, Meningitis
infancy porencephaly phenylketonuria congenital
syphilis

Childhood Birth trauma Hydrocephalus Meningitis, Lead

Parasitic Carbon
infestation monoxide
Infection Toxic

Adolescence Head injury Idiopathic

(10-20 yr)

Young adults Head injury Neoplasm

(20-35 yr) idiopathic

Older patient Head injury Neoplasm

(36-65 yr) CVA
Alzheimer
130 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Classification of Seizures
Types Clinical Features EEG Findings
I. Partial (Focal or Local When only a part of the brain is involved at
Seizure: the onset producing localised seizure.
A. Simple partial seizure Consciousness preserved. Focal spikes or normal
a. With motor signs: Jerking of one hand or twitching of one half
of the face.
b. With sensory sym- Visual, olfactory, auditory or somato-
ptoms sensory.
c. With psychic sym- Dysphasia, hallucination, affective symp-
ptoms toms.
d. Autonomic sym-
ptoms
e. deja vu Feeling of familiarity in unfamiliar situation,
jamais vu Strangeness in a familiar situation.
f. Todd’s paralysis Reversible neurological deficit lasting less
than 48 hours following a partial seizure.

g. Jacksonian march Partial seizure that progresses in orderly

fashion that is from thumb to fingers to face
to leg.

B. Complex partial sei- Consciousness impaired. Shows spokes in the area

zures: Temporal lobe or where seizures originate
psychomotor seizure
a. With seizure follo-
wed by impaired
consciousness
b. With seizure prece-
eded by impaired
consciousness
c. With automatism Picking at clothes, fumbling with objects,
wringing hands, smacking lips or swallo-
wing.
C. Partial seizure evolving
into secondarily gene-
ralised seizures
II. Generalised Seizures: Seizure involved most of the brain at the
onset producing generalised seizure.
A. Non-convulsive: Sudden momentary lapses of consciousness Shows characteristic
i. Absences (Petit with rhythmic blinking and staring. Found three-per-second spikes
mal) in children. Lasts for less than 10 seconds and waves discharged
contd...
contd...
Epilepsy and Seizures | 131

ii. Atonic seizure Seen in children. Sudden loss of muscle Generalised polyspikes
(Akinetic, drop tone in the whole body resulting in a fall with or without followed
attack) or injury by sharp and slow waves
B. Convulsive:
i. Myoclonic seizures Rapid, recurrent jerks involving whole Generalised polyspikes,
body or sometimes only a limb spikes and waves

ii. Generalised tonic Sudden loss of consciousness with tonic
clonic seizure: extension of all four limbs and trunk,
(Grand mal) followed by synchronous clonic muscle
jerking. Incontinence of urine. Teeth
clinching and tongue biting
Interictal EEG shows gen-
eralised polyspikes or
spikes which may or may
not be followed by sharp
or slow waves.

DIAGNOSIS
First step: Whether patient has epilepsy or other types of seizure:

Seizure of epilepsy Differentiating features:

Seizures other than epilepsy:
a. Syncope
Occur in any position (lying down or standing); tongue biting,
incontinence of urine, injury; may occur even patient is alone;
postictal phenomena prominent; EEG changes during seizure
present; any age, nocturnal.
Loss of consciousness brief; precipitants: prolonged standing,
unpleasant sights, heat, hunger, crowded room; never occurs in lying
down.

b. Psychogenic seizure Tongue biting, incontinence of urine or injury absent; patient is never
alone during an episode; movements may be bilateral but
asynchronus with thrashing, or pelvic thrusting; a psychiatric history
is positive; postictal confusion absent.

c. Migraine Headache.

d. Panic attack Hyperventilation.

e. TIA Transitory loss of neurological function

Second step: Determine the type of epileptic seizure

See above “Classification” after observing the seizure or getting details from the attendant.
132 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Third Step: Investigations

Blood tests + CSF ECG EEG CT scan MRI
Haemogram, serum Indicated in arrhy- May be normal in Indicated in when MRI may detect
electrolytes, liver thmia, hereditary half of the patient progressive lesion is lesion missed by
function tests. Anti- history or sudden and in a fifth with suspected, seizure CT scan
epileptic drugs may death in the family refractary seizures. begins in adulthood.
alter their levels. It differentiate Diagnoses cyst-
CSF: Indicated if complex partial icercosis
intracranial infec- seizure from
tion is suspected. absences, non-
epileptic seizures
from epileptic
seizures and find
local abnormalities
⇓
Fourth Step: Determining underlying cause and precipitating factors:
See above “Precipitating factors of Seizure”
Take History
Physical Examination
Laboratory Investigations: EEG
CSF examination
Skull radiography
X-Ray of sinuses and mastoid
CT scan
MRI

Treatment
Goal: 1. To improve the quality-of-life.
2. To control seizure. Antiepileptic drugs are used. See Tables no. 18.1 and 18.2
Table 18.1: Antiepileptic drugs
Phenytoin Valproate
Usual form Dilantin (PD): Epilex (Reckit)
100 mg cap, suspension Epival (SUN):
25 mg/ml, injection 50 mg/ml 200 mg tab, syrup
eptoin (Knoll) 100 mg tab, 200 mg/5 ml
Fentoin-ER (Sun) 100 mg cap

Daily dose 100-300 mg/day Initial dose 600 mg in divided

child up to 6 years 5 mg/kg/day dosages, increased by 200 mg at
3 days interval till control.

contd...
contd...
Epilepsy and Seizures | 133

Phenytoin Valproate
Maintenance dose 300-500 mg/day 1000-2000 mg/day

Frequency of dosing Once or twice/day Twice or thrice daily

Indications All types of epilepsy except Petit Grand mal, Petit mal, myoclonic
mal, specially grand mal and
complex partial

Toxicity Cerebellar (ataxia, dysarthria, Anorexia, nausea, tremor

nystagmus), confusion to coma,
cuneiform movement

Idiosyncracy Skin rash, agranulocytosis, throm- Hepatic necrosis, thrombocyto-

bocytopenia, aplastic anaemia, penia, pancreatitis, hairloss
hepatitis

Side-effects Hirsutism, gingival hypertrophy Weight gain, platelet dysfunction

(minimised by careful dental
hygiene) coarsening of facial
feature, peripheral neuropathy

Contraindications AV block, acute intermittent Pre-existing hepatic disease

porphyria

Drug interaction a. Drugs elevating phenytoin a. Drugs decreasing ser. level of

level: Cemetidine, isonia- valproate: carbamazepine,
zid, diazepam, chlor- phenobarbital, phenytoin
promazine
b. Drugs lowering ser. phe-
nytoin level: Salicylate
Advantages Extremely effective in absent
a. Non-sedative
b. Relatively inexpensive
c. Parenteral also
d. Once a day dose
134 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Carbamazepine Phenobarbitone Ethosuximide Clonazepam

Usual form Mazetol (SPPL) Gardenal (Rhone- Zarontin (Park- Clonotril (Torrent-
Tab: 200, 400 poulenc) Tab 30, 60 davis) Lonazep) (Synergy)
Syrup: 100 mg/5 ml mg, Syr. 20 mg, Syrup: 50 mg/ml 0.5 mg, 2 mg
SR-TAB: 200, 400 Luminal 30 mg tab
Tagretol (Novar)
100, 200, 400 mg

Daily dose Start 200 × 2, 60-180 mg at night Child under 6 year: 1.5 mg/day, increa-
increased by 200 Amp IM/IV 50- 250 mg/day, over 6 sed by 0.5 mg at 3-
mg/day till 600- 200 mg for status year 500 mg/day 4 day interval till
1200 mg/day epilepticus. Child: increased by 250 seizure controlled
5-8 mg/kg mg every 4-7 days
Maintenance dose 600-1200 mg/day

Frequency dosing Twice a day Twice daily In 3 divided dosa-

ges
Indications Grand mal, All forms of epi- Absences (Petit) Absences, grand
complex partial lepsy except petit mal, atonic, temp-
simple partial mal oral lobe epilepsy,
myoclonic, infan-
tile spasm

Toxicity Diplopia, dizziness, Ataxia Drowsiness, ano- Drowsiness, ataxia

drowsiness, ataxia, rexia, nausea, vomi-
tremor, arrhythmia ting

Idiosyncracy Bone marrow dep- Rash, hairloss,

ression in some leukopenia

Side-effect Rash, haematuria Disabling sedation,

impairment of intel-
lectual function,
folic acid defi-
ciency

Contraindications AV conduction Acute intermittent Respiratory depres-

defect, porphyria porphyria sion

Drug-interactions Drugs decreasing Drugs elevating

level of carbamaze- level of phenobarbi-
pine: phenobarbi- tone: Phenytoin,
contd...
contd...
Epilepsy and Seizures | 135

Carbamazepine Phenobarbitone Ethosuximide Clonazepam

tone, phenytoin, valproate
primidone

Advantages Serious toxicity, Extremely effective

rare, parenteral, in absences, very
inexpensive, once little side-effect
daily dose

PRIMIDONE
Usual form: Mysolin (ICI) 250 mg tab
Daily dose: 125 mg in late evening, if necessary
increased by 125 mg every 3rd days up to
500 mg/day; further increment in adult by
250 mg up to 1.5 gm
Maintenance dose: 750-1500 mg/day
Indications: Grand mal, complex partial, simple partial
Toxicity: Drowsiness, ataxia, impaired alertness
Side-effects: Nausea, dizziness, ataxia, somnolence,
impairment of intellectual function.

Table 18.2.: Newer antiepileptic drugs

Gabapentin Lamotrigine Vigabatrin Clobazam Topiramate

Usual form: 300 mg cap Lamitor (Torrent) 500 mg tab 10 mg cap 50, 100, 200 mg
25, 50, 100 mg tab 1000-3000 mg tab 300-600
Daily dose: 900-3600 mg 100-400 mg 10-20 mg

Frequency: 3 2 2 1 or 2 1 or 2

Preparation: Neurontin (PD) Lomitor, Lamtec

300 and 400 mg (Protec)
cap

Indication: Refractory epi- Refractory epi- Refractory epi- Refractory epi- Refractory epi-
lepsy lepsy, as adjunctive lepsy lepsy lepsy
therapy
Side-effect: Somnolence Nausea, rash, tre-
dizziness, ataxia, mor, diplopia, ata-
tremor, diplopia xia, agitation
136 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Management of Status Epilepticus

In status epilepticus seizures occur repeatedly without full recovery of consciousness. It is medical
emergency with high mortality (up to 10%).
General care: Preservation of vital functions:
a. Position: Positioned to avoid aspiration, suffocation and fall.
b. Place: Move the patient to a safer place to avoid fire, machinery and water.
c. Airway: A soft plastic airway should be placed in place without forcing the teeth apart to avoid
dental injury and aspiration of teeth.
d. Respirator may be necessary to maintain respiration.
e. Metabolic acidosis: If present should be treated properly.
Treatment of precipitating factors: See above ‘Precipitating Factors’.
Drug therapy:
A. Paraldehyde: Still used.
Dose: 5 ml diluted in 5 ml of normal saline injected deep IM in each buttock.
Disadvantages: Paraldehyde decomposes to acetaldehyde and acetic acid which are very toxic
compound. Expired ampoules should be destroyed. Gluteal abscesses may result.
B. Phosphenytoin: It is a prodrug of phenytoin and recently introduced. It can be given IM.
C. Different regimes:
i. Diazepam regime: Inject diazepam 10 mg IV slowly in 5 minutes. Repeat half hourly if seizure
persists, total dose in 24 hours not more than 50-70 mg.

If seizure stops: If seizure persists:

Start normal saline Try sodium valproate
drip, add to it 700 mg rectally or by nasogastric
Phenytoin in one and tube
half hour. After 6 hours
maintenance dose If persists anaesthesia by
started thiopentone
ii. Phenytoin regime: Loading dose of phenytoin 13-14 mg/kg IV at the rate of 50 mg/minute
followed after 6 hours first maintenance dose of 100 mg
↓
If seizure persists, inject IV phenobarbitone. See below.
↓
If persists, try sodium valproate rectally or by nasogastric tube
↓
If persists, try anaesthesia
iii. Phenobarbitone regime: Loading dose of phenobarbitone 6-12 mg/kg IV at the rate of 60 mg
per minute
↓
If persists, try phenytoin and sodium valproate
↓
If persists, try anaesthesia
Disadvantages and advantages of antiepileptic drugs in status epilepticus:
Epilepsy and Seizures | 137

Disadvantages Advantages
IV i. Needs several additional dosages to Effective in 60 to 80%
Diazepam control seizures because half-life of patients
diazepam is 15 minutes
ii. Respiratory depression and cardiac arrest

Intravenous i. A bit slower effect than diazepam Safe and effective

Phenytoin ii. Hypotension

Intravenous Respiratory depression

Phenobarbitone Do not combine with diazepam
Urgent investigations in status epilepticus: ECG, blood sugar, haematology, electrolytes, BUN, urine
Pregnancy and epilepsy: Pregnancy does not increase frequency of seizures nor increases obstetric
complications.
Causes of increased frequency of seizures:
i. Decreased compliance of drug
ii. Reduction in dosages of AED
iii. Decreased serum level of AED due to pregnancy
iv. Sleep deprivation.
Safest AED in pregnancy: Carbamazepine.
Additional drugs given in pregnancy in addition to AED:
i. Folic acid 4 mg/day as recommended as soon as pregnancy is diagnosed to reduce the incidence of
neural tube defect.
ii. Vitamin K should be given to women who are taking phenobarbitone or carbamazepine. They may
produce vitamin related bleeding in the infants. Vitamin K is given as follows:
Vitamin K 20 mg/day in the last month of pregnancy and 1 mg IM to the infant at birth.
Other situations:
Situations Recommendation
Schooling: Should not be discontinued though they are underachiever
Leisure activities: Can take part in usual leisure activities with a few exception:
i. Supervised swimming
ii. Cycling allowed but not on busy street
iii. Adventrous sports avoided
iv. Can watch television in a well lighted room from a distance
Employment: i. Not permitted to work at heights or handle machines
ii. Not permitted to join police, defence services, merchant navy or pilot planes.
Driving: In India epileptics are not allowed driving.
Anxiety and i. Tricyclic antidepressants are proconvulsants
depression: ii. Fluoxetines are also proconvulsant but not absolutely
contraindicated in epilepsy
iii. Carbamazepine has some antidepressant property and is a preferred drug.
138 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

General principles of drug therapy: Monotherapy versus polytherapy:

MONOTHERAPY
Advantages:
a. Eighty percent of new patients are controlled by monotherapy
b. Compliance better
c. Drug interactions rare.
Choice of monotherapy: Depends upon type of epileptic seizure:
a. Mixed seizure or generalised seizure or if type of seizure is not clear : Valproate
b. Partial seizure: Carbamazepine
c. Abscences: Valproate, ethosuximide or clonazepam
d. Infantile spasm: Vigabatrin
Drugs to be avoided:
a. Phenobarbitone is avoided in children and students because it affects behaviour and cognition and
can make them hyperactive.
b. Phenytoin is avoided in girls and young women because cosmetically unacceptable side-effects
such as hirsutism, coarsening of facial features and gum hypertrophy. Also avoided in women in
the child bearing age because of teratogenicity.
c. Valproate and lamotrigine are preferred in women on oral contraceptives due to lack of drug
interaction.
Principles of monotherapy:
a. Begin monotherapy with least toxic drug and small dose, increased gradually till seizure is controlled
or side-effects appear or serum level of the drug is achieved.
b. Remember factors associated with failure of monotherapy or inadequate serum concentration;
i. Persistent noncompliance
ii. Drug allergy
iii. Large or progressive brain lesion
iv. Partial seizure or more than one type of seizure
v. Inadequate dosing
vi. Neuropsychiatric handicaps
vii. Pregnancy.

POLYTHERAPY
a. Disadvantages:
i. Possibility of drug toxicity increases
ii. Better left to the expert
iii. Drug allergy and drug interactions increase
iv. Exacerbation seizures.
b. Principles of polytherapy: If monotherapy is pushed to maximum tolerated dose and/or high serum
concentration achieved and seizure is still not controlled a second antiepileptic drug is added and
the first drug is continued.
↓
 ↓
Epilepsy and Seizures | 139

If the seizure is controlled and therapeutic serum concentration of the second drug is achieved, the
first drug should be tapered slowly to avoid the hazards of polytherapy. If the seizure recurs continue the
first drug and later gradual withdrawal may be considered.
↓
A third drug should not be added until it is documented that the seizure cannot be controlled with
maximum tolerated dosages and/or high therapeutic concentration of the first two drugs. If the adequate
therapeutic concentration of the third drug is reached, withdrawal can be done one of the first two drugs.
Management of refractory epilepsy:
First step: Review the diagnosis. Twenty percent refractory patients do not have epilepsy.
↓
Second step : Analyse the history:
a. Thirty to fifty percent patients do not take medicines as advised. Hence ensure compliance.
b. Ensure adequate dosing of failed drug because low serum level may be responsible for failure
↓
Third step: Add second or third drug
↓
Fourth step: Try newer AED.
Try Lonazap (Clonazepam): May be added to already failed regime:
Dose: i. Child: 0.01 to 0.03 mg/kg in 3 to 4 divided dosages
Maximum 0.05/kg
ii. Adult: 1.5 mg/day or less in divided dosages increased by
0.5 mg/day every 3 to 7 days till maximum 20 mg/day.
Maintenance dose 4 to 8 mg/day.
Fifth step: Surgery:
Temporal lobectomy benefits well selected temporal epilepsy. Atonic seizure may respond to corpus
colostomy. Some patients with hemiplegia, hemiatrophy and refractory epilepsy may respond to
hemispherectomy.
 Central Nervous System
19
Parkinson’s Disease
(Paralysis Agitans)

AETIOLOGICAL, PATHOLOGICAL, AND CLINICAL FACTS WHICH YOU CAN USE FOR
MANAGEMENT
Aetiology
A. Idiopathic (Paralysis agitans)
B. Secondary:
• Postencephalitic parkinsonism
• Atherosclerosis
• Drugs and poisons: Reserpine, metoclopramide, tetrabenzine, tetrahydropyridine, manganese,
carbonmonoxide poisoning
• Association with certain diseases
• Creutzfeldt-Jakob disease, Huntington’s chorea.

Pathogenesis
Degeneration of nigro striatal tract containing Lewy bodies
⇓
Depletion of dopaminergic neurons of substantia nigra
⇓
Leading to depletion of following neurotransmitters

↓ ↓
Depletion of Depletion of other neurotransmitters:
striatal dopamine: • Norepinephrine
↓ • Serotonin responsible for depression in Parkinsonism
Leads to acetylcholine • Substance P
hyperactivity • Enkephalins
↓
Produces Parkinsonian
symptoms
Diagnostic Clues
Parkinson’s Disease (Paralysis Agitans) | 141

Clinical features
A. Idiopathic Parkinsonism:
a. Face: Mask-like
b. Attitude: Flexed
c. Posture: Stooped
d. Movement:
i. Voluntary—Bradykinesia, micrography (handwriting becomes slower)
ii. Involuntary—Resting coarse tremor, pill rolling movement
e. Rigidity: Lead pipe type more in legs and trunk, cog-wheel type more in upper limbs
f. Gait: Slow and shuffling, festinant gait (tendency to run with short steps), retropulsion and
propulsion
g. Speech: Slurred and indistinct speech
B. Features suggestive of secondary Parkinsonian disease:
History of taking certain drugs : Suggests drug induced parkinsonism
Mental changes : Suggests Huntington’s chorea
KF ring : Wilson’s disease
Cherry-red colour of face : Carbon monoxide poisoning

TREATMENT: DRUGS FOR PARKINSONISM

Drug preparation Dosages Action Side-effect Advantages
and forms

I. Amanta- Amantrel (Protec) Initially 100 mg i. Uncertain Anorexia, confu- Used as adjuvant
dine 100 mg cap per day, increased ii. Increases sion, psychosis, to L-dopa or
to 100 mg b.d., synthesis of pedal oedema, anticholinergics
Max 400 mg/day dopamine livedo reticularis
(red discoloura-
tion of skin over
leg and feet)
II. Levodopa Levopa (Wallace) Start with 250 mg Increases synthe- Anorexia, nausea, i. 20%, patients
Bidopal (Biddle per day —increa- sis of dopamine vomiting, confu- show dramatic
Sawyer) 500 mg sed to 0.5 to sion, psychosis, response, 60%
tab 1.0 gm/day at postural hypoten- moderate and
interval of 3-4 days sion, dyskinesia, 20% either
till optimum effect. GI and cardiac cannot tolerate
Max 8 gm/day. Cli- disturbance less or respond
nical response with carbidopa poorly
starts 15 mts to 1 hr and beserzide ii. More effective
after an oral dose than anticholi-
and lasts for 1-5 nergics in
hour reducing tre-
mor, rigidity
and akinesia.
III. Carbidopa + a. Syndopa (Sun) Start L100 + C25 Carbidopa Do More effective
Levodopa 110: C10 + t.d.s., increased reduces periphe- than anticholi-
L100 by 1 tab/day every ral metabolism or nergics with
contd...
142 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. Syndopa 275: 1-2 day. Max. 8 L-dopa causing less side-

C25 + L250 tab/day 80% reduction in effects than
c. Syndopa CR: dosages of L-dopa L-dopa alone
C50 + L200 resulting in
d. Syndopa plus: decrease of side
C25 + L100 effects
e. Parkimet (Bid-
dle Sawyer):
C25 + L250

IV. Beserzide + Benspar (Alidec): a. Patient not

L-dopa L-dopa 100 + treated previ-
Beserzide ously: 1 cap
28.5 mg b.d. increased
by 1 cap every
3rd or 4th day.
Effective dose
4-8 cap/day in
divided
dosages

V. Controlled 200-800 mg/day

Release of L-dopa
Carbidopa
+ L-dopa
50/120

VI. Anticholi-
nergics:
a. Trihexy- 4-8 mg/day. i. Opposes increa- • Dry mouth blur- Indicated specially
phenidyl Maintenance dose sed cholinergic red vision, sphin- if associated with
(Artane) 2 6-15 mg/day activity cter disturbances tremor and rigidity.
and 5 mg ii. Inhibits uptake psychosis, palpi- But less effective
tab of dopamine by tation, nausea against akinesia.
presynaptic and vomiting
optic terminals
and thus
increases
dopamine level
b. Procycli- Start 2.5 mg Has desirable
dine HCl t.d.s.—increased effect on autono-
(Kemadrin– by 2.5 mg/day mic features such
Borroough every 2-3 days, as drooling, sebor-
Wellcome) Max. 30 mg/day rhoea and exces-
2.5 and sive sweating.
5.0 mg tab.
c. Benztro- Start with 1.5 mg/ Can be usually
pine (Cog- day. Maintenance combined with
contd...
contd...
Parkinson’s Disease (Paralysis Agitans) | 143

entin) 0.5, dose 2-6 mg/day other anti-Parkin-

1, and sonian drugs
2 mg tab
d. Benzherst
(Pacitane-
Wyeth
Lederle)
2 mg tab

VII. Antihista-
mines:
a. Diphenyl 50-100 mg/day. Anticholiner gic Sedation giddiness It helps insomnia
hydramine Maintenance activity and severe tremor
(Benadryl) dose 50-150 mg/
25 and 50 day No sedation
mg cap,
elixir 12.5
mg/ml
b. O r p h e n a d - 150-200 mg/day
rine (Disi-
pal) 50 mg
tab

VIII. D o p a m i n e
Agonist: 1st day: 1.25 mg Directly acts on Nausea, vomiting, Bromocriptine has
a. Bromocrip- increased by 1.25 dopamine recep- postural hypo- prolonged (4-8
tine (Proc- mg each day until tors in striatum tension psychosis hour). Helps dys-
tinal Biddle 2.5 mg t.i.d. rea- kinesia and fluc-
Sawyer) ched. May be gra- tuation in response
2.5 mg tab dually increased to treatment
till response or
side-effect. Main-
tenance dose 15-
30 mg/day
Subcutaneous – Do – Nausea, vomiting, i. Rapid onset of
b. Apomor- injection 1-6 mg confusion, psy- action (5-
phine chosis 10 mts)
ii. Can revive a
patient from
akinetic spasm
IX. MAO B inhi-
bitor: 5-10 mg/day Reduces break- Hallucination, con- i. Prolongs dura-
Selegiline down of dopamine fusion, postural tion of action
(Selgin— hypotension of L-dopa
Intas, ii. Allows reduc-
Elegilin— tion of dosages
Sun, of L-dopa
Eldepryl-
Themis)
5 mg tab
144 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Plan of Drug Treatment

I. Mild asymptomatic disease: Symptoms do not interfere daily activities: No drug is required. Only
exercise and walking is advised. Selegiline is occasionally used for delaying. Progress of the disease.
II. Symptomatic disease:
A. Try to delay the use of L-dopa as long as possible by using anticholinergics and/or amantadine
specially in young. When daily activities are affected, start L-dopa + carbidopa 100/25 t.i.d.
↓
Increase by 100/25 everyday until patient receives 300 to 400 mg of L-dopa per day.
↓
Then allow a few weeks for full response to occur before making any further enhancement.
Dose enhancement may be achieved by the use of 250/25 strength tablet, reaching the
maintenance dose of 800 mg/day of L-dopa.
↓
If significant disability persists, bromocriptine may be added.

Management of L-dopa Side-effects:

Side-effects Management
Nausea, vomiting, anorexia i. Adding carbidopa to L-dopa reduces nausea
ii. Domperidone (a peripheral dopamine recep-
tor (D 2 type) antagonist 10 mg q.d.s.

Postural hypotension i.Increase dose of carbidopa

ii.Domperidone
iii.Add salt and fluid to the diet
iv. For severe cases: Fludrocortisone 0.1 mg daily
with potassium sparing diuretic (amiloride)
v. Avoid sudden change of posture and pro-
longed standing
vi. Use elastic stalkings in legs

Psychiatric disturbances i. Reduce dose of L-dopa in evening. In severe

hallucination, insomnia psychiatric disturbances stop L-dopa altoge-
ther.
ii. Stop anticholinergics, amantadine and bromo-
criptine
iii. Later when the condition improves, gradually
introduce L-dopa and other drugs.
iv. For depression: Fluoxetine HCl 20 mg/day or
sertaline 50 mg/day (increasing to 100 mg
twice a day). Tricyclic antidepressant can also
be used.
v. Clozapine 12.5 mg at bedtime (gradually
increased).
Fluctuation in disability (wearing off phenomena,
Parkinson’s Disease (Paralysis Agitans)

i. Reduce total protein intake

| 145

fluctuation from mobile to immobile states, on-off ii. Smaller, more frequent dosages of L-dopa
phenomena) iii. Add bromocriptine
iv. Introduce selegiline
Dyskinesia:
Choreoathetosis, dystonia, i. Reduce total daily dose of L-dopa. Give L-
grimacing, tongue protrusion dopa in small and more frequent dosages.
ii. Introduce bromocriptine and selegiline
Treatment of special symptoms of Parkinson’s
disease:
Special symptoms Management
Sialorrhoea Anticholinergics like trihexyphenidyl or Propan-
Constipation theline 15-30 mg 8 hourly
i. Withdraw anticholinergics
ii. High fibre diet
iii. Bulk forming laxatives
iv. Stool softener: Dicotyl sulphasuccinate
Surgery v. Cisapride

Procedure Remarks
1. Stereotactic surgery: With the introduction of L-dopa stereotactic surgery
a. Ventrolateral thalmotomy went out of vogue but of late it has been introduced
b. Stimulation of ventrolateral nucleus of in following selected cases:
thalamus i. Failed medical therapy
c. Medical pallidotomy ii. Unilateral disabling tremor
iii. Advanced disease with “on-off” phenomena
Risk of stereotactic surgery: Stroke, vision loss

2. Transplantation of foetal Ethical issue involved

adrenal medulla and foetal
substantia nigra in the brain
3. Implantation of “Brain Pacemaker” turned on
during the day and turned off during the night.
It stops tremor.

CLINICAL NOTES
There is series of drugs used in the treatment of Parkinson’s disease today. Drugs such as apomorphine
HCl (oral tablet), cerestat aptiganel HCl, destinex cabergoline, dihydrexidine, dopascan injection, neuro
cell PD, pramipexole, rasagiline mesylate, repinirole and tasmar telecapone. Taking the drugs will establish
the necessary balance of dopamine and acetylcholine (Freed, Breeze, and Schneck 1). “The apomorphine
HCl is currently the newest and most successful treatment that is in use. (Dr. Arastu, M.D.). The drugs
act as a helper for the dopamine tissue cells. It helps slowdown the depletion of the cells. Another
treatment is a foetal dopamine tissue transplant. Motor function can be greatly improved by grafting
146 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

dopamine secreting cells into appropriate sites in the brain (Physical Therapy 56). This procedure is
used in order to replace a degenerated nerve with a new foetal nerve. There are also foetal nerves from
adrenal tissue taken glands transplanted has improved the motor function of many patients of Parkinson’s
disease. Foetal dopamine tissue transplant has caused a very controversial issue to arise because of the
use of foetal nerves after an abortion. That is the moral issue.
There is another new development: Use of a robot named Minerva. The robot is used to destroy the
cells in the cerebrum that regulates movement in order to stop tremor.
The most inexpensive treatment for this disease is encouragement. The support of family and friends
proved to be very successful (Kunz 495). Education is another effective treatment. Patients need to be
taught ways to make their lives easier. For example, grab bars in the bathroom, a trapeze over the head
of the bed and velcro closure on clothing.
 Central Nervous System
20
Treatment of Other
Extrapyramidal Disorders

DYSTONIA
Aetiology of Dystonia
A. Idiopathic
B. Secondary: Wilson’s disease, spastic disease, basal ganglia calcinosis, Parkinson’s disease,
Huntington’s chorea, kernicterus, cerebrovascular disease, encephalitis, toxic level of manganese,
L-dopa.
Idiopathic dystonia:
Characteristics Treatment
Characterised by sustained muscle contraction Treatment unsatisfactory
resulting in twisting and abnormal posture a. High dose anticholinergic therapy: Trihexy-
phenidyl 20-50 mg/day
b. Other drugs: Beclofen, tetrabenzine, benzo-
diazepam (clonazepam) and dopamine antago-
nist pimozide 6-25 mg/day
c. Severe dystonia:
i. Tetrabenzine 75 mg/day + Pimozide 6-
25 mg/day + High-dose anticholinergic
ii. Stereotactic thalmotomy
d. Physiotherapy and occupational therapy is
helpful
Small dose of L-dopa helps small group of patients
Juvenile dystonia:
Focal and segmental idiopathic dystonia: Charac-
terised by Treatment
a. Cervical dystonia: Torticollis-rotation of head Local botulinum toxin injection therapy
to one side
b. Cranial nerve dystonia: Blepharospasm, – Do –
involuntary mouth opening and jaw clinching,
tongue protrusion, dysarthria, dysphasia, harsh
hoarse voice
148 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

c. Writer’ cramp i. Adopting different hand posture

ii. Use dictation, typing or other writing devices
Paroxysmal dystonia:
Characterised by paroxysmal chorea—Athetosis Responds dramatically to small dosages of
beginning in childhood phenytoin or carbamazepine

CHOREA
Types and Characteristics Treatment
Rheumatic chorea: Haloperidol, valproate
Irregular, unpredictable, brief, jerky movement
flitting from one part of body to another

Huntington’s chorea No definitive treatment available

• Chorea responds to haloperidol and tetra-
benzine
Hemibellismus Haloperidol, chlorpropamide.
In severe disabling cases: Stereotactic thalmotomy
TREMOR
Parkinsonian tremor
See chapter on Parkinson’s disease
Physiological and essential tremor
Low dose of alcohol may help
(Best seen in outstretched arm-action tremor)

Rubral tremor:
Coarse, slow tremor of arm present at rest most Levodopa, isoniazid, 5-hydroxytryptophan
often due to multiple sclerosis, stroke and head
injury

MYOCLONUS
Treatment
Characteristics Aetiology
• Clonazepam
Sudden, shock like involuntary 1. Physiological
• Valproate
movement 2. Hereditary
• Palatal myoclonus responds to
3. Symptomatic:
clonazepam, trihexylphenidyl
• Storage disease
and carbamazepine
• Wilson’s disease
• Encephalitis
• Creutzfeldt-Jacob disease
• Stroke
• Brain tumour
• Spinal cord lesion
• Drugs and poisons:
Heavy metal, L-dopa,
Tricyclic antidepressant
TICS
|
Treatment of Other Extrapyramidal Disorders 149

Characterised by abrupt transient, Treatment:

stereotype coordinated move- i. Mild cases left alone,
ment repeated at regular intervals ii. If distressing:
Haloperidol 0.25-0.5 mg
t.i.d.
Pimozide
Clonidine

TARDIVE DYSKINESIA
Characterised by stereotyped oro-lingual and masticatory movements (lip smacking, tongue protrusion,
and licking and chewing movements. Women affected mainly above 50 year age. Due to chronic exposure
(more than one year) to dopamine receptor antagonists.
Treatment:
i. Causative drug should be withdrawn.
ii. Drugs: Reserpine and tetrabenzine may be used with some success. Occasional patients may benefit
from baclofen or clonazepam.

VITAMIN DEFICIENCY SYNDROME AFFECTING THE NERVOUS SYSTEM

Vitamin deficiency Syndromes
Vitamin A Night blindness
Vitamin B1 Peripheral neuropathy
Nicotinic acid Polyneuropathy, pellagra, spastic ataxia, psychosis, dementia
Pantothenic acid Burning feet syndrome
Riboflavin Burning feet syndrome
B6 (Pyridoxin) Convulsion in neonates, peripheral neuropathy
B12 (Cyanocobalamin) Subacute combined degeneration, optic atrophy, peripheral
neuropathy dementia
Vitamin E Peripheral neuropathy, spinocerebellar degeneration
 Central Nervous System
21
Multiple Sclerosis

Aetiological facts and diagnostic clues you want to know for divising rational treatment:
Aetiology: Unknown, suggested theories:
A. Genetic susceptibility: As evidenced by significant association of MS with HLA-A3, HLA-B7
and HLA-DWZ.
B. Environment: Viral agent implicated but not confirmed.

Diagnostic clues:
Clinical features:
I. General: Young adult suffer most—20-40 year is the most important age. Rare under 10 years and
above 50 years. Frequency, urgency, or hesitancy of micturition are fairly common. Relapses and
remission are frequent.
II. Focal signs:
Site involved Manifestations
1. Optic nerve a. Optic neuritis with sudden loss of vision in one eye which
improves
b. Optic atrophy with temporal pallor
2. Plaque in midbrain and pons Internuclear ophthalmoplegia. Diplopia
3. Plaque in cerebellum Scanning speech, nystagmus, and intention tremor
4. Plaque in spinal cord:
a. Pyramidal tract Monoplegia, paraplegia, hemiplegia
b. Posterior column Impairment of position and joint sense. Electric current like
sensation radiating through the body (L’Hermitt’s sign) due
to lesion of posterior column in cervical cord.
c. Spinothalamic tract lesion Pain and temperature sensation dissociation.

Laboratory investigation:
No investigation is diagnostic.
a. CSF: Shows nonspecific changes.
b. MRI: Plaques can be demonstrated but not diagnostic.
Treatment
Multiple Sclerosis | 151

I. Drugs:
Drugs Dose Indications Side-effects Advantages and
Remarks
A. Corticosteroids
ACTH 40-80 U/day for 15- Acute attack specia- • Fluid retention Reduces duration of
30 days in acute lly with optic neuri- (treated by diure- exacerbation in
attack tis or interferes with tic), hyperkalae- 50% cases but does
normal lifestyle mia, hyperglycae- not change long-
mia, Cushing’s term disability
syndrome, beha-
viour disorder
treated with psy-
chotropic drugs
Oral prednisolone 40-60 mg/day tape- • Acute attack –Do–
red to lowest dose

Methyl predniso- Given as infusion 1 • Acute attack –Do– Preferred treatment

lone succinate gm/day for 5-7 days in acute attack

B. Immunosup-
pressants:
Azathioprine 100 mg/day orally As an adjunct to Contraindicated in Reduces number
steroid in chronic pregnancy, acute of exacerbation.
relapsing cases infection and bone Monitor by comp-
lete blood count,
liver function tests
and bone marrow
function
–Do–
Cyclophosphamide –Do– –Do–
–Do–
Cyclosporin A –Do– –Do–

C. Other Experimental Drugs:

a. Copolymer 1
b. Monoclonal antibodies to TNF alpha
c. CD 4 molecule
d. Tolerisation with oral myelin
e. Novantrone
f. Interferon alpha and beta
II. Other Methods of Treatment:
A. Plasmapheresis: Removes antibodies involved in pathogenesis of MS. Moderately effective in
severe cases.
152 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

B. Total lymphoid irradiation 2000 rad over 40 days slows deterioration of function in patients
with progressive MS.
III. Treatment of Symptoms:
Symptoms Treatment
A. Spasticity and nocturnal spasm a. Beclofen 10 mg b.i.d. orally increased to
40 mg q.i.d.
b. Diazepam staging 5 mg and increased to
higher dosages
c. Dantrolene
d. Tizanidine
e. Botulinum toxin injection

B. Vision disturbance Transient improvement by 4-aminopyridine IV or

orally
C. Nerve pain and painful tonic spasm Carbamazepine, phenytoin and gabapentine

D. Bladder symptoms: Due to incomplete a. Incontinence and frequency (due to inhibited

emptying of residual urine, overflow fre- bladder contraction) alleviated by control of
quency, incontinence or infection infection, restriction of fluid intake, imipra-
mine, oxybutynin chloride or propantheline.
Other drugs flavoxate (Uripas 100-200 mg
t.i.d. or q.i.d.), ephedrine 15-50 mg q.i.d. or
pseudoephedrin (Sudafed) 30-60 mg q.i.d.
b. Long-term bacterial suppressants such as
mandelamine, nitrofurantoin for infection due
to residual urine.
If drugs fail:
Self-catheterisation has lower risk of infection
than indwelling catheter.
c. For urinary retention: bethanechol chloride

E. Mood disorders: Psychotropic drugs, tranquillizers and antidepres-

sants.

F. Tremor: Clonazepam helps cerebellar tremor—Begun

0.5 mg orally at night and gradually increased to
10-20 mg per day in divided dosages. Propranolol
40-240 mg/day in divided dosages help some
patients. Haldol is effective in certain patients.

G. Weakness and fatigue: Amantadine hydrochloride 100 mg twice daily.

Fluoxetine reduces fatigue. Modofinel may help.
Physical Therapy
Multiple Sclerosis | 153

Helps maintaining muscle and joint function. Exercise programs prevent contracture and maintain the
peripheral circulation and give patient a sense of well-being.

CLINICAL NOTES
A new drug for MS approved by FDA: Novantrone (mitoxantrone hydrochloride): White blood
cells can produce signs and symptoms of MS by attacking myelin, (a fatty substance that surrounds the
nerve cells). Novantrone suppresses the activity of T and B cells, and in this manner slows the progression
of the disease and reduces the frequency of relapses.
Dose: Novantrone 5 mg/m2 to 12 mg/m2 administered in every three months for 2 years. May be
combined with methylprednisolone. No patient developed new MRI demonstrated lesions at six months.
Side-effect: Nausea, vomiting, hypotension, rashes, urinary tract infection and menstrual disorder.
The safety and effectiveness of novantrone in multiple sclerosis were assessed in two randomised,
controlled multicentre trials. One trial was conducted in subjects with secondary progressive or progressive
relapsing multiple sclerosis. Neurological disability was evaluated based on the Kutzke Expanded
Disability Status Scale (EDSS). This scale ranges from 0.0 to 10.0, with increasing scores indicating
worsening condition. Subjects receive a placebo, 5 mg/m2 novantrone, or 12 mg/m2 novantrone
administered intravenously every three months for two years. At 24 months, the mean EDSS change
(month 24 value minus baseline) was 0.23 for the placebo group, –0.23 for 5 mg/m2, and –0.13. A
second trial evaluated novantrone in combination with methylprednisolone (MP) and was conducted in
subjects with secondary progressive or worsening relapsing-remitting multiple sclerosis who had residual
neurological deficit between relapses. A total of 42 subjects received monthly treatments of 1gm of a
total of 42 subjects received monthly treatment of 1gm of intravenous MP alone or approximately 12
mg/m2 of intravenous novantrone plus 1 gm of intravenous MP for 6 months. Subjects were evaluated
monthly, and study outcome was determined after 6 months. The primary measure of effectiveness was
a comparison of the portion of subjects in each treatment group who developed no new Gd-enhancing
MRI lesions, while 90% of subjects receiving novantrone plus MP were without lesions.
Side effects: Possible adverse events associated with novantrone included (but are not limited the
following: Nausea, hairloss, hypotension, rashes, urinary tract infection and menstrual disorder.

Mechanism of Action
Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen
binding, causes crosslinks and strand breaks.
Mitoxantrone also interferes with ribonucleic acid and is a potent inhibitor of topoisomerase II, an
enzyme responsible for uncoiling and repairing damaged DNA. It has cytocidal effect on both proliferating
and non-proliferating cultured human cells, suggesting lack of cycle phase specificity.
Novantrone has been shown in vitro to inhibit B cells, and macrophage proliferation and impair
antigen presentation, as well as the secretion of interferon gamma, TNF and IL-2.
 Central Nervous System
22
Alzheimer’s Disease
A progressive type of dementia.
Aetiological and pathological factors, clinical features you will need for devising rational treatment:
Aetiology: Unknown, suggested theories:
A. Environmental factors:
Nutritional factors, infection, toxin, etc.
B. Genetic susceptibility:
Evidence: All patients of Down’s syndrome develop Alzheimer’s changes in the brain.
Pathophysiology: Progressive neuronal degeneration of selective cells in the association and memory
areas of cerebral. Cortex especially the large pyramidal cells of the hippocampus, the amygdala and the
parietal and frontal association areas.
⇓
Leads to secondary degeneration of ascending cholinergic and adrenergic pathways

Diagnostic Clues
Clinical features:
1. Age: Presenile, before age 65 year; senile—after age 65 years up to 90 years.
2. Impairment of higher mental function: Impairment of vocational activities, managing finances and
finding direction in public places. Memory disorder especially of recent memory. Aphasia, agnosia
and apraxia.
3. Impairment of vegetative function: Tasks of daily activities such as eating, sleeping, bathing, dressing
and continence are impaired.
Investigations: Done for differentiating other causes of dementia.
a. EEG: Provides indications towards metabolic and toxic aetiologies of dementia.
b. MRI: Used to exclude vascular, demyelinating, infectious and space occupying aetiologies of
dementia.

Treatment
Symptomatic Treatment
Symptoms Treatment
Insomnia Ticlophos 500 mg at bedtime
Repetitive behaviour Benzodiazepine or phenothiazine
Incontinence a. Periodic voiding
b. Incontinence devices or intermittent catheterisation
c. Genital care
Agitation
Alzheimer’s Disease

Neuroleptics and sedatives: Short acting benzodiazepines such as

| 155

lorazepam (ativan) and oxazepam.

Psychosis: Hallucination,
increased suspiciousness,
delusion
Depression
Low potency phenothiazine such as chlorpromazine and thioridazine have
less sedation, orthostatic hypotension and extrapyramidal symptoms
a. Tricyclic compounds may produce excessive sedation, orthostatic
hypotension, cardiac effects and cholinergic side-effects. These side-
effects are of concern in the choice of tricyclic compounds.
b. Fluoxetine hydrochloride

Specific Treatment
Aim: To reverse cognitive loss.
A. Acetylcholine precursors: Choline and lecithin with peracetum.
B. Physostigmine.
C. Centrally active acetylcholinesterase inhibitor tacrine up to 160 mg/day is beneficial. Liver
transaminases are monitored. Improves cognitive function in 40% patients. Side-effects are
gastrointestinal upset.
D. Experimental: Newer strategies on designing drugs which would directly stimulate postsynaptic
acetylcholine M2 receptors, thus maximizing the effect and release of this cognitively important
neurotransmitter.

Drugs Under Development

1. Acetylcholine transmits nerve impulses between nerve cells. Nerve cells producing acetylcholine
especially degenerate in Alzheimer’s disease reducing amount of acetylcholine in the cerebral cortex
the only drugs developed in U.K. inhibits enzyme cholinesterase inhibitor that breaks down
acetylcholine and thus increases the level of acetylcholine in the cerebral cortex and give some
improvement in memory problems early on in Alzheimer’s disease, but they do not prevent nerve
cells from dying. Drugs under development that includes chemicals that inhibit the formation of
beta-amyloid which might slow down the disease process.
2. Drugs modifying risk factors. They might slow the development of the disease:
a. Large dose of vitamin E which acts like antioxidant and might prevent degeneration of nerve
cell.
b. Blood pressure lowering drugs which are helpful in vascular dementia, might help Alzheimer’s
disease also.
c. Drugs that might help nerve cell to grow.
d. Gingo biloba: Its action is not understood.

Drugs Available
There are two drugs licenced in U.K. are available for treatment of dementia of Alzheimer’s disease:
a. Donepezil (Aricept): A cholinesterase inhibitor. It improves short-term memory, works only for a
short-time, helps early cases but no effect in advanced cases.
b. Rivastigmine (Exeton): Also a cholinesterase inhibitor and like Donepezil improves short-term
memory, works only for a short-time, helps early cases but no effect in advanced cases.
 Central Nervous System
23
Meningitis (Pyogenic)

Facts you can use for treatment purpose:

A. Organisms responsible for bacterial meningitis and age:
Organisms Age group
Neisseria meningitidis Most common in first year of age
Haemophilus influenzae Most common in children
Streptococcus pneumoniae Most common in adults
B. Predisposing factors:
Upper respiratory tract Lower respiratory tract Others
infection infection
Sinusitis Pneumococcal pneumonia • Alcohol
Chronic otitis media • Closed head injury
Mastoiditis • Sickel cell disease
• Asplenism
C. Pathogenesis: Infection of CSF due to lack of immunity
↓
Infection and inflammation of subarachnoid
space injuring cranial nerves, spinal roots and
adjacent blood vessels by purulent exudates
↓
Obstructing flow of CSF resulting in hydrocephalus

DIAGNOSTIC CLUES
Clinical Manifestations
Common features: Fever, vomiting, impaired consciousness, headache, stiffneck and back with special
characteristics due to different offending organisms and age group as follows:
Age group Organisms
a. Children: Fever and vomiting more a. Meningococcal meningitis: Petechial or purpuric
frequent than headache. Seizure common. rash 50% patients
Classical signs of meningism minimum
b. Elderly: Signs of meningeal irritation b. Pneumococcal: Preceded by pneumonia or sinus
 minimal or absent
Meningitis (Pyogenic)|
infection or ear infection. Cranial nerves 3rd, 4th,
157

and 6th involved more.

⇓
Complications
a. 3rd, 4th, 6th, cranial nerve palsy — Common in pneumococcal meningitis
b. Persistent coma — Common in pneumococcal meningitis
c. Hydrocephalus and subdural
Empyema — In young children
Suggested by prolonged
Alteration of consciousness
d. Brain abscess suspected if CSF WBC above 50000/cmm. CT scan detects it.
e. Partial blockage of subarachnoid space is suspected if CSF pressure normal or low.

LABORATORY INVESTIGATIONS
CSF: Leukocyte count Pressure Protein Sugar
• 5000-20000 • Elevated, low or • Raised 150-500 mg • Low, less than
• Neutrophils++ normal—suggests partial 40 mg/dl
• Count above 50000 blockage of subarachnoid
suggests brain abscess space
Special tests: a. Counter immunoelectrophoresis to detect antigen of H. influenzae, N. meningitidis or
Strep. pneumoniae
b. Polymerase chain reaction
Blood culture may be positive
Blood leukocyte count elevated
Radiological findings: X-ray of chest, skull, and sinuses for pneumonitis, fracture or osteomyelitis of
skull bones.
CT scan: Indicated only if hydrocephalus, brain abscess or subdural empyema suspected.

TREATMENT
Antibiotic therapy should be started immediately without waiting for CSF Gram’s stain result and culture
report. If the organism is not identified empiric antibiotic therapy is started. See Table 23.1: Empiric
antibiotic therapy:
Table 23.1: Empiric antibiotic therapy
Age group Likely pathogens Total daily dose Interval
Infants Group B Streptococcus Ampicillin 100-150 mg/kg 8-12 hourly
Gram’s neg. enteric with or without gentamicin
Bacilli 7.5 mg/kg IV 12 hourly
H. influenzae or
S. pneumoniae Cefotaxime 200 mg/kg IV plus 6 hourly
N. meningitidis Gentamicin
contd...
158 |
contd..
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Age group Likely pathogens Total daily dose Interval

Staph. aureus or
Tobramycin 5 mg/kg IV 12 hourly
or
Amikacin 15 mg/kg IV 8 hourly
Children N. meningitidis Cefotaxime as above
S. pneumoniae or
H. influenzae Ceftriaxone 4 gm IV 12 hourly
or
Ampicillin 100-200 mg/kg IV 3-4 hourly
plus chloramphenicol 50-75
mg per kg IV 6 hourly
Adult N. meningitidis
S. pneumoniae Cefotaxime 12 gm IV In 4-6 hourly dose
H. influenzae 12 hourly doses
or
Cefotriaxone 4 gm IV
or
Chloramphenicol 50-100 mg/kg 6 hourly
IV plus Penicillin G 24 million 2-4 hourly
U IV or ampicillin 12 gm IV/day 2-4 hourly

If the organisms are known by culture and gram stain, see below the Table: Drugs for bacterial
meningitis of known aetiology.
Table 23.2: Drugs for bacterial meningitis of known aetiology
Bacteria First choice Alternative Duration
Strep. pneum. (Gram-positive)
a. Penicillin sensitive Penicillin G Chloramphenicol 10-14 days
b. Penicillin resistant Cefotaxime 10-14 days
c. Allergic to penicillin Chloramphenicol 10-14 days
H. influenzae (Gram-positive)
a. Beta lactamase neg. Ampicillin +chloram- Cefotaxime, 7-10 days
phenicol Ceftriaxone
b. Beta lactamase positive Chloramphenicol, Cefuroxime 7-10 days
Cefotaxime,
Ceftriaxone
Enteric bacilli (Gram-negative)
a. Community acquired 3rd generation cephalosporins:
Cefotaxime At least 21 days
b. Hospital acquired or Cefotaxime + tobramycin – Do –
follows head injury IV (5 mg/kg daily) and
contd...
contd...
Meningitis (Pyogenic) |159

Bacteria First choice Alternative Duration

(Pseudomonas likely)
Staph. aureus
a. Beta lactamase positive
b. Beta lactamase-neg.
Listeria mono-cytogenes
intrathecally (8mg/kg daily)
Naficillin or oxacillin – Do –
(12-18 gm/day either alone
or with rifampicin 600
mg/day + vancomycin 2gm/
day in two divided dosages
Penicillin Vancomycin – Do –
Ampicillin or penicillin 14-21 days
plus gentamicin

Flow Chart for Antibiotic Therapy for Bacterial Meningitis

I. Prehospital antibiotics:
Meningococci spreads like wild fire. If fever and rash present GP should start immediately benzyl
penicillin 2 mega units (1.2 g) IV or IM
⇓
If allergic to penicillin: 25 mg/kg IV or Ceftriaxone 1 gm IV or Cefotaxime 1 gm IV
⇓
II. If clinical manifestation, age and Gram’s staining of CSF do not point to the aetiology, start empiric
therapy
a. Adults less than 50 years: 3rd generation cefalosporins such as cefotaxime 2 gm 6 hourly
Ceftriaxone 2 gm 12 hourly
b. Adults over 50 years: Add ampicillin 2 gm IV 4 hourly because L. monocytogenes is resistant to
cephalosporins
c. Highly resistant to penicillin and cephalosporins pneumococci found in Spain, Eastern Europe,
South Africa and part of US: Vancomycin 500 mg 6 hourly or rifampicin 600 mg 12 hourly IV
should be added to cephalosporin regimen.
d. Patient without meningococcal rash and allergic to beta lactum:
a. Patient under 50 years: Chloramphenicol + vancomycin
b. Patient above 50 years: High dose of Co-trimoxazole should be added to the above regimen.
⇓
III. Specific antibiotics depending upon culture report and Gram’s staining. Empiric therapy should be
modified accordingly:
Bacteria Drug of choice Others
Meningococci (Gram- Benzyl penicillin or ampicillin If allergic to beta lactum:
negative Diplococci) Chloramphenicol
Pneumococci (Gram- Cephalosporin (with or without
positive Diplococci) vancomycin or rifampicin, dependent
on the area of the world)
should be continued
Listeria (Gram-positive Ampicillin 2 gm 4 hourly plus gentamicin
Cocco-bacilli) 5 mg/kg/day
160 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

MISCELLANEOUS REMARKS ON ANTIBIOTIC THERAPY

1. Antibiotics should be given IV throughout the treatment period. Reduction in dosages as the patient
improves should be avoided, because normalisation of blood-brain barrier during recovery reduces
the CSF level of the drug.
2. Bactericidal drugs (such as penicillin, ampicillin, third generation cephalosporins) should be
preferred.
3. Antibiotics which do not reach effective level in CSF (such as first and second generation
cephalosporins and clindamycin) should not be used.
4. If the patient has responded well, a follow-up lumbar puncture is not necessary.
5. Duration usually 10-14 days therapy is sufficient except gram-negative meningitis needs 21 days
therapy.

ADJUNCTIVE THERAPY
1. Seizure: Diazepam slow IV injection 5-10 mg in adult, maintenance therapy thereafter with phenytoin
IV until oral therapy is possible.
2. Corticosteroids: Indicated in marked toxemia.
3. Isolation: Only persued in meningococcal meningitis.
4. Measures to reduce cerebral oedema: Mannitol
Urea
Dexamethasone

Dosages of a Few Antibiotics in Adult and Child

Antibiotics Daily adult dose Daily child dose
Total Interval Total Interval
Ampicillin 12 gm/day 4 hour 200-300 mg/kg/day 6 hour
Nafcillin 12-18 gm/day 4 hour 150-200 mg/kg/day 4-6 hour
Oxacillin 12-18 gm/day 4 hour 150-200 mg/kg/day 4-6 hour
Penicillin G 20-24 million 2-4 hour 200,000-300,000
Units per day units/kg/day
Cefotaxime 12 gm/day 4-6 hour 150-200 mg/kg/day 4-6 hour
Ceftriaxone 4 gm/day 12 hour 100 mg/kg/day 12 hour
Ceftizoxime 9-12 gm/day 8 hour 150-200 mg/kg/day 8 hour
Ceftazidime 6 gm/day 8 hour 100-150 mg/kg/day 8 hour
Cefuroxime 4.5-9 gm/day 8 hour 200-240 mg/kg/day 6 hour
Chloramphenicol 4 gm/day 6 hour 100 mg/kg/day 6 hour
Vancomycin 2 gm/day 6-12 hour 40-50 mg/kg/day 6 hour
Amikacin 15 mg/kg/day 8-12 hour 15 mg/kg/day 12 hour
Gentamicin 5 mg/kg/day 8 hour 5-7 mg/kg/day 8 hour
Tobramycin 5 mg/kg/day 8 hour 5 mg/kg/day 8 hour
Trimethoprim—
Sulfamethoxazole 10 mg/kg/day TMP 6 hour Same as adult
(TMP-SMX) + 50 mg/kg/day SMX
CHEMOPROPHYLAXIS
|
Meningitis (Pyogenic) 161

Rifampin is the recommended drug for chemoprophylaxis of contacts of patients with meningococcal
and H. influenzae meningitis:
Type of meningitis Daily dose of rifampin
1. H. influenzae Adult Child
600 mg/day as a single 20 mg/kg/day as a single
dose for 4 days dose for 4 days
2. N. meningitidis 600 mg every 12 hour for 10 mg/kg every 12 hour for
four doses four dosages

IMMUNOPROPHYLAXIS
Types of vaccine Recommendation
H. influenzal vaccine a. Children upto age 24 months should be immunised.
b. Children from 18-23 months of age should be immunised—if they attend
day care centres, are immunosuppressed, or have apslenia.
Pneumococcal vaccine Recommended for patients with cardiac or pulmonary disease, Sickle cell
disease, Hodgkin’s disease, multiple myeloma—cirrhosis, alcoholism and
conditions associated with compromised immune system.
Meningococcal vaccine Recommended in epidemics of serogroups A and C disease, in military
recruits, and in travellers in areas where disease is endemic.
 Central Nervous System
24
Brain Abscess

Aetiology
A. Primary sources of infection:
a. Ear: Otitis media
b. Paranasal sinus: Sinusitis
c. Metastatic and haematogenous spread: Bronchiectasis, lung abscess, empyema, congenital heart
disease with right to left shunt such as Tetralogy of Fallot associated with septicaemia, endocarditis
d. Penetrating injuries of head and face.
B. Organisms: Anaerobes, Staph. aureus, Strep. pneumoniae, Strep. viridans, Strep. pyogenese, Haemo-
philus influenzae, Enterobacteriaceae, E. histolytica.

Diagnostic Clues
Clinical manifestations: Evidence of primary source of infection, features of space occupying intracranial
lesion (features of raised intracranial pressure such as headache, vomiting and impaired consciousness,
focal neurological signs such as hemiplegia, seizures).

Laboratory Investigations
a. X-ray skull (gas), sinuses, mastoid and chest (lung abscess).
b. CT scan or MRI: Lucent area with dense rim with shifting and compression of ventricle.
c. EEG: Focal abnormalities.
d. Leukocytosis.

Treatment
A. Symptomatic treatment: Urea, mannitol or dexamethasone for reducing raised intracranial pressure
and cerebral oedema. Dilantin sodium for seizure.
B. Medical therapy: a) If culture not available: Penicillin 4 mega units 4 hourly with gentamicin
(80 mg 6 hourly) and chloramphenicol (4-6 gm/day) or metronidazole 500 mg 6 hourly cefotaxime
12 gm/day. Start with IV followed by oral medication.
C. Surgery:
a. When medical treatment fails and progression and persistence of intracranial pressure manifested
by deepening coma needs operative intervention.
b. Mastoidectomy and drainage of the frontal sinus should be done in case of otitis media and
frontal sinusitis.
c. In osteitis of skull bone: Affected skull bone should be removed.
 Central Nervous System
25
Myasthenia Gravis

Aetiological and Clinical Features you must know for Divising Rational Treatment
Aetiology: Pathogenesis:
Myasthenia gravis is an acquired autoimmune disorder
↓
↓
Formation of antibodies to acetylcholine receptors of
neuromuscular junction Evidence of autoimmune disorder:
i. Antibodies to acetylcholine
receptors of neuromuscular
junction found in 90% patients
ii. Strong association between HLA B8,
BW 35 and B21 antigens with Myasthe-
nia gravis
↓ iii. Thymoma or thymic hyperplasia is
Cause complement mediated damage to the neuro- associated with myasthenia.
muscular junction
↓
Neuromuscular transmission affected
↓
Leads to fluctuating weakness of voluntary muscle
(essential feature of myasthenia)

DIAGNOSTIC CLUES
Fluctuating weakness of voluntary muscles:

Muscle involved Manifestation

i.Extraocular muscles → Ptosis, diplopia, strabismus
ii.Facial muscles → Difficulty in eye closure, whistling, smiling, pouting lips and chewing
iii.Bulbar muscles → Dysphagia
iv. Laryngeal and → Low voice, nasal voice
respiratory muscles
v. Neck muscle → Usually extensors of neck are involved
vi. Limb muscles → Proximal muscles of upper limb frequently involved
164 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Diagnostic hallmark of the disease:

a. Weakness which increases on using the muscles and improves on rest
b. Combination of ptosis, ophthalmoplegia, with weakness of orbicularis oculi but pupils never
involved.

INVESTIGATIONS
a. Demonstration of objective improvement on injection of neostigmine or edrophonium.
b. Demonstration of antibodies in serum against acetylcholine receptors.
c. Demonstration of association of thymic tumor by X-ray chest and CT scan.

TREATMENT
Drugs
Anticholinesterase Drugs
Anticholinesterase drugs augment neuromuscular transmission. See table 25.1.

Table 25.1: Anticholinesterase drugs

Drugs Mode of action Preparation Dose Duration of Side effects
action
Pyridostigmine Inhibits anticho- Mestinon 60 mg Less frequent 4-8 hour Vomiting, exces-
linesterase tablet administration sive salivation,
→ acetylcholine than neostigmine sweating
remains longer at because of pro- abdominal colic,
neuromuscular longed duration diarrhoea. They
junction of action. are controlled by
→ neurotransmi- 60 mg orally Pro-Banthine.
ssion activated Cholinergic cri-
sis: Increasing
weakness mimi-
cking myasthenia
weakness.

Neostigmine Do Tilstigmine (Tab. 15 mg on rising 2-4 hours Do

India) 15 mg tab and before each
Injection 0.5 mg/ meal
ml

Edrophonium Do Tensilon 10 mg/ 2-10 mg IV Very short acting Diagnostic use

ml

Other Drugs
Ephedrine sulfate 25 mg orally b.i.d. or t.i.d. (avoided in prostatis) or potassium chloride
1-2 gm orally in 10% solution bid or tid or calcium gluconate bid or tid are helpful in some patients.
Other Measures
Myasthenia Gravis | 165

Methods and procedures Indications Remarks

1. Thymectomy: Removal of Patient with generalised disease 60-70% remission
thymic tumour preceeded
by medical therapy. If
tumour is locally invasive
radiotherapy is indicated.
2. Immune suppression by:
a. Corticosteroids: Predni- Severally disabling or life threat- Obese, hypertensive and diabetic
solone 1 mg per kg per ening myasthenia who fail to are best not treated with steroids
day in single dose; star- respond to thymectomy or if Remember side-effects of
ting by smaller dose (20 operation is contraindicated chronic steroid therapy
mg/day), increased gra-
dually and tapered to
minimum effective dose
for several months after
patient remains asymp-
tomatic for 2-3 months.
Alternate day therapy is
also recommended.
Methyl prednisolone
pulse therapy is occa-
sionally practiced
b. Cytotoxic drugs; Patient in whom steroid contra- Regular blood monitoring is
i. Azathioprine: Imu- indicated or steroid and thymec- essential
ran 1.5-2 mg per kg tomy failed. Also used to reduce
per day high dose of steroids
ii. Cyclosporine
c. Plasmapheresis: i. For tiding over crisis Short acting
Exchange of 2 litres of ii. For preparing a severly ill-
plasma for equal amount patient for thymectomy
of human albumin or iii. Can be used with steroid to
saline every other day act faster
three times a week.
d. Intravenous immuno- – Do – Costly side-effects more
globulin given 0.4 gm/
kg per day for 5 days

MANAGEMENT OF PRECIPITATING FACTORS

a. Avoid the following: Emotional upset, febrile illness, exposure to extremes of heat (hot bath) and
bright sunlight and overwork specially during pregnancy, puerperium, menstruation, inoculation
and vaccination.
b. Practice relaxation technique and meditation.
166 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

c. Avoid following drugs: Procainamide, quinidine, quinine, chlorpromazine, streptomycin and amino
glycosides.

PLAN OF TREATMENT
Anticholinesterase Drugs Therapy
Start gradually with half of 15 mg tab of neostigmine (7.5 mg) or half of 60 mg tab of pyridostigmine
(30 mg) at 4-hour intervals or bid to tid dosing. If patient has weakness in chewing and swallowing give
the drug 30-60 minutes before meals and refrain from talking while eating. Give small amount of milk,
bread or other bland food before the drug to minimise gastrointestinal side-effect.
↓
Dosages gradually increased at about 2 days intervals. Increase of one-fourth to one-half tab per dose
are recommended.
↓
Next assess the effects of anticholinesterase drugs as follows:
Examine patient just before the next dose and 45-75 minutes after as follows:

Clinical tests Result

Sustained upward gaze test
Continuous counting on a
single breath
Tight jaw closing against
resistant test
If unable to gaze: Suggests fatigue of extraocular muscles and lid
elevators.
If unable to count: Suggests respiratory muscle weakness
Unable to close jaw tightly: Suggests oropharyngeal muscle weakness

Edrophonium Chloride Test

One hour after oral dose of anticholinesterase drug patient ‘strength is tested and then given 2 mg
(0.2 ml) edrophonium chloride IV and strength is tested in 30 seconds to 2 minutes:

Strength unchanged or Strength very much improved If weakness increased with

Decline side-effects
↓ ↓ ↓
Dose of anticholinesterase Acetylcholinesterase drug Dose of acetylcholi-
Drug is not changed is increased nesterase drug is lowered

Management of Mysthenic and Cholinergic Crisis

Increasing muscle weakness with inability to maintain a patient’s airway free of secretions and/or in
adequate respiratory exchange points to crisis. It may be due to:
a. Increase in myasthenia (Myasthenic crisis).
b. Use of too much use of anticholinesterase drugs (Cholinergic crisis).
c. Or both a and b.
Myasthenic crisis Cholinergic crisis
Myasthenia Gravis | 167

Recognised by ptosis, dysarthria dysphagia, Recognised by myasthenic feature (sweating, sali-

dyspnoea and facial weakness, infection, menses,
pregnancy, surgery, overexertion and emotional
upset. Also edrophonium test may help.
Management:
A. Emergency measures: Provide adequate
airway with tracheal intubation if necessary.
Suck secretion and maintain fluid balance and
nutrition.
B. Other measures: Manage precipitating factors
(respiratory infection, overwork, certain
drugs). Start anticholinesterase drugs if
omitted.
vation lacrimation, nausea, vomiting, diarrhoea)
and nicotine clinical features (fasciculation, trismus,
dysphagia, coma, confusion, restlessness and con-
vulsion) due to excess acetylcholinesterase drugs.
Management:
A. Emergency measures: Same as myasthenic
crisis. Atropine is best avoided as it dries
secretions. Change the position frequently,
give postural drainage and percuss the chest,
B. Other measures: Stop acetylcholinergic drugs
for 3 or more days. Preferably done in hospital
because the patient may need. Airway or
mechanical respiration.

Corticosteroid Therapy
Regimes:
a. Alternate day regime: Start prednisolone 25 mg on alternate days, increased by 5 mg every second
or third dose cycle and the dose maintained till the strength begins to improve, dose not exceeding
100 mg on alternate days.
b. Daily regime: Patient requiring respiratory support higher initial dose up to 100 mg daily or methyl
prednisolone 60 mg IM or dexamethasone 12 mg orally, individed dosages daily is recommended.
c. Mixed daily and alternate day regime: Prednisolone 60 mg daily initially and when improvement
occurs, switch on to alternate day therapy.
Since some paradoxical worsening of myasthenia gravis occurs when corticosteroids are first begun,
they are best started in hospital. The patient on corticosteroids should take diet high in protein, potassium
and calcium add antacid and a CID inhibitor drugs.
 Central Nervous System
26
Headache

Classification:
A. Idiopathic or primary headache:
a. Migraine: i. Common migraine (90% cases)
ii. Classic migraine
b. Tension headache : i. Episodic
ii. Chronic
c. Cluster headache

B. Secondary headache:
a. Intracranial causes: i. Vascular headache: Cerebrovascular accident,
Subarachnoid haemorrhage, venous thrombosis.
ii. Nonvascular headache: High CSF pressure, low
CSF pressure
b. Metabolic and hypoxic headache: i. Sudden ascent to altitude above 3000 ft
ii. Chronic pulmonary disease
iii. Sleep apnoea syndrome
c. Reflex headache: i. Cervical spine disorder
ii. Eyes: Acute glaucoma, refractive error
iii. Nose and sinuses: Sinusitis
iv. Temporomandibular joint disorder
d. Neuralgias: i. Trigeminal neuralgia
ii. Glossopharyngeal neuralgia
iii. Occipital neuralgia
iv. Atypical facial neuralgia
C. Miscellaneous headaches:
i. Cold stimulus headache
ii. Benign cough headache
iii. Benign exertional headache
iv. Headache associated with sexual activity
v. Hypertensive encephalopathy
vi. Post-traumatic headache
Diagnostic Clues
Headache | 169

Table 26.1: Some important headaches

Types of head- Site Age and sex Characteristics Diurnal pattern Provoking Associated
ache of pain and duration factors features
Common migra- Fronto-temporal, Child, adult, mid- a. Throbbing or More on awake- See Table 26.2 Nausea, vomi-
ine without aura occipital uni or dle age dull ache ning or later in ting, photophobia
bilateral, retro- More in females b. Disturbs daily the day.
bulbar common activity Duration:
c. Premonitary Hours 1-2 days
symptoms:
Elation, depre-
ssion, pares-
thesia, incre-
ase in urina-
tion and defae-
cation
Classic migraine – Do – – Do – – Do – – Do – – Do – Blindness, unila-
or migraine with Aura: Homony- teral numbness,
aura mous visual dis- disturbed speech,
turbances, hemi- vertigo, confu-
sensory symp- sion
toms, hemipare-
sis, fortification
figures (star sha-
ped), dysphasia

Tension head- Generalised Child, adoles- Pressure not thro- Episodic or con- Fatigue, stress Depression,
ache cent, adult. bbing, tightness, tinuous for weeks anxiety, insom-
Both sexes head-neck pain, and months nia.
local tenderness Nausea absent

Cluster head- Orbital, tempo- Adolescent, adult Non-throbbing, Usually noctur- Alcohol stress, Congested eye,
ache ral, unilateral males 90% intense nal. nitroglycerine lacrimation,
(always on the Duration: 1-2 nasal discharge
same side) hours

Meningeal irri- Generalised or Any age, both Intense to steady From days None Neck stiffness,
tation (SAH) nuchal sexes weeks Kernig’s positive

Brain tumour a. Homolateral to Deep seated pain, Lasting for minu- None Papilloedema,
tumour in 90% variable intensity tes to hours, inc- projectile vomi-
cases. reasing in inten- ting, slow menta-
b. Supratentorial sity tion
tumour ante-
rior to inter-
auricular cir-
cumference of
skull and
posterior
contd...
170 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

fossa tumour
posterior to
this line
Temporal Unilateral tem- Over 50 years Persistent Continuous or Scalp sensitive Intermittent or
arteritis poral or occipital Both sexes intermittent, permanent loss of
lasting for weeks sight, rheumatic
to a few months myalgia, high
ESR and fever.

Diagnostic Evaluation of Chronic Headaches

Two broad clinical categories of chronic headaches of primary type are as follows:

Long duration chronic headaches Short duration chronic headaches

↓ ↓
(Duration more than 4 hours) (Duration less than 4 hours)

1. Migraine 1. Cluster headache

2. Tension headache 2. Chronic paroxysmal hemicrania
3. Daily persistent headache
⇓
Next step is to find out the causes of secondary headaches. See classification. Specially noted are
intracranial (vascular and nonvascular), metabolic, reflex, cranial neuralgias, post-traumatic headache
and also cold, exertional, sexual activity and hypertensive headaches.
⇓
Next find out the provoking factors (See Table 26.2: ‘Migraine Provoking Factors’) and comorbid and
psychiatric conditions.
⇓
Next consider rebound headache which has been recently emphasised. In some cases headache medicines
are taken in excessive amount and more frequently for immediate relief of headache. They are:
a. Analgesic or narcotic rebound headache
b. Ergotamine rebound headache.
⇓

Investigations
1. Chronic benign headache such as migraine or tension headache does not need expensive
investigations, history and physical examination are suffice.
2. Headaches that need investigations are as follows:
Investigations Indications
MRI and CT scan Headaches of recent origin or progressive in nature or persistent focal
distribution or follow trauma or begin after age of 30 years
EEG Never useful in headache
Headache | 171

Skull radiograph a. Suspicion of pathology at the base of the brain such as sellar or
suprasellar regions.
b. Immediately after head trauma
Diagnostic lumbar In acute headache accompanied by fever or explosive and severe onset
puncture as in SAH: LP should be deferred until after CT scan (especially with
stiff neck without fever) is done to prevent herniation of cerebellar
tonsil into foramen magnum secondary to an intracranial mass lesion.

TREATMENT OF HEADACHES
I. Management of causative factors: See classification. Note the causes of secondary types.
II. Management of provoking factors: See the Table 26.2 specially migraine provoking factors: Also
avoid excess cough, cold, exertion, sexual activity, hypertensives.

Table 26.2: Migraine provoking factors

A. Psychological : Stress
Sleep: Too much or too little
B. Physical : Dazzling light
Marked weather change
C. Hormonal : Menarche
Menstruation

III. Non-pharmacological management: Biofeedback, stress management, psychotherapy, lifestyle

regulation, family therapy, acupuncture, massage of back of neck.
IV. Pharmacological therapy: Specially of primary headaches:

Migraine
Table 26.3: List of drugs used in migraine

Drugs Preparations Side effects Advantages (Remarks)

Ergotamine alkaloids: Parenteral (IV, IM, SC)
Ergotamine tartrate, Oral: Cafergot 1 mg tab
Dihydroergotamine Sublingual
Inhalant, rectal
Migril (BW): Ergota-
mine
Tartrate 2 mg + Cycli-
zine HCl
50 mg + Caffeine 100 mg
tab
Gangrene, MI, renal failure, Effective up to 90% within
muscle cramps, paresthesia, first 1-2 hours when given
C/I: Hypertension, vascular parenterally, up to 80% if
and valvular disease, given rectally and up to 50%
pregnancy when given orally
Drug interactions: Beta
blocker and methysergide
increases risk of vascular
occlusion, oral contraceptives
increases risk of thrombosis

Vasograin (Cadila): Ergot. tar.

1 mg + Caffeine 100 mg +
Paracetamol 250 mg tab.
contd...
172 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

NSAID: Naproxen sodium, mec- Hypertension aggravated,

lofenate, ibuprofen, keto- peptic ulcer aggravated Effective both as sympto-
profen matic and preventive
treatment
Prednisolone
Effective only for symp-
tomatic treatment
Hydrocortisone
Indicated in acute and
refractory cases
Beta blockers
Only for prevention

Methysergide
Prevention for difficult to
manage cases

Calcium antagonists Isoptin, diltiazem, nifedipine Not as effective as beta Indicated if beta blockers
blockers contraindicated

Antidepressant Amitriptyline, nortriptyline As prophylactic: Can be of

fluoxetine benefit in cases with
frequently occurring
headache

MOIs Phenelzine (nardril) Hypertensive reaction As prophylaxis

If used with imipramine Refractory cases

Sumatriptan Suminat (Natco) 100 mg tab Cardiac arrhythmia, MI, Acute attack of migraine
Sumitrex (Sun) 25, 50, 100 angina, dizziness, nausea
mg tab C/I: CAD, not used as
prophylactic in migraine
uncontrolled hypertension
Clonidine HCl Catapres
Carbamazepine Tegretol As prophylaxis
Cyproheptidine Periactin As prophylaxis
As prophylaxis. Considerable
importance in childhood
migraine
Dosages and Treatment Plan of Migraine
Headache | 173

Symptomatic Treatment
A. Mild Attack:
Analgesics Antiemetics Sedatives
Aspirin 600 mg Reglan 10 mg Any sedative
or or
Naproxene 500 mg Domperone
or
Mefenamic acid
or
Ibuprofen
B. Severe Attack:
a. Ergotamine tartrate: Oral: At the onset of the attack 2 mg, repeated 2 more dosages
separated by one and half hour (Total dose 3). This sequence may be
repeated 3 times per week but not on daily basis for chronic use.
Rectal suppository: 2 mg → Repeat after one hour. Maximum daily
dose 4 mg.
Sublingual: 2 mg tab given at the onset of attack, may be repeated
once.
b. Tolfenamic acid : 200 mg. As effective as ergot.
c. Fluenamic acid : 200 mg—repeated every 2 hours till 1000 mg given
d. Sumatriptan : i. 3 mg subcutaneous relieves 60% cases in 30 minutes and
80% cases if repeated in 30-60 minutes.
ii. Oral tab: 100 mg, if no relief after 2 hours, 100 mg repeated up to
3rd dose. Even occasionally 25-50 mg is enough. Doses should
not exceed 6-8 mg per month.
Contraindication: Coronary artery disease and hypertension.
e. Lidocaine nasal drop: Relieves headache in 5 minutes in 50% cases.
C. Very Severe Attack:
a. Dihydroergotamine mesylate:
i. IM 1 mg, repeated every hour till 3 mg given in single episode (maximum upto 6 mg in a
week). It must be combined with 10 mg of reglan or 12.5 mg of prochlorperazine.
ii. IV 0.5-1 mg with 10 mg reglan.
or
b. Chlorpromazine : 50-100 mg/day for 7-10 days.
or
c. Prochlorperazine : IV 10 mg
d. Corticosteroids : In refractory cases. Prednisolone 40-60 mg orally per day for 3-5
days. Hydrocortisone: 100 mg IV + 100 cc of 5% dextrose IV given
over 20 to 30 minutes 4 times a day on 1st day, 3 times on the 2nd day,
twice daily on the 3rd day and once daily on the 4th day.
174 |
HEADACHE
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Table 26.4: Summary of headache medications in general

Drugs Preparations Dosing guidelines

NSAIDs i. Ibuprofen 200 mg i. Ibuprofen 1-2 tabs every 4-6 hours

ii. Ketoprofen 12.5 mg ii. Ketoprofen 1-2 tabs every 6-8 hours
iii. Naproxen sodium iii. Naproxen sodium 1-2 tabs every 8-12 hours
200 mg

Ketorolac 15 mg/ml or 30 mg/ml 60 mg IM for adults or 30 mg IM for very slender or elderly

patients; may be repeated every 6 hours maximum of 120
mg/daily or 60 mg/daily

Tramadol 50 mg oral tab 50-100 mg as needed every 4-6 hours not to exceed 400
mg/day

Nortriptyline Oral tab = 10, 25, 50 and 75 mg. 10-25 mg at bed time and may increase as tolerated and as
Solution 10 mg/5ml necessary. As prophylaxis for migraine and tension
headache.

Sertaline 50-100 mg tab 25-50 mg every morning. As prophylaxis for migraine and
tension headache

Ergotamine 2 mg sublingual tab Onset of attack: 1 tab, may repeat every 30 min to maximum
of 3 tabs in 24 hours as needed, do not exceed 10 mg/week

DHE 45 (dihydroergo- 1 mg/ml for IM or IV injection 1 mg IM at the onset of attack, repeat at 1 hour intervals to
tamine) total of 3 mg. For more rapid relief 1 mg IV to maximum
of 2 mg; do not exceed 6 mg/week

Sumatriptan 25 mg and 50 mg tab or i. Oral: 25-100 mg, may repeat 100 mg after
12 mg/ml injection 2 hours if no relief; maximum dose 300 mg in 24
hours
ii. Injection: 6 mg/SC, may repeat 6 mg in 1 hour if no
relief; maximum 12 mg in 24 hours

Methysergide 2 mg oral tab 4-8 mg daily with meals; drug free interval
Is needed every 3-4 months to avoid fibrotic complications

Lithium 300 mg capsule or controlled 600-900 mg daily in divided dosages, serum level should
release capsules be maintained between 0.6 to 1.2 mEq.
contd...
contd...
|
Headache 175

Drugs Preparations Dosing guidelines

Ciproheptadine Syrup 2 mg/ml (with alcohol); Pediatric: 0.25 mg/kg/day in divided dosages. Maximum
4 mg tab daily dose: Less than 6 years = 12 mg, above 7 years =
16 mg

Propranol i. SR capsule = 60, 80, Start at 10 mg b.d. and increases gradually (over 3-4
120, and 160 mg weeks) to maximum 160 to 240 mg/day may switch to
ii. Tab = 10, 20, 40 mg sustained release when daily dose becomes stable.
iii. 4 mg/ml injection

Calcium i. Tablet 40, 80, 120 mg Usual effective dose 160 to 480 mg starting with 120
Channel ii. Sustained release 120, mg. As prophylaxis in migraine.
Blocker 180, 240 mg

Methadone 20 mg tab 20 mg/day. Side-effects: Nausea, fatigue sweating

Acetominofen Crocin 500 mg tab 1-2 tab three times a day. Aborts migraine

Lidocaine Nasal drop Aborts migraine and cluster headache. Relieves headache
in 5 minutes in 50% cases.

Valproate Prophylaxis for migraine

Valproate +Verapamil Prophylaxis for cluster headache

Aspirin Prophylaxis for vascular headache

Oxygen Symptomatic treatment for cluster headache

Table 26.5: Comparison of prophylactic drug in chronic headache

Drugs Clinical benefits Side-effects

Amitriptyline +++ ++
Doxepin +++ ++
Fluoxetine ++ +
Divalporex +++ ++
Verapamil ++ +
Methysergide +++ +++
176 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Approach to the Treatment of Chronic Headache: Flow Chart:

First give antidepressant or beta blocker
↓
If fails: NSAID
↓
If fails: Calcium channel blocker
↓
If fails: Methadone 20 mg/day for one year. No addiction

Indications for Prophylactic Therapy

i. Frequency greater than 1-2 headaches per week
ii. Medical contraindications for symptomatic treatment
iii. Failure of symptomatic treatment
iv. Predictable regularity of attack such as at menstrual period
v. Known substance abuse tendencies

Chronic Tension Headache

I. Non-pharmacological therapy: See behind.
II. Pharmacological therapy:
1. Withdrawal of aspirin, acetaminophen and other analgesics to prevent analgesic rebound
headache.
2. Drugs:
A. Symptomatic treatment:
i. Analgesics: NSAIDs
ii. Muscle relaxants: Metaxolone, cyclobenzaprine, carisoprodol, methocarbamol,
benzodiazepines
iii. For more frequent attacks: Combination of beta blocker 60-160 mg + amitriptyline 50-
150 mg at bedtime. NSAID may be added if necessary.
B. Preventive treatment: See migraine.

Cluster Headache
I. Non-pharmacological therapy:
a. Discontinuence of alcohol
b. Discontinuence of smoking
c. Avoid day time napping
II. Pharmacological therapy: A. Symptomatic treatment:
a. Inhalation of 100% oxygen for 15 minutes or more
b. Persistent chronic cases:
i. Lithium carbonate
ii. Calcium channel blockers
iii. Rectal ergotamine
iv. Chlorpromazine
 B. Preventive treatment:
Headache | 177

Daily intake of ergotamine or methysergide

Prednisolone more effective
Lithium carbonate 300 mg, 2-4 times a day
Calcium channel blockers
NSAIDs: Indomethacin 25-50 mg, 3-4 times a day
Chlorpromazine 75 mg to several hundred milligrams per day
III. Surgical treatment: Surgery or other ablative procedures on the sphenopalatine ganglion, nervous
intermedius or the branches of trigeminal nerve. May be effective in some absolutely intractable
cases.

Migraine
Proven and effective relievers:
a. Tranquilizers: Haloperidol, chlorpromazine
b. Anticonvulsant: IV valproate is very effective.
Unproven preventive: Verapamil, magnesium, fluoxetine HCl, aspirin

Tension Headache
Best reliever is tricyclic antidepressant
Others: Buspirone, d-amphetamine, tizanidine

Cluster Headache
Best reliever is sumatriptan
DHE IM
Established preventers : Prednisolone, methysergide, verapamil, lithium
Best combination:
Start verapamil + prednisolone
↓
When symptoms stabilized : Gradually taper prednisolone to prevent steroid side-effects.
Unestablished preventer:
Divalporex, melatonin (10 mg nightly), beclofen, topamax.

Chronic Paroxysmal Headache

Indomethacin
Celecoxib
Diomox
 Central Nervous System
27
Treatment of Certain Neurological
Symptoms and Diseases Not
Already Described

Symptoms and diseases Treatment

1. Raised intracranial pres- i. Mannitol (20%) 110 ml 4-8 hourly IV
sure ii. Glycerol (10%) IV 1 to 2g/kg over 4 hours
iii. Dexamethasone 12-20 mg/24 hours

2. To reduce raised intra- a. Acetazolamide reduces secretion of CSF by inhibiting enzyme

ventricular pressure in carbonic anhydrase
mild hydrocephalus b. Oubain, isosorbide and frusemide also reduce CSF secretion
c. Oral glycerol is also used successfully
d. Progressive postmeningetic hydrocephalus of tuberculous origin can
be helped by intrathecal corticosteroid or hyaluronidase apart from
tuberculous chemotherapy
e. Hydrocephalus of pyogenic meningitis origin helped by antibiotics

3. Dementia i. For sleep: Triclofos 500 mg at bedtime

ii. Incontinence: Periodic voiding, incontinence devices, intermittent
catheterisation.
iii. Repetitive behaviours: Tranquilisers, e.g. short acing benzo-
diazepines or phenothiazines
iv. Ergot alkaloids may improve mood
v. Cholinergics: Acetylcholine precursors, choline and lecithin
coadministered with piracetam have some beneficial effects
vi. Physostigmine sometimes used to improve overall function
vii. Centrally active acetylcholinesterase inhibitors, such as tacrine in
dosages up to 160 mg daily may benefit
viii. Experimental drugs: Drugs which may directly stimulate
postsynaptic acetylcholine M1 receptors and block presynaptic
autoregulatory acetylcholine M2 receptors, and thus maximizing
the effect and release of the cognitively important neurotransmitter.
 Treatment of Certain Neurological Symptoms and Diseases Not Already Described

ix. Alcoholic induced dementia: Thiamine 100 mg IV, followed by 50

| 179

mg daily.

Trigeminal neuralgia i. Most effective drug: Carbamazepine 200 mg t.d.s. or q.d.s.,

increased gradually till symptoms completely relieved within a few
weeks to months and then withdrawn gradually. If the pain recurs,
restart the drug again.
ii. Other drugs: Phenytoin, beclofen and amitriptyline
iii. Patients not responding to drugs or intolerant to drugs, injection of
alcohol, radiofrequency thermocoagulation of gasserian ganglion
and microvascular decompression.

Bell’s palsy Protection of eye, facial exercise, faradic stimulation and splints to
prevent drooping of the lower face. Prednisolone 1 mg/kg/day during
initial 10 days has variable results.

Méniére’s disease i. During an attack: Must rest lying down. Chlorpromazine 50 mg

IM dimenhydrinate 50 mg or promethazine 25 mg or prochlora-
perazine 5 mg may be used regularly as a vestibular sedative.
ii. If after 6 months drugs fail and attack is severe surgery should be
considered. Endolymphatic subarachnoid shunt, ultrasonic
irradiation and decompression or cannulation of endolymphatic sacs.
Cochleovestibular neurectomy performed when there is no useful hearing.

Tinnitus Treatment is disappointing. Local lesions should be treated appropriately.

Sedatives, hypnotics and tranquilizers have some palliative action.
Antidepressants sometimes help. In occasional cases with severe,
intolerable tinnitus cochlea is destroyed.

Bulbar palsy Recently antiglutamate agents, riluzole, improve the survival. In the past
guanidine hydrochloride, injection of cobravenom in small dosages and
thyrotropin-releasing hormone have been tried with variable results. Treat
the cause.

Glossopharyngeal neuralgia Carbamazepine 200 mg tds or qds can control the pain satisfactorily in
majority of patients.

Sleep-apnoea syndrome i. Weight reduction

(SAS) ii. CNS depressants should be discontinued such as alcohol or
sedatives.
iii. Avoid supine posture (apnoeic events common in supine posture).
iv. Medroxyprogesterone acetate helps mild cases but feminising side-
effects in males restrict its use.
v. Protriptyline (a tricyclic antidepressant) reduces daytime somno-
lence but beware of anticholinergic side effects (constipation, impo-
tency, difficulty with micturition).
180 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

vi. Continuous positive airway pressure (CPAP) is very effective even

in severe cases.
vii. Tracheostomy: Most effective treatment of severe and life-threate-
ning SAS.
viii. Surgery: Uvulopalatopharyngoplasty effective in 50% cases of mild
to moderately severe cases of SAS. Anatomical lesions if any should
be corrected such as tonsillectomy, adenoidectomy, maxillomandi-
bular surgery.

Narcolepsy/Cataplexy: i. Excessive somnolence: Treated by CNS stimulant such as

Excessive daytime sleepiness dextroamphetamine (5-50 mg/day), methylphenidate (5-80 mg/day)
with cataplexy, sleep para- or premoline (18.75-150 mg/day). The dose is adjusted according
lysis to patient’s need and the dose should be kept as low as possible.
The drug is stopped on week days to prevent tolerance.
ii. Cataplexy and sleep paralysis: Tricyclics suppresses them.
Imipramine (50-150 mg/day) or protriptyline (10-40 mg/day) is
effective in 80% patients. Fluoxetine is also effective.

Periodic leg movement: Con- i. Clonazepam (0.5 mg-2 mg at bedtime)

sists of dorsiflexion of foot ii. In severe cases: Dopa/carbidopa (Sinmet 25/100) starting with small
and flexion of knees and hips. dose.
May cause insomnia or day-
time sleepiness

Restless leg syndrome: Clonazepam (0.5-2 mg) at bedtime. In severe cases dopa/carbidopa or
Characterised by uncomfor- propoxyphene or codeine may be effective.
table paresthesia inside
calves + insomnia. May be
idiopathic or secondary to
anaemia, polyneuropathy,
cancer, motor neuron disease,
etc.

Sleep walking: Diazepam, imipramine and anticonvulsants may help

Enuresis Imipramine is helpful in older children

Subarachnoid haemorrhage i. General nursing and medical care is like cerebrovascular accident
(see chapters on cerebral thrombosis and haemorrhage) is essential.
ii. Acetaminophen, meperdine and phenobarbitone can be given.
Aspirin is contraindicated.
iii. Chlorpromazine sedates and controls nausea and vomiting.
iv. Gama aminocaproic acid and related derivatives like tranexamic
acid 20-40 g IV 8 hourly reduces rebleeding but there is increased
risk of cerebral infarction.
 Treatment of Certain Neurological Symptoms and Diseases Not Already Described
Acute viral meningitis
Herpes simplex; Encephalitis
Slow viral disease:
Child shows behavioural dis-
turbance and poor perfor-
mance in school, myoclonic
jerks, visual disturbance,
pyramidal and extrapyra-
midal signs and dementia
Neurosyphilis:
v. Symptomatic vasospasm is prevented by calcium channel blockers
| 181
like nemodipine (0.7 mg/kg followed by 0.35 mg/kg every 4 hours
for 21 days).
vi. Surgery: Aneurysm in accessible territories should be operated upon
as soon as possible. Subdural bleed or clot should be evacuated
immediately.
i. Supportive measures and symptomatic treatment
ii. Raised intracranial pressure: Mannitol 0.5 gm/kg of 20% solution
over 20 minutes every 4-6 hours reduces pressure.
iii. Cerebral oedema: Steroids used to decrease oedema.
iv. Anticonvulsants such as phenytoin or carbamazepine may be used
as prophylactic.
i. Supportive care: Reduction of cerebral oedema, control of seizure,
circulatory and respiratory support.
ii. Drug of choice: Acyclovir as IV infusion over 1 hour at a dose of
10 mg/kg every 8 hours for 10 days. To avoid renal insufficiency
proper hydration is essential. It reduces mortality and residual
symptoms.
It is almost always fatal
Anti-viral drugs: Inosine pranobex, ribavirin, and interferon have been
reported to prolong survival. Clonazepam controls myoclonus.
i. Penicillin regimes: Believed to be inadequate: Procaine penicillin
1.2 million U b.d. + Probenecid 2 gm daily for 15 days
↓
If fails:
Penicillin 2 million U IV 4 hourly for 15 days
ii. Oral amoxycillin 3 gm daily for 15 days + Probenecid for 15 days
↓
If sensitive to penicillin:
Tetracycline 500 mg 6 hourly either as one month’s course or
three 15-days courses at monthly intervals
iii. Jarisch-Herxheimer reaction occurring at the start of treatment
(worsening of neurological features + fever + headache + arthralgia).
Treated with steroids because it is allergic reaction to killed
spirochaetes.
After treatment repeat CSF examination and check after 6 weeks
and then 3 months. The CSF cells and protein should become
normal. If VDRL titre rises repeat therapy.
182 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

iv. Lightening pain responds to carbamazepine.

v. Gastric crisis: Treated by adrenaline 0.5 ml 1: 1000.

i. Metronidazole 1 gm IV, followed by 500 mg IV 6 hourly until oral

Cerebral amoebiasis: medication is possible
Oral metronidazole 800 mg 8 hourly (in children 35-50 mg/kg/day
in three divided doses) for 10 days
or
ii. Emetine regime: Emetine 1 mg/kg/day (maximum 60 mg/day) IM
for 5-10 days.
or
iii. Chloroquine regime:
First day : 1200 mg/day (loading dose)
Second day : 1200 mg/day (loading dose)
Afterwards : 600 mg/day for 2-3 weeks
iv. Amoebic meningoencephalitis : Amphotericin B + Rifampicin
Neurocysticercosis
i. Seizure : Anticonvulsant
ii. Cysticidal drugs : They are still controversial. Because most forms
are benign and self-limited. In encephalitic and disseminated forms
they must be used with great caution. Albendazole (15 mg/kg/day
for 7-28 days) or praziquantel (50 mg/kg/day for 14 days). Steroids
may be required.
iii. Surgery: Shunting or by removal of obstructing cysticercus.
Cysticercosis:
Repeated, month long courses of albendazole (400 mg b.i.d.). It causes
shrinkage of cysts but partially successful.

Treatment of Some Important Industrial and Chemical Poisons

Poisons Treatment
Arsenic used in rat poisons, pesticide, paint and BAL, pencillamine
glass enamel; causing encephalopathy and neuro-
pathy

Ethylene glycol used in antifreeze; causing stupor, Ethanol

coma, convulsion

Lead used in storage battery, polishing, soldering, BAL, Ca-EDTA, pencillamine

silver refining; causing encephalopathy, neuropathy

Manganese used in mining, smelting, dry batteries; Ca-EDTA

causing hallucination, confusion, psychosis,
parkinsonism, dystonia, spastic paraplegia
 Treatment of Certain Neurological Symptoms and Diseases Not Already Described

Methylbromide used in fumigant, insecticide, BAL

| 183

refrigerant; causing acute psychosis, convulsion,

ataxia, tremor

Methyl alcohol used in solvent, antifreeze; causing Ethanol

visual symptoms, blindness

Methyl mercury used in industrial effluent; causing BAL, pencillamine

polyneuropathy, choreothetosis, parkinsonism,
visual and hearing loss

Organophosphate used in pesticide; causing ----------------

peripheral neuropathy

Thallium used in extraction from ore, pesticide, Prussian blue, potassium chloride
firework, optical lens industry; causing acute
confusion, delirium, coma, hair loss ataxia, foot
drop, tremor

Guillain-Barré syndrome: Characterised by sudden i. General nursing care, care of skin, preventing
weakness in limbs in a previously healthy individual contractures
ii. Plasmapheresis: Reduces duration of illness.
2000 ml plasma removed from a patient at a
time and replaced with albumin. Up to 5-6
sittings on alternate days (total 200-250 ml/
kg) are advocated.
Indications: Any patient (not only serious
patient) as soon as he looses the ability to walk
unaided or show early bulbar affection.
iii. IV immunoglobulin 0.4 gm/kg daily for 5
days. It is very expensive.
iv. Ventilatory support for 2-6 weeks.
Indications:
a. Unexplained tachycardia
b. Unexplained sweating
c. Fall in single breath count below 10
d. Paradoxical respiration
184 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Peripheral Neuropathy
Entrapment neuro- Neuralgic amyo- Porphyric neuro- Post-antirabies Diabetic neuro- Guidelines for
pathy trophy pathy vaccine pathy treatment of
neuropathy
( C a r p a l - Tu n n e l Severe pain in i. IV haematin 4 Neuropathy: i. Control of dia- i. Eliminate causes
syndrome) shoulder with mg/kg for 3- Steroids betes specially in toxic
i. Mild cases: weakness of 10 days ↓ ii. For pain and and deficiency
anti-inflamma- shoulder muscles: ii. Anticonvulsant- If fails: Cyclophos- paresthesia: disorders
tory drugs and benzodiazepine phamide Carbamazepine ii. For immune
diu- retic or valproate 300-400 mg/ mediated neu-
ii. Severe cases Physiotherapy only day or ropathies:
with clearcut amitriptyline a. Steroids in
motor symp- 30-50 mg/day GIDP, colla-
toms: Decomp- ↓ gen disease,
ression surgery If fails: Capsaicin ARV neuro-
ointment 0.75% pathy, etc.
Occasionally b. IV immuno-
maxiletine 100 globulin and
mg b.i.d. helps. plasmaphe-
resis in GBS,
gammopathy,
GIDP
c. C y c l o p h o s
phamide in
multifocal
neuropathy
d. Certain
deficiency
disorder
neuropathy:
Pyridoxin in
INH
neuropathy
and vit E in
abetalipo-
proteinemia
e. For pain and
paresthesia:
Carbamaze-
pine, amit-
riptyline
Mexiletine
and capsai-
cin ointment
f. Splint and
crutches for
foot drop or
wrist drop
contd...
contd...
Treatment of Certain Neurological Symptoms and Diseases Not Already Described | 185

g. Postural hypotension if
present: Raise head end of
bed, elastic bandage or
elastic stockings for legs
before getting out of bed,
2 cups of coffee daily,
indomethacin and fludro-
hydrocortisone 1-2 mg/
day if the other above
measures do not helpful.
 Central Nervous System
28
Psychiatric Disorders

SCHIZOPHRENIC DISORDERS
Aetiological, pathophysiological and diagnostic clues:
Aetiology and pathophysiology: Unknown. An abnormality in functional integration of sensory and
cognitive information exists in schizophrenia. Suggested theories:
A. Genetic factor: 10-15% of offspring of a schizophrenic parents at risk for the disease
B. Biochemical factor: Altered dopamine metabolism resulting in excess dopamine in basal ganglia
may be responsible.

Diagnostic Clues
Clinical features: Delusion ++++; hallucination ++++; incoherent speech ++++; depressed mood;
grandiosity ++.
Prodromal symptoms: Marked social isolation; markedly peculiar behaviour (collecting garbages,
talking to self in the public); hoarding of food.
Recurrent illusions: Sensing the presence of a force or a person not actually present.

TREATMENT
Drug Therapy
Neuroleptics
Drugs Daily dose Side-effects Remarks
Range (mg) i. Drugs such as benztropine
I. Phenothiazines mesylate (cogentin), diphenhydra-
a. Chlorpromazine 300-800 i. Extrapyramidal side-effects mine HCl (benadryl) and trihexy-
ii. Tardive dyskinesia: Choreo- phenidryl artane are added to
athetoid movements involving neuroleptics to prevent extra-
mouth, lips, tongue, limb, and pyramidal side-effects.
trunk. Frequent early sign is ii. Tardive dyskinesia: No effective
vermicular movement of tongue treatment is available. Gradually
decrease the dose of neuroleptics
b. Thioridazine 150-800 – Do – – Do –
(melleril)
c. Perphenazine 8-60 mg – Do – – Do –
d. Trifluoperazine 4-60 – Do – – Do –
contd...
contd...
Psychiatric Disorders| 187

II. Butyrophenones: – Do – – Do –
Haloperidol 2-40
III. Thioxanthenes 6-60 – Do – – Do –

Plan of Drug Therapy

Increase the dose till hallucination, delusion and disorganised thinking decrease or extrapyramidal side-
effects appear. There is no difference in efficacy of neuroleptics. A recommended regime is as follows:
Start with phenothiazine
↓
No response. Change to butyrophenones or thioxanthenes.
 Central Nervous System
29
Affective Disorders (Depression)

CLASSIFICATION
Major depression Minor Depression
Appetite Poor or excess Same as major depression
Sleep Insomnia or hypersomnia Do
Energy Loss of energy or fatigue Do
Self-esteem Feeling of guilt Low
Weight Significant weight loss or gain Not much
Concentration Poor Poor
Hope a. Loss of interest in all activi- Pessimism
ties
b. Suicidal tendency
Agitation or Present Usually not marked
Retardation No manic swing Never had manic episode
Mania At least present for 2 week period At least for two years duration
Duration during which there has been
depressed mood most of the day

Psychotic No No
Symptoms like schizophrenia
Organic aetiology of symptoms

TREATMENT
Treatment of major depression:
Drug therapy: Antidepressant drugs:
Drugs Daily dose Side-effects Remarks—Advantages
range (mg)

A. Tricyclic or tetracyclic antidepressants:

Imipramine 150-300 Anticholinergic side-effects,
sedation, hypotension, cardiac
(palpitation, tachycardia, depres-
sed ST segment, flattened T,
Imipramine and desipramine are
alerting antidepressant, useful in
patients with retardation and
hypersomnia less anticholinergic
side-effects.
Desipramine 150-300 prolonged QT), neurological Nortriptyline, amitriptyline, tri-
|
Affective Disorders (Depression) 189

Amitriptyline 150-300 (tremor), weight gain, impotency, mipramine, doxepin are sedative
Trimipramine 150-300 antidepressants, useful in patients
Nortriptyline 50-150 with agitation and insomnia.
Protriptyline 15-60 Amitriptyline more anticho-
Doxepin 150-300 linergic +++; imipramine nortrip-
Amoxapine 150-400 tyline and doxepin are moderately
Clomipramine 150-250 anticholinergic
Mianserin 30-90 Side-effects ++; and
Desipramine has least side-effects

B. MAOIs:
Phenelzine 15-90 Orthostatic hypotension, weight Anticholinergic side-effects
gain, sexual dysfunction, insom- moderate ++
nia, myoclonus, renal disorder,
seizure, cardiac (palpitation),
hyperthyroidism, hypertensive
crisis if taken with tyramine
containing food, sudden rise of
blood pressure, may precipitate
headache and stroke.
Isocarboxazid 10-30 – Do – – Do –
Selegiline 10-15
Moclobemide 150-600

C. Serotonin specific reuptake inhibitors (SSRI):

Fluoxetine 20-80 Anorexia, nausea, diarrhoea, No anticholinergic side-effect, no
Sertraline 50-200 insomnia, tremor, dizziness weight gain

D. Miscellaneous Antidepressant Drugs:

a. Trazodone 200-600 Sedation, orthostatic hypotension, Safer

priapism, dizziness
b. Amineptine 100-300 Insomnia, headache
c. Bupropion 200-300 Agitation, insomnia, headache, No anticholinergic side-effect, no
tremor, seizure, nausea, vomiting cardiac effect
constipation
d. Dextro- 15-30 Insomnia, anorexia, agitation
amphetamine
e. Alprazolam 1-6 Drowsiness, dizziness, ataxia
190 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Other Modes of Treatment

A. Management of stress.
B. Support of family and friends must be enhanced
C. Other biological therapies:
a. ECT: Indications:
i. Patients with suicidal tendencies
ii. Drug resistant depression
b. Phototherapy
c. Sleep deprivation
D. Psychotherapy: Short-term psychotherapies are found to be useful in depression. Cognitive therapy
is useful in cognitive disorders. Behaviour therapy helps some patients. Interpersonal therapy
manages patient’s interpersonal problems.

Plan of Treatment of Major Depression

Determine whether the patient has agitation and insomnia or psychomotor retardation and hypersomnia
↓ ↓
Patient with agitation, insomnia and anxiety Patient with retardation and hypersomnia
↓ ↓
Give sedating antidepressants (amitriptyline, Give alerting antidepressants (imipramine,
Nortriptyline, doxepin, trimipramine) at bedtime desipramine) in the morning in divided dosages.
Older patients should be given lower dosages. Dosages should be increased progressively every 3-
4 days as tolerated. Special attention should be paid to cardiovascular status while dosages are increased.
Patients should be maintained on antidepressant drugs for 2-6 months. Then the dose can be gradually
reduced by about 10% reduction in dosages every week or every other week. The patient is advised not
to stop the drug suddenly.
Prophylaxis : Chronic administration of tricyclic antidepressant drugs reduces the frequency of episodes
in recurrent depression. Usually 100-150 mg of amitriptyline or imipramine is used.
Depression in elderly : Usually lower dosages is used for example 10-25 mg of amitriptyline daily
and very slowly increased, monitored by blood pressure measurement and cardiovascular status. New
antidepressants lacking in cardiovascular effect such as fluoxetine or bupropion can be used.
 Central Nervous System
30
Grief Reaction

Relatives of patients who died show depressed mood, sleep disturbances and crying lasting for two to
six months. Panic attack may develop.
Supportive treatment by physician himself:
i. Share his feelings.
ii. Review the relationship of the decreased with the important people in their lives.
iii. Find new persons with whom the bereaved can develop relationship.
iv. Suggest to the bereaved measure to combat stress
v. Organise support groups.
Medications:
i. Treat depression with antidepressant drugs.
ii. Treat panic disorder. See further.
iii. Mild sedation and hypnotics may be needed.

Suicidal Tendencies
Suicide is high in:
i. Depressed patients
ii. Alcoholics
iii. Schizophrenics
Diagnostic clues:
i. Age 20-45 years more prone to suicidal tendencies.
ii. Widows, divorced, solitude, unemployed or retired
iii. Enquire whether they have had thoughts about death or suicide (“better off dead” or “people would
be better off without me”).
iv. Preoccupation with funeral, cemetery, burning ghat
v. Planning to buy weapons
vi. Patient agitated or depressed
Management:
i. Need psychiatric consultation
ii. Arrange for supportive environment
iii. Avoid prescribing heavy dosages of sedatives, hypnotics and antidepressants. Inspite of physician’s
instruction the patient may take them in excess dosages.
192 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

MANIC—DEPRESSIVE DISORDERS (BIPOLAR DISORDER)

Diagnostic Clues
Mood changes from episodes of major depression to significant manic episodes (expansive euphoric
mood with grandiose plan, agitation and aggressiveness, feels rested after only three hours of sleep,
talkative, flight of ideas, buying sprees, reckless driving). There is usually a return to normal behaviour
between episodes.

Treatment
Acute manic phase: Better treated in hospital. Sedative such as benzodiazepine particularly lorazepam
effectively controls acute episode. Lithium is not indicated in acute episode.
If marked agitation is not controlled:
i. Psychiatric consultation is needed.
ii. ECT may be considered.
Use of lithium:
Indications: i. For preventing relapses specially manic relapses than depressive episodes.

ANTIMANIC DRUGS
Table 30.1: Antimanic drugs
Drugs Daily dose range (mg) Side-Effects
A. Lithium: Mirtazepine 15-45 Tremor, diarrhoea, weight gain, polyuric
diabetes insipidus, headache, oedema,
seizure and dysrythmias
Do
Lithium carbonate 900-2100 (serum level
1.2 mEq/L)

B. Anticonvulsants: Carbama- 600-1000 (serum level 8-12 mg/ml) Leukopenia, agranulocytosis, aplastic
zepine (adjuvant for resistant anaemia hepatitis, GI disturbances
depression) Tremor, alopecia, weight gain, GI
Sodium valproate 20 mg/kg/day symptoms, blood dyscrasias
Drowsiness, dizziness, ataxia
Clonazepam 1-6
Hypotension, tachycardia, bradycardia,
C. Calcium channel 120-360 heart block, GI symptoms, headache,
blockers constipation

Drugs for acute mania:

a. Haloperidol; 5-10 mg IM every one to two hour. Add antiparkinsonian drugs to prevent parkinsonian
side-effects.
b. Thioridazine: Starting dose 200-400 mg perday. It does not raise blood pressure nor any
extrapyramidal side-effects.
c. Occasionally lithium carbonate is combined with antipsychotic drugs. Starting lithium 300-600 mg
first day, then dose is increased daily until therapeutic blood concentration is reached.
Procedure of Lithium Therapy
Grief Reaction | 193

Prior to the beginning of lithium therapy complete blood count, urine analysis, electrolytes, BUN,
creatinine should be done. Exclude renal insufficiency and marked other medical ailments.
Start lithium 300-600 mg on the first day, increased daily till therapeutic serum level is reached. Half-
life of lithium is 24-36 hours and it takes at least 4 days to achieve a steady state and successful effect.
Serum level should be monitored.
If lithium fails or would not be tolerated or contraindicated : Carbamazepine and other anticonvulsants
may be effective. Benzodiazepine may also be effective.

Depressive Phase
Treated like any depressive illness.
Prognosis: Two-third of patients do well, about 15% will have some improvement and the remainder
will do poorly.

ANXIETY DISORDERS
Classification and Diagnostic Clues
I. Generalised anxiety disorder: Characterised by dyspnoea, palpitation, chest pain, sweating dizziness,
nausea, paresthesia, hot flushes, trembling, simple phobias (fear of dying, flying, heights and snakes).
Exclude any organic aetiology for example hyperthyroidism.
II. Panic attack: Chest pain, tachycardia, irregular heart beat, epigastric distress, headache, dizziness,
syncope and paresthesia.

Treatment
Panic attack:
A. Usual drug:
a. Tricyclic antidepressant. Most effective is imipramine.
b. MOI: Most effective is phenelzine
c. Benzodiazepine particularly alprazolam 1-6 mg/day
d. Fluoxetine
e. Beta blocker can be used for tachycardia and palpitation.
B. Psychological treatment: Reassure the patient that it is well known treatable illness. Encourage
family therapy and other supportive relationship. Behaviour therapy also can be helpful. Occasionally
hypnotherapy, yoga and meditation help.
Generalised anxiety disorder:
A. Drugs:
a. Tricyclic antidepressants
b. Benzodiazepine
c. Fluoxetine
194 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

d. Beta blocker
e. Buspirone
B. Psychological intervention
C. Other measures:
i. Counselling
ii. Relaxation technique
iii. Behaviour modification
iv. Exercise.
Phobic disorders:
i. MOI
ii. For social phobia : Propranolol
Obsessive compulsive disorders:
i. Clomipramine 150-200 mg/day in divided dosages
ii. MOI
iii. Fluoxetine or sertraline.
 Central Nervous System
31
Alcohol

Determine the following points from the history for devising rational treatment:
a. Drinking pattern
b. Average daily consumption
c. Relation of leisure activity with drinking.

Diagnostic Clues
Clinical features:
a. Light eating or skipping meals
b. Scarring and bruising due to injury
c. Coating of tongue
d. Conjunctival injection
e. Facial telangiectasis
f. Tachycardia and hypertension
g. Soft and tender hepatomegaly
Investigations: Mean corpuscular volume, serum glutamic pyruvic transaminase (SGPT), other liver
function tests.
Markers of heavy drinking:
Tests Values
Gamma glutamyl transferase (GGT) > 30 U/L
Mean corpuscular volume (MCV) > 91 µm2
Serum aspartate aminotransferase (AST) > 45 IU/L
Serum alanine aminotransferase > 45 IU/L

Treatment
Detoxification and winning off:
A. Drug therapy:
Drugs Remarks
Benzodiazepine Relatively safe. Replacement with benzodiazepine and then win off. It is used
Lorazepam for 5-10 days.
Chlordiazepoxide Advantage: Can be abruptly reduced and stopped.
Diazepam – Do –
196 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Other drugs used for withdrawal:

Propranolol
Clonidine
Carbamazepine
Nutritional supplements: Parenteral thiamine 100 mg daily for 5-7 days. Other nutritional
supplements should be given.
B. Management and maintenance of abstinence:
Disulfiram: 250-500 mg once daily acts as detergent. It is used in consenting patients. It is important
to involve a reliable family member in whom patient has also trust, to ensure compliance. He
should be thoroughly explained about the possible reactions such headache, nausea, dizziness, and
loss of consciousness, which can occur in the event of consuming alcohol. Such reactions can
occur up to a week after stopping disulfiram.
C. Management associated psychiatric illness:
i. Should be treated appropriately by psychotherapy.
ii. Oral haloperidol 1-1.5 mg thrice daily used in chronic alcoholic hallucination.
iii. Lithium or tricyclic antidepressants may help to control primary psychiatric illnesses that
predispose individuals to consume alcohol. Recently fluoxetine (20-60 mg/day) or clomipramine
50-15 mg/day have been used to reduce craving.
D. Psychosocial therapy includes behaviour therapy, family support and self help group.
E. Seizure: Treated with diphenylhydantoin 100 mg twice or thrice daily.
 Central Nervous System
32
Drug Abuse and Dependency

DRUG ABUSE AND DEPENDENCY

Drugs Withdrawal symptoms Other disorders Treatment

Opioids: Dysphoric mood, i. Intoxication: A medical emergency requir-

i. Oral: Oral raw nausea/vomiting, ing respiratory support. Naloxone 0.5-0.8
opium (Northern muscle ache, lacrima- mg IV—repeated at interval of 3-5 minutes
India), buprenor- tion if no response.
phine (in cities) ii. Opiate withdrawal: Methadone 15-30 mg
and methadone orally, repeated after 2 hr, if required
(in the West) maximum of 40-50 mg/day. L-alpha-acetyl
ii. Inhalant: Brown methanol (LAAM). Clonidine 0.1-0.8 mg/
sugar days in divided dosages
iii. Parenteral: Mor- iii. Maintenance of abstinence after detoxi-
phine, pethidine, fication:
pentazocine a. Medications: Methadone or naltrexone
(opioid antagonist) 100-150 mg orally
twice weekly
b. Counselling and group therapy

Cannabis: Nausea, anorexia, a. I n t o x i c a t i o n : a. Acute: Haloperidol 10 mg/day

Bhang, Charas, irritability, insomnia delirium, confu- b. Chronic: Abstinence. Psychotherapy
Hashish orally or sion, disorien-
cigarettes smoking tation
b. P h y s i o l o g i c a l :
Increased appetite,
diarrhoea, dry
mouth
c. Urine analysis is
specific.

Sedative, hypnotic, Sweating, tachycar- Intoxication: Treatment of withdrawal: Hospitalise:

anxiolytic: dia, tremor, insomnia, Slurred speech, inc- 1st day: Stabilise on the dose he was used to.
Highest abuse: Barbi- nausea, vomiting, agi- ordination, unsteady 2nd day and 3rd day: Reduce the dose to 30%
turates tation gait, nystagmus, imp- and revaluate. Gradually taper the dose in steps
Moderate abuse: Ben- aired memory of 10-20% over a couple of weeks.
zodiazepine
contd...
198 |
contd...
Beside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Withdrawal symptoms Other disorders Treatment

Least abuse: Chlordia-
zepoxide

Hallucinogens: Acute effects: Hyper- Treatment is symptomatic.

Lysergic acid diethyla- acusis, synaesthesia,
mide (LSD) mescaline, change in body image
N-dimethyl-tryptamine and time-space percep-
(DMT), phencyclidine tion, vivid dream like
and amphetamine imageries, hallucina-
tions, intense emotion,
increased suggestibility

Cocaine: Acute intoxication: a. For withdrawal symptoms and reducing

Extract of coca plant Delirium, delusion, craving: Bromocriptine 20 mg/day or
Routes of adminis- dysphoria, euphoria, amantadine 100 mg b.d.
tration: Oral, smoking or increased self esteem, b. Treatment of dependence: Psychotherapy
injection cardiac complications, such as behaviour modification, group
CVA, convulsion have therapy and supportive therapy.
been reported craving.

Amphetamine: Toxicity: Acute phase:

Amphetamine, metham- Hypervigilance, grandi- Haloperidol 2-5 mg/day
phetamine, methylphe- osity, agitation, inappro- Post-withdrawal phase:
nidate, phentermine. priate behaviour, mydri- Fluoxetine 20 mg/day
Routes: Oral or injection asis, hypertension, Psycho-social therapy.
sweating, vomiting.
 Central Nervous System
33
Sexual Dysfunction

CHARACTERISTICS OF SEXUAL DYSFUNCTION

A. Desire disorders: Hypoactive sexual desire due to fear, chronic stress and depression.
B. Arousal disorders:
i. In female: Failure to obtain lubrication, swelling response during sexual excitement due to
anxiety, guilt, or fear and drugs such as antihistaminics and anticholinergic drugs.
ii. In males: Impotency, failure to achieve erection, may be due to age, disease (diabetes, peripheral
vascular diseases, CVS dysfunction), fear and anxiety.
C. Orgasm disorders:
i. In female: Inhibition of female orgasm due to fear of pregnancy, rejection by sexual partners,
damage to vagina and premature ejaculation in males.
ii. In males: Inhibition of male orgasm due to misconception (sex is sin and genitals are dirty),
diseases (diabetes, hypertension) and drugs (antihypertensives and antibiotics).
D. Sexual pain disorders:
i. Dyspareunia: Recurrent genital pain occurring during coitus due to local infection, vaginismus,
rape, childhood sexual abuse and anxiety.
ii. Vaginismus: Involuntary contraction of the outer third of the vagina leading to difficulty in
penile insertion. Causes are same as dyspareunia.

Treatment
Drug therapy
A. General: Anxiolytic and antidepressant drugs are helpful.
B. Premature ejaculation: Benzodiazepine, thioridazine, tricyclic antidepressant like imipramine.
C. Decreased sexual desire in female: Bromocriptine to increase sexual desire.
D. Aphrodisiacs: Ginseng root, yohimbine.
E. Erectile dysfunction in males:
Table 33.1: Drugs used in drug therapy
Treatment Cost Advantages Disadvantages Remarks
Psychosexual Costly Non-invasive curative Time consuming First line treatment.
therapy May be combined with
other treatment

Oral therapy: Cheap Oral and effective i. One hour wait i. First line treatment
contd...
200 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Treatment Cost Advantages Disadvantages Remarks

a. Sildenafil ii. Contraindication: ii. Mechanism of
(Viagra)— Nitrate (viagra action: Sexual
Edegra (SUN), potentiates hypo- stimulation—
Androz (Torrent) tensive effect of release of nitrous
Caverta (Ranbaxy) nitrate) and oxide which inc-
Penagra (Zydus) cardiovascular reases cGMP
25, 50, and 100 mg tab disorder. Keto- level in corpus
conazole, erythro- cavernosa—
Dose: 50 mg one mycin and ceme- smooth muscles
hour before coitus, tidine increases of penis relaxes—
increased to maximum level of viagra. blood flow increa-
of 100 mg/day, dec- Rifampicin ses—erection
reased to 25 mg/day in reduces plasma occurs viagra
elderly above 65 years, level of viagra. enhances effect of
cirrhosis, severe renal iii. Prescribe with nitrous oxide by
impairment, and when caution in CAD, inhibiting phos-
used with ketocona- unstable angina, phodiasterase
zole, erythromycin arrhythmias, hypo- which is respon-
tension, hyperten- sible for degra-
sion, and in pati- dation cGHP.
ents who have suf-
fered from acute
myocardial infarc-
tion, stroke
iv. Side-effects:
Headache, flus-
hing, dyspepsia,
diarrhoea, diz-
ziness, rash

Apomorphine Cheap Competes strongly Side-effects: Nausea, Placed under tongue

sublingually with viagra dizziness and sweating encourages erection by
2-4 mg stimulating release of
dopamine which medi-
ates the cerebral role in
triggering erection.
Second line of treat-
ment.

Transurethral Costly Local therapy. Few Moderately effective. Second line of treat-
Alprostadil systemic side-effects Requires office ment
training. Causes
penile pain

Intracavernous Cheap Highly effective. Few Requires injection.

Alprostadil systemic side-effects Can cause priapism,
contd...
contd...
Sexual Dysfunction | 201

Treatment Cost Advantages Disadvantages Remarks

Dose: 5-20 Fibrosis or penile pain
microgram (Lower incidence of
pain than papaverine)

Vacuum Expensive No systemic side-effect i. Un-natural erec-

constriction tion
device: ii. Petechiae, numb-
ness and trapped
ejaculum

Papaverine Cheap Effective upto 80% Priapism in 35% cases. Mode of action:
Intracavernous Corporal fibrosis in Increases cyclic AMP
Injection 33% cases. and GMP in penile
Dose: 15-60 mg erectile tissue.

Phentolamine Cheap Effective in 60–80% Hypotension

Usually combined with cases if combined with Reflex tachycardia
papavarine. papaverine
Dose: 30 mg papa-
verine + 0.1 ml to 1 ml
phentolamine intra-
cavernous injection

Androgen IM Cheap Only effective in male- Contraindications:

hypogonadism Prostatic cancer or
obstruction of bladder
neck by prostatic
hypertrophy

Surgical treatment: Expensive Highly effective i. Un-natural erec- Advised when not
A. Prosthesis tion satisfied with medical
ii. Infection treatment.
iii. Requires replace-
ment 5-10 years

B. Vascular surgery Very expensive Curative Poor result in elderly Usually best indicated
with generalised in young with con-
disease genital or traumatic
erectile dysfunction.

Other Modes of Treatment

A. Dual sex therapy: This helps if difficult relationship exists in the couple. Aim is to increase the
sensuous awareness.
To touch, sight, sound and smell. Initially, sexual intercourse is prohibited. In case of vaginismus
the woman is advised to use dilators or finger to dilate her vaginal opening.
202 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Squeeze technique: Used in case of premature ejaculation, to increase the threshold of penile
excitability. The partner stimulates the penis to erection till the sensation of impending ejaculation
is felt. Then the partner forcefully squeezes the coronal ridge of the glans. This reduces the erection
and stops ejaculation. A variation is the stop-start technique—stimulation of the penis is stopped,
but no squeeze is used.
B. Sexual education:
a. Teach sexual anatomy and physiology.
b. Manage family relation and resolve conflict.
c. Remove myths and misconception about sex.
d. Ensure healthy sexual attitude and appropriate sexual hygiene.
C. Relaxation therapy.
D. Cognitive behaviour therapy
E. Biofeedback using penile plethysmograph.
 Heart
34
Diuretics

Congestive cardiac failure is characterised by fluid and salt retention resulting in oedema. Aim of the
treatment of CCF is the elimination of water and salt. Diuretics have very important role to play in this
aspect.

Mechanism of Action
CCF
↓
Activation of renin-angiotensin system in kidney
↓
a. Resulting in reduced renal blood flow and increased glomerular filtration
fraction leading to increased reabsorption of sodium and water by proximal
tubule.
b. Also plasma angiotensin II is elevated leading to increased vascular
resistance and increased aldosterone release from adrenal cortex causing
sodium retention.
↓
Diuretics reduce reabsorption of sodium and water by renal tubule.
Table 34.1: Classification and dosages of diuretics

Brand names Usual dosages

A. Thiazide and related compounds
(Potassium wasting diuretics)
• Chlorthiazide
• Hydrochlorthiazide
• Chlorthalidone
• Indapamide
B. Carbonic anhydrase inhibitor:
Acetazolamide
C. Loop diuretics:
• Frusemide
Esidrex 500 mg tab 500-1000 mg oral/day
20-100 mg/day in 1-2 divided dosages
Hygroton or hythalton 100 mg tab 50-100 mg alternate day
Lorvas 2.5 mg tab 2.5-5 mg/day
Natrilix SR
1 tab/day
Diomox 250 mg tab 250-500 mg/day
Lasix 40 mg tab 20-80 mg oral or IV, if no response 20-
Amp 20 mg/2 ml 40 mg after 6 hours
contd...
204 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Brand names Usual dosages

• Bumetanide Bumet 1 mg tab 0.5 mg-4 mg/day. Maximum 15 mg/day

• Ethacrynic acid Edecrin 50-150 mg/day

D. Potassium-sparing diuretic:
• Spironolactone Aldactone 25, 100 mg tab 25-200 mg/day in single or divided
dosages
• Triamterene 100-300 mg/day
• Amiloride 5-10 mg/day
• Bidiuret (Amiloride 5 mg plus 1 tab/day
hydrochlorothiazide 50 mg)

E. Osmotic diuretic: Mannitol 50-200 μ/day

INDICATIONS, CONTRAINDICATIONS, SIDE-EFFECTS AND DRUG INTERACTIONS

Diuretics are indicated in oedema due to CCF, cirrhosis and nephrosis and hypertension. They are
contraindicated in severe renal disease. They deplete potassium and disturbs electrolyte and acid base
balance.

Table 34.2: Management of diuretics

Diuretics Indications Contraindications Side-effects and drug interactions
Thiazide: • Mild to moderate CCF • Anuria and severe renal • Side-effects: Potassium depletion,
disease hyperuricaemia, glucose intolerence,
• Used in refractory oedema • Refractory hypokalaemia lipid elevation.
with loop diuretic and hypernatraemia • Drug interaction:
• Hyperuricaemia a. Potentiates antihypertensives
• Hypertension • Diabetes mellitus b. With digoxin increased risk of
• Oedema of hepatic and • Liver disease-potentiates hypokalaemia
renal failure coma c. Interactions with diamox,
• Renal diabetic insipidus • Pregnancy potentiates folic acid antagonist
• Idiopathic hypercalciuria potentiates oral hypoglycaemic
drugs and oral anticoagulants
Loop diuretics: • Most potent diuretic— • Metabolic acidosis of renal • Side-effects: Vertigo, visual dis-
Special value in acute and hepatic failure turbance, calf muscle cramp, ano-
pulmonary oedema, severe • Renal failure with anuria rexia, vomiting, deafness. Deafness
refractory heart failure and • Potassium deficiency more with ethacrynic acid and less
when renal function is • Hypersensitivity with bumetanide.
impaired • Hyponatraemia a. Aminoglycoside enhances risk
• Hypertension • Hepatic coma of deafness, potentiates anti-
• Oedema of hepatic and • Pregnancy hypertensive effect and causes
renal failure lithium toxicity
• Toxaemia of pregnancy b. Aspirin and NSAID reduces
Bumetanide more potent diuretic effect
than frusemide
contd...
contd...
Diuretics | 205

Diuretics Indications Contraindications Side-effects and drug interactions

Spironolactone: • Oedema of CCF, cirrhosis
and nephrosis
• Hypertension
• Female hirsutism
• Efficacy increases if used
with other potent diuretics
• Renal failure with anuria
• Potassium excess
• Lactation
• Addison’s disease
• Side-effects: Headache, drowsiness,
ataxia, rash, gynaecomastia
• Drug interaction:
a. Increases digoxin level
b. Reduces effects of warfarin
c. Hyperkalaemia with ACE
inhibitor

MECHANISM, SITE, EFFECTS ON URINARY ELECTROLYTES, EFFECTS ON

BLOOD ELECTROLYTES AND OTHER EFFECTS
Table 34.3: Mechanism of diuretics

Diuretics Site and mechanism of Effects on urinary elec- Effects on blood elec- Other effects
action trolytes trolytes

Thiazide: Distal tubule Na+ Na+ Glucose

Cl– Cl– LDL/triglyceride
K+ HCO3
H+ (Mild metabolic acido-
Mg++ sis)
Ca++ Uric acid
Ca++
Indapamide: (Related Smooth muscle vasodi- Electrolyte disturbance Ventilatory drive
to thiazide) lator and K+ loss minimum

Acetazolamide: Carbonic anhydrase Na+ Metabolic acidosis Intraocular pressure

inhibitor K+ decreases
HCO–3
Furosemide: • Site: Thick ascending Na+ Hypochloremic alka- Acute: Venous cap-
loop of Henle losis citance
• Inhibits Na + /K + /Cl HCO–3
co-transport
Bumetanide: Cl– Systemic vascular
resistance
Ethacrynic acid: Renin Ototoxicity
Angiotensin II
Prostaglandin

Spironolactone: Aldosterone antagonist K+ K+

Na+ Metabolic acidosis • Gyanecomastia
Cl– • Antiandrogen effect

Triamterene: • Site: Collecting duct HCO–3

• Inhibits Na+/H+
exchange
Amiloride: Site: Distal nephron
206 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

SUMMARY OF WATER AND ELECTROLYTE DISTURBANCE

DUE TO PROLONGED DIURETIC THERAPY
Table 34.4: Water and electrolyte disturbance

Complications Reasons

Intravascular volume depletion Due to vigorous diuresis

Hypotension Due to water and sodium loss

Hyponatraemia Vigorous diuresis with inadequate sodium intake and

excessive water intake

Hypokalaemia predisposing to digitalis intoxication Due to use of thiazide or loop diuretic or both with
inadequate potassium supplementation

Hyperkalaemia Due to use of potassium sparing diuretics with potassium

supplements
Metabolic alkalosis with or without potassium depletion
Hyperuricaemia

Magnesium depletion Due to thiazide or loop diuretic

Increase in low serum low density lipoprotein and Often occurring in parallel with potassium losses
triglyceride level
Due to thiazide diuretic
 Heart
35
Digitalis Glycosides

Digitalis glycosides have been used for cardiac failure for more than 200 years and became established
after Withering’s famous treaties of 1785.

MECHANISM OF ACTION
A. Mechanical effects at cellular level: Binding of digitalis to NaK-ATPase enzyme inhibits the
enzyme, resulting in increase of sodium in cells which in turn augments exchange of sodium for
extracellular calcium and thus intracellular calcium increases. Increase in calcium increases myocardial
contractility.
Cardiac glycoside
↓
Binds to NaK-ATPase enzyme (Sodium pump) in myocardial cells
↓
NaK-ATPase inhibits outward transfer of sodium from cells
↓
Na increases in cells
↓
Augments exchange of Na for calcium (extracellular)
↓
Excess calcium influx into cells
↓
Excess Calcium

Increases myocardial Also interferes impulse

contractility formation and conduction
B. Electrophysiological effects: Table 35.1 depicts the effects of digitalis on cardiac electrophysiology
producing alterations in the electrical properties of myocardial cells. This explains the disturbance
of impulse formation and conduction during digoxin toxicity.
Table 35.1: Electrophysiological effects
Electrical properties Effects Clinical effects
1. Automaticity and conductivity of SA node No significant effect Ectopics formed
2. Resting potential reduced
contd...
208 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Electrical properties Effects Clinical effects

3. Diastolic depolarisation Augmented

4. Effective refractory period:

a. Atrium Shortened Slowing of ventricle
b. Ventricle Shortened rate in A. fibrillation,
c. AV node Prolonged mainly due PSVT and heart failure
to vagal effect
5. Conduction:
a. Atrium Increased
b. Ventricle Increased
c. AV node Decreased

C. Haemodynamic effects: In cardiac failure digitalis increases cardiac output and lowers filling
pressure of both right and left ventricles. The patients who are most likely to benefit are those
having cardiomegaly with impaired systolic contraction, associated with S1 gallop. There is no
tolerance to cardiac effect which are sustained over prolonged period. Thus, digitalis is useful in
dilated, failing ventricles with poor systolic function.

Pharmacokinetics
Preparations Absorption Onset Peak effect Half-life Excretion
of digitalis (min) (hours)
Oubain Unreliable 5-10 1/2-2 21 hr Renal
Digoxin 70% 10-30 1-2 33 hr Renal
Digitoxin 90% 25-120 4-12 4-6 days Hepatic
Lanatocide C 10-40% 4-6 days Hepatic

Factors Influencing Plasma Concentration of Digitalis

Deciding Toxicity of Digitalis
Absorption:
Excretion:
Electrolyte concentration:
Endocrine effect:
Tissue binding:
Chronic pulmonary :
disease especially with
acute respiratory insufficiency
Antacids, cholestyramine, neomycin reduce absorption, increase digitalis
concentration and increase susceptibility to toxicity.
Quinidine reduces excretion of digitalis and increases digitalis concentration
in plasma.
Hypopotassaemia, hypomagnesaemia and hypercalcaemia increase digitalis
plasma concentration and increase sensitivity to digitalis and prone to digitalis
toxicity.
Hypothyroidism increases sensitivity to digitalis. Hyperthyroidism decreases
sensitivity to digitalis.
Quinidine, amidarone, verapamil and nifedipine increases tissue binding of
digitalis and increases digitalis concentration.
Prone to digitalis sensitivity and toxicity.
Digitalis Toxicity
|
Digitalis Glycosides 209

Digitalis produces both cardiac and extracardiac toxic symptoms. They are due to abnormal toxicity and
decreased conduction:
A. Cardiac toxicity

Abnormal automaticity Decreased conduction

a. Slowing of sinus rate in CCF
Increased Decreased and atrial fibrillation
automaticity automaticity b. Slowing of conduction
↓ ↓ through AV node leads to
a. Increased automaticity Depression of sinus AV block (1st, 2nd and 3rd
of AV node causing node automaticity leads degree block)
AV dissociation in to SA node exit block
atrial fibrillation with bradyarrhythmia
b. Increased automaticity
of Purkinje cells lea-
ding to ventricular
premature beat, ven-
tricular bigemina and
ventricular tachy-
cardia
B. Extracardiac toxicity
1. Gastrointestinal: Anorexia, nausea, vomiting
2. Neurological: Headache, fatigue, malaise, disorientation, confusion, delirium and disturbance
of colour vision.

Treatment of Digitalis Toxicity

Early recognition of toxicity from symptoms and signs
↓
Withdraw digitalis
↓
Determine types of arrhythmias
↓ ↓ ↓
Bradyarrhythmia Ventricular tachycardia Ectopic tachyarrhythmia with
• Sinus bradycardia a. Lignocaine (See arrhy- potassium depletion
• Sinoatrial arrest thmia) Treatment:
• SA exit block b. Phenytoin: 100 mg IV, a. Potassium given
• 2nd and 3rd degree AV block repeated every 5 minute b. Phenytoin
Treatment: until control of arrhyth- c. Beta blockers
Atropine 0.5-1 mg IV mia, followed by 400-
↓ 600 mg orally per day
If atropine fails: Pervenous elec-
trical pacing instituted
⇓
contd...
210 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

If the above treatment fails

Oral cholestyramine can bind Digoxin specific anti- Controversial treatments:

digitalis and enterrupts entero-
hepatic cycle and thus toxicity
is made less persistent.
bodies: Purified Fab frag-
ments of digoxin-specific
antibodies have been
recently released for
severe digitalis toxicity.
This is efficacious with-
out major side-effect.
a. Cardioversion is con-
traindicated.
b. Beta blockers, quini-
dine and procainamide
are not widely used
because they decrease
conduction and as well
as myocardial contrac-
tility.

INDICATIONS OF DIGITALIS
A. For urgent digitalisation by parenteral route
Tachyarrhythmia:
i. Auricular fibrillation with rapid ventricular rate.
ii. Supraventricular tachycardia: Recurrent or refractory to cardioversion or beta blockers
contraindicated.
iii. Atrial flutter: Recurrent or refractory to cardioversion or beta blockers contraindicated.
iv. Severe acute left ventricular failure.
v. Unable to take oral preparation as in nausea or vomiting, coma and postoperative.
B. For slow digitalisation by oral route
i. Cardiac failure—Right, left or combined with sinus rhythm or auricular fibrillation.
ii. Auricular fibrillation or auricular flutter with fast ventricular rate.
iii. Paroxysmal supraventricular tachycardia
iv. Prophylaxis:
• PSVT
• Prior to cardiac surgery especially mitral valvotomy with sinus rhythm to prevent auricular
fibrillation occurring during or following surgery.

CRITERIA OF ADEQUATE DIGITALISATION

Clinical:
a. In CCF with sinus rhythm, relief of symptoms, appropriate diuresis with relief of oedema, shrinking
of liver, decrease in cardiac size and decrease in pulse rate.
b. In auricular fibrillation, pulse rate reduction below 80 minutes after exercise (bed patients sit up
5 times and ambulatory patients to hop up and down on one feet 5 times).
Electrocardiographic: Sagging of S-T segment (boat shaped) and displacement of T-wave in a direction
opposite to that of main deflection— these are not the evidence of toxicity, but suggests that the patient
is on digitalis.

Choice of Digitalis Preparation: Classification

They vary in speed of action and duration of action. See the Table 35.2.
 Digitalis Glycosides

Table 35.2: Digitalis preparations: Speed of action and duration of action

| 211

Digitalis preparations Speed of action Duration of action

A. Very fast acting preparation: Onset Peak
Ouabain (only parenteral) Few min 1/2-1 hours 2-4 hours
B. Fast acting preparation
Digoxin parenteral 1/2 hour 1-2 hours 3-6 hours
Digoxin tab 4-6 hours 2-6 days
Lanatocide oral (Cedilanid) 4-6 hours 2-6 days
C. Very slow acting preparations
Digitalis leaf 6-8 hours 14-21 days
Digitoxin

Method of Digitalisation
Methods of digitalisation depend on speed of digitalisation whether urgent, rapid or slow.
Preparations Digitalising dose Maintenance dose Method of administration
A. Urgent digitalisation:
Oubain: 0.25-0.5 mg No 0.25-0.5 mg (1–2 ml) diluted in 10 ml
1-2 ml amp = saline slow IV followed by other
0.25 mg/ml digitalis preparation

Digoxin 1.5 mg (3 ml) 0.25-0.75 mg 1 mg (2 ml) IV stat, 0.5 mg after 4 hr

1 ml amp = and then 0.25 mg, 4 hourly till response
0.5 mg
B. Rapid digitalisation by oral preparations
Digoxin: 2-3 mg 0.25-0.5 mg 1 mg stat and 0.5 mg 6 hourly till
0.25 mg tab per day 2-3 mg reached

Lanatocide C
(Cedelanid): 7.5 mg 0.5-2.5 mg 3.5 mg state, 1 mg after 6 hours and
0.5 mg tab then 0.5 mg 6 hourly
C. Slow digitalisation by oral route
Occasionally it is desirable to digitalis slowly over a week when patient cannot be closely observed
during this period. For example, 0.25-0.5 mg three times a day for 4-6 days.

Remarks on Method of Digitalisation

Never administer full digitalising dose IV in a single injection unless it is certain that no digitalis has
been taken in the preceding two weeks. IV dose should be given slowly. Observe carefully for digitalis
toxicity especially during IV administration. To avoid toxicity of IV dose, digoxin is given in 5% dextrose
infusion 500 microgram over 30 minutes followed by 500 microgram over one hour. If digitalis has been
taken within 2 weeks, give one-fourth of the estimated total digitalising dose and then give additional
digitalis cautiously and observe the response.
 Heart
36
Beta-adrenoreceptor
Blocking Drugs

The beta-adrenergic blocking drugs are antagonists of the effects of catecholamines (adrenaline or
isoprenaline) at the beta-adrenergic receptors.

CLASSIFICATION
Different beta blockers differ in membrane stabilising activity, intrinsic sympathetic stimulating activity
and cardioselectivity. Classification is based on these differences. For classification of beta blockers See
Table 36.1.
Clinical significance of membrane stabilising activity, intrinsic sympathetic activity and cardioselectivity
are depicted Table 36.2.

Table 36.1: Classification of beta blockers

ASA Membrane stablising Half-life
activity (in hour)
I. Non-selective:
Group 1: Oxprenolol (Trasicor-Novartis) + +
Group 2: Propranolol (Inderal-ICI) – + 3-4 hr
Group 3: Pindolol (Visken-Novartes) + – 3-4 hr
Group 4: Sotalol (Sotagard-Glaxo) – – 13 hr
Tomolol – –
II. Cardio-selective:
Group 1: Acebutolol (Sectral-Rhone Poulence) + + 8-9 hr
Group 2: Practolol + –
Group 3: Atenolol – – 8-9 hr
Metoprolol – – 3-4 hr
III. Non-selective + alpha-blockers
Labetolol – +
Carvedilol – +
 Beta-adrenoreceptor Blocking Drugs

Table 36.2: Clinical significance between membrane stabilising activity, intrinsic sympathetic activity
| 213

and cardioselectivity

Intrinsic sympathetic activity Membrane stabilising activity Cardioselectivity

• Drugs with ISA reduces
resting heart rate less and
cardiac output less
• Reduces less peripheral
blood flow
• Drugs oxprenolol, pindolol,
acebutolol, propranolol have ISA
effect
• Useful in peripheral vascular
disease
(Local anaesthetic or “Quinidine-
like activity”
Seen with propranolol, oxpre-
nolol and alprenolol. Dosages
used in man do not show any
significant membrane stabilising
activity.
• Acebutolol, practolol, atenolol
and metoprolol are cardioselec-
tive.
• They increase resistance in
bronchial tube and vascular
smooth muscle and hence harmful
in asthma in smallest dosages.
• They raise plasma triglyceride but
not cholesterol.

Table 36.3: Pharmacokinetics

Absorption Peak plasma Metabolism Half-life (in hr) Penetration of Protein binding
concentration CNS
1. Metoprolol, Most drugs peak 1. Propranolol, 1. Propranolol, 1. Propranolol 1. P r o p r a n o -
pinodolol, concentration 1- and oxpro- oxpronolol, penetrates lol—90%
propranolol, 3 hours nolol metabo- metopronolol easily due to 2. M e t o p r o -
sotalol and lised in liver and pinodolol lipid lol—12%
timolol well 2. Atenolol, have 3-4 hour solubility
absorbed sotalol exc- 2. A t e n o l o l , 2. Atenolol and
from upper GI reted un- acebutolol 8- sotalol do not
tract changed by 9 hours penetrate
2. Atenolol only kidney 3. S o t a l o l - 1 3
45%-60% hours
absorbed 4. Nodolol 20
hours

Table 36.4: Side-effects, contraindications, special precautions and drug interactions

Contraindications Special precautions Side effects Drug interactions

• Asthma Be careful in following con- • Bronchospasm • Hypertension and brady-
• COPD ditions: • Heart failure cardia with adrenaline
• Heart block • Renal failure • Neurological: Depression • Reduction of heart rate with
• CHF • Hepatic failure Sleep disturbance anaesthetic agents
• Bradycardia • Pregnancy Nightmare • Severe bradycardia with
• Pheochromocytoma • General anaesthetics Fatigue digitalis and calcium
• Cardiogenic shock • Diabetes mellitus • Gastrointestinal: channel blockers
Anorexia, nausea, • Cemetidine elevates blood
vomiting diarrhoea level of beta blockers
• Reduces peripheral blood • Additive effect with anti-
flow cholinergics
214 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Uses of Beta Blockers

Main use of beta blockers is in hypertension, angina pectoris and arrhythmias. See the Table 36.5.
Table 36.5: Uses of beta blockers

Indications Mode of action Characteristics

Hypertension Theories of mechanism:
a. Central effect
b. Reduces plasma renin
resulting in lowering of
blood pressure
c. Due to resetting of baro-
receptors
a. Blood pressure lowering potency is similar to
guanithidine, bethanidine and methyldopa.
b. Unlike older sympathetic inhibitory drugs no
postural or exercise hypotension occurs with beta
blockers.
c. Used in all grades of severity of hypertension alone
or with diuretics and other hypotensive drugs

Angina pectoris: Reduces myocardial oxygen a. Excellent prophylactic for angina

demand by reducing heart rate and b. All beta blockers are same so far anti-anginal activity
systolic intraventricular pressure is concerned.

Acute myocardial infa- a. Reduces infarct size if given Reduces mortality and reinfarction rate
rction: within 4 hours of infarction
b. Reduces platelet aggregation

Arrhythmias: PSVT and a. Reduces sinus and ectopic

ventricular ectopics: pacemaker activity
b. Increases refractory period
of AV node activity

Uses of Selective Beta Blockers

Indications Inderal Metoprolol Atenolol Acebutolol Labetolol
1. Angina ++ ++ ++ + +
2. Arrhythmia ++ –
++ + ++
3. CHF (mild to moderate) 0 + 0 0 0
4. Dissecting aneurysm: (Reduces rise of ++ + + 0 0
systolic BP)
5. Fallot’s tetralogy: (Reduces obstruc- ++ 0 0 0 0
tion during exercises)
6. Hypertension: ++ ++ ++ ++ ++
7. Hypertrophic cardiomyopathy: (redu- ++ + + 0 0
ces obstruction of obstructive cardio-
myopathy during exercise)
8. Myocardial infarct: (Follow-up) ++ ++ ++ (+) (+)
9. Pheochromocytoma: (Reduces tachy- 0 0 0 0 ++
cardia, rise in BP and arrhythmia
induced by excess catecholamines)
10. Prolonged QT (Congenital): ++ 0 0 0 0
11. Silent myocardial ischaemia: ++ ++ ++ (+) +
12. Hypertensive crisis (IV): + + + 0 ++
Dosages of Inderal (10, 40 mg tab)
|
Beta-adrenoreceptor Blocking Drugs 215

Starting initial dose Usual dose

Hypertension: 40 × 2 160-480/day
Angina: 10 × 3-4 (increased 160-240 mg/day
every 3rd or 7th day)
Arrhythmia: 10 mg × 3-4 times 40-80 mg/day
Hypertrophic cardiomyopathy: 20-40 mg × 3-4 times/day Before meals and at bedtime
Migraine: 10 mg × 3-4 times/day 160-240 mg/day
 Heart
37
Drugs (Catecholamines and their
Synthetic Derivatives) in the
Treatment of Circulatory Failure

The pumping action of the heart depends upon preload, contractility and afterload. Catecholamines
influence all these actions particularly when the pump fails as in acute circulatory failure. These drugs
help to restore the circulation. Catecholamines are of two types:
1. Naturally occurring:
• Noradrenaline
• Adrenaline
• Dopamine
2. Structurally related synthetic derivatives:
• Isoprenaline
• Dobutamine
• Salbutamol

Mechanism of Action
Catecholamines act on five types of receptors:
Table 37.1: Mechanism of action of drugs
Receptors C a rd i o v a s c u l a r Major sites of action of catecholamines
effects Noradre- Adrena- Isopre- Dopa- Dobut- Salbut-
naline line naline mine amine amol
Alpha-1 (Post- Arteriolar cons- + + + (+)
synaptic) triction and veno-
constriction
Alpha-2 (Pre- Vasodilatation + + (+)
synaptic)
Beta-1 Positive chrono- + + + + +
tropic and iono-
tropic cardiac effect
Beta-2 Peripheral vaso- + + + +
dilatation
contd...
 Drugs (Catecholamines and their Synthetic Derivatives) in the Treatment of Circulatory Failure

Receptors C a rd i o v a s c u l a r Major sites of action of catecholamines

| 217

effects Noradre- Adrena- Isopre- Dopa- Dobut- Salbut-

naline line naline mine amine amol
Dopaminergic rece- Renal and mes- +
ptors in renal and enteric vasodila-
mesenteric vascu- tation
lature

Haemodynamic Effects
Individual catecholamines differ in their haemodynamic effect.

Effect on blood vessels

Effect on Effect on blo- Arteriole Venule Coronary Renal hepatic Ionotrophic
heart rate od pressure cerebral mesenteric effects
Noradrenaline Reduced due Increased due Peripheral Coronary Increases Increased
to elevated to arteriolar blood flow blood flow renal blood contractility,
blood pres- constriction reduced due reduced less flow afterload (due
srue via baro- and positive to vasocons- than periphe- to arteriolar
receptor ref- ionotropic triction ral blood constriction)
lex effect on • Prolonged flow preload (due
heart administra- to venocons-
tion reduces triction)
peripheral causes large
perfusion, increase in
increases myocardial
tissue aci- oxygen con-
dosis and sumption.
results in These factors
irreversible improve
shock myocardial
performance.
But this posi-
tive iono-
tropic effect
is reduced in
CCF and thus
cardiac per-
formance is
impaired.

Adrenaline: Increased due Coronary Renal blood Myocardial

to increased blood flow flow decrea- contractility
myocardial increases ses increases,
contractility because vaso- cardiac auto-
unlike nor- dilatation but maticity inc-
adrenaline compromised reases, AV
due to tachy- conduction
contd...
218 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Effect on blood vessels

Effect on Effect on Arteriole Venule Coronary Renal hepatic Ionotrophic
heart rate blood pressure cerebral mesenteric effects
cardia and increases cau-
arrhythmia sing arrhyth-
mia. Cardiac
output incre-
ases.

Isoprenaline: Heart rate inc- Diastolic BP Coronary per- Same as adre-

reases due to decreases due fusion redu- naline but arr-
hypotension to peripheral ced due to tac- hythmia more
vasodilatation hycardia and than adrena-
(Beta-2 recep- reduced blood line (a serious
tor effect) pressure disadvantage)
Dopamine:
a. Low dose: Diastolic BP Renal blood
decreases flow increases
b. High dose: BP increases Myocardial
contractility
increases and
cardiac output
increases
Heart rate dec- Maintain cor-
reases, less onary circu-
arrhythmia lation with
large increase
in myocardial
oxygen con-
sumption.

Dobutamine: Increase in BP increases Enhances

heart rate less coronary
than isopre- blood flow.
naline

Salbutamol: Heart rate BP reduced Peripheral a. R e d u c e s

increases due vasodilatation left ventri-
to hypoten- systemic vas- cular systo-
sion and cular resis- lic pressure
vasodilatation tance decrea- and increa-
(B-2 effect) ses. Fascilita- ses myocar-
tes myocardial dial oxygen
ejection and demand
reduces both b. Decreases
systolic left LV end
ventricular diastolic
wall tension pressure
contd...
contd...
Drugs (Catecholamines and their Synthetic Derivatives) in the Treatment of Circulatory Failure | 219

Effect on blood vessels

Effect on Effect on Arteriole Venule Coronary Renal hepatic Ionotrophic
heart rate blood pressure cerebral mesenteric effects
and fasci- latates
blood flow to
subendocardium
during diastole.
(a) and (b) imp-
roves myocardial
performance.

USES OF CATECHOLAMINES
Catecholamines Uses
Noradrenaline i. Used in the past in acute circulatory failure, but now rarely used due to
reduced coronary blood flow, prolonged vasoconstriction producing tissue
acidosis resulting in irreversible shock and reduction in positive ionotropic
effect and increase in myocardial oxygen consumption due to increase
myocardial contractility, increased afterload and increased preload.
ii. Useful during acute phase of resuscitation when it shunts blood from skin
and muscle to vital organs particularly to coronary circulation.
iii. Useful in septic shock when peripheral vascular resistance is greatly
reduced.
Adrenaline Not recommended in circulatory failure due to reduction in renal blood flow
and compromised coronary blood flow.
Isoprenaline i. Not useful in acute circulatory failure of acute myocarditis infarction due
to reduced coronary blood flow.
ii. Useful in circulatory failure with bradycardia particularly in acute heart
block.
Dopamine i. Useful in acute circulatory failure due to raised blood pressure, increased
renal blood flow with low dose and lesser risk of arrhythmias unlike
isoprenaline.
ii. Frequently used following cardiac surgery as an ionotropic supporter.
iii. Used in chronic cardiac failure with low blood pressure.
iv. Used in acute renal failure to improve renal blood flow in low-dose.
Dobutamine i. Useful in acute circulatory failure after cardiac surgery.
ii. Used in condition with low cardiac output associated with ischaemic heart
disease.
Salbutamol i. Useful in bronchial asthma.
ii. Not frequently used in acute circulatory failure with IHD due to increased
heart rate.
iii. Useful in circulatory failure with prolonged vasoconstriction.
220 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Dosage, Contraindications, Side effects and

Drug Interactions of Important Catecholamines

Dosage Contraindications Side-effects Drug interactions

Dopamine: Dopa- 2-50 mcg/kg/min Pheochromocytoma, Nausea, vomiting, Anaesthetic cause
mine (TTK) 200 infusion. Low- tachycardia and tachycardia, ecto- arrhythmia
mg/5 ml dose (2–5 mcg/kg/ hyperthyroidism pics, anginal pain,
min) increases headache. Inacti-
renal blood flow, vated by alkaline
increased every solution (sod. bi-
15-30 min till carb). Subcutane-
above 5 mcg/kg/ ous leakage causes
min. High dose vasoconstriction
stimulates heart, and necrosis.
raises cardiac out-
put and increases
BP and tachycar-
dia produced.

Dobutamine: Dob- 2.5-10 mcg/kg/min Idiopathic hyper- Tachycardia, ventri- Nitroprusside

utrex (Ranbaxy) Even up to 40 mcg/ trophic subaortic cular ectopic
250 mg vial kg/min can be given stenosis

Adrenaline 0.06-0.18 mcg/kg/

min
Isoprenaline 0.02-0.18 mcg/kg/
min
Salbutamol 0.2-0.5 mcg/kg/min
 Heart
38
Vasodilators

Vasodilators are recently added to the treatment of heart failure. For “Beneficial effect of vasodilators in
heart failure” See Table 38.1.
Table 38.1: Beneficial effects of vasodilators in heart failure
Effect on arterioles Effect on venules Effect on myocardium Effect on ventricles
Arteriolar dilatation Venodilatation Decreases myocardial Increases ventricular
↓ ↓ oxygen demand diastolic compliance
improving ischaemia improving ventricular
function
Decreases ventricular Decreases intracardiac
outflow resistance and volume, preload, pul-
postload effect monary and systemic
↓ venous pressure
Increases cardiac output ↓ ↓
↓

Improves cardiac function

↓

CLASSIFICATION OF VASODILATORS
I. Classification Based on Mechanism of Vasodilation
Table 38.2: Mechanism of vasodilators
Mechanism Drugs
A. Direct vascular smooth muscle relaxation Nitroglycerine, nitrate, hydralazine,
nitroprusside
B. Ganglion blockade Trimethaphan, hexamethonium
C. Inhibition of inward flow of calcium current to smooth Nifedipine
muscles of peripheral vascular bed
D. Blocking of presynaptic (alpha-2) alpha-adrenergic Prazosin, phentolamine
receptors
E. Inhibition of angiotensin II (causing vasoconstriction) Captopril, losartan
F. Stimulation of beta-2 receptors Salbutamol, terbutaline
G. Accumulation of cyclic AMP (vasodilator) in vascular Prostacyclin (PGI2)
smooth muscle Prostaglandin (PGE)
I. Inhibition of peripheral sympathetic outflow (vaso- Clonidine
constrictor effect) by stimulating alpha-adrenergic
receptors located in CNS.
222 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Classification Based on Principal Site of Action

Table 38.3: Classification of vasodilators based on principal site of action
Site of action Vasodilators
A. Venodilation Nitroglycerine, nitrate
B. Arterial dilation Hydralazine, minoxidil,
nifedipine, salbutamol,
PGI, PGE
C. Both arteriolar and Nitroprusside, prazosin,
venodilation (balanced captopril, clonidine
vasodilator)
Haemodynamic effects
a. Decreases right atrial pressure, pulmo-
nary wedge pressure and pulmonary
arterial pressure (b.) Decreases LV end
diastolic volume and pressure
(c.) Decreases pulmonary vascular
resistance if increased during LVF
a. Decreases systemic vascular resistance
b. Increases cardiac output and stroke
volume
a. Decreases systemic vascular resistance
b. Increases cardiac output
c. Decreases pulmonary and systemic
venous pressure

Use of Vasodilators
Vasodilators are indicated in the following clinical circumstances:

Pump failure Chronic Pulmonary Primary right

congestive hypertension ventricular
Acute Heart failure Valvular heart cardiac (Primary) failure
myocardial complicating disease failure
infarction cardiac surgery

Use in Acute Myocardial Infarction with Pump Failure

The following categories of patients need different therapy according to clinical circumstances:
Table 38.4: Different therapies used during pump failure
Clinical categories Clinical features Therapy Prognosis
I. • No pulmonary congestion Not required Good
• No hypoperfusion
II. • Hypoperfusion Volume expansion Improves
• No pulmonary congestion
III. • No hypoperfusion Diuretics Improves
• Pulmonary congestion ↓
If fails: Venodilators
IV. • Moderate hypoperfusion Vasodilators: Combined Bad
• Pulmonary congestion arteriolar and venodilators
such as nitroprusside
+
Inotropes (Dopamine)
V. • Severe hypoperfusion Vasodilators
• Pulmonary congestion +
• Shock Inotropes
Intra-aortic balloon counterpulsation worst
 Vasodilators

The potentially hazardous complications under the above circumstances is hypotension and increasing
| 223

myocardial ischaemia. Increase in myocardial ischaemia is controversial.

Dosages and Side-effects of Vasodilators in AMI with Pump Failure

These are listed in Table 38.5.
Table 38.5: Dosages and side-effects of vasodilators in AMI with pump failure
Vasodilators Usual dose Duration of action Complications
A. Non-parenteral: 0.5-5 cm every 4 hours Average 4 hours • Hypotension
• Topical nitroglycerine • Tachycardia
• Oral sorbide dinitrate 20-100 mg every 4 hours Average 4 hours • Hypotension
• Tolerance
• Headache
• Fluid retention
• Sublingual dinitrate 2.5-10 mg every 2 hours
B. Parenteral vasodilators
• Nitroprusside 15 microgram/min
• Nitroglycerine 10 microgram/min
Precautions for parenteral vasodilators in AMI with pump failure: Start therapy with low-dose:
Nitroprusside 15 microgram/min or nitroglycerine 10 microgram/min
↓
Gradually increase the infusion rate every 5-15 minutes. Monitor blood pressure and heart rate.
If BP is constant, maintain the same infusion rate. If BP decreases, discontinue vasodilators and add
inotropes (dopamine drip)
↓
Monitor thiocyanate level during prolonged nitroprusside infusion
↓
Substitute non-parenteral vasodilator when chronic therapy is indicated.

Use of Vasodilators in Valvular Heart Disease

Vasodilators help valvular heart disease by improving haemodynamic effect. For “haemodynamic effects
of vasodilators on valvular diseases” See Table 38.6. Corrective surgery is the treatment of choice in
valvular heart disease. Vasodilators are indicated only:
a. Surgery contraindicated or need to be deferred.
b. Inacute bacterial endocarditis who develops mitral or aortic regurgitation.
c. Vasodilator can be used in MR complicating AMI to defer corrective surgery.
Table 38.6: Haemodynamic effects of vasodilators on valvular heart disease

Vasodilators Valvular heart disease Haemodynamic and clinical benefit

Nitroprusside a. Indicated in mitral regurgitation
Prazocin and aortic regurgitation parti-
Hydralazine cularly if associated with heart
failure, elevated left ventricular
a. Increases cardiac output and
forward stroke volume.
b. Decreases pulmonary capillary
wedge pressure, right atrial
contd...
224 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Vasodilators Valvular heart disease Haemodynamic and clinical benefit

end diastolic pressure, low
cardiac output and elevated
systemic vascular resistance
b. Also indicated in aortic stenosis
pressure and pulmonary artery
pressure
c. Decreases systemic and pul-
monary and systemic vascular
resistance
d. Reduces regurgitant blood
volume resulting in reduction in
end-diastolic volume and end-
systolic volume
e. In aortic stenosis increases
cardiac output and decreases
pulmonary venous pressure.

Nitroglycerine Indicated in mitral stenosis and aortic
stenosis with low cardiac output and
increased pulmonary venous hyper-
tension
Use of Vasodilators in Heart Failure Complicating Cardiac Surgery
Pump failure complicating cardiac surgery need vasodilators under following clinical circumstances:
a. Relieves angina even without
obstructed coronary artery
disease specially in aortic
stenosis by decreasing myo-
cardial oxygen demand.
b. Decreases pulmonary venous
pressure and relieves symptoms
of pulmonary venous congestion
in mitral stenosis.

When cardiac output low + systemic When pulmonary venous pressure raised
vascular resistance high without +
raised pulmonary venous pressure Low cardiac output
↓ +
Hydralazine beneficial High systemic venous pressure
↓
Nitroprusside or nitroglycerine
+
Hydralazine

Use of Vasodilator in Primary Pulmonary Hypertension and Right Heart Failure

Hydralazine, verapamil and diltiazem are used to reduce pulmonary vascular resistance and pulmonary
hypertension. Occasional mild cases are benefitted but ineffective in far advanced cases.

Use of Vasodilators:
In chronic congestive cardiac failure
Chronic CCF is usually associated with low cardiac output, elevated systemic vascular resistance and
elevated pulmonary venous pressure, elevated right atrial pressure and elevated pulmonary vascular
 Vasodilators

resistance. Vasodilators improve these haemodynamic abnormalities. Most vasodilators also benefit by
|
225

not increasing heart rate and decreasing blood pressure. For “Effect of vasodilators on the haemodynamics
of CCF” See Table 38.7.
Table 38.7: Effect of vasodilators on the haemodynamics of chronic CCF
I. Cardiac output
No change Moderate increase Marked increase
• Nitroglycerine • Prazocin • Hydralazine
• Isosorbide dinitrate • Captopril
• Salbutamol
II. Systemic vascular resistance
No change Moderate decrease Marked decrease
• Nitroglycerine • Prazosin • Hydralazine
• Isosorbide dinitrate • Captopril
• Salbutamol
III. Pulmonary venous pressure and right atrial pressure
No change or slight decrease Moderate decrease Marked decrease
• Hydralazine • Pirbuterol • Nitroglycerine
• Salbutamol • Isosorbide dinitrate
• Nifedipine • Prazosin
• Captopril
IV. Pulmonary vascular resistance
Slight decrease Decrease
• Hydralazine • Nitroglycerine
• Salbutamol • Isosorbide dinitrate
• Prazosin
• Captopril
V. Vasodilators for both increasing cardiac output and pulmonary venous pressure in chronic CCF
• Prazosin
• Captopril
• Hydralazine
• Salbutamol + nitrates

Table 38.8: Dosages and side-effects of non-parenteral vasodilators used in chronic CCF

Vasodilators Dosages Duration of action Side-effects

Topical nitroglycerine: 0.5 to 5 cm every 4 hours 4 hours • Hypotension
• Tachycardia
Isosorbide dinitrate: 20-100 mg every 4 hours Average 4 hours • Tolerance
Sublingual isosorbide dini- 2.5 to 10 mg every 2 hours Average 2 hours • Headache
trate: • Fluid retention
• Headache
Hydralazine: 100 mg t.d.s. 8 hours Headache, tachycardia, hypo-
Maximum 1200 mg/day tension, drug fever, rash,
lupus syndrome, fluid reten-
tion
Prazosin: 2-5 mg 4 times/day Average 6 hours Hypotension, postural
hypotension, fluid retention
 Heart
39
Arrhythmias

For treatment of arrhythmias not only antiarrhythmic drugs but also other forms of treatment are required:
1. Management of precipitating factors such as hypokalaemia, digitalis toxicity, hypertension, ischaemic
heart disease, thyrotoxicosis, etc.
2. Vagal maneuver such as carotid sinus massage, etc. in tachyarrhythmias.
3. Anti-arrhythmic drugs
4. Cardioversion
5. Artificial pacing
6. Cardiac surgery

DRUG THERAPY
Mechanism and Classification
According to mode of action antiarrhythmic drugs are classified into 2 groups:
I. Transmembrane action potential classification: It is based on the effect of drugs on the
transmembrane action potential of the myocardial cells. It is helpful in understanding how drugs
act at cellular levels but it is of little clinical
significance. It can be divided into four classes:
See Figure 39.1.

Fig. 39.1: Myocardial cell action potential. When cardiac

cells activate, a complex sequence voltage changes
occurs showing its phases 0 to 4: Rapid depolarisation
(0), early repolarisation (1), the plateau (2), rapid
repolarisation (3), and diastole (4). It indicates the mode
of action of antiarrhythmic drugs showing classes I, II, III
and IV and Na+ and Ca++ indicating the times at which
sodium and calcium respectively enter the cell
Class Mechanism
Arrhythmias

Drugs
| 227

Class I Impedes transport of sodium across cell membrane during initial

cell activation resulting in reduced rate of rise of action potential
(Phase 0)
Subgroups:
Class I a : Affects atria, ventricles and bundle of KENT activity • Quinidine
slowing AV conduction. No effect on CNS. Effective in both • Procainamide
atrial and ventricular arrhythmias. • Dispyramide

Class I b : Do not impair AV conduction. Effective only in • Lignocaine

ventricular arrhythmias. May affect CNS. • Mexiletine
• Phenytoin
Class II Interferes effect of sympathetic nervous system. Reduces slope • Beta blockers
of diastolic depolarisation (Phase 4) of pacemaker cells and thus • Bretylium tosylate
rate of pacemaker discharge.

Class III Prolongs duration of action potential and hence length of • Amiodarone
refractory period • Sotalol
• Beta blockers

Class IV These drugs antagonise transport of calcium across cell • Verapamil

membrane which follows inward flux of sodium during cellular
activation. Cells in AV node are particularly susceptible.

II. Clinical Classification: It is based on the effects of drugs on the different anatomical parts of the
heart. For clinical purpose drugs can be divided into three groups according to their principal sites
of action: See figure 39.2.

Fig. 39.2: Clinical classification of antiarrhythmic drugs showing their principal site of action. Group 1. Slows conduction
in AV node useful in supraventricular arrhythmias. Group 2. Act on ventricles useful for ventricular arrhythmias. Group
3. Act on atria, ventricles and bundle of Kent, useful in both supraventricular and ventricular arrhythmias
228

Groups
| Bedside Approach to Medical Therapeutics with Diagnostic Clues

Principal sites of action Drugs

Group I AV node: Slows conduction in AV Digoxin, verapamil, beta blockers
node. Hence useful in supraventricular
arrhythmias.
Group II Ventricle: Useful in vent. arrhythmias Lignocaine, mexiletine, tocainide, phenytoin
Group III Atria, ventricles and bundle of Kent: Lignocaine, mexiletine, tocainide, phenytoin
Useful in both supraventricular and
ventricular arrhythmias.

Table 39.1: Classification of antiarrhythmic drugs

Type Mechanism Drugs
Type I
a. IA Sodium channel blocker Lidocaine
Mexiletine
Tocainide
Phenytoin
b. IB Do Quinidine
Procainamide
Disopyramide
c. IC Do Encainide
Flecanide
Type II Beta adrenergic blocker Propranolol
Metoprolol
Atenolol
Acebutolol
Type III Prolongs repolarisation Amiodarone
Bretylium
Sotalol
Type IV Calcium channel blocker Diltiazem
Verapamil
Type V Cholinergic, speeding conduction Digitalis

Indications of Antiarrhythmic Drugs

Ventricular arrhythmias Supraventricular arrhythmias

Acute Chronic Digoxin PSVT A. fibrillation Recurrent WPW

induced A. flutter
Lidocaine: More effec- Ineffective Effective
tive than
Mexiletine
Mexiletine: Less effective 60%
than lido- effective in
caine, encai- unsustained
nide and fle- V. arrhythmia
cainide
contd...
contd...
Arrhythmias | 229

Ventricular arrhythmias Supraventricular arrhythmias

Acute Chronic Digoxin PSVT A. fibrillation Recurrent WPW

induced A. flutter
Phenytoin Less than Effective
lidocaine

Tocainide Effective 60% effective

similar to in unsustai-
mexiletine ned V. arrhy-
thmia

Disopyramide: Effective in Effective Effective Effective

unsustained V.
arrhythmia

Procainamide: Effective in V. Effective Effective Effective

tachycardia

Quinidine: Malignant V. Effective in Effective Effective

arrhythmia unsustained V.
arrhythmia
Encainide: Effective Effective Effective

Flecanide: Effective

Propranolol: Effective Effective APB Controls rapid Effective

ventricular
Amiodarone: Effective in rate
V. fibrillation
and tachycar-
dia

Bretylium Life-threate-
ning VT and
V. fibrillation
Verapamil: IV effective Do

EFFECTS OF DRUGS ON THE CONDUCTION PATHWAYS OF THE HEART

Physiological effects of different antiarrhythmic drugs on the sinus node, atrium, ventricle and AV node
are depicted below:
I. Sinus node
No effect Slows sinus rate First increase in sinus rate
followed by decrease
Digoxin, quinidine, pro- • Propranolol Bretylium
cainamide, Disopyramide, • Verapamil
230 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

lidocaine, phenytoin, tocai- • Amiodarone

nide, mexiletine
II. Atrium and ventricle
No effect Increase in effective Increase in ERP and decreased
refractory (ERP) period conduction velocity
Propranolol, verapamil, lido- Bretylium Procainamide
caine, phenytoin, tocainide, Amiodarone Disopyramide
mexiletine
III. AV node
No effect Increase in ERP, decreased Decrease or no Variable effect on ERP
conduction velocity change in ERP and on conduction
Lidocaine Digoxin Quinidine Mexiletine
Phenytoin Propranolol Procainamide
Tocainide Verapamil Disopyramide
Bretylium Amiodarone

EFFECT ON ARRHYTHMIAS
a. Digoxin due to increase in ERP with decrease in conduction velocity in AV node slows ventricular
rate in auricular fibrillation, auricular flutter and other atrial tachycardias in the absence of pre-
excitation.
b. Beta blockers decreases sinus rate in sinus node, decreases conduction velocity due to increase in
ERP in AV node results in slowing of ventricular rate in AF, atrial flutter and other atrial tachycardias
in the absence of pre-excitation, arrhythmia induced by exercise, thyrotoxicosis and polymorphic
VT associated with congenital long QT syndrome.
c. Verapamil has same effect as digoxin.
d. Quinidine increases ERP, decreases conduction velocity in atrium and ventricle and decreases
automaticity of HIS Purkinje system resulting in improving atrial and ventricular premature beats,
atrial and ventricular tachyarrhythmias and controls ventricular rate in pre-excitation syndrome,
atrial fibrillation and flutter.
e. Disopyramide has same effect as quinidine.
f. Procainamide has same effect as quinidine.
g. Phenytoin decreases ERP and automaticity in HIS Purkinje system resulting in control of
tachyarrhythmias induced by digitalis and polymorphic VT associated with increased QT.
h. Bretylium initially increases sinus rate followed by decrease, increases ERP in atrium and ventricle
resulting in control of VT, VF.
i. Amiodarone decreases sinus rate, increases ERP in atrium and ventricle, increases ERP and decreases
conduction velocity in HIS Purkinje system resulting in control of refractory atrial and ventricular
tachyarrhythmias.
j. Mexiletine increases ERP in HIS Purkinje system resulting in control of ventricular tachyarrhythmias.
 Table 39.2: Dosing and side-effects of antiarrhythmic drugs
Arrhythmias | 231

Drugs Dose Side-effects Contraindications Drug interactions +

Precautions
Digoxin: a. Oral: Loading • Anorexia, nausea, i. Hypersensitive to i. Reduce dose in
i. Tab 0.25 mg 0.5–1 mg. vomiting, visual dis- drug renal insufficie-
ii. Amp 2 ml 0.25 Men—0.25 to turbance, abdominal ii. WPW with A. ncy hypocalcae-
mg/ml 0.5 mg/day pain fibrillation (inc- mia, hypomag-
iii. Child: Elexir Child: 10-20 • Ventricular arrhy- reases ventricular nesaemia, hyper-
(Welcome) 0.05 mcg/kg 6 hourly. thmias, atrial tachy- rate) calcaemia (cau-
mg/ml Amp. 0.5 Men—10-20 cardia with AV block iii. HOCM (may ses digoxin toxi-
mg per 2 ml mcg/kg in single worsen outflow city)
Action: Reduces heart or divided dose/ obstruction) ii. Quinidine and
rate and AV conduc- day verapamil increa-
tion. b. IV 0.5 mg-1 mg ses digoxin con-
Increases force of con- followed by centration
traction 0.125 mg 6 hrly iii. Use cautiously
Indications: CCF, (0) R 0.25 mg 4 with beta blockers
PSVT, A. fib and flutter hourly till vent- or calcium chan-
ricular rate 70- nel blockers in
80 min atrial fibrillation

Quinidine: Sulfate tab 200–300 mg t.d.s. or i. Nausea, vomi- i. Hypersensitivity Quinidine increases
200 mg (Wellcome). q.d.s. ting, diarrhoea ii. Complete AV digoxin level if used
Increases threshold ii. Cinconism (tin- block. Complete concurrently, may
excitation, reduces nitus, deafness, BBB worsen heart failure,
conduction. vertigo, visual iii. Myasthenia may change anti-
Indications: A Fib. and disturbance gravis coagulant dose
Flut., PSVT, VPB, VT iii. H y p o t e n s i o n , iv. Arrhythmia due
asystole, may to digitalis toxi-
increase AV or city
bundle branch
block, may inc-
rease QT or QRS
interval
iv. Thrombocyto-
penia, granulo-
cytopenia,
haemolytic
amaemia, rash
Procainamide HCl a. IV: 500 mg-1 GI distress, confu- SLE, AV block preg- Myasthenia, cardiac
Pronestyl (Sarabhai): gm loading dose sion, agranulocytosis, nancy, child failure
Tab 250 mg, Inj. 100 (25 mg per min) thrombocytopenia,
mg/ml = 10 ml followed by lupus-like syndrome,
An alternative drug for 2 mg/kg/hour. hypotension
quinidine, same indica- Maintenance
tions. 500 mg every 4-
For IV use safer than 6 hours. For
quinidine and has more cardiac arrhy-
rapid action thmia
contd...
232 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Dose Side-effects Contraindications Drug interactions +

Precautions
Indications: PVB, VT, associated with
atrial fibrillation, PS- anaesthesia and
VT, arrhythmia asso- surgery: 100
ciated with anaesthesia mg-500 mg IM
and surgery b. Oral: 500 mg-
1 gm followed by
0.25-0.5gm
every 3 hours
c. IM: For abolition
of arrhythmia
0.5-1 gm IM
Lidocaine a. B r a d y c a r d i a , a. Hypersensitivity a. Accumulates in
(Lidnocaine) a. IV 1 mg/kg or hypotension to amide group of heart failure,
Xylocard (Astra) 100 mg bolus b. Drowsiness, local anaesthetic renal and hepatic
Gesicard (SPPL) over 5-10 mts, confusion, vis- SA block, AV insufficiency
20 mg/ml, 5 ml amp followed by 1 gm ual disturbance, block, intraven- b. Reduce dose in
or 50 ml amp in 500 ml 5% convulsion tricular block children and
Action: A local anaes- dextrose infusion elderly
thetic suppresses auto- 20-40 drops/mt c. Drug interaction:
maticity in ectopic foci. (2-4 mg/min) Cemetidine and
Indications: Acute b. 300 mg IM propranolol inc-
ventricular tachyarrhy- reases plasma
thmias lidocaines con-
centration and
toxicity

Disopyramide: Oral: Initial loading a. Urinary reten- a. Cardiogenic a. Be cautious in

Norpace (Searle) dose 300 mg followed tion, constipa- shock, AV block, LVF, Sick sinus
Cap 100 and 150 mg by 100-150 mg tion, blurred vis- congenital pro- syndrome, AV or
Regubeat (B. Sawyer) 6 hourly ion, dry mouth. longation of QT BBB block
cap 100 mg b. Hypoglycaemia, b. Known hyper- b. Prior digitali-
Action: A cardiac jaundice, hypo- sensitivity to sation suggested
depressor, marked anti- tension drug for atrial fibril-
cholinergic action but c. Prolongs QRS lation and flutter
no alpha blocking and QT interval c. Drug interaction:
property Serum level low-
Indications: Atrial and ered by pheny-
ventricular arrhy- toin
thmias, WPW synd-
rome

Mexiletine: a. IV: 1/2 amp IV a. GI distress a. Bradycardia, a. BP and ECG

Mexitil (German rem- followed by 2 b. Dizziness, con- hypotension, monitoring
edies). Cap 50, 150 amp + 500 ml fusion, blurred conduction b. Be careful in
mg Injection 250 mg/ 15% dextrose vision, tremor defect, sinus hypotension,
contd...
contd...
Arrhythmias | 233

Drugs Dose Side-effects Contraindications Drug interactions +

Precautions
10 ml 30-40 drops/min, node dysfunc- heart failure,
Action: Like lidocaine, followed by 1 tion. conduction
a local anaesthetic amp + 500 ml 5% defect
Indications: Postin- dextrose 15-20 c. Drug interac-
farction ventricular drops/min, tions: Level inc-
arrhythmias (Acute). followed by 1 rease by ceme-
Chronic unsustained cap t.d.s. tidine
ventricular arrhyth- b. Oral: Initial loa-
mias. Cardiomyopathy ding dose 300-
400 mg follo-
wed by mainte-
nance dose 200-
400 mg t.d.s. or
q.d.s.

Phenytoin: Day 1, 400 mg orally a. Gum hypertro- Bradycardia, II and III Discontinue if rash
Dilantin (Parke-Davis) Day 2, 300 mg phy, hirsutism, AV block, SA block. develops. Monitor
cap 100 mg, suspen- Day 3, 300 mg acini ECG.
sion 100 mg/4 ml (1000 mg total) b. Ataxia, vertigo, Drug interactions: Anti
Eptoin (Knoll), Tab 50 IV: 100 mg IV over nystagmus -coagulant, contracep-
and 100 mg 5 min to a maximum of c. Ly m p h a d e n o - tive, rifampicin
Stabilises cell memb- 1000 mg pathy, megalo-
rain and affects arrhy- blastic anaemia,
thmias. pancytopenia
Indications: Digitalis
induced arrhythmias.
Acute vent. arrhythmia
after AMI but less than
lidocaine
IV amp: 2 ml, 5 ml,
50 mg/ml

Propranolol a. Oral: 10 mg b.d. a. CCF, bradycar- a. Cardiogenic a. Abrupt with-

Tab inderal 10, 40 mg to 160 mg t.d.s. dia, increases AV shock, sinus drawal produces
IV amp: 1 mg amp (average 40-160 block bradycardia, II AMI
Action: Decreases mg/day) b. Bronchospasm or III AV block, b. May mask symp-
heart rate, force of b. IV: 0.5 to 1 mg c. Depression, CCF toms of hypo-
contraction IV every 5-10 sleep disturba- b. Asthma glycaemia
Indications: PSVT, min up to 5 mg nce, impotency, c. Drug interac-
WPW, SYND, reduces fatigue tions:
vent. rate in auricular d. Arterial insuffi- Digitalis, cal-
fibrillation, flutter ciency, Raynau- cium channel
d’s phenomenon blockers

Amiodarone 600-1200 mg/day; a. Sinus bradycar- a. Marked sinus Raises serum digoxin
Cardaronex (Torrent) maintenance dose 200- dia bradycardia, AV level, potentiates effect
contd...
234 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Dose Side-effects Contraindications Drug interactions +

Precautions
200 mg tab 400 mg per day b. Pulmonary fibro- block of anticoagulant, inc-
sis reases quinidine level,
c. Photosensitivity may potentiate brady-
d. Nausea, vomi- cardia or AV block
ting, anorexia when used with beta-
e. Tremor, gait dis- blockers or calcium
turbance, myo- antagonists
pathy or neuro-
pathy

Verapamil a. Oral: 40-80 mg a. Hypotension, a. II and III AV a. Reduce oral dose

Calaptin (Boehringer- t.d.s. or q.d.s. AV block, heart block, sick sinus in hepatic and
M) Maximum 480 failure, asystole syndrome, LVF, renal insuffici-
Tab 40, 80 mg mg/day (with IV use) shock ency
Vasopten (Torrent) b. IV: 5 mg initially b. Nausea, consti- b. Avoid use with
Tab 40, 80, 120 mg over 2-5 min, pation, oedema, Disopyramide,
IV vial: 5 mg vial and further 5 mg IV if headache beta blocker, qui-
10 mg vial needed after nidine
SR tab calaptin: 120, 30 minutes
240 mg
Action: Delays impulse
conduction in AV node.
Indications: PSVT,
Controls vent. rate
inchronic auricular
fibrillation and flutter,
premature beats

Diltiazem: 60, 90 mg 30-90 mg 6-8 hourly Hypotension, IV block, Sick sinus syndrome, Be cautious in renal
Angizem (SUN), bradycardia, headache, II, III, AV block, sys- and hepatic insuffi-
Angizem CD 80, 120 oedema, dizziness tolic BP less than ciency and use with
and 180 mg tab. Dil- 90 mmHg beta blockers or digi-
contin (Modi) Tab CR talis
60, 90, 120 mg, Dilzem
(Torrent) 30, 60 mg
Dilzem SR 90 mg

Bretylium tosylate: 5-10 mg/kg IV Hypotension, especia- Severe hypotension,

IV 50 mg/ml lly postural may aggravate digitalis
Indications: Resistant 5-10 mg/kg IM toxicity, reduced dose
VT and V. fibri. used in in renal insufficiency
intensive care unit

Encainide: Oral 25-50 mg t.d.s. Worsens new VT or V Heart block, shock Reduce dose in renal
Tab 25, 35, 50 mg fib. or AV block insufficiency. Cemeti-
dine increases level
Medical and General Management of Cardiac Arrhythmias
Arrhythmias| 235

Medical management General management

Ventricular premature A. High-risk VPB (more than 5 VPB per minute, Treat underlying cause
beat (VPB) multifocal VPB, VPB occurring early in diastole such as hypoxia, pro-
on T wave of the preceding beat (R-on-T longed QT, CCF, AMI,
phenomenon): IV lidocaine 100 mg as bolus. ischaemia, mitral valve
Recurrence: Prevented by lidocaine infusion with prolapse and digitalis
500-1000 mg in 500 ml of 5% dextrose. toxicity.
B. Persisted benign VPB: Beta blocker or diso-
pyramide
C. VPB occurring in acute myocardial infarction or
with cardiac surgery: IV lidocaine or procainamide

Ventricular tachy- A. Emergency treatment of sustained VT: Without Remove precipitating

cardia (VT) hemodynamic deterioration IV lidocaine (Gesicard factors: Hypokalaemia,
or Xylocard) 2% 50-75 mg bolus in one minute hypomagnesaemia,
and followed by 500 mg (1 vial = 1000 mg in 50 quinidine, tricyclic
ml) in 50 ml dextrose 2 mg/min for 24-48 hours at antidepressant, IHD
the rate of 20-40 drops per minute
↓
If ineffective: Inject IV procainamide (Pronestyl)
250-500 mg 4 hourly or loading dose 1 gm over
20 mts. Stop if VT terminates or hypotension
develops or widening of QRS develops (more
than 15%). A maintenance infusion of 2-6 mg
per minute
Or
Inject disopyramide (Norpace, Rhythmodan)
200 mg bolus followed by every 6 hour
Or
Inject Mexiletine half amp. IV stat, followed by
2 amp. in 5%, 500 ml dextrose, 30 drops per minute
followed by 1 amp in 5%, 500 ml 5% dextrose 15-
20 drops per minute followed by orally 1 cap t.d.s.
↓
If ineffective: Inject amiodarone 300 mg IV over
30 minutes followed by orally cap 600-1200 mg
per day, after 1 week 400 mg per day and finally
200 mg per day
Or
Atenolol IV 5 mg slowly, 1 mg per minute, if no
response, repeat
↓
236 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

↓
If ineffective: Inject IV bretylium 5-10 mg/kg infused over
30 min followed by continuous infusion of 1-2 mg/min.
Hypotension may occur

B. Emergency treatment of sustained VT with haemodynamic

deterioration: DC conversion
↓
If successful: Followed by IV lidocaine for 24 hours

C. Polymorphic VT:
a. With normal QT interval: Quinidine
b. With prolonged QT interval:
i. Acquired: Atrial and ventricular pacing. Lidocaine
or bretylium help in isolated cases
ii. Congenital: Beta blocker
D. Digitalis induced VT: Phenytoin IV 50 mg/min. Maximum
dose 10-15 mg/kg
E. Propranolol preferred in ventricular tachyarrhythmias
believed to be due to catecholamine excess. Inject IV
propranolol 1 mg/min till a maximum dose of 0.1 mg/kg
to 0.15 mg/kg is given or arrhythmia stops or side-effects
occur.

Treatment of Chronic Ventricular Arrhythmias in Different Settings

1. VT with CCF:
a. Angiotensin converting enzyme inhibitor decreases frequency of ventricular arrhythmia and
helps CCF also.
b. Amiodarone 400-600 mg/day as loading dose for 5-7 days followed by maintenance dose of
100-200 mg per day.
2. Postmyocardial patients:
Beta blockers stop ventricular arrhythmias, reduces myocardial ischaemia and catecholamine excess.
3. VT with mitral valve prolapse:
Beta blocker
4. VT with exercise:
Beta blocker
5. VT with prolonged QT:
Beta blocker
6. Ventricular arrhythmias with sinus node disease:
Mexiletine, tocainide
7. Ventricular arrhythmias with renal failure:
Mexiletine, tocainide, amidarone
Combination Therapy in Ventricular Arrhythmias:
Arrhythmias| 237

a. Mexiletine + Disopyramide
b. Do + Propranol
c. Do + Amiodarone

Prophylaxis of Recurrent Ventricular Arrhythmias

I. Inject IV lidocaine infusion (50 ml vial containing 1000 mg + 500 cc 5% dextrose 20-40 drops per
minute (contraindication: AV block, hypotension) for 5 days, followed by:
Tab Pronestyl 250 mg 6 hourly
Or
Tab Quinidine 200 mg 6 hourly
Or
Tab Propranol 20 mg 6 hourly
Or
Tab Disopyramide 100 mg 6 hourly
Or
Cap. Mexitil 200 mg t.d.s.
Or
Tab Amiodarone 200 mg t.d.s.
(Contraindication: Pregnancy or lactation, don’t use with lidocaine, propranol, verapamil or
disopyramide
II. Polarising solution: 500 cc of 5% dextrose + 10 units of soluble insulin + 20 mEq (10 cc of 15%
solution IV drip).

Atrial premature beat

If heart abnormal or intermittent If heart is normal and APB

sustained APB: not sustained:
| |
• Digitalis • Rest
• Disopyramide • Stop smoking, alcohol and caffeine
• Propranolol
• Verapamil, dilzem
Paroxysmal supraventricular tachycardia (PSVT)
I. General measures if no hypotension:
a. Vagal maneuver: Valsalva, carotid sinus massage
b. Sedation
II. Drugs and electrical therapy:

Haemodynamic preservation: a. When haemodynamic deterioration and heart failure

• Verapamil 2.5 to 10 mg IV ↓
• Or Propranol 0.5 to 1 mg IV
• Dilzem IV DC cardioversion (50 watt/sec)
238 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. If with hypotension: Raise the blood pressure by

mephentermine (Mephentine 15 mg or 30 mg amp.)
1 amp. IV or Dopamine drop.
III. Flow chart of treatment:
↓
Try vagal maneuvers
↓
If fails: Adenosine (Adenoject (Inca) 1 amp 6 mg
rapid IV over 1-3 seconds—wait 1-2 mts
↓
If fails: Adenosine 12 mg rapid IV over 1-3 sec
↓
If fails: Determine width of QRS

For narrow complex For wide complex:

Determine blood Lidocaine 1 mg/kg IV
pressure ↓

Normal or Low or unstable If fails: Procainamide 20-30 mg per minute

elevated
↓ ↓ ↓
Verapamil Cardioversion If fails: Cardioversion
2.5 mg-5 mg
IV—wait for 15-30
minutes
↓
Verapamil
5-10 mg IV
↓
Consider:
• Digoxin
• β-blockers
• Dilzem
↓
If fails: Cardioversion
IV. For prevention of recurrence:
First try digoxin
↓
If fails: Quinidine, procainamide, norpace
(Avoid if QRS wide and QT prolonged)
Encainide and Flecanide
Effect of carotid sinus pressure on tachyarrhythmias:
Arrhythmia Effect
1. Sinus tachycardia Gradual slowing pressure, gradual speeding after pressure
 2. PSVT • No effect
Arrhythmias| 239

• Abrupt conversion to sinus rhythm

3. Atrial flutter
4. Atrial fibrillation
5. Ventricular tachycardia
• Slight slowing
• Produces AV block and slowed V rate
• No effect
• Produces AV block slowing V rate
• No effect
• No effect
• Atrioventricular dissociation

Sinus Tachycardia
No haemodynamic disturbance Symptomatic with haemodynamic disturbance
↓ ↓
Treat the cause Propranol 1 mg IV over 5-10 minutes up to 5 mg

Sinus Bradycardia
a. If with hypotension, chest pain, CCF:
IV Atropine 0.6-1 mg over 5 minutes up to total 2 mg
b. If asymptomatic, no treatment indicated
c. If profound hypotension, shock, occasional asystole and cardiac arrest: No response to atropine
(Give IV 0.6 mg, if rate less than 40/mt, additional dose of 0.2 mg up to 2 mg given in divided
doses)
↓
Pacemaker needed

Sick Sinus Syndrome

Digitalis controls tachyarrhythmia and contrary to expectation usually does not aggravate coexistent
bradyarrhythmia
↓
If fails: pacemaker

2nd and 3rd degree AV block:

a. Recent 2nd and 3rd degree AV block:
i. QRS normal width: Inject Atropine 0.6 mg IM or IV every 4 hour
Or
Alupent tab 10 mg 6 hourly
(Amp 10 mg/5m) IM 1-2 amp 6 hourly
Tab Pro-Banthine 15 mg t.d.s.
Tab Ephedrine
ii. QRS wide: Tab Neoepinine sublingually 30 mg 8 hourly
b. If established block with haemodynamic deterioration (giddiness, hypotension, attacks of asystole,
ventricular rate less than 50/minute):
↓
Temporary or permanent pacemaker
240 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

c. Precursors of complete heart block requiring pacemaker:

i. Bifascicular block (when any two of the peripheral branches or fascicles of the conduction
system blocked).
ii. Combination of RBBB + either left anterior or left posterior hemi-block
iii. New left bundle branch block
iv. Mortality rate increases more in complete heart block with anterior infarction than in inferior
wall infarction. Pacing is more needed and beneficial in infero-posterior infarction.
v. Chronic symptomatic 2nd and 3rd degree heart block needs implanted pacemaker.

Bundle Branch Block

i. Acute RBBB and left BBBK, bifascicular block (RBBB + Block of one of the fascicle of left
bundle)
↓
Temporary pacemaker
ii. Trifascicular block
↓
Permanent pacemaker

Ventricular Fibrillation
a. Acute attack: Emergency treatment:
Flow chart:
Immediate thump on the chest
↓
Alternate chest compression and DC shock:
15 times chest compression followed by shock of 320J
Repeat 15 times chest compression followed by shock of 320J
↓
Inject Adrenaline 1 ml of 1:1000
Continue chest compression and cardioversion by 320J
↓
Inject Lidocaine 100 mg IV followed by another shock of 320J
↓
Following successful cardioversion, correct acidosis, hypokalaemia,
Hypomagnesaemia. Infuse magnesium sulfate.
↓
If VF repeated:
IV Bretylium tysolate 5 mg/kg bolus followed by infusion 2 mg/minute
b. Recurrent VF: Lidocaine
Bretylium tysolate
Propranolol

Nodal Tachycardia
a. Treatment needed in stable case
b. Inhaemodynamic disturbance cases: IV Atropine 1.2 mg
Auricular Fibrillation (AF)
Arrhythmias | 241

I. Control of ventricular rate:

A. AF with slow ventricular rate:
Tab Digoxin
Tab Verapamil 80 mg 6 hourly
B. AF with very fast rate: (110-140 beats per minute)
With haemodynamic disturbance (CCF, With no haemodynamic disturbance
hypotension)
Cardioversion. i. Slow IV Verapamil 5 mg, if no response
Warfarin for 3 weeks before cardioversion 10 mg IV (Total 15 mg) followed by mainte-
and 4 weeks after cardioversion nance infusion 0.05 mg-0.2 mg/min
ii. IV Dilzem 0.1 mg/kg over 5 min. Some may
require continuous infusion (10-15 mg per
hour) to maintain ventricular rate
iii. IV Esmolol (ultra-short acting beta blocker)
iv. IV metoprolol 5-15 mg over 5-15 min
Major side-effect of dilzem and verapamil is
hypotension.
C. Moderately fast ventricular rate (90-140
beats per minute): IV Digoxin 0.25 mg
3-4 hourly until ventricle rate 70-80/min
D. WPW with AF with fast ventricular rate:
Unstable patient: Cardioversion Stable patient: IV Procainamide is the treatment of
choice.
Other drugs: Disopyramide, amiodarone, quinidine.
Beta blockers, verapamil and digitalis are contra-
indicated because they may produce hypotension
or precipitate cardiac arrest.
II. Restoration of sinus rhythm: In chronic AF: Quinidine, procainamide, propafenone, sotalol, flecainide
and amidarone (600 mg/day for 4 weeks followed by 100-200 mg/day
If fails: Cardioversion
III. Anticoagulation: Since chronic auricular fibrillation are always at risk of systemic embolisation,
anticoagulation must be considered. Anticoagulants are decided according to risk factors. Based on
risk factors patients are divided into 3 categories:
a. Patient at high-risk: Characterised by diabetes, history of previous stroke, age above 75 years
hypertension, left ventricular dysfunction, CCF, IHD, valvular disease or prosthesis or
thyrotoxicosis, echo shows intracardiac thrombus, large left atrium (greater than 4.5 cm, mitral
valve annular calcification).
b. Patient at moderate risk: Age 65 to 75 years, without any other risk factor.
c. Patient at low-risk: Age below 65 years without any other risk factor.
for Anticoagulation in AF See Table 39.3
IV. General management: Treat and manage the precipitating factors: Exercise, hypertension, emotional
stress, surgery, acute alcohol intoxication, mitral stenosis, chronic lung disease, atrial septal defect,
thyrotoxicosis, IHD.
242 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Table 39.3: Anticoagulation in AF

Clinical risk factors in AF: Previous TIA or CVA, previous arterial thromboembolism, clinical heart disease (CCF, IHD,
valvular disease or prosthesis), diabetes, hypertension, age above 75 years, thyrotoxicosis, left ventricular dysfunction

Clinical risk factors present Clinical risk factors not present

↓ ↓
Transthoracic echocardiographic risk factors present Transthoracic echocardiography
(enlarged left atrium, impaired left ventricular function, ↓ ↓
annular calcification of mitral valve, intracardiac thrombus) Echocardiographic No echocardiographic
↓ risk factor present risk factor present
High-risk factor ↓
↓ Warfarin
a. Warfarin ↓ ↓
b. Aspirin if warfarin contraindicated Moderate risk factor: Low risk factor: Age less
Age 65-75 years, labo- than than 65 years or
ratory control less effi- Low AF
cient and patient’s com-
pliance less reliable ↓
↓ Aspirin or Warfarin
Aspirin

Review risk factors Annually

Table 39.4: Another approach to control fast ventricular rate in auricular fibrillation
First try digoxin
↓ If fails
Verapamil or Diltiaz or beta blockers monotherapy
↓ If fails
Digoxin + Beta blockers or Digoxin + Verapamil
↓ If fails
Add or substitute amidarone

Table 39.5: Treatment of AF in different situations

Situations Drugs
1. AF with hypertension — — Diltiazem
2. AF with thyrotoxicosis — — Inderal
3. AF with IHD — — Diltiazem
4. AF with heart failure — — Digoxin, Amiodarone
5. AF with hypertrophic cardiomyopathy — — Beta blocker or Diltiazem
6. AF with rheumatic heart disease or lone — — Amiodarone
AF or sick sinus syndrome
 Table 39.6: Effect of drugs on permanent AF
Arrhythmias | 243

Thrombo- Resting heart Exercise heart Symptoms Haemodynamic

embolic risk rate rate benefit benefit
1. Digoxin Continues Controlled Not controlled  
2. Digoxin + Do Do Controlled 
 
Beta blocker
3. Digoxin + Do Do Do 

calcium ch.
blocker
4. Radiofrequency  
ablation or modi-
fication

Electrical Therapy for Cardiac Arrhythmias

There are three electrical devices used in the treatment of cadiac arrhythmias:
1. Cardiac pacemaker
2. DC cardioversion
3. Automatic implantable cardiovertor defibrillator

Cardiac pacing Indications Complications Contraindications Technical points

External energy used to 1. Bradyarrhythmia: i. Cardiac perforation a. Types:
stimulate the heart in a. Complete heart ii. Arrhythmia i. Temporary
bradyarrhythmia. It is block with bra- iii. Infection pacing: In emer-
used to terminate or dycardia, CCF, iv. Thrombosis embo- gency and to
prevent recurrent supra- asystole greater lism stabilise heart
ventricular and ventri- than 3 seconds v. Pacemaker synd- prior to perma-
cular tachyarrhythmias or ventricular rome: Lighthead- nent pacing
rate less than edness, syncope, ii. Permanent
40/min, mental episodic weakness pacing
confusion and if b. Modes:
CHB persists i. Normal AV
after AMI conduction:
b. Advanced 2nd Fixed rate
degree heart atrial pacing
block with tran- ii. AV block: Both
sient dizziness, atria and ven-
light-headed- tricle paced
ness, syncope,
CCF and mar-
ked exercise
intolerance
c. Chronic bi or tri
fasicular block
with intermit-
tent CHB or
with 2nd degree
contd...
244 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Cardiac pacing Indications Complications Contraindications Technical Points

heart block with

symptomatic
bradycardia
2. Tachyarrhythmia:
a. Drug refrac-
tory supraven-
tricular tachy-
cardia
b. To prevent
VT
c. Polymorphic
VT with long
QT interval
and brady-
cardia (tor-
sade de poin-
tes) is most
likely to res-
pond
DC cardioversion: i. Drug resistant Occasionally transient i. Chronic atrial fib- Energy for cardio-
atrial fibrillation SA or AV block, vent- rillation. Digitalis version
and flutter, PSVT, arrhythmia, worsening is preferred. i. Atrial flutter: 50
VT, VF heart failure or pulmo- ii. Chronic atrial fibri- Joules
ii. Rapid atrial arrhy- nary oedema llation due to ii. Atrial fibrillation
thmia, sustained hyperthyroidism, 200 Joules
VT or VF: Cardio- pericarditis, pulmo- iii. PSVT 100 J
version preferred nary embolism, iv. VT 50 J
than drug therapy COPD, alcohol v. Vent. fibrillation
abuse, CCF, enlar- 300-400 Joules
ged left atrium:
First treat causes
and then cardio-
version. Anti-
coagulation used
before cardiover-
sion in atrial fib-
rillation in MS

Automatic implantable i. Life-threatening i. Depletion of bat-

Cadioverter defibril- vent. tachycardia tery
llator: ii. Cardiac arrest ii. Lead breakage
iii. Drug resistant iii. Inappropriate dis-
Vent. fibrillation charge
iv. Infection
v. Skin erosion
SURGICAL TREATMENT OF CARDIAC ARRHYTHMIAS
Arrhythmias | 245

AIM
1. Ablation of arrhythmogenic foci
2. Obstruction of a re-entrant pathway of arrhythmia
3. Prevention of ventricle from responding to supraventricular tachycardia.

Type of Surgery
Arrhythmias
Auricular fibrillation, auricular flutter, with fast
ventricular rate not amenable to drugs and pacing
Types of surgery
a. Ablation of AV node and implantation of
ventricular pacemaker
b. Catheter ablation of bundle of HIS by large
energy source
c. Maze operation: Multiple atrial incisions made
to Channelise sinus impulse through a path or
maze to reach AVN.

Ectropic atrial focus Excision of the focus

PSVT refractory to drugs or pacing Surgical division of anomalous AV pathway

WPW syndrome with auricular fibrillation with fast Success 85%

ventricular rate, recurrent arrhythmias

Recurrent sustained ventricular tachycardia Removal of arrhythmogenic tissue with a cryoprobe

80% success

Multiform VT (long QT syndrome) Stellate ganglionectomy

CLINICAL NOTES
Any tachycardia (except sinus tachycardia) that produces hypotension, myocardial ischaemia or hear
failure or refractory to drugs needs DC conversion.
Auricular fibrillation and auricular flutter are the two most common arrhythmias where cardioversion
is most appropriate if they are not responding to drugs.
In digitalis toxicity cardioversion may cause dangerous arrhythmias and should only be resorted as
last resort.
In atrial fibrillation, particularly associated with mitral stenosis cardioversion can precipitate
thromboembolism, hence cardioversion is avoided provided anticoagulation is done for at least 2 weeks
prior to cardioversion.
246 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

CLINICAL NOTES
On Arrhythmias
PSVT:
a. IV Lidocaine (50-100 mg) bolus will convert 25% of PSVT to normal sinus rhythm.
b. PSVT with hypotension: Increase blood pressure by dopamine drip or IV mephentine.

Ventricular Arrhythmias
a. Quinidine is used to suppress both VPB and VT.
b. By many observers sotalol is best for ventricular arrhythmias.

Both Supraventricular and Ventricular Arrhythmias

a. Procainamide is useful for both supraventricular and ventricular arrhythmias.
b. Propranolol is effective in both groups of arrhythmia.

Auricular Fibrillation
a. In fast auricular fibrillation digoxin does not control effectively ventricular rate during exercise nor
convert to sinus rhythm or may prolong duration of paroxysmal auricular fibrillation. Hence except
in heart failure digoxin is not first line therapy in fast auricular fibrillation.
b. Clonidine 0.075 mg orally and after 2 hours repeat it if heart rate does not decrease by 20% in fast
auricular fibrillation. Blood pressure decreases slightly.
c. Frequent use of amiodarone in arrhythmia such as auricular fast fibrillation is associated with life-
threatening side-effects (tremor, pulmonary toxicity, neuropathy, liver toxicity, photosensitivity),
hence use in reduced dose (200-400 mg/day).
d. Amiodarone is better in elderly patients with auricular fibrillation associated with myocardial
dysfunction and when other agents fail.
e. Paroxysmal auricular fibrillation: “Pill in the pocket” approach: One or two oral dose of
antiarrhythmic drug.
f. Low auricular fibrillation with infrequent attacks: Antiarrhythmic drug is not indicated. If symptoms
are troublesome: (a) Associated with IHD hypertension: Use beta blockers (b) With heart failure:
Use amiodarone
g. For fast ventricular rate in auricular fibrillation:
i. With defective heart: Beta blockers or verapamil or diltiazem
ii. With heart failure: Amiodarone
↓
If unsuccessful:
Digoxin + Beta blockers
Or
Digoxin + Calcium channel blockers
h. Systemic embolism is a complication of electrical or pharmacological cardioversion of auricular
fibrillation to sinus rhythm. Hence about 3 weeks before and 4 weeks after cardioversion antico-
agulation should be instituted.
 Arrhythmias | 247

i. Annual rate of stroke for anticoagulated control group in 5 large anticoagulation trial (“Risk factors
for stroke and efficacy of antithrombotic therapy in auricular fibrillation, analysis of pooled data
from randomised control trials: Arch. Intern. Med. 1994, 154: 1449-60) was 4.5% and reduced to
1.4% (Risk reduction 68%) for warfarin group. Aspirin 325 mg/day produced 44% risk reduction.
The annual rate of major haemorrhage was 1% for control group and 1% for aspirin group and
1.3% for warfarin group.

CLINICAL NOTES ON ANTIARRHYTHMIC DRUGS

Quinidine
a. Quinidine is useful as an adjunct to digoxin for converting both atrial fibrillation and flutter to
normal sinus rhythm.
b. Quinidine can be effective in both supraventricular and ventricular arrhythmias but its use has been
limited because of causing dangerous arrhythmias especially ventricular tachycardia.
c. Quinidine prolongs QT interval with therapeutic doses. It is contraindicated in patients with prolonged
QT interval.
d. Quinidine raises digoxin level and precipitate toxicity.

Amiodarone
a. It is highly effective in both supraventricular and ventricular arrhythmias.
b. Even in other drug resistant arrhythmias it is successful in 70% cases.
c. It has remarkably long half-life (about 28 days) so the drug can be given once daily or even less
frequently (200 mg alternate day).
d. It does not significantly impair myocardial contractility.
e. A delayed onset of action (4-7 days) and relatively ineffective parenteral preparation makes it
unsuitable for emergency use. It may take 50 days to reach the maximum effect.
f. The main unwanted effect of amidarone are corneal microdeposits and skin photosensitivity (skin
burns more easily in the sun). Corneal deposits produce visual haloes and blurring but visual acuity
is never permanently damaged.
g. It potentiates the effect of both anticoagulant and digoxin.
h. It may prolong QT interval.

Verapamil
a. Verapamil is the drug of choice for the termination of AV re-entrant (Paroxysmal supraventricular)
tachycardia.
b. Orally it is less effective because much of the dose is metabolised in liver. Large doses (40-120 mg
t.d.s.) are needed.
c. IV Verapamil is contraindicated if the patient has already received an oral or intravenous beta
blocker. Profound bradycardia or hypotension may occur and may be fatal.
d. Verapamil should not be given to patients with digoxin toxicity unless there is ventricular pacing
wire in situ because of risk of heart block.
e. It is more useful in supraventricular tachycardia than beta blockers, and since the verapamil cannot
be safely administered once beta blockers have been given, verapamil is the drug of choice.
248 |
Lignocaine
Bedside Approach to Medical Therapeutics with Diagnostic Clues

a. Lignocaine is a vasoconstrictor and rarely impairs myocardial contractility. Hence heart failure and
hypotension are rare.
b. Bolus injection (50-100 mg) should be followed by continuous infusion because plasma level falls
rapidly.
c. It can be difficult to maintain therapeutic levels of lignocaine. With subtherapeutic levels the patient
is at risk from ventricular arrhythmias and toxic level may produce CNS toxicity (light headedness,
confusion, twitching, paresthesia and epileptic fits). A number of regimens have been developed to
avoid sub-therapeutic level-administration of second bolus 10-15 minutes after the first and/or
giving higher early infusion dosages. However, they increase toxicity.
d. It is metabolised in liver and in presence of liver disease where hepatic blood flow is reduced by
heart failure or by cardiogenic shock, dosages should be halved to avoid toxicity.
e. Hypokalaemia may impair the efficacy of lignocaine.

Mexiletine
a. It is like lignocaine but sometimes be effective when lidocaine fails.
b. There is narrow margin between therapeutic and toxic effects and thus toxicity are common.

Disopyramide
a. Widely used for ventricular and to a lesser extent, supraventricular arrhythmias.
b. Given IV, the drug is more likely to cause hypotension and heart failure than lignocaine and other
related drugs. Its use can be disastrous if the recommended minimum period of administration is
ignored.
c. It impairs sinus node function and so contraindicated in sick sinus syndrome.
d. Excreted by kidney and hence reduce dose in kidney failure.

Tocainide
a. It is similar to lignocaine and mexiletine.
b. 40% excreted by kidney.
c. Therapeutic toxic margin wider.
 Heart
40
Acute Myocardial Infarction

GENERAL MANAGEMENT
Pain
For management of severe pain see the Table 40.1.

Table 40.1: Pain management in AMI

Drugs Dose Side-effects and their management
Morphine: a. Repetitive small dose of a. Lowers arterial pressure and cardiac output. Treated
Relieves pain and anxiety. 2-4 mg every 5 min IV by elevation of legs and in some patients volume
Reduces myocardial oxygen b. Or, 10 mg subcut. expansion with IV saline
consumption by reducing c. Or, dissolved in 25 cc of b. Bradycardia or advanced heart block particularly in
sympathetic discharge and distilled water one amp., postero-inferior infarction. Treated by IV 0.4 ml
afterload (due to vasodilation) given 2 cc IV every atropine.
minute. c. Keep patient supine to prevent vomiting.
d. Occasionally sudden hypotension. Treated by IV
atropine.
Pethidine HCl 75-100 mg IM preceded by
promethazine to prevent
vomiting
Norphine 1 ml (0.2 mg) IM or slow IV
(Buprenorphine) preceded hyperchlorperazine
(Stemetil) IM to prevent
vomiting
Tidigesic (TDPL) sublingual
tab or IM amp.
Nitroglycerine: a. Sublingual: 3 doses of Headache, hypotension. Not prescribed systolic if pressure
0.3 mg tab every 5 min below 100 mmHg.
b. Drip IV 5 mg/min and
gradually increased till
pain is relieved.

Beta blockers: a. Propranol 0.1 mg/kg

b. Metoprolol 15 mg IV
Oxygen: Given by facemask or nasal Heart block, left ventricular failure.
Reduces area of ischaemia prongs
250 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

REST AND ACTIVITY

First 2-3 days: Complete bedrest for first 24 hours is prescribed. Afterwards bedrest with one or two
periods of 15-30 minutes in bedside chair is advised. Bedside comode may be used and may be bathed.
The bed should have foot board and the patient should push both feet against the footboard firmly ten
times during waking hours and passive movement of legs from the first day to prevent thromboembolism.
Deep breathing off and on is advised.
Third to fifth day: Stay for 30-60 minutes in chair twice a day is prescribed. Standing (blood pressure
is measured on standing to detect postural hypotension) and gradual ambulation is advised. Initial walking
is to the bathroom.
Sixth to twelveth day: The total duration of stay in hospital should be 7-12 days. A limited exercise
tolerance may be performed before discharging from the hospital.
Third to eighth week: The patient may convalescence at home. He should be advised to walk about
the home and outdoor in good weather. Bedrest for 8-10 hours in night should be observed.
After 8th week: The physician must regulate his activity according to exercise tolerance. Most patients
return to work after 12 weeks.

Diet
First 4-5 days: Semisolid or liquid diet (Fruit juice, coconut water, thin soup) is given during 24-48
hours. The low caloric diet with multiple small feedings is recommended. Salt is restricted if heart
failure is present, and potassium rich food (fruits) is given if diuretics are used.
Second week onwards: Liberalise the diet but restrict calories, cholesterol and saturated fat. Smoking
and tobacco is stopped.

Bowel
Bedside comode is allowed. Stool softener (dicotyl sodium) 100 mg twice daily orally. Proctosedyl
enema is used if needed.

Sedation
Diazepam 5 mg or alprazolam should be given three times a day.

Drugs for Saving Ischaemic Myocardium and Improving Survival

1. Oral aspirin : 160-320 mg/day.
2. Sublingual or parenteral nitroglycerine: For doses see further. It reduces infarct size by altering
oxygen supply and demand favourably.
3. IV metoprolol 15 mg given slowly followed by oral treatment alters survival favourably.
4. ACE inhibitors: Captopril 6.25 mg t.d.s. or enalapril 5 mg/day or lisinopril 5 mg/day. They enhance
left ventricular remodelling and thus prevents left ventricular aneurysm.
5. Thrombolysis: Thrombolytics should be given within 4-6 hours after the onset of chest pain. For
Thrombolytics See Table 40.2.
 Table 40.2: Thrombolytics
Acute Myocardial Infarction | 251

Drugs Action Dose Recanisation rate Complications Contraindications

Streptokinase: Removes occlu- 1.5 million units IV 50% i. R e p e r f u s i o n i. Recent surgical
sion, reduces over 2 hours. 100 arrhythmias operation.
short-term morta- mg hydrocortisone ii. Bleeding, trea- ii. Recent cere-
lity and left ventri- IV given prior to ted by capro- bro-vascular
cular function prevent allergic stat 5 to 10 ml accident
reaction. Cannot be IV in dextrose iii. Bleeding dia-
repeated. saline followed thesis
by tab. 2-10 in iv. Cardiopulmo-
divided doses. nary resusci-
tation
Urokinase: Do 1.5 to 2 million 50% Do Do
units IV. Can be
repeated if required

Acetylated strepto- Do 100 mg IV 75% Do High cost

kinase tPA To prevent reocclu-
sion
Heparin: a. Improves sur- Following throm-
vival and long- bolytic therapy IV
term prognosis heparin given for
Aspirin: b. Secondary pre- 24-8 hours.
vention of AMI

TREATMENT OF COMPLICATIONS
I. Heart failure (Acute)—Acute left ventricular failure:
1. Keep the patient propped up.
2. Administer oxygen by mask.
3. Treat arrhythmias. See further.
4. Administer frusemide 40 mg IV or orally 1-2 tab daily.
5. ACE inhibitor is given to prevent ventricular dilation. Enalapril can be given orally in gradually
increasing doses of 2.5-10 mg daily. Captopril 25 mg × 2.
6. Digitalis is seldom used in acute heart failure because of its side-effects.
7. Theophylline (Deriphylline retard tab or amp) IM or IV.
8. If failure persists:
• Inject nitroglycerine 20-30 mcg/min
Or Sublingual nitrate (Angiced, isordil 5 mg)
Nitroglycerine amp: 25 mg/5 ml or 50 mg/ml. Amp. mixed with 250 ml of water, 10 mcg/
min or 3 drops/min, one point in 24 hours.
• Inj. aminophylline 0.15 gm IV slowly with hydrocortisone. Repeat after 6-8 days.
• Nitravet tab one at bedtime (5 mg to 10 mg)
• Recently amrinone (a phosphodiesterase inhibitory) in a loading dose of 0.75 mg/kg followed
by infusion of 10 mcg/kg/min has been used with encouraging result.
252 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

9. If medical measures fail:

• Intra-aortic balloon counterpulsation may occasionally be life-saving.
• Percutaneous transluminal coronary angioplasty (PTCA) has been tried with good result.
II. Management of cardiogenic shock: Cardiogenic shock may be associated with left ventricular failure.
Cardiogen shock is characterised by systolic blood pressure less than 90 mmHg, oliguria, cold
clammy skin, narrow pulse pressure and altered sensorium. Chest X-ray shows pulmonary venous
congestion.

Management
1. Oxygen continuously.
2. Inject sodium bicarbonate 7.5%. Start 60 cc, repeat 40 cc every 15 minute till improvement or
100 ml reached.
3. Dopamine drip: 200 mg + 500 ml 5% dextrose, 5-30 drops per minute.
4. Fluid: 5% dextrose 100 ml, if improvement after 1-2 hour, repeat. If no improvement with
development of pulmonary congestion and dyspnoea, give diuretic to reduce preload.
Other fluids: Isotonic saline, Ringer’s lactate, dextrose 10%.
5. Dobutamine: In place of dopamine, dobutamine can be given.
6. Inject sodium nitroprusside 20-200 mcg/min.
7. Nitroglycerine drip.
8. Both dopamine and nitroglycerine drips are indicated in shock with basal crepts. They reduce
preload.
9. Both dopamine and sodium nitroprusside drip reduces both preload and afterload, improves cardiac
output and diminish myocardial oxygen demand.
10. Inject amrinone (Inocor) 0.75 mg/kg bolus over 2-3 minute, followed by intravenous infusion of 5-
10 mcg/kg/min (Dilute in saline).
11. Hydrocortisone 200 mg IV 6 hourly.
12. Treat bradycardia by atropine.
13. Give carbohydrate to reduce hypoglycaemia.
14. When hypotension occurs in presence of right ventricular infarction (ECG changes of inferior wall
infarction + raised JVP): Infuse normal saline or dextran.
15. Catheterise for urinary output. If no urine for 6 hours:
• Tab Lasix 1-2/day or 40-80 mg IV
• Mannitol
• Oxygen
16. Horizontal position with legs slightly elevated
III. Cardiac arrest:
Characterised by:
Heart beat absent
Pulses in large arteries absent
Pallor, cynosis
Gasping
Arrest of respiration
Dilated pupil
ECG: Ventricular fibrillation or asystole
 Cardio-pulmonary resuscitation: CPR
Acute Myocardial Infarction | 253

I. Basic cardiac life support (BCLS): ABC:

A = Airway
Extend patient’s head and
press chin down, it removes
obstruction by tongue. Clear
pharynx with fingures
covered with gauze
B = Breathing
After making a tight seal over
patient’s mouth start mouth-
to-mouth breathing raising
chest wall. One breath every
5 seconds
C = Circulation
a. Precordial thump if appropriate.
Rapid sharp blow to sternum with
fist from a distance of 8-12 inches
above chest.
b. If conscious ask to repetitive
rhythmic coughing which can
maintain cardiac output despite of
ventricular fibrillation at least for
brief intervals.
c. External cardiac massage or
compression: If after two mouth
breaths palpable pulse is not felt,
external cardiac massage is started:

Position of rescuer: Position of hand: Rate of compression and Ratio of breaths and
state of carotid pulse: compression:
Rescuer kneels at the side Heel of left hand Give firm compression with Single rescuer
of the patient placed over lower the weight of rescuer’s body 2:15
half of sternum, to push the sternum one inch Two rescuer
other hand placed or more. Rate of compres- 1:15
on top of this hand sion 60 to 100 times per
and fingers are minute. The effect of comp-
interlocked. ression is assessed by peri-
odically palpating carotid
pulse.
II. Advanced cardiac life support (ACLS):
See Table 40.3: “Drugs used in ACLS”
Table 40.3: Drugs used in ACLS
Dose Complications Indication Remarks
A. Essential drugs:
1. Adrenaline: i. Ventricular fibril- Do not coadminister
Dilute 1 ml amp. to
lation with sodium bicarbo-
20 ml. Give 1 ml IV
ii. Asystole nate in the same IV
every 10 minutes
Or
0.5 mg-1 mg (0.5 ml to
1 ml of 1: 1000) IV,
repeat every 5-10
minutes till 2 mg (2 ml)
given
contd...
254 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Dose Complications Indication

2. Atropine: 1 mg IV, repeat after 5 minute. i. Ventricular tachycardia
Maximum 2 mg. ii. Ventricular fibrillation
iii. Increased myocardial
oxygen consumption
due to tachycardia.
i. Persistent ventricular
fibrillation
ii. Asystole
iii. Severe bradycardia

3. Lidocaine: 1 mg/kg (50-70 mg) as bolus. Myocardial depression, CNS

Additional bolus of 0.5 mg/ depression, seizure Ventricular tachycardia,
kg at 10 minutes intervals to ventricular fibrillation
a total of 3 mg/kg and then
followed by continuous infu-
sion of 1-4 mg per minute

B. Useful drugs:
1. Mephentermine Mephentine 60 mg IV. 15 and Excessive vasoconstriction
30 mg amp. Shock
2. Corticosteroid
C.Additional drugs with
special indications:
1. Dopamine See arrhythmia and shock Tachycardia, ectopics, angina
Dobutamine Shock
2. Bretylium: 5 mg/kg IV bolus Postural hypotension, severe
nausea and vomiting Persistent ventricular fibril-
lation
3. Procainamide: 30 mg/minute Hypotension, AV conduction
disturbance Persistent ventricular
4. Sodium bicarbonate: 1 mEq/kg fibrillation
Or Hyperkalaemia or acidosis
Start 50 ml 7.5% IV, repeat
after 10 minutes

5. Frusemide: 40 mg IV injected over 1-2 Cardiac failure

minutes
6. Calcium chloride: 2-5 ml 10%, repeat every 15 Hyperkalaemia, hypocalcae-
minutes mia,

7. Isoproterenol: 1 mg in 500 ml 5% dextrose Increases myocardial oxygen Marked bradycardia, asystole

consumption, may provoke
arrhythmia
8. Magnesium sulphate: 1-2 gm IV Refractory ventricular fibril-
lation
9. Propranol: 1 mg IV over 1-2 minutes. Used to prevent recurrent
May be repeated at 5 minute ventricular tachycardia if
intervals up to 3-5 mg lidocaine fails
Procedure for ACLS
Acute Myocardial Infarction | 255

Cardiac monitoring and management Ventilation and oxygen admi- Circulation

of arrhythmia nistration
Do ECG By: Oropharyngeal airway, Chest compression:
ECG shows ventricular tachycardia or endotracheal intubation, bag automatic or manual
ventricular fibrillation: valve device
Start direct current counter-shock with
200 joules
↓ If ineffective
2nd delivery of 200-300 joules
↓ If ineffective
3rd delivery of 300 joules

Do ECG again. There are 4 possibilities

Return of sponta- Persistent VT/VF: Asystole Pulseless elec-

neous circulation a. VT: Lidocaine • Adrenaline trical activity
DC 25-50 joules • Atropine (PEA):
Inderal IV • Isoproterenol in Pulse absent but
b. VF: Adrenaline 1 mg IV, repeat 360 joules severe brady- ECG shows acti-
shock after 30-60 seconds. Adrenaline and cardia due to vity. It is due to
DC shock repeated every 3-5 minutes until heart block ref- severe hypovo-
pulse is normal ractory to atro- laemia, massive
pine pulmonary emb-
↓ If ineffective olism cardiac
Give lidocaine 1 mg/kg IV and defibrillate tamponade and
with 360 J tension pneumo-
↓ If still ineffective thorax. Treat
Give bretyllium 5 mg/kg as an IV bolus accordingly.
dose and defibrillate again with 360 J. Also
give IV sodium bicarbonate
↓ If still ineffective
• Magnesium sulphate
• Procainamide
• Internal cardiac defibrillation
IV Arrhythmias
See the chapter on “Arrhythmias”.
V. Other complications
256 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Complications Mechanism Effects Diagnostic features Treatment

Mitral regurgitation: Due to ischaemic rup- Severe mitral regurgi- Apical pansystolic mur- Severe MR needs coro-
ture of papillary mus- tation and acute left mur, occasionally para- nary angioplasty, by-
cles ventricular failure. Car- sternal thrill pass surgery and mitral
diogenic shock valve replacement

Ventricular septal Rupture of infarcted Severe left ventricular PSM at left sternal Needs immediate sur-
defect (VSD) interventricular septum failure edge, confirmed by gical intervention
Echo-Doppler studies

Left ventricular aneur- Dilatation of infarcted Left vent. failure, arrhy- Paradoxical movement i. Aneurysmectomy
ysm septum thmia, systemic embo- of dilated segment, ii. Bypass surgery
lism double diffuse or dis-
placed apical impulse

Right vent. infarction Usually associated with Left vent. haemodyna- In ECG ST elevation Needs fluid replace-
inferior wall infarction mics normal. Right greater than 1 mm in ment to improve
vent. failure V4R, hypotension, forward flow
right heart failure.

Thromboembolism Formation of thrombus Paralysis, gangrene Pulses diminished or Immediate embolec-

in left ventricle leading absent tomy
to systemic arterial
embolism

Pulmonary embolism Originates in leg due to Massive embolism Acute chest pain, hae- i. Prevented by anti-
prolonged imbolisation leads to shock and moptysis, ECG: Right coagulant and early
death vent. strain mobilisation
ii. Embolectomy
Pericarditis Pericardial rub Aspirin 650 mg q.d.s.,
indomethacin. If severe
steroid

Dressler’s syndrome Due to autoimmune Fever, pleuropericar- Salicylate, hydrocorti-

reaction to necrosed ditis, ESR high sone
myocardial cell

Management of AMI After Acute Stage is Over in Hospital

A. Uncomplicated case: Discharged on aspirin 160 mg daily and oral beta blockers unless con-
traindicated.
B. Cases associate with left ventricular dysfunction: Discharged on sustained release nitroglycerine
2.5 mg b.d. and ACE inhibitor (Captopril, Enalapril, ramipril). Recently ramipril is considered as
drug of choice.
C. Cases associated with left ventricular failure: Discharged on digoxin and diuretic.
D. Resumption of work:
Patient with uncomplicated infarction will return to work in about 6 weeks.
In complicated case work may be resumed after 10 weeks.
E. High-risk patients: They are prone to reinfarction and sudden death in the first 2 months. See Table
40.4 “High-risk Patients”.
 Table 40.4: High-risk patients
Acute Myocardial Infarction | 257

Investigations to assess risk factors Features suggesting high-risk patients Management

a. Stress test a. Complicated course in ICCU Arrange for coronary angiography.
b. Exercise thalium testing b. Angina Accordingly PTCA or by pass surgery
c. Echocardiography c. Positive stress test is indicated.
d. Holder monitoring d. Reversible thalium perfusion
defect
e. Reduced left ventricular ejection
(Less than 35%) in echocardio-
graphy
f. More than 10 premature ventri-
cular beat per hour on Holter
monitoring

F. Secondary Prevention
1. Keep total cholesterol to less than 200 mg/dl, keep LDL less than 100 mg/dl. Reduce LDL by
antioxidants (Vitamin C, E and betacarotine). Raise HDL by exercise, high fibre diet and small
amount of alcohol. Climbing stairs up to 2 floors after 3 months. Air journey is allowed after
3 months. By judicious use of drugs (Lovastatin or simvastatin) level of lipids can be controlled.
2. Weight reduction.
3. Smoking should be stopped.
4. Diabetes mellitus and hypertension should be controlled.
5. 160 mg aspirin/day life-long.
6. Oral beta-blockers reduces mortality.
7. ACE inhibitor reduces dilation of left ventricle.
8. Tyclid (Torrent), an antiplatelet drug 250 mg b.d.
9. Adding 2 portions of oily fish (Salmon, trout, mackerel, herring, sardine, rohu) reduces mortality.

CLINICAL NOTES
Digoxin has no role to play in acute myocardial infarction with acute left ventricular failure or cardiogenic
shock and may precipitate arrhythmias.
Diabetic patient on insulin is treated with regular insulin for the initial several days after AMI.
Resuption of sexual activity is allowed after 4 weeks of acute myocardial infarction without symptoms.
Measures capable of limiting infarct size in experimental models:
a. By reducing myocardial oxygen demand: Beta blockers, calcium antagonists, intra-aortic balloon
counterpulsation.
b. By augmenting coronary blood flow to ischaemic myocardium; nitrates, calcium antagonists,
hypertonic mannitol, corticosteroids, intra-aortic balloon counterpulsation.
c. By anti-inflammatory agents: Hyaluronidase, corticosteroids, hypertonic mannitol, glucose +
potassium + insulin, cobra venom, calcium antagonists, anti-inflammatory agents.
Bypass surgery does not prevent AMI or death in long-run. The benefit begins to diminish after
5 years.
PTCA is done even in elderly with 3 vessel disease.
Amidarone 200 mg/day may be given in stable AMI to prevent ventricular tachycardia.
In some trial magnesium IV reduces arrhythmia and death. It is safe.
258 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Advanced age and hypertension is not contraindicated for thrombolysis.

ST elevation in ECG during thrombolytic therapy suggests benefit.
Pulmonary congestion and cardiogenic shock is not improved by thrombolysis.
Drugs other than verapamil and digoxin used for auricular fibrillation:
a. Amidarone 200-600 mg/day
b. Diltiazem: diltiazem vial (Diltiazem) 25 mg/5 ml, 5 mg/1 ml, 20 mg bolus IV over 2 minutes, if no
response 25 mg IV after 15 minutes in auricular fibrillation with fast ventricular rate.
Contraindication: Heart block, WPW syndrome, sick sinus syndrome, severe hypotension, beta
blockers, ventricular tachycardia.
c. Clonidine 0.75 mg orally and after 2 hours repeat IV procainamide.
Verapamil is contraindicated in WPW syndrome with auricular fibrillation.
Felodipine and nitrendipine can be used in left ventricular failure. Felodipine and nitrendipine can be
combined with ACE inhibitor, diuretic and beta blockers in hypertension.
Benign VPB may be controlled by beta blockers, and disopyramide.
Coronary bypass surgery is undertaken if left main coronary artery or 3 major coronary arteries blocked
on angioplasty.
Nitroglycerine drip combined with streptokinase 1.5 million units IV for 1 hour reduces infarct size.
Atenolol in acute myocardial infarction: Atenolol 5 mg IV given over 5 minutes and stopped if heart
rate fell below 40 beats per minute or if any other contraindication develops.
↓
If after 10 minutes heart rate is 60 beats per minute or greater oral atenolol 50 mg is given, followed
by further 50 mg 12 hours later.
↓
Atenolol then given 50 mg b.d. or 100 mg/day until discharge from the hospital.
EDTA (Ethylenediaminetetraacetic acid) has new use as alternative to coronary bypass surgery. It
removes and chelates heavy metals (lead, calcium) from the body. It removes calcium from atheromatous
plaques of blood vessels. Robin of Georgetown University gave to IHD patients twice weekly infusion
of EDTA over 3 months had dramatic effect. Heart showed significant decrease in calcium deposits and
patient showed marked improvement in symptoms. It has also antioxidant property and reduces blood
pressure and is also cheaper than bypass surgery.
Chlamydia infection is responsible for some causes of acute myocardial infarction. Hence giving
roxythromycin 150 mg b.d. is an wise proposition.

CLINICAL NOTES
A clinical trial has shown the following 3 drugs given at the same time effectively produces thrombolysis:
• Streptokinase (Cheaper than urokinase)
• Metoprolol 5 mg IV t.d.s.
• Magnesium sulphate 4-6 gm infused over 3 hours and 3-5 gm over 12 hours for 4-5 days.
Relative benefit of different measures in acute myocardial infarction:
Significant mortality benefit No significant mortality benefit Ongoing evaluation of benefits
• Thrombolysis • Magnesium • Heparin
• Beta blockers • Nitrate • Oral anticoagulant
• ACE inhibitor • Hirudin
• PTCA
 • Coronary bypass surgery
Acute Myocardial Infarction | 259

No benefit possibly harmful

• Calcium antagonists
• Lidocaine
• Class I antiarrhythmic
Low-dose streptokinase (7.5 lac units) is usually prescribed in elderly patients in acute myocardial
infarction.
In cardiac arrest sodium bicarbonate is not recommended as routine and indicated only in hyperkalaemia
or acidosis. Similarly, calcium chloride is only indicated in hyperkalaemia, hypocalcaemia, hypovolaemia
or calcium antagonist overdose.
Intracardiac injection of drugs in cardiac arrest is not recommended.
DC shock is not helpful in asystole. It can increase parasympathetic discharge and may prevent recovery.
Future treatment of AMI: Combination of
a. Platelet receptor blockers: Abciximab, eptifibatide, tibrofiban and lamifiban
b. A small dose of thrombolytic agents
c. Low-dose heparin
d. Genetic therapy where feasable.

Postmyocardial Infarction Investigations and Management

Uncomplicated Complicated (cardiac Persistent post-

failure, angina, arrhy- infarction angina
Exercise test thmia)

Negative Positive Exercise test Exercise test not Coronary angio-

possible graphy
• Aspirin With angina Without angina
• Beta blockers Assess left ven-
• Left vent. angio- • Aspirin tricular function:
graphy • Beta blockers • Clinical
• ACE inhibitor • Radionucleotide
• Coronary arte- ventriculography
riography • Echocardiogra-
phy

Impaired left ven-

tricular function

No angina With angina

• Aspirin • Left vent. angiography

• ACE inhibitor • Coronary arteriography
• Beta blockers
 Heart
41
Congestive Cardiac Failure

In congestive cardiac failure (CCF) the heart is unable to meet the flow of blood into organs and body
tissues during exertion and even at rest.

Pathophysiology
CCF results in elevated left and right heart filling pressure, a low cardiac output and decreased left
ventricular ejection fraction (less than 40%).

Cardinal Clinical Features

Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, weakness, fatigue and oedema of the feet.

TREATMENT
General measures:
1. Salt reduction: Salts in cooking is omitted. Salt is restricted to less than 3 gm/day (Normal intake 6-
10 gm/day). In severe heart failure salt is restricted to 500-1000 mg/day. Avoid cheese, milk, bread,
cereals, soup, spinach, celery and beets. Use salt substitute.
2. Add fresh fruit, green vegetables to the diet.
3. Water intake is restricted if the patient is unable to excrete water load.
4. Obese patient should reduce weight.
5. Activity: Moderate restriction of activity is instituted. Absolute bedrest is not essential unless acute
and severe heart failure exists when rest in bed or in chair is prescribed. Hazards of absolute bedrest
such as phlebothrombosis and pulmonary embolism can be reduced by anticoagulant, leg exercise
and elastic stockings.

Drugs
1. Diuretics: Diuretics relieve symptoms of cardiac failure but there is no direct proof of prognostic
benefit. See Table 41.1.
2. Digoxin: Use of digoxin in cardiac failure is more in Germany than in U.K. It is invaluable in
cardiac failure with auricular fibrillation. It is also used in chronic cardiac failure secondary to left
ventricular dysfunction with sinus rhythm. See Table 41.2.
3. ACE inhibitors: ACE inhibitors have consistently shown beneficial effect on mortality, morbidity
and quality-of-life and are indicated in all stages of symptomatic heart failure resulting from left
ventricular systolic dysfunction. See Table 41.3.
 Congestive Cardiac Failure

4. Vasodilators: Vasodilators not only relieve symptoms of cardiac failure (moderate to severe) but
| 261

also showed survival benefit. See Table 41.4.

5. Beta-blockers: Due to negative ionotrophic effect of beta blockers it was generally not prescribed
in cardiac failure. But recently it is shown that it benefits cardiac failure. It should be started in low
dose and very slowly raised to the target dose (maximum dose). It improves left ventricular function,
reduces sympathetic tone, improves autonomic nervous system balance, up regulation of beta-
adrenergic receptors, reduces arrhythmias, further infarction and fibrosis of myocardium. See Table
41.5.
Table 41.1: Digoxin

Action Preparations Total digitalising Maintenance dose Method of adminis- Side-effect

dose tration
Improves cardiac 1. Oral: 0.25 mg 2-3 mg 0.15 to 0.5 mg a. Rapid digita- Mild: Anorexia,
contraction. Car- tab. lisation as in nausea, vomiting
diotonic auricular fibril- Moderate: Diarr-
lation with fast hoea, ectopics usu-
ventricular rate ally bigeminy, con-
and acute pul- fusion
monary oedema: Severe toxicity
1 mg stat—fol- variable AV block
lowed by 0.5 mg auricular fibril-
6 hourly till lation ventricular
3 mg is reached fibrillation
b. Slow digitali-
sation: 0.25 mg
t.d.s. for 5 to
7 days.

2. I n t r a v e n o u s 1 ml amp = 0.5 mg, 1.5 mg (3 ml) Indicated in auri- Treatment of toxi-

(dilute before cular fibrillation city:
use) with fast ventricular i. Tachyarrhyth-
rate and acute pul- mia oral K,
monary oedema. 0.5 phenytoin,
mg IV stat followed inderal
by 0.25 mg ii. Heart block:
6 hourly. Cardiac pace-
maker but
electrical
cardioversion
not helpful

Table 41.2: Vasodilators

Action
Reduces after load and enhances cardiac
output by venodilatation (by nitrogly-
cerine, isosorbide, salbutamol),
arteriolar dilatation (by hydralazine,
minoxidil, nifedipine) and both
Adverse effect
i. Hydralazine: Palpitation,
angina, arthralgia and serum
sickness like.
ii. ACE inhibitors: Hypo-
tension, rise in BUN, rash,
Preparations and doses
i. Nitrate:
a. 2% ointment, 1/2 to 1 inch t.d.s.-
Nitroderm THS (Novartis)
b. Transdermal patch 10 mg/24 hours,
maintenance 20-60/day
contd...
262 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Action Adverse effect Preparations and doses

arteriolar and venous dilation (by cough c. Sublingual—1 mg t.d.s. to 2-5 mg

Captopril, nitroprusside, prazosin,
terbutaline)
iii. Nitrate: Headache, dizziness t.d.s.
d. Iososorbide: 20 mg t.d.s.—main-
tenance 40-80 mg t.d.s.
e. Parenteral: See “Intravenous drugs
for CCF”
ii. ACE inhibitors:
a. Captopril: 12.5 mg t.d.s.—main-
tenance 12.5 to 50 mg t.d.s.
b. Enalapril: 5 mg b.d.s.—main-
tenance 10-20 mg b.d.s.
c. Lisinopril: 5 mg/day 10 to 40 mg/
day
iii. Others:
a. Hydralazine: Neprosol (Novartis):
75-100 mg 4 times a day
b. Prazocin: Prazopress (Sun), 1 and
2 mg tab 0.5 × 2-1 mg twice or
thrice daily. Minipress XL Gyst, 2.5
to 5 mg/day
c. Amlodipine, 2.5 to 20 mg/day
d. Felodipine
Felogard ER (Cipla) 5 mg, 10 mg
tab, Renedil (Hoest), Plendil
(Astra) 5-10 mg/day
e. Nitroprusside:
Both arterio-venodilator. See
“Intravenous drugs for CCF”

Clinical Pearls
Frusemide’s action is enhanced by combining with thiazide, potassium sparing diuretic, carbonic anhydrase
inhibitor and osmotic diuretics.
ACE inhibitor ramipril (Cardace-Hoest) + diuretic + digoxin not only ameliorate failure but also
reduces mortality.
L-carnitine (Carnitor-Elder; Ree-Emcure; Nucarnit-Nucron) 333 mg tab, two tabs twice or three times
a day benefits cardiac failure with IHD or cardiomyopathy.
In severe heart failure low-dose amiodarone (300 mg) reduces mortality.
If cardiac failure is associated with hypercholesterolaemia, treat with simvastatin.
Carvedilol plus ACE inhibitor is specially indicated in cardiac failure with low ejection fraction and
systolic dysfunction.
Do not stop the benefit of ACE inhibitor in cardiac failure due to cough or mild azotaemia.
Older patient with cardiac failure should have thyroid function and haemogram obtained if the aetiology
of cardiac failure is not clear.
Maintain serum K at 3.8 mEq per litre if the patient is on diuretic therapy.
 Congestive Cardiac Failure

To prevent nitrate tolerance incorporate a nitrate free interval of 8-12 hours into the drug regime or
| 263

apply intermittently nitroglycerine patches (14-17 hours on, 10-12 hours off).
Usually potassium sparing diuretics are not combined with ACE inhibitors due to risk of hyperkalaemia.
But recently low-dose spironolactone is combined with ACE inhibitors monitored by serum creatinine
concentration and potassium concentration with good result.
ACE inhibitor also helps asymptomatic left ventricular dysfunction.
Combination of oral nitrate and hydralazine is indicated in heart failure with severe renal impairment
when ACE inhibitors are contraindicated.

Steps in the Management of Heart Failure : Gyst

Comments
Mechanism Quality-of-life
Step 1
Asymptomatic left ventricular dysfunction should be treated with Afterload reduction by Improved
maximal doses of ACE inhibitors. Larger doses are better than ACE inhibitor
conventional low doses.

Step 2
If congestion develops after ACE inhibitor, add diuretics Preload reduction caused Improved. Spironolactone
including spironolactone by diuretics lengthens life

Step 3
After symptoms of congestion relieved, add beta blockers Beta blockers decrease Improved
(Carvedilol or metoprolol or bisoprolol). contractility

Step 4
If symptoms recur on the above therapy digitalis should be added. Digoxin increase con- Improves quality-of-life
tractility
Step 5
Acute episode with hypotension and renal perfusion should be They increase contractility Improves quality-of-life
treated with dopamine. Amrinone, milrinone may also help and
of electrolyte imbalance due to diuretics, (such as hypokalaemia,
hyponatraemia) treat them.

TREATMENT OF ACUTE HEART FAILURE—ACUTE LEFT VENTRICULAR FAILURE

Emergency measures are applied simultaneously.
1. Morphine intravenous 2-5 mg if no respiratory disorder and if naloxone is available to combat
respiratory depression. It allays anxiety. Morphine is contraindicated in hypotension.
2. 100% oxygen preferably under positive pressure.
3. Maintain sitting position with legs hanging along the side of the bed.
4. Intravenous frusemide 40-100 mg or bumetanide 1 mg.
5. If systolic blood pressure exceeds 100 mm start IV sodium nitroprusside 20-30 microgram/min.
6. In auricular fibrillation with fast ventricular rate digoxin 0.5 mg IV stat followed by half ample IV
6 hourly for two doses. Contraindicated in acute myocardial infarction. Digoxin IV is given only if
it is not given already. It should never be given intramuscular.
7. Aminophylline 240-480 mg IV.
264 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

8. Treat infection.
9. Nitrate: IV nitroglycerine mixed with 250 cc water for injection—3 drops per minute, one pint is
given in 40 hours. Systolic blood pressure must be at least 90 mmHg.
10. Measures in special situations:
i. Arrhythmias:
a. Auricular fibrillation with rapid ventricular rate: Esmolol (Miniblock—USV, 10 ml ample
containing 2500 mg) initiate 50 microgram/kg/min. up to 300 microgram/kg/min.
b. Ventricular ectopics: IV ligocaine 75-100 mg given over one minute.
ii. Marked hypotension: Cardiogenic shock in acute myocardial infarction setting:
Dopamine drip
Or
Dopamine + sodium nitroprusside drip have been used with occasional success. Prognosis is
very grave.
iii. Severe heart failure with normal blood pressure: Dobutamine drip
iv. Severe heart failure with hypertension: Vasodilators.

Table 41.3: Intravenous drugs for cardiac failure

Drugs Initial dose Maintenance dose

Sodium nitroprusside (Prusside-Troika; 0.1 mg/min Titrated upward with response -0.2 to
Sonide-Gufic) 50 mg per 5 ml ampoule 0.3 mg per minute

Nitroglycerine (Millisrol-Khandelwaal; 10-20 microgram/min 40-300 microgram/min

Nitrocure-Panacea; Nitroget-sun)
5 mg/10 ml
25 mg/5 ml

Dopamine TTK 2-5 microgram/kg/min 3-10 microgram per kg per min

200 mg/5ml

Dobutamine
(Dobutrex-Ranbaxy) 250 mg vial 3-5 microgram/kg/min 5-10 microgram/kg/min

Approach to the Management of Cardiac Failure

Cardiac failure may be mild, moderate and severe and management varies accordingly.
Mild cases: First try simple measures such as moderate restriction of activity, salt restriction and daily or
intermittent thiazide diuretics.
Moderate cases:
i. More rigorous restriction of salt intake activity
ii. Loop diuretics
iii. Digoxin may or may not be prescribed
iv. ACE inhibitor
Severe cardiac failure:
Congestive Cardiac Failure | 265

i. Activity limited to house-bedrest or chair rest

ii. Rigid salt restriction (See general management)
iii. Look for precipitating factors such anaemia, arrhythmias, pulmonary and urinary infection, recurrent
pulmonary embolism and arterial hypoxaemia and treat them.
Treatment of arrhythmias in heart failure:
a. Atrial fibrillation: Digoxin for controlling fast ventricular rate. Amidarone in resistant cases.
b. Ventricular arrhythmias: Amiodarone is effective in symptomatic control of ventricular
arrhythmias.
iv. Digoxin
v. Diuretics: Thiazide plus loop diuretic. If no adequate response, add potassium sparing diuretics.
vi. Vasodilators
vii. ACE inhibitors
viii. Nitrate
ix. IV nitroprusside
x. Dopamine, dobutamine
xi. Low-dose beta blockers. Only carvedilol is recommended out of all beta blockers.
xii. Look for underlying and overlooked causes that may be amenable to specific medical or surgical
treatment (such valvular diseases, constrictive pericarditis.
xiii. Look for therapeutic misadventure: Digitalis intoxication.

Table 41.4: Choice of diuretics

Chronic cardiac oedema with mild to Moderate heart failure diuretics

moderate cardiac failure without
hyperuricaemia and hypokalaemia

Thiazide Thiazide with spironolactone or Thiazide with loop diuretic with

Triamterene or amiloride potassium sparing diuretics
Severe heart failure refractory to other

Table 41.5: Dose of beta-blockers

Beta blockers Initial dose Weekly titration dose (Mg) Total daily dose
1 2 3 4 5 6 7

Metoprolol 5 mg 10 15 20 50 75 100 150 100-150 mg

Carvedilol 3.125 6.25 12.5 25 50

(Carvetrend, cardivas)
266 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Table 41.6: Guidelines for using ACE inhibitors

• Stop potassium sparing diuretics and potassium supplements.

• Omit or reduce all diuretics for 24 hours before first dose.
• Start low-doses for example captopril 6.25 mg twice daily, enalapril
2.5 mg once daily, lisinopril 2.5 mg once daily.
• Increase dose unless there is rise in serum creatinine or potassium.
• Review after 1-2 weeks for symptoms, blood pressure and renal chemistry
and electrolytes.

Table 41.7: Guidelines for using digoxin

• Give a reduced maintenance dose in elderly, when renal impairment is present and when used
with amidarone, verapamil.
• Monitor serum potassium and renal function. Avoid hypokalaemia.
• Look for digoxin toxicity. Stop digoxin with first symptoms-anorexia, nausea.
• Serious digoxin toxicity should be treated by correcting serum potassium, beta blockers,
cholestyramine and in severe cases specific digoxin antibodies (Digibind).

Table 41.8: Inotropes used in cardiac failure

Inotropes Action Doses

Dopamine In low-dose dilates renal and mesenteric 1-2 microgram/kg/min in continuous

blood vessels augmenting their blood infusion
flow. Increases cardiac output
Dobutamine Do 2.5 to 10 microgram/kg/min

Table 41.9: Choice of vasodilators

Depending upon cardiac failure whether acute or chronic

A. Acute cardiac failure: IV nitroprusside monitored by ECG and blood pressure.
B. Chronic heart failure: Captopril, hydralazine, prazosin, isosorbide, oral nitrate.
Starting with small dose and gradually increasing it.
Depending on pathological and physiological states
A. Cardiac failure with low cardiac output or mitral regurgitation: Arteriolar dilator such as hydrazine, minoxidil
B. Cardiac failure with pulmonary congestion: Venodilator such as nitroglycerine, isosorbide nitrate
C. Cardiac failure with both low cardiac output and pulmonary congestion: Both arteriolar and venodilators such as
Captopril, prazosin, combination of hydralazine and nitrate.
Combination therapy: Isosorbide plus hydralazine decreases morbidity in cardiac failure. Hydralazine plus captopril is
indicated in refractory cardiac failure.
 Table 41.10: Diuretics
Congestive Cardiac Failure | 267

Diuretics Site of action Effect on uri- Effect on blood Other effects Dose Adverse effects
nary electrolyte electrolyte
Thiazide: Reduces reab- ↑ Na ↓ Na ↑ Glucose i. Chlorothia- K loss, meta-
sorption of ↑ Cl ↓ Cl ↑ Uric acid zide:500 mg bolic acidosis,
sodium and ↑K ↑ HCO3 6 hourly hyperuricaemia,
chloride chiefly ↑H Mild metabolic ii. H y d r o c h - hyperglycaemia,
in distal tubules acidosis lorothiazide: rashes
water excreted (Esidrex-
with NaCl Novartis):
50 mg tab.
25-75 mg 1-2
times a day or
alternate day

Loop diuretics: Inhibits reab- Na ↑ HCO3 i. F r u s e m i d e Same as

sorption of Na, Hypochloraemic ( L a s i x - Thiazide
K and Cl in alkalosis Hoest) 40 mg
ascending limb tab
of Henle’s loop 20 mg/2ml
amp.
Oral 20-80
mg/day
Repeat 20-40
mg after 6
hour if no
satisfactory
response
ii. Bumetanide
(Bumet-
Montari)
1 mg tab.
1-4 mg/day
Potassium spa- Acts on distal ↑K ↑K i. Spironolac- → Gynaecomas
ring diuretics: tubule. Compe- ↑ Na tone: tia, antian-
titive inhibition ↑ Cl a. Aldactone- drogenic eff-
of aldosterone, ↑ HCO Searle Lac- ect, anorexia
thereby blocking tone-Sun rash
the exchange b. C o m b i n e d
between sodium with fruse-
and both K and mide: Frus-
hydrogen produ- elac-Lupin,
cing Na diuresis Lasilactone-
and K retention Hoest
c. C o m b i n e d
with thiazide:
Aldactide 25
+ 50
contd...
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Diuretics Site of action Effect on uri- Effect on blood Other effects Dose Adverse effects
nary electrolyte electrolyte
Dose 25-
100 mg
t.d.s. or
q.d.s.
ii. Triamte-
rene:
Dytide-
Beecham

Triamterene
50 mg +
benzthia-
zide 25 mg
1-2 tab/day
 Heart
42
Hypertension

The goal of antihypertensive therapy is not only to reduce blood pressure but also reduce cardiovascular
morbidity and mortality. The high-risk group includes target organ damage and diabetes mellitus. These
patients should be attended vigorously and risk factors should be managed as much as possible (Table
42.1: “Goals”).
Table 42.1: Goals
Primary goals
a. Isolated hypertension: Goal is to reduce blood pressure below 140/90 (JNC = V1)
b. Hypertension with diabetes and renal disease: Blood pressure lowered to 135/85 (JNC-V1)
c. Isolated systolic hypertension: Lower systolic blood pressure to 140 mmHg or below
Secondary goals
Treatment of risk factors and target organ damage

Non-pharmacological Treatment: Life Style Management

In many patients non-pharmacological treatment (Table 42.2) reduces the BP. If these measures do not
succeed after 4-6 month period, drug should be started. See Table 42.3: For characteristics of non-
pharmacological measures.
Table 42.2: Non-pharmacological measures
Measures How to acheive? Remarks
Stoppage of smoking and
tobacco chewing:

Salt restriction: 2 gm salt/day a. Reduction of salt intake of

Eliminate table salt, reduce salt in cooking, more
natural food, less processed food, avoiding dairy
products, avoiding salty snacks like pickle, papad,
chatney, salty nuts, biscuits. Also avoid drugs
containing sodium like antacids.
100 mmol a day reduces systolic
BP of 2.2 mmHg and diastolic
BP 0.1 mmHg
b. Most efficacious measure
c. Leukocytes of hypertensive
patients have reduced sodium
pump activity resulting in high
intracellular sodium with
relative increase in extracellular
fluid volume and increased
vascular tone producing high
contd...
270 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues
Measures
Potassium intake:
Calcium supplement:
Reduction of alcohol intake:
Weight control:
Physical exercise:
Biofeedback, stress reduction, Shavashan (Yoga) is best.
relaxtion, transcendental medi-
tation and yoga:
Table 42.3: Characteristics of non-pharmacological measures
How to achieve? Remarks
BP. Salt restriction interrupts
this chain.
Potassium rich food, i.e. fruits, vegetables help d. Marked sodium restriction is
hypertensives counterproductive due to
stimulation of renin-angio-
tensin-aldosterone axis.
Ensure proper intake of calcium in diet Perhaps calcium induced natriuresis
reduces blood pressure
Alcohol should be curtailed or prohibited Avoid sudden withdrawal to
prevent sudden rise in blood pressure.
Obese should reduce weight more vigorously by a. Obese children more prone to
reducing caloric intake and regular exercise. hypertension
b. Obesity is a risk factor for CAD.
c. Weight reduction also decreases
salt sensitivity.
d. Every 1 kg weight loss reduces
systolic blood pressure by
3 mmHg and diastolic BP by
2 mmHg.
Regular dynamic exercise is recommended. Brisk Physical exercise also protects against
walking, swimming, bicycling for 15 minutes 3-5 coronary events
times a week. Avoid bull worker exercise and weight
lifting
Their effects are mixed and produce
moderate BP reduction in selected
group.
Measures that definitely lower blood pressure:
Weight reduction
Salt restriction
Moderate alcohol intake
Increased physical activity
Measures that reduce associated risk factors:
Stoppage of smoking
Dietry fat manipulation
Control of diabetes
Measures with unproven or limited efficacy:
Stress management
Biofeedback
Dietary K1+ K+, Ca2+, Mg2+
Fibre and fish diet
Yoga
DRUG THERAPY
Hypertension | 271

Ideals for drug therapy: See Table 42.4.

Table 42. 4: Ideals for drug therapy

1. Treatment should be inexpensive, long acting, effective over prolonged period associated with minimum side-effect.
2. It should control both systolic and diastolic hypertension whether the patient is supine or upright without producing
postural hypotension.
3. Simplest regime possible fewest drugs with lowest dose.
4. Therapy should be started with a small dose of a single drug which is gradually increased till the BP is controlled or
maximum dose is reached. If the BP is not controlled additional drug is added in increasing dose till BP is controlled.
5. In severe hypertension combination of drugs is used. This is called “Step up therapy”. Recently “Step down therapy”
is recommended. In Step up therapy drug with long duration of action is started with once a day dose or combining
smaller dosages of two drugs with different pharmacological action till BP is controlled and after maintaining the
drug for about one year, start cutting down (Step down therapy) the drug and dose till the BP is again controlled.
6. There is sufficient evidence to recommend drug therapy for patients with sustained diastolic pressure above
90 mmHg and/or systolic BP above 150 mmHg.

Classification of Antihypertensive Drugs

I. Beta-adrenoreceptor blocking drugs:
A. Non-selective:
a. With intrinsic sympathetic activity (ISA): Pinodolol, Penbutolol, Oxprenolol
b. Without ISA: Propranolol, Timolol, Sotalol, Nadolol
B. Selective: Great effect on beta-1 receptors than on beta-2 receptors:
a. With ISA: Acebutolol (Practolol), celiprolol
b. Without ISA: Atenolol, esmolol, metoprolol, bisoprolol
C. With alpha-blocking activity: Labetalol, carvedilol
II. Alpha-adrenoreceptor blockers: Prazosin, Tetrazosin, Doxazosin, phentolamine (Regitine)
III. Alpha and beta-adrenoreceptor blockers: Labetolol
IV. Peripheral neuronal inhibitors (Peripheral acting sympatholytics):Reserpine, guanethidine,
trimetaphan, camsylate (Arfonad)
V. Centrally acting alpha-adrenergic drugs: Clonidine, methyldopa, guanfacine, guanabenz
VI. Diuretics:
a. Thiazides: Chlorothiazide, hydrochlorothiazide, bendroflumethiazide, Benzthiazide,
polythiazide, indapamide, chlorthalidone.
b. Loop diuretics: Frusemide, ethacrynic acid, bumetanide
c. Potassium sparing diuretics: Spironolactone, triamterene, amiloride.
VII. Angiotensin—Converting enzyme inhibitor:
a. Short acting: Captopril
b. Long acting: Ramipril, enalapril, lisinopril, quinapril
VIII.Calcium channel-blockers:
a. Verapamil, Diltiazem
b. Dehydropyridine: Nifedipine, amlodipine, felodipine
IX. Direct vasodilators: Hydralazine, minoxidil, sodium nitroprusside, diazoxide.
X. Angiotensin receptor blockers: Losartan potassium.
272 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Table 42.5: Classification and characteristics of antihypertensive drugs

Special characte- Special indications Precautions Contraindications
ristics and side-effects
Beta blockers: 1. Atenolol: Less 1. Younger and mid- 1. Use with caution in Contraindications:
lipid soluble, dle aged patients. COPD, diabetes Asthma, cardiogenic
hence less CNS 2. Useful in CAD arr- 2. Avoid abrupt with- shock, heart block,
side-effect. Longer hythmia, anxiety, drawal overt heart failure,
half-life hence hyperkinetic states, 3. Heart failure sinus bradycardia
once daily dose. after acute myocar-
2. Beta blockers with dial infarction Side-effects:
ISA reduces heart (Non-ISA beta- Bronchospasm,fatigue,
rate less, reduces blockers) and pre- depression, increases
less cardiac output gnancy. triglyceride, decreases
and plasma renin 3. Limited value in HDL
activity black subject and
3. Beta blockers with atheletes
ISA do not have
adverse metabolic
effect such as dys-
lipidaemia

Alpha adrenoreceptor 1. Reduces serum 1. Hypertension with Due to first dose post- First dose postural
blockers: lipids prostatic hyper- ural hypotension and hypotension and syn-
2. Improves insulin trophy syncope first dose is cope. This is much less
sensitivity 2. Hypertension with given at bedtime. with doxazosin, tetra-
hyperlipidaemia zosin and minipress
and diabetes excell
3. Limited value in
elderly

Alpha and beta adreno- 1. No effect on car- 1. Effective in all

receptor blocker diac output degree of hyper-
2. Reduces peripheral tension
vascular resistance 2. IV labetalol rapi-
dly controls severe
hypertension

Centrally acting adre- Usual as monotherapy Methyldopa in preg- Abrupt withdrawal can Impotency, sedation
nergic drugs or other antihyperten- nancy lead to hypertension dry mouth
sive drugs especially
diuretic

Diuretics 1. Reduces morbi- 1. Useful as mono- 1. Be cautious in Contraindications:

dity and mortality, therapy hypertrophic car- 1. Anuria
especially stroke 2. Thiazide useful in diomyopathy and 2. Hypersensitivity
and CAD compli- mild to moderate pre-eclampsia
cations specially hypertension with 2. Use lower dose to Side-effects:
in elderly patients normal renal func- avoid metabolic 1. Mg, K, Na dec-
tion effect rease
contd...
contd...
Hypertension | 273

Special characte- Special indications Precautions Contraindications

ristics and side-effect

3. Severe hyperten- 3. Avoided in gout 2. Cal. cholesterol,

sion with renal 4. Dont use first line glucose and tri-
insufficiency res- drug in diabetic glyceride and uric
ponds to loop diu- 5. Can be combined acid increase
retics with potassium
4. Diuretics useful in sparing diuretic or
patients with oed- K supplement to
ema as in hyper- prevent hyper-
tension with CCF kalaemia
5. Additive effect
with other anti-
hypertensive drugs
6. Long acting indap-
amide produces
less hyperlipidae-
mia and hypergly-
caemia
7. First line drug for
hypertension
8. Particularly indica-
ted in systolic
hypertension in
elderly
Angiotensin-conver- 1. Reduces BP with- 1. Work equally well 1. To be used with • Rash
ting enzyme inhibitors out causing tachy- in young and old caution in bilateral • Serum potassium
cardia or low car- 2. Effective in CCF renal artery steno- maintained. It may go
diac output due to reduction of sis and hypertro- up in renal failure or
2. Potency similar to afterload phic cardiomyo- who are receiving
beta blockers, cal- 3. Useful in diabetic pathy with severe potassium.
cium channel bloc- nephropathy with diastolic dysfunc-
ker and diuretics hypertension, red- tion
3. Insulin sensitivity ucing proteinuria 2. Avoided in preg-
may improve 4. Reduces coronary nancy due to foetal
4. Reduces left ven- events in CCF and death
tricular dilatation acute myocardial
and hypertrophy infarction
5. Refractory hyper-
tension not respon-
ding to diuretics
6. Malignant hyper-
tension
7. Hypertension with
chronic renal fail-
ure

contd...
274 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Special characte- Special indications Precautions Contraindications

ristics and side-effect

8. Coarctation of
aorta
9. Hypertension with
hyperlipidaemia

Direct vasodilatations: Refractory hyperten- Tachycardia, palpita-

sion with or without tion, minoxidil pro-
renal failure. Minoxidil duced hirsutism in
more potent than women
hydralazine

Calcium Peripheral Nodal Contractility

channel vasodilatation conduction Oedema, headache,
blockers: bradycardia, dizziness,
AV block, CCF, urinary
Diltiazem: ++ Reduced Reduced frequency
Same as diltiazem but
Verapamil: ++ Much Much more constipation and
reduced reduced CCF

Amlodipine +++ Less-0 Less-0 Oedema, dizziness,

palpitation, flushing,
Felodipine: +++ Do Do headache, tachycardia,
GI disturbance urinary
Nicardipine: +++ Do Reduced frequency, less CCF

Nifedipine: +++ Reduced More reduced

 Table 42.6: Drugs in hypertension—Trade name, dosages and remarks
Hypertension | 275

Drugs Trade name Tablet size Daily dose Favourable remarks

(mg) (mg) (F) unfavourable
remarks (U)
I. Diuretics:
Benzothiazide:
Thiazide
Chlorothiazide Saluric 500 500-1000 (F) Cheap, well-tole-
rated, can be added to
other diuretics, preg-
nancy
(U) K depletion, gout,
diabetes, rashes, impo-
tency, agranulocytosis
Hydrochlorthiazide Esidrex 50 25-100 (F) Rapid onset, long
acting

Indapamide Natrilix 2.5 2.5-5 (F) Longer acting (24

hour plus)
Chlorthalidone Hygroton, Hythalton 100 50-100
alternate day
Loop diuretic
Furosemide Lasix (Hoest) 40 mg tab. 20-80

Ethacrynic acid Edecrin (MSD) 20 mg/2ml 50-400

Bumetanide Bumet 1 1-4 (F) Refractory oedema

Potassium sparing (U) Pregnancy
Diuretic
Spironolactone Aldactone (Searle) 25,100 25-200 (F) K sparing
(U) Gynaecomastia
Triamterene (F) K sparing
Amiloride 5 50
5-10

Combination Diuretics
Frusomide + Amiloride Amifrue 40 (Elder)
40 mg 5 mg
Furosemide + Spironolactone Fruselac (Lupin)
20 mg 50 mg
Frusemide + Spironolactone Lasilactone (Hoest)
20 mg 50 mg
Amiloride + Hydrochlorothiazide Biduret (Crydon)
5 mg 50 mg
Triamterene + Benzthiazide Ditide (Beecham)
50 mg 25 mg
contd...
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Trade name Tablet size (mg) Daily dose Favourable remarks
(mg) (F) unfavourable
remarks (U)
II. Sympatholytic
agents:
A. Centrally acting
alpha-adrenergic
agents:
Methyldopa Aldomet (MSD) 250 500-2000 (F) Safe in pregnancy,
Emdopa (IDPL) cheap
(U) Sedation, loss of
libido, diarrhoea, fati-
gue, depression, fluid
retention, C/I in phe-
ochromocytoma, drug
interaction with tri-
cyclic antidepressant,
avoid concomitant
administration of hal-
operidol and reserpine

Clonidine Arkamin (Unichem) 100 mcg 0.05-0.1 (F) Migraine, diarrhoea

Catapres (G. remedies) 150 mcg (U) Dry mouth, seda-
tion, constipation, imp-
otency, potentiated by
antidepressants

Reserpine Serpasil (Novartes) 0.25 0.25-0.5 increased to (F) Hypertensive emer-

Adlephen (Novartes) 1-1.5 gency, Toxaemia of
(Reserpine + dihydra pregnancy
lazine (U) C/I in peptic ulcer
0.1 mg 10 mg depression, Parkinso-
nism, pheochromocy-
toma.
Side-effects: Depre-
ssion suicidal tendency,
stuffiness of nose,
impotency

B. Beta-adrenergic—
blocking agents
Propranolol Inderal (ICI) 10, 40, 80 10 mg b.d. to 160 mg (F) In angina, arrhy-
Ciplar (Cipla) b.d. thmia especially tachy-
cardia, additional effect
with diuretic, migraine,
AMI
contd...
contd...
Hypertension | 277

Drugs Trade name Tablet size (mg) Daily dose Favourable remarks
(mg) (F) unfavourable
remarks (U)
(U) C/I: Sinus brady-
cardia, heartblock
greater than 1st
degree, cardiogenic
shock. Avoid sudden
withdrawal. Severe
bradycardia with
verapamil.
Side-effect: Tiredness,
Metoprolol Lopresor (Novartis) 50,100 100-200 mg in 2 divi- bronchospasm
Betalock (Astra-IDL) ded dosages
Atenolol Aten (Kopran) 25, 50, 100 50-100
Atpark (PD)
Betacard (Torrent)
Tenormin (ICI)

Acebutolol Sectral (Rhone-Poule- 200 400-1.2 gm daily in

nce) divided dosages
Pinodolol Visken (Novartis) 10 10-30 mg daily in
2-3 divided dosages
Oxprenolol Trasicor (Novartis) 40, 80 20-30 mg b.d. or t.d.s.

C.Alpha-blocking
agents:
Prazosin Minipress (Pfizer) 0.5, 1, 2, 5 2-20 mg (F) Less reflex tachy-
cardia
(U) First dose hypo-
tension-start with small
dose 0.5-1 mg and give
at bedtime. Minipress
X1 has no first dose
D.Mixed alpha-and hypotension
beta-adrenergic-
blocking agents
Labetalol 100, 200 200-800 (F) Pregnancy
(U) Postural hypo-
E. Ganglion-blocking tension. Not too much
agent of a problem
Mecamylamine Inversine (MSD) 25 mg b.d.

F. Peripheral acting
sympatholytic agent
Guanethidine Ismelin (Ciba) 10-300

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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Trade name Tablet size (mg) Daily dose Favourable remarks
(mg) (F) unfavourable
remarks (U)
III. Direct Neprosol (Novartis)
vasodilators 25 25-50 mg (F) Useful in renal fail-
Hydralazine b.d. or t.d.s. ure. Malignant hyper-
tension (IV slowly)
(U) Reflex tachycardia
(to obviate it add beta
Loniten (Upjohn) blockers) SLE
2.5, 5, 10 10-50 (F) Useful in resistant
Minoxidil hypertension
(U) Sodium retention,
hypertrichosis, tachy-
cardia
Eudemine
30-300 IV (F) Rapid action,
Diazoxide within 1-2 minute
(U) Nausea, diabetes,
tachycardia
IV. Calcium channel Depin (Cadila),
blocking agent Nicardia (Unique), 5, 10 mg retard or SR- 5-20 mg t.d.s. (F) Hypertension with
Nifedipine Myoguard (Searl), 10, 20, 30 mg angina, useful in asth-
Depicor (Merk), matic
Cardule (Nicholos), (U) Constipation,
Calciguard (Torrent) headache CI in preg-
nancy peripheral
Calaptin (Boehringer- oedema
M), Vasopten (Torrent) 40-80 mg tab Calaptin 40-80 mg t.d.s. or q.d.s.
Verapamil Inj= 5 mg/2 ml Maximum oral dose
480 mg/day
Angizem (Sun),
Channel (Microlab), 30, 60 CD, CR, SR-90, 30 mg b.d. or t.d.s. or
Diltiazem Dlicontin (Modi), 120 mf q.d.s. Maximum
Diltiaz (Plethico), 240 mg in three or four
Diltiazem (Torrent), divided doses daily
Masdil (Lupin)

Plendil (Astra),
Renedil (Hoest) 5, 10 5-10, may be increased
Felodipine
Cardiff (Concept),
Nitrepin (U.S. Vit) 10, 20 5-20/day in morning.
Nitrendipine Maximum 40/day
Amdepin (Cadila),
Amlocor (Torrent), 2.5, 5, 10 5-10
Amlodipine Amlong (Micro),
contd...
contd...
Hypertension | 279

Drugs Trade name Tablet size (mg) Daily dose Favourable remarks
(mg) (F) unfavourable
remarks (U)
Amlopres (Cipla),
Amlosun (SUN),
Amloz (Ethico),
Amtas (Intas),
Calchek (IPCA),
Corvadil (Unichem),
Myodura (Wockhart)

V. Converting enzyme Aceten (Wockhardt),

inhibitors Angiopril (Torrent), 25 25 t.d.s. increased up to (F) Indicated in resis-
Captopril Captopril (Lupin) 100 mg t.d.s. in CCF tent hypertension.
start with 6.5 mg t.d.s. Hypertension with
CCF and diabetes
Converten (Khandel- (U) Dry cough
wal), Enam (Stangen), 2.5, 5, 10 5-10-20 in CCF start
Enalapril Envas with 2.5 increased to
10-20/day
Cipril (Cipla), Hipril
(Micronova), Lipril 2.5, 5, 10 Start with 10 increased
Lisinopril (Lupin), Lisoril to 20-40. Maximum 80
(IPCA), Listril day. In CCF start with
(Torrent) 2.5 increased to 20/day

Cardace (Hoest),
Ramace (Astra) 1.25, 2.5, 5 2.5/day. Maximum
Ramipril 10/day
Losacar (Cadila),
Losar (Unisearch, 25, 50 In CCF start with 1.25 (F) No cough
Losartan Repace (SUN), Trozar maximum 10 mg/day (U) Oedema, diarrhoea
Potassium (Torrent) 25-100 once or b.d.
Key: (F) Favourable; (U) Unfavourable

Recently Introduced Two Anti-hypertensive Drugs

Doxazocin Mesylate
Trade name : Duracard (SUN)
Favourable remarks : Improves lipid profile. Increases insulin sensitivity.
Regresses left ventricular hypertrophy
Unfavourable remarks : Postural hypotension. Headache, oedema, vertigo, ability
to drive may be impaired.
Tablet size : 1 mg, 2 mg, 4 mg
Dosage : Start with 1mg/day increased after 1 week. 2 mg/day and
may be increased to 4 mg. Maximum 16 mg/day.
280 |
Carvedilol
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Trade Name : Cardivas (Aztec)

Favourable remarks : Beta blockers with alpha-blocker. Advantage—Cardio-protection, vascular
protection.
Unfavourable remarks : C/I in 2nd and 3rd degree heart block, bronchospasm
Tablet size : 12.5, 25 mg
Dosage : Start with 6.25 mg—increased to 12.5-25 mg –50 mg/day.

Step Care Therapy in Hypertension

Step care therapy has enjoyed popularity but now the Step down therapy is added to it.

Step 1
Start monotherapy with diuretic or beta blockers or ACE inhibitor. Majority of patients with mild to
moderate hypertension respond with minimum side-effects. Dosages gradually increased till BP is
controlled.

Step 2
If BP is not controlled, add the following drugs to the above regime if not used initially as monotherapy:
If beta blocker fails : Add diuretic or ACE inhibitor
If diuretic fails : Add beta blocker or ACE inhibitor
If ACE inhibitor fails : Add diuretic or beta blocker
Start the second drug in small dose and increased till BP is controlled.

Step 3
If step 2 fails add a third agent as follows:
If diuretic and beta blocker fails : Add hydralazine or ACE inhibitor or prazosin
If diuretic and ACE inhibitor fails : Add beta blockers or hydralazine or prazosin
If beta blockers and ACE inhibitor fails : Add diuretic or hydralazine or prazosin.

Step 4
If step 3 fails, add minoxidil or frusemide or reserpine
If BP is controlled for 1 year on the above regime, Step down therapy is attempted.
Reduce dosages till the lowest maintenance dose is reached.

Management of Refractory Hypertension

1. Ensure salt restriction
2. Ensure regular compliance of antihypertensive drugs
3. Prescribe diuretic if not prescribed already
4. Stop NSAID, antidepressant, chlorpromazine, antacid, ampicillin, steroids, oral contraceptives and
salbutamol.
 5.
Hypertension

Add hydralazine, or monoxidil or reserpine or beta blocker or diazoxide if not prescribed already.
| 281

6. Exclude secondary type of hypertension.

7. Ensure that non-pharmacological therapy is strictly followed.
8. Following drug combination is effective:
— Hydrochlorthiazide + frusemide
— Alpha + beta blocker (Labetalol or Prazosin or Minipress XL)
— Methyldopa + Prazosin

Treatment of Systolic Hypertension in Elderly Patients

Treatment of systolic hypertension in elderly lowers the incidence of stroke.

Table 42.7: Drugs for systolic hypertension in elderly patients

1. Start with diuretic or calcium channel blocker, then changing to or adding beta blocker.
2. Diuretics + beta blocker
3. Calcium channel blockers + beta blockers (Avoid verapamil).
4. One study suggests felodipine is superior to beta blocker and ACE inhibitor.

HYPERTENSIVE EMERGENCIES
Sometimes very high blood pressure needs rapid lowering of BP. Clinical examples of hypertensive
emergencies are as follows:
1. Hypertensive encephalopathy 5. Malignant hypertension
2. Pulmonary oedema 6. Postoperative hypertension
3. Cerebral haemorrhage 7. Hypertension with IHD
4. Eclampsia 8. Acute aortic dissection
9. Pheochromocytoma crisis

Table 42.8: Parenteral drugs used in hypertensive crisis

Drugs Dosages Onset Duration Cardiac output Remarks
Intramuscular Intravenous
(mg)
Single dose Continuous
(mg) infusion (mg)
Direct vasodi-
lators:
Sodium nitro- — 0.3 mcg per IV infusion 1/2 to 1 min 1-2 min to Decreased Requires
prusside kg to 0.5-0.6 rate 0.03-0.5 3-5 min arterial line.
mcg per kg mg/min Nausea
minute Vomiting
Apprehension
Thiocynate
intoxication
contd...
282 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Dosages Onset Duration Cardiac output Remarks

Intramuscular Intravenous
(mg)
Single dose Continuous
(mg) infusion (mg)
Diazoxide 50-100 mg at Rarely used 1-2 min 2-3 min to Increased Sedation
— 5 to 10 min 4-12 hr Na retention,
intervals until hyperglycae-
satisfactory mia, tachy-
BP response cardia.
Must be given
in bolus in 10-
20 sec. rapidly

Hydralazine 10-40 at 30 10-20 at 30 — IM in 30 min, 20-40 min Increased Tachycardia,

minute inter- min intervals IV in 5-10 3-8 hour flushing. C/I
vals until until satisfac- min in angina aor-
satisfactory tory BP res- tic dissection,
BP response ponse CCF
Ganglionic
blocking
drugs
Trimetaphan Rate 1-15 mg 1-2 min 2-5 to 10 min Decreased Urinary reten-
/min tion, blurred
vision, ileus,
aggravates
CCF. Requi-
res arterial
line. Can be
used for maxi-
Central ner- mum 24-48
vous system hours
active agents
Methyldopa 250-500, may 2-3 hour 3-5 to Unchanged S e d a t i o n ,
be repeated at 6-12 hour positive
6 hr interval Coombs’ test,
drug fever.
Slow onset,
response
highly vari-
able.
Labetalol 5-15 IV 2mg/min 5 min or less 3-6 hour Decreased Prompt res-
or 20 mg ponse, can be
every 10 min followed ora-
(up to 80 mg lly. Avoid in
doses) or 50 CCF.
over 1 min
period
contd...
contd...
Hypertension | 283

Drugs Dosages Onset Remarks (side-effect)

Nitroglycerine 5-100 microgram as
IV infusion
Enalapril 0.625-1.25 mg every
6 hour
Nicardipine IV 5 mg/hr, may
increase by 1-
2.5 mg/hr every
15 min to 15 mg/hr.
Oral agents for hypertensive emergencies
Nifedipine 10-20 mg sublingually
repeat after 30 min
Captopril 25 mg sublingually
repeat as required
Clonidine 0.1-0.2 mg PO, repeat
every hour as required to
a total of 0.6 mg
Labetalol 200-400 mg PO, repeat
every 2-3 hour
2-5 min Headache, tachycardia, vomiting,
flushing, methaemoglobinaemia
15-60 min
1-5 minutes Most potent IV long acting calcium
3-6 hours channel blockers causing arterial vasodila-
tation resulting in reflex tachycardia and so
always used with beta-blocker in patients
with coronary artery disease. May precipi-
tate myocardial ischaemia.
15-30 min May precipitate circu-
latory collapse in aortic
stenosis
15-30 min Hypotension, renal
failure in bilateral renal
artery stenosis
30-60 min Hypotension, drowsiness,
dry mouth
30 min-2 hour Bronchoconstriction,
heart block, orthostatic
hypotension

Special Indications of Parenteral Drugs in Hypertensive Crisis

Nitroprusside Labetalol Nicardipine

Severe hypertension Yes Yes Yes
Severe hypertension with AV block Yes No Yes
Severe hypertension with CCF Yes No Yes
Severe hypertension with COPD Yes No Yes
Severe hypertension with renal insufficiency No ? Yes
Severe hypertension with CVA ? Yes Yes
Severe hypertension with vascular disease ? ? Yes
Aortic dissection ? Yes Yes
284 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Individualised Drug Therapy in Hypertension

1st Line Drug 2nd Line Drug
Old age Diuretic Alpha blocker, calcium channel
blocker, ACE inhibitor
Angina Beta blocker, calcium channel Alpha blocker, ACE inhibitor
blocker (Non-DHP)
Myocardial infarction Beta blocker, (Non-ISA) ACE Diltiazem, verapamil
inhibitor (with systolic dysfunc
tion
Heart failure ACE inhibitor, diuretic carvedilol Very small dose of beta-blocker
Diabetes with microalbuminuria ACE inhibitor Calcium channel blocker, alpha-
blocker
Isolated systolic hypertension Diuretic, calcium channel blocker Beta blocker, ACE inhibitor
(Long acting DHP)
Renal insufficiency (caution in Diuretic, ACE inhibitor (C/I
renovascular hypertension and bilateral renal artery stenosis)
creatinine above 265.2 mml/L
(3 mg/dl)
Asthma Alpha blocker
Cerebrovascular accident Calcium channel blocker
Black subject Diuretic, calcium channel blocker,
beta blocker
Pregnancy Beta blocker
Left ventricular hypertrophy ACE inhibitor
Peripheral vascular disease Calcium channel blocker
Hyperlipidaemia Alpha blocker
Uncomplicated hypertension ACE inhibitor, calcium channel Methyldopa, hydralazine
blocker, doxazosin, beta blocker,
thiazide
Atrial tachycardia and fibrillation Beta-blocker, calcium channel
blocker (Non-DHP)
Diabetes mellitus (Type II) Low-dose diuretic
Essential tremor Beta blocker (Non-CS)
Hyperthyroidism Beta blocker
Migraine Beta blocker (Non-CS), calcium
channel blocker (Non-DHP)
Osteoporosis Thiazide
Postoperative hypertension Beta blocker
BPH (Prostatism) Alpha blocker
 Hypertension |285

Thiazide diuretic Beta blockers

Non-pharmacological
advice (salt, weight,
alcohol, exercise

ACE inhibitors or Dehydropyridine calcium

angiotensin II receptor channel blockers
blockers

Fig. 42.1: Birmingham hypertension squire

The Birmingham squire is for optimal choice of add-in-drugs for the management of resistant
hypertension regardless of which drug is initially used as monotherapy. Logical-add-on-drugs are dictated
by directional arrows.
Table 42. 8: Antihypertensive drugs in pregnancy
Drugs 1 to 25 week pregnancy Pregnancy after 25 weeks
Methyldopa Safe and effective Safe and effective
Hydralazine Safe and effective Safe and variably effective
Beta blocker Unsafe for foetus Safe and effective
Labetalol Effective
Nifedipine Effective
ACE inhibitor Contraindicated Contraindicated
Diuretics Contraindicated Contraindicated

Treatment of Secondary Hypertension

Mild hypertension
BP less than 160/105
With hypertensive
complications
↓ ↓
i. Withdraw pill
ii. Immediate anti-
hypertensive therapy
iii. Investigate for causes
of secondary hyper-
tension
Hypertension due to oral contraceptives
Moderate to severe
hypertension
BP greater than 160/105
↓
Without hypertensive i. Withdraw pill
complications ii. Immediately start
anti-hypertensive drugs
i. Withdraw pill
ii. No antihypertensive drug
for 6 months
If no hypertension If hypertension persists
↓ ↓
Dont give pill ever Start drug
286 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
Renovascular Hypertension
Choice of treatment
1. Revascularisation with per- Anatomy favourable lesion of Favourable remarks: Non-inva-
cutaneous transluminal
angioplasty
2. Medical treatment: ACE a. Anatomically unfavourable a. Controls BP sparing renal
inhibitor with or without
diuretic
3. Renovascular surgery
Primary aldosteronism
1. Unilateral adrenalectomy:
2. Surgical adrenalectomy
3. Medical treatment: Spirono-
lactone and aminoglutethi-
Indications Remarks
renal artery sive, low cost, low morbidity
makes angioplasty as initial proce-
dure of choice in renovascular
hypertension
lesion function and maintaining
b. Patient above 50 year with negative sodium balance
atherosclerotic renal artery b. For proper management
disease monitor size and function of
kidney by intravenous pyelo-
graphy and ultrasound with
medical treatment may cause
rapid loss of renal mass and
function in atherosclerotic
disease
a. Patients who are not candi- Overall surgical cure rate of
date for angioplasty renovascular hypertension due to
b. Patient whose artery cannot unilateral renal artery stenosis is
be successfully dilated by 40-50%. Better result in fibromus-
angioplasty because of ana- cular disease than in athero-
tomical lesion sclerotic disease. Result better in
c. Unilateral renal artery steno- unilateral than bilateral disease
sis is a better candidate than
bilateral disease.
Adrenal adenoma Surgery restores BP and electro-
lytes to normal level. Adminis-
tration of spironolactone in 200 to
400 mg dosages per day for 4 to 8
weeks can be used to predict the
response to surgery. If spironolac-
tone restores BP to normal, a good
surgical result can be expected
Adrenal carcinoma specially with
metastasis
Adverse effect of spironolactone:
a. Adrenal carcinoma Nausea, vomiting, gynaecomastia,
b. Bilateral adrenal hyperplasia impotency, hirsutism, intermens-
contd...
contd...
|
Hypertension 287

mide (inhibitor of steroid trual bleeding

biosynthesis) or adrenolytic
agents (DDD). Patients who
are intolerant to spironolac-
tone amiloride may be given
Pheochromocytoma Patient is prepared for surgery
1. Surgery Tumour with alpha-adrenergic blocking
agents (Phenoxybenzamine, pra-
zosin or labetalol) for 1-2 weeks
before surgery to block the pres-
sure effect of circulating norepine-
phrine and expand intravascular
volume
Side-effects of alpha-methyl-para-
2. Medical therapy: Alpha and tyrosine: Sedation, diarrhoea,
beta-adrenergic blockers or galactorrhoea, anxiety, tremulous-
combined alpha + beta-adre- ness, crystalluria
nergic blocker (Labetalol).
Alpha-methyl-paratyrosine
(Demser) inhibits tyrosine
hydroxylase, the rate limi-
ting enzyme in catechola-
mine biosynthesis, thus
reducing catecholamine
production by the tumour
and secondarily lowering
BP.
Combination Therapy
Thirty to fifty percent of patients are not controlled by monotherapy. They need combination therapy.
The following are the rational and clinically useful combinations:
ACE inhibitor: With beta blocker
With clonidine
With methyldopa
With diuretic
With calcium channel blocker
Angiotensin II: With diuretics (Hydrochlorothiazide)
Receptor antagonists: With calcium channel blockers
Beta blockers: With diuretics
With calcium channel blocker (Of Dihydropyridine class)
With alpha-blockers
288 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Calcium channel blocker: With ACE inhibitors

Dihydropyridine class with beta blockers
With lacidipine (New long acting lipophilic calcium channel blocker)
With hydrochlorothiazide

CLINICAL NOTES
Hypertensive Crisis
Two types of drugs are available for hypertensive crisis:
1. Rapid acting ones; Sodium nitroprusside, diazoxide.
2. Slower acting ones: Hydralazine, reserpine, methyldopa, etc. Diazoxide is contraindicated in coronary
artery disease. It is, however, the drug of first choice for young patients with hypertensive crisis if
monitoring facilities and ICU unit is not available. Majority prefer nitroprusside in ICU setting.
Reserpine is contraindicated in toxaemia of pregnancy because it increase the likelihood of seizures.
Hydralazine (IM or IV) is not predictably effective and causes reflex tachycardia and increased
cardiac output and contraindicated in coronary artery disease and dissecting aneurysm. In
hypertensive crisis of pheochromocytoma oral phenoxybenzamine (10-40 mg/day) with propranolol
IV 1 mg to blunt tachycardia should also be begun immediately. Diazoxide which increases cardiac
output and renal profusion, is the drug of choice in intercurrent renal insufficiency with hypertensive
crisis. Nifedipine sublingual has been effective in severe hypertension, so is the oral captopril and
enalapril. After acute stage is over, beta blocker + vasodilator + diuretic should be used. Minoxidil
has been shown to be effective in patients with renal insufficiency and should be added in place of
vasodilator (initial dose of minoxidil 2.5 mg orally q.d.s.; 40-60 mg is divided dosages has been
reported effective).

Diabetes and Hypertension

Hypertension is twice as common in diabetes. When renal disease is evident (microalbuminuria of nephro-
pathy) hypertension should be treated aggressively to slow the decline in renal function and glomerular
filtration. ACE inhibitors are the first line choice for hypertension in diabetes. Calcium channel blocker
and alpha-adrenergic blockers are second line choice.
Reduce the BP to 130/80 mmHg in diabetes.

Metabolic profiles of Anti-hypertensive Drugs

Drugs Effect on blood glucose Effect on lipid profile Comments
Thiazide Increases glucose Increase LDL
Decreases HDL
Increases triglyceride
Beta blockers (Increases) glucose Increase triglyceride Decreases awareness of
hypoglycaemia
Calcium channel blockers Neutral Neutral Dihydropyridines may
increase proteinuria
ACE inhibitor Probably neutral, but pos- Neutral Probably has specific
sibly decreases glucose reno-protective effect in
nephropathy and micro-
Alpha-adrenergic blockers Neutral Increases HDL albuminuria
Decreases LDL
 Heart
43
Treatment of Angina

Treatment of angina consists both of medical and surgical treatment.

MEDICAL TREATMENT
Goal
Goal of treatment are four-fold:
1. Prevention of acute myocardial infarction and sudden death
2. Prolongation of life span
3. Improvement of quality-of-life
4. Improvement of effort tolerance.

Risk Factors
Management of risk factors is essential part of medical treatment. Treat hypertension, diabetes mellitus
and dyslipidaemia. Stop oral contraceptive drugs in females. Stop smoking. Avoid anxiety and worry.

Precipitating Factors
Cold, heavy meals and excess exertion precipitate anginal pain. Avoid exposure to cold. Frequent small
meals are advised in postprandial angina.

Treatment of Co-existing Conditions

Treat anaemia, hypertension, diabetes mellitus and hypo- and hyperthyroidism.

Non-Pharmacological Therapy
Proper amount of exercise is advised. In stable angina routine work is allowed. Prudent diet is
recommended, for example, avoidence of high fat diet; chicken, fish and poultry are recommended;
nuts, fruits and spices will be wise addition. Some recommends Yoga and meditation.

Drug Therapy
Anti-anginal drugs: The Table 43.1 depicts the dosages, frequency of administration, onset and duration
of action and mode of action.
290 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Table 43.1: Principal antianginal drugs

Drugs Dosages Frequency of Onset Duration Mode of action
administration
Nitrate Prepara- a. Venodilatation
tions — reduced ven-
Nitroglycerin: Sub- 0.3-0.5 mg SL every 3 min till 1-3 min 10-30 min ous return to
lingual: Angiced pain stops heart and redu-
(Wellcome) 0.5 mg Prophylaxis: ced preload—
0.5 mg prior to reduced myocar-
activity dial oxygen con-
sumption
b. Dilates coronary
artery and relie-
ves coronary
spasm
Oral: Nitrocontin 2.6-6.4 mg Twice daily 20-45 min 4-6 hour
(Modi) 2.6 and
6.4 mg
Ointment: Myovin 1.5-3 cm Thrice daily 15-60 min 3-6 hour
(Cadila) 2%
Transdermal patch: 5-20 mg Once daily 30-60 min 24 hour
Nitroderm
(Novartis)
TTS 5 (25 mg)
TTS 10 (50 mg)

Inj. Nitrocure
Panacea: 25 mg/
5 ml

Inj. Nitrojet (Sun)

5 mg/ml

Isosorbide Dini-
trate:
Isordil 5 and 10 mg 5-10 mg SL for SL: 2-5 min 90-120 min
tab (John Wyeth) quick relief Oral: 15-45 min 4-6 hr
Sorbitrate (Nicho- Prophylaxis: 5-10
las) 5 and 10 mg tab mg TDS
SR 40-80 mg/day
Isosorbide 5 mono-
nitrate:
Angicor 20, 40, 20 mg OD-SR b.d. or t.d.s. once Same as isosorbide
60 mg daily dinitrate
Angitrit (Unichem)
20 mg
Ismo (Boeh) 10,
20, 40 mg
contd...
contd...
Treatment of Angina | 291

Drugs Dosages Frequency of Onset Duration Mode of action

administration
Imdur (Astra) SR 30,
60 mg
Monit (Intas) 20 mg,
OD-SR 50 mg

Monocontin-OD
(Modi) SR 50 mg
Monotrate (SUN) 10,
20, 40 mg
OD-SR 25, 50 mg
Vasotrate (Torrent)
10, 20, 40 mg

Beta-adrenergic Cardioselectivity Intrinsic sympatho- Dose range Beta blockade potency

blocking drugs mimetic activity (mg/day) Ratio (Propranolol-
1.0)
1. Atenolol + 0 50-100
1.0
(Tenormin, Aten,
Atpark)
2. Propranolol 0 0 10 mg b.d. to 480 mg/
1.0
Inderal (ICI) 10, day
40, 80 mg
Ciplar (Cipla) 10,
40, 80 mg
3. Metoprolol: + 0 100-200 mg in two
1.0
Betaloc (Astra) divided doses
Tab 50, 100 mg
Inj. 1 mg/ml
Lopresor
(Novartis) 50, 100
mg
Metolor (Cipla)
Tab 50, 100 mg
Inj. 1 mg/ml
4. Acebutolol: + + 400 mg-1.2 gm in divi-
0.3
Sectral (Rhone) ded dosages
200 mg tab
5. Pindolol: 0 + 2.5-5 mg in angina
6.0
Visken (Novartis) 10-30 mg/day in hyper-
10 mg tab tension, max 45 mg

6. Sotalol: Sotagard 0 80-480 mg/day

0.3
(Glaxo)
40 mg, 80 mg tab
292 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

First Generation Calcium Channel Blocking Drugs

Heart rate Conduction Myocardial Coronary Dosages Peripheral Negative Combination Combination
AV node contractility blood flow Oral IV vasodilata- inotropic with beta with nitrate
and demand tion effect blocker

Diltiazem: D D D I 30-90 mg 10-20 mg I+++ I+ OK OK

6-8 hourly

Nifedipine: I I D I++ 5-40 mg I++++ I+++ OK Caution

t.d.s.

Verapamil: D D D++ I 80-120 mg 10-20 mg I++ I++ Caution OK

6-12 hourly

Second Generation Calcium Channel Blockers

Dose Remarks
Amlodipine 5-10 mg o.d. Safe in mild and moderate heart failure
Felodipine Extended release 5-100 D Beneficial role in CCF
Nicardipine 20-40 mg t.d.s., SR 30-60 mg .b.d. Less cardio-depressant than nifedipine
Nitrendipine 2.5-10 mg o.d.
Bepridil 200-400 mg o.d. Class I antiarrhythmic effect also. Risk of QT
prolongation and Torsades. Approved in angina

Nimodipine 60 mg q.d.s. Cerebroselective action in subarachnoid

haemorrhage and ischaemic stroke.
Key: I = Increase D = Decrease

Table 43.2: Side-effects of calcium channel blockers

Nifedipine Diltiazem Verapamil Amlodipine Felodipine
Overall incidence 0.35 0.3 10-14
of side-effects (%)

Headache +++ ± + + +

Flushing +++ ± ± +

Dizziness +++ + ++ +

Ankle oedema +++ ± + + +

Constipation 0 0 ++

AV block 0 + ++

Sinus bradycardia 0 ++ +
OTHER HELPFUL DRUGS IN ANGINA
Treatment of Angina | 293

A. Antiplatelet Drugs
Mode of action Dose Side-effect and remarks
Dipyridamol: i. Diminishes platelet aggregation 200-300 Headache, flushing,
mg/day coronary steal
Cardiwel (Torrent) ii. Dilates coronary and colaterals
25, 75, 100 mg tab
Persantin (G Remedies)
25, 100 mg tab
Dynacard (US Vitamin)
100 mg tab
Aspirin: Inhibit thromboxane A2 75-150 Chronic use causes gastric
which aggregates platelets and mg/day ulcer and haemorrhage
a potent vasoconstrictor
Ticlopidine 250 mg Can be used in those who
b.d. cannot tolerate aspirin
B. Combination of Drugs in Severe Angina and to Prevent Complications
i. Aspirin + Sotalol prevent complications of angina
ii. Captopril + Isosorbide: Captopril potentiates isosorbide in resistant angina
iii. Other combination therapy for severe angina:
Atenolol + Mononitrate o.d. (Isosorbide 5 mononitrate)
Beta blocker + Amlodipine
Verapamil + Isosorbide
Diltiazem + Isosorbide
C. New Drugs
a. Nicorandil 5 mg, 10 mg (Korandil-Aztec).
Opens potassium channels, cardioprotective. Used in all types of angina. Nicoran, Corflow, Zynicor-
5, 10 mg tab twice daily.
b. Trimetazidine: Ipca-Metagard, Flavedan 1 tab t.d.s.
c. Carnitor-Nucarnit (Nucron), REE, Carnitor: 1-2 tab t.d.s.

TREATMENT OF DIFFERENT TYPES OF ANGINA

Treatment of stable angina
a. Monotherapy betablocker or
Calcium channel blocker
↓ If fails
If fails
Combined beta blocker +
Calcium channel blocker
b. Aspirin
Treatment of unstable angina Treatment of Prinzmetal’s angina
a. Nitrate a. Calcium channel block
↓ ↓
If fails
Calcium channel blocker Add Diltiazem
↓ b. Aspirin
If fails c. Sublingual nitrate or nifedipine
Nitroglycerin drip 10 microgram/min if d. For prevention isosorbide,
BP right diltiazem or verapamil beta
b. Aspirin blocker contraindicated
c. Angioplasty or Bypass surgery
may be required
294 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Algorithm Treatment of Stable Angina

Aspirin Nitrate 75-150 mg/day
Lipid lowering agent
↓
Can the patient tolerate beta blockers?

Yes No
↓ ↓
Beta blocker Isosorbide di or mononitrate
↓ or
Still symptomatic Calcium antagonists
↓ or
Add: Trimetazidine
Trimetazidine or
or Nicorandil
Isosorbide ↓
or Still symptomatic
Calcium antagonists ↓
or Combine trimetazidine with
Nicorandil calcium antagonists or oral
↓ nitrate ↓
Still symptomatic Still symptomatic

Revascularisation
(PTCA, CABG)

FLOW CHART FOR MANAGEMENT OF UNSTABLE ANGINA

Admit in ICU. Bedrest, oxygen, sedation with morphine or pethidine. Treat precipitating factors and
concomitant diseases. Look for acute myocardial infarction and arrhythmias by continuous ECG
monitoring.
↓
A. Nitrate sublingually or IV drip (10-200 microgram per minute). Systolic blood pressure should not
go below 100 mmHg.
B. Calcium channel blocker or beta blocker in maximum dosages. Nifedipine 10-20 mg t.d.s. +
propranolol 20 mg t.d.s. Dosages gradually increased till therapeutic effect is achieved.
C. i. Aspirin 160-325 mg/day
ii. Several studies have shown a beneficial effect of low molecular weight heparin in dosages of
5000-7000 units every 6 hour for 3-5 days.
iii. Since 25-50% of the patients have thrombosis in the coronary arteries, thrombolytic treatment
with streptokinase, urokinase or tissue plasminogen activator (tPa) has been tried with promising
results.
↓
contd...
After the end of a week when patient is stabilised, evaluate ischaemia by:
Treatment of Angina | 295

• Stress testing
• Thallium scan
• Holter monitoring for silent ischaemia
• Coronary angiography

If ischaemia is severe If ischaemia is mild +

good exercise capacity
PTCA Indication: CABG Indication: ↓
a. Severe disease on angiography a. Severe disease on angio- Medical therapy with aspirin,
graphy nitrate, beta blocker and
b. Single or double vessel disease b. Left main artery obstruction calcium channel blocker
↓
c. Severe triple vessel disease
d. If PTCA is not possible
↓ ↓
If patient has diffuse disease and poor distal vessels,
he should be treated as a case of chronic stable angina
with nitrate, beta blockers, calcium antagonists and aspirin.
Manage risk factors.
Treatment of silent ischaemia (Ischaemia without symptoms with ST depression)
It occurs more in treadmil positive patients, diabetes, diabetes on insulin. It precipitates ventricular
arrhythmias and acute myocardial infarction specially in morning. Investigated by radionuclide
scintigraphy, Holter monitoring and coronary angiography. It is treated by beta blocker, calcium
antagonists, CABG and angioplasty. Aspirin, nitrate and anxiolytics are also prescribed. If episode occurs
during exercise use beta blockers.

CLINICAL NOTES ON ANGINA

Oedema produced by calcium channel blockers is obviated by adding small dose of ACE inhibitors.
Verapamil and diltiazem are not used in bradycardia, conduction disturbances and left ventricular
failure. They are used in tachyarrhythmias associated with angina. They can be combined with ACE
inhibitors, diuretics and centrally acting antihypertensive drugs but not with beta blockers.
Felodipine (costly), nitrendipine and amlodipine can be used in left ventricular failure because they
cannot depress left ventricular function. They can be combined with beta blockers, ACE inhibitor, diuretics
and centrally acting antihypertensive drugs. Felodipine and nitrendipine are best for hypertension. Drug
of choice for angina associated with hypertension and left ventricular dysfunction is amlodipine.

Calcium Channel Blockers in Cardiac Arrhythmias

Diltiazem 120 mg (Single dose) + Propranolol 160 mg (Single dose) are used in supraventricular
tachycardia.
Lanoxin + diltiazem useful in auricular fibrillation.
Verapamil is contraindicated in WPW syndrome with auricular fibrillation.
296 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Verapamil may prevent ventricular fibrillation.

Calcium channel blocker, ACE inhibitor and alpha blocker regress LVF
Nifedipine causes hyperglycaemia
Felodipine can be used in renal failure because it is renal protector.

Parenteral Diltiazem
To control heart rate in supraventricular tachycardia, fast auricular fibrillation.
Also used in unstable angina.
Preparation: Viral 25 mg/5ml, Amp 5 mg/1 ml
IV inject 20 mg as bolus in 2 minutes → If no response repeat 25 mg IV after 15 min infusion 5-
15 mg/hour
Calcium channel blockers increases bleeding during surgery.
Nitrate tolerance is reduced by:
a. Less frequent administration—at 8 AM and 2 PM
b. Nitroglycerine paste during night and isosorbide during day.

New antianginal drug trimetazidine: Comparison with other antianginal drugs:

Nitrate Beta blocker Calcium channel blocker Trimetazidine
Heart rate Increased Decreased Variable effect No effect
Contractility Increased Decreased Variable effect No effect
Conduction No effect Decreased Variable effect No effect
Vasodilatory Yes No No No
side-effect
 Heart
44
Valvular Heart Diseases

Medical management of problems associated with valvular heart diseases.

Arrhythmias
I. Auricular fibrillation: Aim is to control ventricular rate, convert to sinus rhythm and long-term
anticoagulation to prevent thromboembolism specially in mitral valve diseases:
A. To control ventricular rate and conversion to sinus rhythm:
Start digoxin or verapamil or diltiazem or beta blocker as monotherapy
↓ If fails
Digoxin + Beta blocker or Digitalis + Verapamil
↓ If fails
Amidarone 600 mg/day for 4 weeks
↓ If fails
Cardioversion and give amidarone 200 mg/day after cardioversion
B. Cardioversion:
a. Prior to cardioversion 2-6 week course of anticoagulant given quinidine started 2 days prior
to cardioversion. If digitalis has been given this may be stopped one day prior to cardioversion
↓
Start cardioversion and if successful
↓
Followed by oral quinidine 200-400 mg three times a day with digoxin to maintain sinus
rhythm. Keep patient on anticoagulant for long-term.
b. Another regime:
Amidarone 600 mg/day for 4 weeks
↓
Start cardioversion
↓
Followed by amidarone
C. Anticoagulation: Auricular fibrillation associated with valvular disease, prosthesis or heart failure.
↓
Do echocardiography

High risk patients Moderate and low risk patients

Characterised by intracardiac thrombus, Echo shows only valvular disease
large left atrium (larger than 4.5 cm), No echo, or clinical risk factor
298 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

valvular disease (such as history of thrombo-

↓ embolism, TIA and heart failure)
Anticoagulant ↓
Aspirin 75 mg to 300 mg per day
Warfarin Warfarin contraindicated
↓
Aspirin 75-300 mg/day
2. Ventricular ectopy and palpitation in mitral valve prolapse: Beta blockers or other antiarrhythmic
drugs amidarone, norpace, sotalol.
II. Associated coronary artery disease as in aortic stenosis: Confirm the diagnosis of CAD by cardiac
catheterisation and angiography. Be careful in use of nitrates, since BP may fall and further reduce
coronary blood flow.
III. Heart failure: Needs diuretic, digitalis, vasodilators, ACE inhibitors. See chapter on “Heart Failure”.

SURGICAL MANAGEMENT OF VALVULAR HEART DISEASE

Surgical Procedures Sequelae and complications
of surgery
Valvular diseases: Types of surgery Indications
Mitral stenosis: a. Balloon mitral valvo- Restenosis
tomy Atrial arrhythmia
b. Closed mitral valvotomy: Recurrent respiratory tract
Orifice dilated by Tbbs’ infection
dilator Embolism
c. Open mitral valvotomy Left atrial thrombus, calcified Persistent pulmonary hyper-
using heart-lung machine mitral valve, chronic atrial tension
dilated under vision fibrillation, embolisation, Persistent right heart failure
significant mitral incompe-
Medical management:
tence, associated aortic or
• Treatment of right heart
tricuspid disease, associated
failure
congenital or ischaemic heart
disease. • Dipyridamole
• Prevention of infective
endocarditis
d. Mitral valve replace- Extensively damaged, heavily • Control of respiratory infec-
ment—replaced by mec- calcified or infected valve tion
hanical ball valve or
tissue valve
Mitral incompetence a. Repair: Grossly dilated • Myocardial dysfunction,
valve can be narrowed or atrial arrhythmias, residual
expensive commercially incompetence and stenosis
available readymade ring
can be applied. Torn
leaflets can be sutured.
b. Replacement Grossly incompetent valve
Aortic stenosis a. Balloon aortic valvotomy
b. Open aortic valvotomy
contd...
contd...
Valvular Heart Diseases | 299

c. Aortic valve replacement Badly formed, deformed or

calcified valve
Aortic incompetence a. Valve repair Grossly damaged valve, gross
b. Valve replacement aortic refurgitation and gross
left ventricular enlargement
Pulmonary stenosis a. Balloon valvotomy Excellent long-term result
b. Surgical valvotomy

Pulmonary incompetence a. Repair

b. Replacement

Tricuspid incompetence a. Repaired by narrowing

by sutures or ring
b. Grossly damaged valve
replaced

Tricuspid stenosis a. Balloon valvotomy

b. Open valvotomy
c. Valve replacement

IV. Thromboembolisation Needs long-term anticoagulation on long-term basis

V. Treat chest infection
VI. Other problems
A. Mitral valve prolapse:
i. Majority of patients do not need any treatment.
ii. Ventricular ectopy and palpitation need beta blocker.
iii. Syncope and prolonged QT interval need antiarrhythmic drugs.
iv. Chest pain is usually due to non-cardiac causes. Beta blocker may help.
B. Mitral stenosis: Try aspirin anticoagulants.
i. Treat anaemia and infection if present.
ii. Symptomatic patients are helped by restriction of activity, restriction of salt and diuretic. Digitalis
is only indicated to reduce ventricular rate in auricular fibrillation.
iii. Haemoptysis: Treated by bed rest, sitting position and diuretic.
C. Mitral regurgitation:
a. Mild decompensation: Digoxin provides support to dilated left ventricle.
b. Moderate decompensation: Add diuretic and salt restriction.
c. Severe decompensation: Add vasodilators. Carvedilol helps.
D. Aortic regurgitation:
a. Digitalis is indicated in severe regurgitation and dilated left ventricle.
b. Syphilitic aortitis need penicillin therapy.
c. Anginal pain may be helped by nitrates but not very useful.
d. ACE inhibitor helps chronic AR.
E. Mitral stenosis: Beta blocker is the cornerstone in treatment of MS with pregnancy.
300 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Surgery is not required in the following clinical types of valvular diseases:

A. Isolated tricuspid regurgitation without severe decompensation.
B. Mild to moderate aortic regurgitation.
C. Mild mitral regurgitation.
D. Mitral valve prolapse.

Prophylaxis
I. Prevention of bacterial endocarditis
Procedures Oral antibiotics
Dental and respiratory tract proce- a. Penicillin V 2 gm one hour
dures: before, then 6 hours after 1
gm after.
b. Patient allergic to penicillin:
Erythromycin orally 1 gm
one hour before and later 500
mg 6 hours
Parenteral antibiotics
a. Penicillin G IV or IM
2 million units 30-60 minutes
before and 1 million units
after surgery.
b. For prosthetic valve ampi-
cillin 1-2 gm IV or IM plus
gentamicin IV or IM one and
half hour before, followed by
oral penicillin V 1 gm
6 hours later.
c. Patients allergic to penicillin:
Vancomycin 1 gm IV slowly
one hour before and no
repeat dose.

Genitourinary and gastrointestinal Ampicillin 2 gm IV or IM plus

procedure: gentamicin 1.5 mg/kg IM or IV
one hour before and same dose
repeated after 8 hours.
Minor or repeated procedures: Amoxicillin 3 gm one before and
1.5 gm 6 hours after the procedure
II. Prevention of streptococcal infection
Benzathine penicillin 1.2 mega unit every 3rd week for adult
Benzathine penicillin 6 lac units every 15 days for children.
 Heart
45
Congenital Heart Disease

MANAGEMENT OF COMMON PROBLEMS ASSOCIATED WITH

CONGENITAL HEART DISEASE

Chest Infection
Many congenital heart diseases are associated with chest infection specially ASD, VSD, PDA. They
should be treated with proper antibiotics.

Cyanosis
1. Fourty percent humidified oxygen is necessary.
2. Treat metabolic acidosis (pH less than 7.25).
3. Treat hypoglycaemia, hypocalcaemia and anaemia if present.

Congestive Cardiac Failure

General: Bed rest, low sodium diet. Start feeding sick infants with 10% dextrose in water and solid
food then added. Infants should be propped up. If the patient restless and agitated, sedation with morphine
sulphate 0.1 mg per kg given subcutaneously.

Drugs
Drugs Preparations Doses Advantages Disadvantages
Digoxin Oral: Elexir 0.05 mg/ml Total loading dose Has positive ionotropic A. Contraindications
Tab 0.125 mg (TLD) effect, enhancing con- • Fallot’s Tetralogy
Injectable: Oral: Preterm infant tractility. with hypoxaemic
Digoxin 0.1 mg/ml 0.03 mg/kg spell.
Newborn, 0-6 weeks • Idiopathic hyper-
0.04 mg/kg trophic subaortic
6 weeks-2 years stenosis.
0.06-0.08 mg/kg • Ventricular tachy-
2-5 years—0.04-0.06 cardia.
mg/kg B. Digoxin toxicity:
5 years and older— Premature beats,
0.03-0.04 mg/kg varying degree of
Parenteral: Three- AV block including
fourths of the oral dose prolonged P = R
contd...
302 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Preparations Doses Advantages Disadvantages

Initial digitalisation: interval and any

First dose: 3/4 oral arrhythmia. Ano-
TLD IV rexia, nausea and
2nd dose: 1/4 oral TLD vomiting
in 6-8 hours oral C. Treatment of digo-
3rd dose: 1/4 TLD in 6- xin toxicity:
8 hours given orally • Give K if it is low
• Treat arrhythmias
Maintenance Dose by phenytoin, lid-
12 hours following ocaine, propra-
TLD maintenance dose nolol
should be started 1/4 of • Pacemaker for
TLD in two divided CHB
doses • Used only in
severe CCF
Diuretics: Frusemide 1 mg/kg IV—After Decreases preload
stability oral 2-4 mg/
kg/day—Later 3 times
a week. If no response,
aldactone 3 mg/kg/day
in 2-3 divided dosages

Dopamine a. Only oliguria pre- No chronotropic effect Do not add sodium-

sent: 2-5 micro- and dilates renal ves- bicarbonate to dopa-
gram per kg per sels used in refractory mine infusion
minute in 5% dex- failure
trose in water IV
b. Both oliguria and
hypotension pre-
sent: 5-20 micro-
gram per kg per
minute

Dobutamine 5-8 microgram per kg Better than dopamine

per minute IV infusion with regard to incre-
asing stroke volume
and to decreasing pul-
monary systemic vas-
cular resistance. No
chronotropic effect and
produce no VPB. Used
in refractory CCF.

Vasodilators 1-8 microgram per kg • Modify preload and

Sodium nitroprusside per minute IV Monitor afterload
BP • Refractory heart
failure
contd...
contd...
Congenital Heart Disease |303

Drugs Preparations Doses Advantages Disadvantages

Prazosin 1 mg/kg per day in 4 Reduces afterload Tachycardia

divided dosages orally Used in refractory heart
every 6 hour—increa- failure
sed to 4-5 mg per kg
per day.

Other vasodilators: Captopril Orally 1-4 mg/kg/day

• IV sublingual nitro- in 3-4 divided dosages
glycerine
• Topical nitrogly-
cerine
• Sublingual or oral
isosorbide dinitrate or
5 mononitrate

Pulmonary Oedema
Measures:
1. Prop. the patient at 45 degree 2. Morphine sulfate 0.1 mg per kg intravenously
3. Furosemide 0.1 mg per kg IV 4. Rapid digitalisation by IV route over 2-4 hour period
5. Humidified oxygen in high concentration 6. Refractory cases: Dopamine or nitroprusside

Hypercyanotic Spell
Occurring in: Tetralogy of Fallot’s
Tricuspid atresia
Severe pulmonary outflow obstruction
Usually seen between 1-12 months old with a peak frequency in 2-3 months old.
Measures:
Mild spell Severe spell
• Place infant in knee-chest position If the measures for mild spell do not succeed:
• Humidified oxygen. • Vasopressor: Methoxamine (Vasoxyl)—20-40 mg
• Morphine sulfate 0.1 mg per kg subcuta- in 250 ml of 5% dextrose in water IV till systolic
neously BP is raised by 15-20%.
• Treat metabolic acidosis with sodium • Beta blockers: Propranolol 0.1 mg/kg, diluted in
bicarbonate, anaemia by blood transfusion 50 ml of 5% dextrose in water IV—Monitor heart
and dehydration if present. rate by ECG. If marked bradycardia, stop. If it is
effective give orally 1-4 mg/kg per day in 3-4 divided
dosages.
• Surgery can be postponed for several months by
propranolol orally (dosages as above).
• Surgical correction.
304 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Other Measures for Management of Congenital Heart Diseases

1. For small VSD no specific therapy is needed except for infective endocarditis prophylaxis.
2. PDA; Medical closure of PDA using indomethacin (0.2 mg/kg 12 hourly for 3 dosage can be
attempted. It is contraindicated in presence of jaundice or renal insufficiency.
3. Coarctation of aorta: Treat hypertension.
4. Congenital aortic stenosis: Restrict physical activity. Give infective endocarditis prophylaxis.

Surgical Management of Congenital Heart Disease

There are two types of surgical therapy:
1. Palliative procedures
2. Corrective surgery (Anatomical correction)

Palliative Procedures
A. For decreased pulmonary blood flow
Associated cardiac defects
1. Pulmonary atresia with intact
ventricular septum or with VSD
2. Severe Tetralogy of Fallot’s
3. Tricuspid atresia
4. Severe pulmonary stenosis
B. For increased pulmonary blood flow
Associated cardiac defects
1. Muscular type of VSD
2. Single ventricle
3. Transposition of great arteries with
large VSD
4. Tricuspid atresia
C. Inadequate interatrial mixing
Associated cardiac defects
1. Pulmonary atresia with intact VSD
2. Tricuspid atresia
3. Total anomalous pulmonary venous
connection
4. Transposition of great arteries with
intact VSD
Procedures for increasing blood flow
a. Blalock-Taussig anastomosis between subclavian
and ipsilateral pulmonary artery.
b. Modified Blalock-Taussig shunt: Subclavian artery
to ipsilateral pulmonary artery with an interposition
of Gore-Tex graft.
c. Pott’s anastomosis: Descending aorta to left
pulmonary artery shunt.
d. Waterston-Cooley shunt: Ascending aorta to right
pulmonary artery anastomosis.
e. Balloon pulmonary valvoplasty indicated in patients
in whom total correction cannot be done because
of size and complexity of lesion.
Procedures for decreasing blood flow
a. Past procedures: Surgical constriction or banding
of main pulmonary artery.
b. Now primary surgical correction is possible due
to improvement in open heart surgery.
Procedures
Balloon atrial septostomy
Corrective surgery:
Congenital Heart Disease| 305

Surgical correction is possible in the following defects:

Acyanotic defects Cyanotic defects

Left to right shunt: Tetralogy of Fallot’s
Atrial septal defect Single atrium
Ventricular septal defect Total anomalous pulmonary venous
Patent ductus arteriosus Connection
Endocardial cushion defect Transposition of great arteries
Partial anomalous pulmonary venous connection Truncus arteriosus
Obstructive defects:
Aortic stenosis
Coarctation of aorta
Pulmonary stenosis

Types of Procedures
a. Due to deep hypothermia and cardiopulmonary bypass for open heart surgery primary surgical
correction of defects are possible.
b. Balloon dilatation of valvular stenotic lesions is preferred due to low cost, less prolonged stay in
hospital and no scar of operation.
c. Balloon dilatation of coarctation.
d. Transcatheter closure of PDA.
 Heart
46
Rheumatic Fever

BEDREST
Bedrest is advised till the activity of rheumatic fever subsides.
A. Bedrest:
Categories of patients Advice
a. Active carditis in young children Strict bedrest for 2 weeks followed by moderate bed-
rest for 4 weeks
b. Patients with only polyarthritis or Bedrest for 2 weeks
polyarthralgia
B. Mobilisation begins when blood count and ESR return to normal.

Drug Treatment
Drugs neither cure nor prevent the subsequent evolution of rheumatic heart disease. Antibiotics eradicate
group A streptococci remaining in the tonsils and throat. Anti-inflammatory agents suppress many of the
signs and symptoms of ARF. See Table 46.1. “Drugs in the Treatment of Rheumatic Fever”.
Table 46.1: Drugs in the treatment of rheumatic fever
A. Antibiotics:

Preparations Dosages

a. Benzathine 6,00,000 units IM for child for 10 days

b. Penicillin G 12,00,000 units/day IM for adults for 10 days
c. Penicillin V 125-250 mg four times a day for 10 days
d. Erythromycin (for penicillin 20-40 mg/kg/day divided in 2-4 equal dosages
allergic patients)
Following completion of the above therapy, continuous anti-streptococcal prophylaxis should commence.
B. Anti-inflammatory drugs

Polyarthritis cases Mild carditis No cardiomegaly Moderate, severe carditis CCF

Aspirin 100 mg/kg/day in 6 Aspirin Prednisolone 20-60 mg/day for

divided dosages for 2 weeks 100 mg/kg/day continued 1 week
↓ for 6-8 weeks ↓
Then 75 mg/kg/day for ↓ 5 mg 4 times a day for 3 weeks
contd...
contd...
Rheumatic Fever | 307

Polyarthritis cases Mild carditis No cardiomegaly Moderate, severe carditis CCF

6 weeks (continued for Change to prednisolone if signi-
4 weeks after prednisolone ficant cardiomegaly develops
is stopped) 5 mg twice daily and the drug is
withdrawn after 6 weeks when
ESR comes to normal
↓
Begin aspirin in final week of
prednisolone and continued for
6-8 weeks
C. Drugs for chorea
a. Haloperidol 0.25 mg three times a day
or
Phenobarb 60 mg twice or thrice daily
or
Diazepam 5 mg three times a day
or
Chlorpromazine 0.5 mg/kg per dose orally every 6 hours for 4-6 weeks (Thorazine)
b. Penicillin prophylaxis
D. Drugs for CCF
Digitalis, diuretic, sodium restriction, oxygen, steroid.

PREVENTION
Primary Prevention
Appropriate treatment of streptococcal sore throat.

Secondary Prevention
Penicillin is the treatment of choice.
a. Benzathine penicillin : IM 0.6 mega units every three weeks for children
: IM 1.2 mega units every 3 weeks for adult
b. Phenoxymethyl penicillin: : Orally 250 mg/day for children
: Orally 250 mg twice daily for adults
c. Erythromycin (Penicillin allergy) : 250 mg 4 times a day
 Heart
47
Infective Endocarditis

Infective endocarditis results from bacterial infection but infection due to fungi and chlamydia are not
rare infection. It involves abnormal valves, prosthetic valves and congenital defects in heart.

GENERAL PRINCIPLES OF TREATMENT

1. Confirm microbiological diagnosis by culture and sensitivity.
2. Empiric antibiotics should be started in acute cases before the result of culture is known.
3. An attempt should be made to find out the source of infection, such as dental, urogenital and other
infections of the body.
4. Bacteriocidal drugs should be used and not bacteriostatic drugs.
5. The duration of antibiotic therapy should be at least for 4-6 weeks and longer in case of fungal
infection.

MEDICAL THERAPY
Empiric Therapy
When the causative organism is not known, the choice of empiric therapy depends upon whether the
patient has acute or subacute endocarditis:
A. For acute bacterial endocarditis:
Ampicillin 2 gm IV every 4 hours
+
Gentamicin 1.5 mg/kg/IV every 8 hours
+
Nafcillin 2 gm IV every 4 hours
B. For subacute bacterial endocarditis:
Ampicillin 2 gm IV every 4 hours
+
Gentamicin 1.5 mg per kg IV every 8 hours

ANTIBIOTIC THERAPY
For appropriate antibiotic therapy see Table 47.1 “Antibiotics for Infective Endocarditis”.
PROPHYLAXIS
Infective Endocarditis| 309

Because endocarditis is associated with high mortility, antibiotics are usually prescribed in susceptible
patients during dental procedures and oral or upper respiratory tract or gastrointestinal or genitourinary
surgery known to cause bacteriaemia.

Indications for prophylaxis

High risk patients
Prosthetic heart valves
Aortic valve disease
Mitral insufficiency
Patent ductus arteriosus
Ventricular septal defect
Coarctation of aorta
Marfan’s syndrome
Antibiotic regimens for prevention of infective endocarditis:
For dental procedures and oral
and upper respiratory tract
surgery
For intermediate risk patients
Intermediate risk patients
Mitral valveprolapse
Pure mitral stenosis
Tricuspid valve disease
Pulmonary valve disease
Previous infective endocarditis
Oral Regimens
1. Amoxicillin 3 gm, one hour
prior to procedure and
1.5 gm 6 hour after first dose
2. For penicillin allergic patients:
erythromycin 1gm 2 hour prior
to procedure and 0.5 gm 6 hour
after first dose
or
Clindamycin 300 mg 30
minutes before procedure and
150 mg 6 hour later
Parenteral Regimens
1. For genitourinary and gastro-
intestinal procedures and high
risk patients
Ampicillin 2 gm IV +
Gentamicin IV 1.5 mg/kg
30 minutes before procedure
and followed by one dose 8 hour
later of amoxicillin 1.5 gm
2. For penicillin allergic patients:
Vancomycin IV 1 gm +
Gentamicin IV 1.5 mg/kg
1 hour prior to procedure, both
to be repeated after 8 hours.

Types of Organisms Found in Infective Endocarditis

According to types of valve involvement and precipitating and predisposing factor:
A. Native valve endocarditis:
Dental manipulation
Parenteral drug addicts
Urinary tract procedure
Alcoholics
Genital surgery
a. Strep. viridans in 98% cases
b. If acute endocarditis develops, suspect staphylococcal
infection
Responsible for right sided endocarditis. Suspected infection
Staph. aureus, Pseudomonas and P. cepacia
Enterococci
Gram-negative rods
Pneumococcus
Gram-negative bacteria
310 | Beside Approach to Medical Therapeutics with Diagnostic Clues

B. Prosthetic valve endocarditis:

a. Less than 2 months after surgery:
S. epidermitis 20% cases
S. aureus
Gram-negative rods less than 10%
Enterococci
Fungal less than 1% cases
b. Above 2 months after surgery:
Streptococci 80%
S. aureus 40%
S. epidermitidis 40%
Gram-negative bacilli 20%
Fungal less than 1%
C. Culture negative endocarditis:
Slow growing penicillin sensitive streptococci.
Caxiella
Chlamydia
D. Acute bacterial endocarditis: S. aureus

Surgical Therapy
Modern surgery is the greatest advance in treatment of infective endocarditis since the advent of antibiotics.

Indications of Surgery
1. Aortic or mitral valve incompetence resulting in left ventricular failure
2. Replacement of infected prosthetic valves
3. Repeated major emboli from large vegetations
4. Patients remains septic in spite of antibiotics
5. Closure of PDA
6. Closure of septal defects
7. Excision of coarctation of aorta
8. To relieve asymmetrical septal hypertrophy
9. Cardiac failure if medical treatment fails
10. Fungal prosthetic valve endocarditis
11. Repeated relapses
12. Myocardial abscess
Table 47.1: Antibiotics for infective endocarditis
Organisms Regimens Comments
Streptococcus viridans 1. Penicillin G IV 4 million units Vancomycin may cause ototoxicity, and
Strep. bovis 6 hourly thrombophlebitis
+
Strep. pneumoniae Gentamicin IV 1 mg/kg (Max
80 mg) 8 hourly
contd...
contd...
Infective Endocarditis | 311

Organisms Regimens Comments

2. Penicillin allergic patients:
Ceftriaxone IV 2 gm once daily
3. Penicillin and cephalosporin
allergic patient:
Vancomycin IV 30 mg/kg/day in
2 divided dosages (Max 2 gm/day)

Staph. aureus 1. Nafcillin IV 2gm 4 hourly Produces acute endocarditis, usual on

(additional Gentamicin IV 1 mg/ prosthetic valves.
kg 8 hourly may be given for the Because staph. aureus is penicillinase
first 3-5 days producing organism in endocarditis,
2. For penicillin allergic patients: start with flucloxacillin IV 1 gm
Cefazolin IV 2 gm 8 hourly. 6 hourly + Gentamicin + Penicillin. For
Additional gentamicin 1 mg/kg prosthetic valve: Nafcillin + Rifampin
8 hourly may be given for the first 300 mg 8 hourly + Gentamicin
3-5 days.
3. For penicillin and cephalosporin
allergic:
Vancomycin IV 30 mg/kg/day in
2 divided dosages

Enterococcus faecalis and other peni- 1. Ampicillin IV 2 gm 4 hourly

cillin resistant streptococci +
Gentamicin IV 1 mg/kg (Max
80 mg) 8 hourly
2. For Penicillin allergic patients:
Vancomycin IV 30 kg/day in
2 divided dosages
+
Gentamicin IV 1 mg/kg 8 hourly

Haemophilus 1. Ampicillin IV 2 gm 4 hourly

Actinobacillus +
C. hominis Gentamicin 1 mg/kg 8 hourly
E. cocorrodens 2. For Penicillin allergic patients:
Ceftriaxone 2 gm o.d. IV/IM

Enterobacteriacae Cefotaxime IV 8 gm/day in 4 divided Ampicillin + Gentamicin + Cephalo-

dosages sporin is another approach
or
Imipenem IV 2-4 gm/day in 4 divided
dosages
or
Aztreonam IV 8 gm/day in 4 divided
dosages
contd...
312 |
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Beside Approach to Medical Therapeutics with Diagnostic Clues

Organisms Regimens Comments

+
Gentamicin 5 mg/kg/day in 3 divided
dosages

Pseudomonas aeruginosa Piperacillin IV 8 gm/day in 6 divided Amikacin and colistin are other possible
dosages antibiotics.
or Surgical removal of infected valve is
Ceftazidime IV 6 gm/day in 3 divided often necessary
dosages
or
Imipenem IV 2-4 gm/day in 4 divided
dosages
+
Tobramycin IV 5 mg/kg/day in 3 divided
dosages
or
Aztreonam IV 8 gm/day in 4 divided
dosages
+
Gentamicin IV 5 mg/kg/day in 3 divided
dosages
Amphotericin B IV 1 mg/kg/day

CLINICAL NOTES
Antibiotics in infective endocarditis
1. For pencillinase producing staphylococci: Nafcillin, Flucloxacillin, vancomycin, cephalosporins,
rifampin + gentamicin, clindamycin + cephalosporin
2. For methacillin resistant staphylococci: Vancomycin 1 gm every 12 hour.
3. If metastatic infection is present rifampin is usually added at a dose of 600-1200 mg daily and
continued until abscesses are drained and excised. Rifampin must not be used alone since resistant
organisms quickly emerge.
4. For culture negative endocarditis: Ampicillin or penicillin + Gentamicin.
5. P. aeruginosa: Tobramycin + Carbenicillin.
6. Chlamydia: Tetracycline, doxycycline 200 mg/day. Valve replacement is necessary.
7. Q fever endocarditis: Difficult to eradicate with tetracycline. Cotrimoxazole + rifampin is advisable
but finally surgery is required.
8. Fungal endocarditis:
Dose of amphotericin B (Fungizone):
IV test dose 1 mg over 4 hour
If tolerated give 10 mg dose in 500 ml 5% dextrose over 12 hour
Then 0.25 mg/kg/day.
Increase by 0.25 mg/kg/day to reach 0.5-1 mg/kg/day. Usually 25-50 mg is given in 500 ml 5%
dextrose over 6 hour once daily.
 Add IV hydrocortisone 100 mg + Diphenhydramine 50 mg before each dose. Monitor renal
|
Infective Endocarditis 313

function, blood count platelets.

Flucytosine can be added in a dose of 37.5 mg/kg every 6 hour, then the dose of fungizone should be
reduced to 0.3 mg/kg/day.
 Heart
48
Treatment of Cardiomyopathy

Cardiomyopathy is characterised by myocardial dysfunction of unknown aetiology unlike CAD,

hypertensive heart disease, valvular disease, pericardial disease and congenital heart disease.

TREATMENT
Medical
Types of General Drugs
cardiomyopathy:

Drugs Advantages Disadvantages Remarks

Dilated cardio- Avoid excess exer- Diuretics Decreases preload, hence relieves
myopathy: cise. Walking or systemic and pulmonary venous
bicycling within congestion
patient’s exercise
capacity Vasodilators First line of drug. ACE inhibitors
with hydralazine + Isosorbide
imp- rove effort tolerance and
prolongs life

Digoxin Effective in severe heart failure

but does not prolong life

Beta blocker Act by decreasing myocardial Due to negative iono-

oxygen consumption, harmful tropic effect, consider
effect of catecholamines and imp- them after serious
roves diastolic function. Trials are deliberation
in progress.

Amiodarone Decreases arrhythmias (supraven- Effect on prognosis not

tricular and ventricular tachyar- clear
rhythmias)

Immunosuppres- Steroids, azathioprine, cyclospo-

sive therapy rine improves haemodynamic
symptoms in patients with short
history (less than 6 months) of
contd...
 Treatment of Cardiomyopathy

symptoms and myocardial histology

| 315

showing myocarditis.

Anticoagulants Long-term anticoagulants used in

patients who have had episodes of
embolism or have a thrombus in
cardiac chamber on echocardiogra-
phy.

Alcoholic Stop alcohol. Antiarrhythmic

cardiomyopathy: Reversible at least drugs
in early stage

Hypertrophic Stop excess exer- Beta blockers Avoid hypovolaemia and

cardiomyopathy: cise. 55% are fami- Extensively used. They reduce hypotension. Don’t use
lial, genetic coun- exercise induced tachycardia and digoxin, excessive diure-
selling needed. reduce symptoms like chest pain and tics and vasodilators. Beta
dyspnoea blockers have no effect on
Prophylaxis for long-term prognosis and
infective endocar- do not prevent sudden
ditis needed when cardiac death and does not
HCM associated improve diastolic dysfunc-
with mitral regur- tion.
gitation

Calcium It may produce AV distur-

antagonists Used in patients unresponsive to beta bance and sinus arrest.
blockers. Verapamil improves
exercise tolerance and relieves symp-
toms
Disopyramide Cannot sudden death and
Treat arrhythmias. Can be combi- alter long-term prognosis.
ned with calcium antagonists.
Amiodarone
Drug of choice for supraventricular
and ventricular arrhythmia
Diuretics Avoid excessive use of
Controls pulmonary venous conges- diuretics
tion
Digoxin
Used only to control rapid ventri-
cular rate in auricular fibrillation and
during dilated stage of HCM.
Restrictive Digoxin Not useful in sinus rhythm
cardiomyopathy: Useful in auricular fibrillation
Calcium antago- Role in improving symp-
nists May improve diastolic function toms or long-term course
is controversial.
 Heart
49
Surgical Management of
Coronary Artery Disease

Investigations for Selection of Patients for Surgery

For proper evaluation the following investigations are done to evaluate left ventricular function and
anatomy of coronary blood vessels.
Left ventricular function Anatomy of diseased vessels
A. Radionuclide angiocardiography: It is Coronary arteriography: It demonstrates
non-invasive method of evaluating left reasonable lumen (1-1.5 mm in diameter)
ventricular function including end-systolic and obstructed coronary artery.
and end-diastolic ventricular volume, ejection
fraction, cardiac output, and left ventricular wall
motion. They are assessed both at rest and
during exercise.
B. Thallium scan: It also determines ventricular
function and demonstrates abnormalities of
wall motion.
The above two investigations show the type,
location and extent of myocardial perfusion
abnormalities and point to indication for CABG.
Cardiomegaly, low ejection fraction (below 25%),
an increased left ventricular volume, large arterio-
venous oxygen difference and elevated left ventri-
cular end-diastolic pressure are associated with
increased surgical risk.
C. Exercise electrocardiography:
Many now consider this investigation less reliable
than the above investigations.

Types of Surgery
There are two surgical procedures:
1. CABG (Coronary artery graft)
2. PTCA (Percutaneous transluminal coronary angioplasty)
Indications for Surgery
Surgical Management of Coronary Artery Disease | 317

CABG
1. Left main coronary artery lesions
2. Proximal left anterior descending disease
3. Two vessel disease
4. Two or three vessel disease with positive exercise test for ischaemia
5. Patients with left ventricular dysfunction
6. Chronic stable angina:
• Relieves myocardial ischaemia
• Improves long-term survival in:
a. Left main coronary artery disease
b. Three vessel disease
c. Proximal left anterior descending disease (Part of two vessel disease)
d. Positive exercise test for ischaemia in two or three vessel disease
• Left ventricular dysfunction due to myocardial ischaemia
7. Unstable angina:
• If anginal pain is not rapidly controlled with IV nitroglycerine, nifedipine, CABG is performed.
Operative mortality is less than 4%.
8. Acute myocardial infarction:
• AMI developing acquired ventricular septal defect
• Intractable cardiac failure

PTCA
• Chronic myocardial ischaemia in angina.
• Acute myocardial infarction: CABG is done especially in association with the intracoronary
administration of thrombolytic agents.
• Patients with early symptoms, single vessel disease, short segment stenosis and favourable anatomy of
coronary artery disease.
• Recently it is tried in severe disease and multiple lesions with good results.

PROBLEMS OF PTCA
Problems Methods for preventing restenosis and abrupt vessel closure
A. Abrupt vessel closure
B. Restenosis

Rotablation atherec- Stent Newer antiplatelet Other drugs Genetic therapy

tomy laser ablation drugs
Remarks: Acts as scaffold i.
a. Periprocedural i. Plane stent: More
complications abrupt vessel clo-
b. Higher rates of ste- sure and restenosis ii.
nosis ii. Heparin coated iii.
Aspirin: A week i. Paclitaxel: An Introduction of DNA or
platelet antago- immunosuppres- RNA within appro-
nist sive drug priate cell alters pattern
Ticlopidine ii. Rifamycin: An of expression of gene
Clopidogrel antitumour drug and exerts therapeutic
effect.
contd...
318 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Methods for preventing restenosis and abrupt vessel closure

Rotablation atherec- Stent Newer antiplatelet Other drugs Genetic therapy

tomy laser ablation drugs
c. Higher cost stent: 16% reduc- iv. Platelet glyco- iii. Low molecular
Done in 80s and tion in restenosis
early 90s iii. Genetic material
coated stent:
More promising
protein receptor weight heparin
blockers: Glyco-
protein II b/III a
receptors found
on platelets agg-
regate platelets.
Drugs abcixi-
mab, eptifiba-
tide, tirofiban and
lamifiban selec-
tively block these
receptors. They
are most powerful
agents in preven-
ting restenosis
and abrupt vessel
closure after angi-
oplasty. They are
also useful in
unstable angina
and AMI.
 Heart
50
Cor Pulmonale

Cor pulmonale is a cardiac disorder caused by an underlying pulmonary disease characterised by

pulmonary hypertension causing right ventricular dilatation and hypertrophy and right heart failure.

Clinical Diagnosis
A. Compensated cor pulmonale: Characterised by tachycardia and cardiomegaly—Dilatation and/or
hypertrophy.
B. Uncompensated cor pulmonale: Tachycardia, cardiomegaly and CCF (Jugular vein distension +
hepatomegaly + ankle oedema + oedema + ascites).

Roentgenographic Diagnosis
Both PA and lateral chest X-ray is needed.
Evidence of right ventricular enlargement:
i. Anterior enlargement obliterates retrosternal space in the lateral projection. Left lower border of
heart has a characteristic rounded border and apex is elevated.
ii. Indirect evidence of RV enlargement: Enlargement of main pulmonary outflow tract.

Electrocardiographic Diagnosis
i. Acute cor pulmonale due to acute pulmonary embolism: (a) A new S1-Q3-T3 pattern, (b) A new
incomplete or complete right bundle branch block.
ii. Chronic cor pulmonale: (a) An S1-Q3 pattern, (b) Right axis deviation, (c) An S1-S2-S3 pattern,
(d) R/S ratio in V6 of 1.0 or less.

Causes
I. Acute cor pulmonale:
• Massive pulmonary embolism
• Acute exacerbation of chronic cor pulmonale
II. Chronic cor pulmonale:
1. Obstructive lung disease: COPD, cystic fibrosis.
2. Restrictive lung disease: Idiopathic pulmonary fibrosis, sarcoidosis, scleroderma, tuberculosis,
alveolar proteinosis.
3. Vascular disease: Multiple recurrent thromboemboli, schistosomiasis, sickle cell anaemia, primary
pulmonary hypertension.
320 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

4. Chest wall deformities: Kyphoscoliosis, thoracoplasty.

5. Neuromuscular diseases: Poliomyelitis, myasthenia gravis.

Prevention
A. Management of predisposing factors:
a. Avoidance of dusty atmosphere
b. Avoidance of smoking
B. Measures for delaying development of serious emphysema and cor pulmonale:
a. Vigorous preventive and symptomatic treatment of asthma and bronchitis
b. Early treatment of infection, pneumonia
c. Obesity present, should be corrected
d. Treatment of other decompensating factors associated with cor pulmonale:
• Pneumonia
• Pneumothorax
• Pulmonary emboli
• Pleural effusion
• Chest wall injury
• Drug sedation
• Primary metabolic acidosis
• Electrolyte abnormalities: Low PO4, low K+, low Mg2+
• Poor nutrition

Treatment of CCF
I. Correction of hypoxaemia: Administration of oxygen:
A. Acute administration:
Method of administration Advantages Disadvantages
a. Intermittent O2 via Venturi Essential May not work in severe
mask Reduces life-threatening respiratory depression and
hypoxia while maintaining respiratory failure
hypoxic respiratory drive
b. Intermittent positive pressure Indicated in severe respiratory
breathing with a respirator depression and failure
c. Nebuliser
B. Chronic administration: Long-term oxygen therapy at home in chronic cor pulmonale can
considerably enhance the quality-of-life as well as prolong life by several years.
II. Correction of fluid retention
a. Diuretic: Frusemide is preferred diuretic. Add potassium salt
b. Low sodium diet
III. Treatment of pulmonary hypertension:
a. Oxygen reduces vasoconstrictive pulmonary hypertension.
b. Vasoactive drugs: They cause pulmonary vasodilation.
 Hydralazine
Cor Pulmonale | 321

Diazoxide
Verapamil
Nifedipine
Prostaglandin E1
Nitroglycerine
Terbutaline
c. Venesection: A role of venesection has been demonstrated only in patients with haematocrit
above 55%.
d. Theophylline IV lowers pulmonary and systemic vascular resistance.
IV. Treatment of infection: Antibiotics of choice: Bactrim, amoxicillin, doxycycline, ciprofloxacin.
V. Management of specific treatable causes: See other decompensating factors associated with cor
pulmonale.
V. Controversial treatment:
a. Treatment of CO2 retention by carbonic anhydrase inhibitor. They enhance renal excretion of
bicarbonate and thus reduces CO2 retention.
b. Phlebotomy: See above.
c. Digoxin: Digoxin is only indicated if associated left ventricular failure is present. Digoxin
toxicity is very common in hypoxic patient and respiratory acidotic patients of cor pulmonale.
 Heart
51
Pericarditis

AETIOLOGY
I. Acute pericarditis: Dry and effusive:
A. Dry:
• Idiopathic
• Rheumatic pericarditis
• Infective:
– Viral: Coxsackie, mumps, echo, influenza, polio
– Bacterial: Tuberculosis or pyogenic
– Fungal
– Parasitic: Echinococcus, amoebiasis, filariasis
• Metabolic: Uraemia
• Collagen disorders: Systemic lupus erythematosus
• Postmyocardial infarction
• Neoplasm of pericardium
B. Effusive: Commonest cause: Tuberculous. Other causes: Coxsackie, echo, Staph., parasites,
protozoa, neoplasm, end-stage uraemia, AMI
II. Chronic: Chronic constrictive pericarditis:
• Tuberculosis (50% cases) Neoplasm
• Bacterial: Pneumococcal, Staph. Trauma
• Neoplasm Radiation
• Idiopathic

Diagnosis
See Table 51.1: “Diagnosis of Pericarditis”
I. Acute pericarditis
Table 51.1: Diagnosis of pericarditis

Classical Benign Rheumatic Tuberculous Purulent Uraemic Postinfarct

Viral
Clinical diagnosis:
A. Symptoms:
Fever, body ache, Acute rheumatic Started with TB High fever, toxic Seen in terminal Seen in first
central chest fever, carditis, symptoms, later uraemia week or 3rd week
contd...
contd...
Pericarditis | 323

Classical benign Rheumatic Tuberculous Purulent Uraemic Postinfarct

viral

pain aggravated joint pain cardiac (Dressler’s

inspiration, cou- symptoms (chest syndrome) of
ghing, sneezing pain, dyspnoea) acute myocardial
dyspnoea infarction
B. Signs:
Pericardial friction Usually dry Pericardial effu- Pericardial rub.
rub. Dry pericar- sion: Symptoms Cardiac tampo-
ditis like dry type but nade. See “Tuber-
Pericardial effu- dyspnoea more, culous”
sion: Enlargement relieved by sitting
of heart detected up and leaning for-
by palpation and ward
percussion, muf- Cardiac tampo-
fled heart sound nade:
shifting dulness Ta c h y c a r d i a ,
dyspnoea, pulsus
paradoxus, fall in
BP, JVP raised,
heart sound dis-
tant, audible 3rd
ECG diagnosis: heart sound
S-T elevation with
concavity up-
wards
X-ray diagnosis:
Pericardial effu-
sion: Heart size
enlarged. Cardiac
pulsation reduced
Echo diagnosis:
Pericardial effu-
sion: Seen as echo
free space behind
left ventricular
posterior echoes

Laboratory diagnosis: Blood count, erythrocyte sedimentation rate, blood chemistry (e.g. blood urea)
and other investigations point to specific causes.
Diagnostic pericardiocentesis: Used for pericardial effusion, aspirated fluid should be sent for microscopy,
chemical and microbiological and other required tests.
Viral studies: Positive culture, rise in neutralising antibody titre.
Other investigations: Pericardial biopsy, radio-isotope scanning.
II. Chronic constrictive pericarditis
Ascites, oedema feet, loss of weight, enlarged liver
Fast low volume pulse, pulsus paradoxus
Raised JVP with rapid Y descent. JVP increasing during inspiration (Paradoxical)
324 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Pericardial knock of auscultation

ECG: Low voltage QRS, flattened or inverted T wave
X-ray chest: Normal sized heart, cardiac pulsation diminished or absent, pericardial calcification
aetiology.

Treatment of Pericarditis
A. Treatment of causes:
Tuberculosis: Anti-tuberculous drug
Acute rheumatic fever: Aspirin, steroids
Purulent pericarditis: Antibiotics
Uraemia: Frequent dialysis, steroid
B. Supportive treatment for symptoms:
Acute: Analgesics: Aspirin for acute rheumatic fever
Chronic: Chronic constrictive pericarditis: Diuretic and salt restriction to relieve venous congestion.
C. Drugs:
a. Analgesics: Aspirin and indomethacin for Dressler’s syndrome.
b. Steroid: Indicated in severe pain, resistant effusion, severe symptoms in Dressler’s syndrome
and recurrent pericarditis.
D. Pericardocentesis:
Premedication Site Precaution Colour of fluid
Sedative, atropine Epigastrium preferred: i. If blood comes, needle a. Purulent: Drained
Local anaesthesia Needle introduced withdrawn and reposi- through indwelling tube
between xiphisternum tioned connected to under water
and left costal arch ii. Preferably done seal
Under image intensifier b. Straw coloured or hae-
iii. Resuscitative facilities morrhagic with predomi-
should be available nant lymphocytes sugg-
ests tuberculous, ask for
culture
E. Surgical treatment:
1. Pericardiactomy in purulent pericarditis if no response to antibiotics.
2. Chronic constrictive pericarditis: Pericardial resection. Result satisfactory.
F. Steps in the management of pericardial tamponade:
• A preliminary infusion of normal saline or colloid for raising filling pressure and increasing
cardiac output without provocating pulmonary oedema. Resuscitative measures and ECG should
be available.
• Subxiphoid area anaesthetized and needle inserted just to the left of midline and directed cranially
and little to the left.
• Fluid aspirated through a large needle.
• After acute emergency is over, open biopsy through a limited thoracotomy is needed to know
the cause by histological biopsy.
 Heart
52
Shock

Due to failure of circulation to maintain cellular perfusion and function results in shock.

Types of Shock
Hypovolaemic Cardiogenic Vasodilation Obstructive Miscellaneous
shock shock shock shock
Causes: i. Excessive blood (Pump failure) Septic shock, Pericardial tam- Hepatic failure,
loss: Trauma, ble- AMI, arrhythmia, neurogenic shock, ponade, constric- thyroid storm,
eding peptic ulcer, myocardial rup- anaphylactic tive pericarditis, myxoedema
ruptured ectopic ture, myocardial shock, drugs such massive pulmo- coma, adrenal
pregnancy and depression by as nitrates, cal- nary embolism. insufficiency,
aortic aneurysm. drugs, acidosis, cium antagonists, cyanide carbon
ii. Excess fluid loss: anoxia, tension ganglion bloc- monoxide poiso-
Vomiting, diarr- pneumothorax). kers. ning.
hoea, burns, dia-
betes, excess diu-
retics, peritonitis,
pancreatitis, intes-
tinal obstruction.

MANAGEMENT
Clinical, haemodynamic Management
and biochemical disturbances
1. Pain and anxiety a. Morphine sulphate IV in small repeated dosages
of 2-5 mg. If side effects (such as hypotension,
cold skin, bradycardia, nausea, vomiting) atropine
may provide some relief.
b. Meperidine 50-100 mg IV
c. Put in horizontal position with legs slightly elevated
2. Underlying causes
A. Hypovolaemia suggested by oliguria Hydrate with volume expanding agents
326 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Crystalloids Colloids
Isotonic normal saline Blood, plasma, human albu-
and Ringer’s lactate. Do min, dextran 40, dextran 70.
not increase pulmonary They are expensive but
vascular pressure, no stays longer than crystalloid
anaphylaxis, less expen- in circulation. Dextran 40
sive than colloids and stays for a few hours for up
effective to 24 hours. Dextran 40 may
cause acute renal failure but
not dextran 70. If dextran
given above 1 litre may
cause bleeding disorders.

If oliguria persists after adequate hydration

Dopamine drip 2.5 mcg/min

+
IV Frusemide 100-200 mg
B. Cardiogenic shock See Chapter on AMI. Treat arrhythmias
C. Septic shock Pending culture reports empiric antibiotic therapy
stated: Penicillin, cloxacillin, third generation
cephalosporin + gentamicin, tobramycin or amikacin
to cover both gram positive and negative organisms
Metronidazole used for anaerobes.
D. Anaphylactic shock Adrenaline, steroid
E. Pericardial tamponade, constrictive Treat them appropriately.
pericarditis, massive pulmonary
embolism, myxoedema coma,
adrenal insufficiency
3. Hypoxia O2 inhalation methods:
i. Low flow systems: By nasal prongs, simple
face mask
ii. High flow system: By Venturi mask
If inhalation method fails:
The following methods are employed:
i. Endotracheal intubation
ii. Positive pressure ventilation
Arterial O2 saturation should be maintained around 90%
or higher.
4. Acidosis Acidosis depresses myocardium. If arterial pH is less
7.3 and respiratory acidosis is excluded:
i. Give 1 amp of sodium bicarbonate IV (50 mEq
per 50 ml).
 Shock |
ii. If arterial pH is less than 7.2, give 2 amp and
327

repeated in 15-30 minutes. Excess NaHCO3 may

produce pulmonary oedema. Arrange for serial
assessment of arterial blood gases.
5. Arrhythmia Arrhythmias may reduce cardiac output.
i. Sustained ventricular tachycardia: IV lidocaine in
a bolus of 1.5 to 2 mg/kg. If associated hypotension
or haemodynamic deterioration, synchronised
electrical countershock given.
ii. Ventricular fibrillation: Give immediately counter-
shock. If the first or second shock is unsuccessful,
patient must receive closed chest massage, mouth
to mouth respiration, and possibly IV sodium
bicarbonate before again attempting electrocardio-
version.
If fails to respond, Bretylium tosylate given in a bolus
dose of 5 mg/kg IV
6. Hypotension See Table 52.1 “Vasopressors used in Shock”
7. Hypokalaemia Treat properly
8. Management based on central venous Measured by Swan-Gauze balloon tipped catheter and
pressure measurement: at bedside by noting degree of distension of external
jugular vein

Ext. jugular vein distended External jugular vein collapsed. CVP low less than
CVP high above + 1 cm 3 cm
↓
Give dopamine, sodibicarb and oxygen Haematocrit and Haematocrit or Hb high
Hb normal or low
Suggest

Suggest haemorrhage. Fluid loss Renal loss

Give blood. IV ceme- from GI tract
tidine if PU bleed
Treat vomiting
diarrhoea. Give
fluid
Suggests
diabetic
ketoacido-
sis, polyuric
renal failure

Give fluid
328 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

9. Vasodilators: Indications:
Acutely failing heart following
AMI without shock and with elevated left
ventricular end diastolic pressure or capillary wedge
pressure over 20 to 25 mmHg.
Action: Reduces preload and after load and thus
decreases myocardial oxygen demand. It also dilate
microcirculation and improves tissue perfusion.
Contraindication: Hypotension or patients with
fixed obstruction to cardiac flow like critical aortic
stenosis. Under these circumstances both dopamine
+ vasodilator combined should be used.

10. Steroid Indication:

30 mg/kg of methylprednisolone in patients with
septicaemia and hypotension and acute adrenal
crisis. It is unwise to use in cardiogenic shock.

11. Mechanical and artificial cardiopulmonary Under special circumstances the following devices
assistance: are used:
– Intra-aortic balloon pump
– Right ventricular assist
– Left ventricular assist

12. Nutritional support: As soon as possible the patient should receive

nutritional support via the enteral or parenteral
routes.
Table 52.1: Vasopressors used in shock
Dose IV Action on Action on Action on beta Cardiac output Comments
beta 1 receptor alpha receptor 2 receptor
cardiac stimu- vasoconstriction vasodilation
lation
Dobutamine 2.5-15 micro- ++++ + ++ Increased As compared to dopa-
gram per kg/min mine lowers pulmonary
wedge pressure more, less
arrhythmia. In AMI with
low cardiac output but no
significant hypotension
dobutamine preferred over
dopamine for increasing
cardiac output.

Dopamine 20-2000 micro- ++ ++ ++ Elevated Effect depends on dose:

gram/min a. Low-dose (3 micro-
gram per kg/min

contd...
contd...
Shock | 329

Dose IV Action on Action on Action on Cardiac Comments

beta 1 receptor alpha receptor beta 2 receptor output
cardiac stimu- vasoconstric- vasodilation
lation tion

vasodilate renal, cor-

onary, cerebral and
mesenteric vessels
through beta 2
b. 3-10 mcg/kg/min inc-
reases myocardial con-
traction and cardiac
output
c. Above 20 mcg/kg/min
vasoconstricts through
alpha receptor and
divert blood from limbs
towards kidney, heart,
brain and gut. Produces
ventricular arrhythmias,
nausea and vomiting.

Levarterenol 2-8 mcg/min ++ ++++ 0 Slightly decrea-

(Levofed) sed
Specific therapy in ana-
Epinephrine 0.1-0.25 mg ++++ ++++ ++++ Elevated phylactic shock. Produ- ces
(Adrenalin) palpitation, angina and
arrhythmia.

Not indicated in cardio-

Isoproterenol genic shock or septic
shock due to arrhythmo-
genic property and myo-
cardial O2 demand except
in atropine resistant, hae-
modynamically compro-
mised high grade AV block
until temporary pacemaker
is inserted.

May be considered as
Amrinone alternative to dobutamine
or dopamine in severe
cardiogenic low output
syndrome. May be com-
bined with dopamine or
dobutamine if one agent
alone fails.
 Heart
53
Cardiac Arrest

CAUSES
Cardiac Causes
1. Acute myocardial infarction 2. Extensive ischaemic heart disease
3. Left ventricular outflow obstruction 4. Cardiomyopathy
e.g. aortic stenosis 6. Mitral valve prolapse
5. Chronic valvular disease 7. Wolff-Parkinson-White syndrome
8. Advanced atrio-ventricular conduction block 9. Hereditary prolonged QT interval
10. Ruptured cardiac aneurysm 11. Overdose of cardiac glycosides

Non-Cardiac Causes
1. Cerebral haemorrhage 2. Subarachnoid haemorrhage
3. Massive pulmonary embolus 4. Dissecting aortic aneurysm
5. Ruptured aortic aneurysm

Potentially Reversible Causes

1. Hypoxia and hypoxaemia 2. Hyper and hypokalaemia
3. Other metabolic disorders 4. Hypothermia
5. Tension pneumothorax 6. Tamponade
7. Toxic and therapeutic disturbances 8. Thromboembolic/Mechanical obstruction

DIAGNOSIS
Signs: Sudden collapse
Absent heart beats
Absent pulsations in carotid, femoral and brachial arteries
Pallor
Cyanosis
Gasping respiration followed by total arrest of respiration
Dilated pupil
Electrocardiogram: Ventricular fibrillation/ventricular tachycardia
Asystole
Pulseless electrical activity (PEA)—ECG shows organised cardiac rhythm but
pulses absent
MANAGEMENT
Cardiac Arrest| 331

I. Basic Cardiac Life Support (BCLS)

Aim is to provide oxygen to brain and heart by ventilation and external cardiac massage until advanced
cardiac life support (ACLS) arrives to restore cardiac and respiratory function. These steps are airway,
breathing and circulation (ABC):

Airway
a. Put him on a firm flat surface in a supine position.
b. Open the mouth and wipe out vomitus and debris.
c. Don’t remove dentures. Dentures facilitate a good mouth-mouth seal.
d. Head tilting: The palm of one hand is placed on the patients’ forehead and firm pressure is applied
to tilt the head backward. At the same time, the index and middle fingers of the other hand are
placed under the chin to support it. This will also raise the tongue away from the chin and thus
remove the obstruction to airway.

Breathing
Make a tight seal over the patient’s mouth and start ventilation with 2 full breaths (mouth-to-mouth).
Thereafter, a breath should be delivered once every 5 seconds in adult, each lasting 1-5 seconds.

Circulation
Combined external cardiac massage or compression: If pulse is not palpable even after 2 breaths of
artificial ventilation, start external cardiac compression:
Kneel down on a firm surface at the side of the victim. The heel of one hand is placed parallel to and
over the lower half of the sternum. The other hand is placed on top of this hand and the fingers are
interlocked. Your shoulders are directly above. The sternum is compressed 4-5 cm, pushing straight
down towards the spine. The compression rate is 80-100 per minute. Periodically palpate the carotid
pulse. Two breaths are given after every 15th beat of cardiac compression.

II. Advanced Cardiac Life Support

1. Restoration of respiration: Ventilate by adjunctive equipments:
a. Oro-pharyngeal airway
b. Endotracheal intubation
c. Bag-valve devices
2. Restoration of circulation: Chest compression, either automatic or manual
3. Restoration of cardiac rhythm: ECG shows ventricular fibrillation/ventricular tachycardia:
First a single blow to precordium with the side of a clenched fist.
Defibrillate: Direct current counter-shock should be given as rapidly as possible:
First shock with 200 joules
↓
If not effective: Second shock with 200-300 joules
↓
If not effective: Third shock with 360 joules
332 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

↓
Next, assess the cardiac rhythm on ECG monitor. It shows 4 possible outcomes

Persistent ventricular Asystole Pulseless elec- Restoration of

fibrillation trical activity normal circulation
(PEA)
Continue CPR i. Continue Treat common
Intubate at once if not done already. CPR causes:
Obtain IV access ii. Intubation i. Severe hypo-
↓ iii. Adrenaline volaemia
Adrenaline 1 mg IV— after 30- iv. Atropine ii. Cardiac tamponade
60 seconds repeat a 360 J shock. If fails: iii. Tension pneumo-
Repeat adrenaline followed by DC Emergency thorax
shock every 3-5 minutes until pulse cardiac iv. Massive pulmonary
is established pacing embolism
↓
If unsuccessful, give lignocaine 1 mg
per kg as an IV bolus and defibrillate
again with 360 J
↓
If still unsuccessful, give bretyllium
5 mg/kg as an IV bolus and defibril-
late again with 360 J
+
Also give IV sodium bicarbonate
1 mEq/kg. Repeat every 10 minutes
↓
If still unsuccessful:
i. Procainamide 30 mg/min (Max.
17 mg/kg)
ii. Internal cardiac defibrillation
iii. Try magnesium sulphate
1-2 gm IV

III. Aftercare
1. If cardiac arrest is due to VT/Vent. fibrillation, give prophylactic anti-arrhythmic drugs, e.g.
amidarone, norpace.
2. If asystole, arrange for temporary pacemaker.
3. If consciousness impaired: Dexamethasone + frusemide to relieve cerebral oedema.
4. Treat acid-base and electrolyte disturbances.

IV. Termination of CPR

If inspite of the above measures patient may not regain normal circulation, persistent deep
unconsciousness, absence of respiration reflexes and absent pupillary reaction point to cerebral death
and CPR should be terminated.
 Table 53.1: Drugs used in ACLS
Cardiac Arrest | 333

Drugs Preparations Dosages Complications Comments

I. Essential drugs
Adrenaline Amp.1 ml (1 mg in 0.5 mg IV, repeated at Do not combine with
1:1000 dilution 5 min intervals sod. bicarb in IV drip

Atropine 1 mg/ml 0.5 mg IV, repeated at VT/VF Increased myocardial

5 min intervals (Max O2 consumption from
2 mg) tachycardia used in
severe symptomatic
bradycardia

Lidocaine 5 ml (50 mg/ml) Initial bolus 50-100 Myocardial depres- First line drug in VT
5 ml (100 mg/ml) mg IV, may be sion, CNS depression-
repeated 3-5 min upto seizure
300 mg. Continuous
infusion 20-5 mcg/kg/
min

Morphine 1 ml amp (8 mg/ml) 3-4.5 mg IV Respiratory depres- For analgesia, appre-

II. Useful drugs sion, hypotension hension

Levarterenol 4 ml amp (8 mg) Titrate IV infusion to Excessive vasocons- Be sure that hypoten-
(Levophed) keep systolic pres- triction; ischaemic sion is due to inade-
sure about 90 mmHg necrosis at site of quate peripheral vaso-
extravasation constriction and not
due to hypovolaemia

Isoproterenol Vial 1 mg in 500 ml 2-20 mcg/min. Increased myocardial Severe bradycardia

Titrated to blood pres- O2 consumption
sure and heart rate
response

Propranolol Vial 1 ml (1 mg) 1 mg IV over 1-2 min. Prevents recurrent VT

May be repeated at 5 and arrhythmia due to
min intervals up to 3- digoxin toxicity
5 mg
III. Additional useful
drugs
Dopamine See Chapter on Arrhy-
thmias
Frusemide See Chapter on Heart
Failure
Sodium bicarbonate 1 mEq/kg IV followed Should be used in
by 0.5 mEq/kg every 10 acidosis or hyper-
min till acidosis is cor- kalaemia
rected

contd...
334 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Preparations Dosages Complications Comments

Calcium chloride IV bolus of 2-4 mg Use in hyperkalaemia,
per kg as a 10% hypocalcaemia or cal-
solution cium antagonist over-
dose
Vial 10 ml (1000 mg)
Procainamide 0.2 to 1 gm IV at the Monitor ECG for QRS
rate of 25-50 mg per widening and
See the text minute prolongation of P-R
Bretyllium and QT intervals
 Heart
54
Treatment of Syncope

Aim is to treat the causes, precipitating factors and associated phenomena. See the Table 54.1: “Causes,
diagnosis and management of syncope”:
Table 54.1: Causes, diagnosis and management of syncope
Causes Diagnosis Management Prevention
Vasovagal syncope i. Precipitating factors: i. Put in horizontal
Overcrowding in a hot position
room, needle prick, ii. Loosen tight clothing
surgical manipulation, and collar
severe injury, sudden iii. Sprinkle water on face
blood loss, stress,
hunger, fatigue
ii. Age: Young patient
usually due to con-
genital heart disease
and tachyarrhythmias
iii. Clinical features:
Bradycardia, hypoten-
sion

Carotid sinus hypersensi- i. Precipitating factors: Result of head-up tilt test: 1. If head-up-tilt test nega-
tivity: Turning of neck, direct a. Positive: Beta blockers, tive:
pressure on carotid disopyramide and ephe- a. Reassure
sinus during shaving, drine may help. b. Avoid tight collar
tight collar and bending b. Negative: No cardiac c. Avoid sudden neck
neck backwards anatomical lesion movement
ii. Association: Elderly found: See prevention. 2. Frequent symptoms
diabetes, hypertension, associated with severe
atherosclerosis, carotid bradycardia need per-
sinus tumour. manent pacing
iii. Investigations:
a. ECG
b. Extended Holter
monitoring
c. Carotid sinus pres-
sure:
Patient supine—
contd...
336 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Causes Diagnosis Management Prevention

gentle pressure on
one carotid for no
more than 20 seco-
nds—Record ECG
and BP: 50 mmHg
fall of systolic pres-
sure or asystole of
3 second or more
indicates abnormal
response. Be ready
with atropine,
dopamine and for
cardio-pulmonary
resuscitation.
d. Head-up-tilt test:
Preceeded by over-
night fast with
intravenous hydra-
tion—Record
ECG, BP and heart
rate and table is
tilted upto an angle
of 60-80 degree for
20-60 minutes
while recording BP
every 2 minutes
and a continuous
ECG. Bradycardia
or hypotension
indicates positive
test.

Causes: CAD,
Cardiac syncope: aortic stenosis,
cardiomyopathies,
conduction defects,
brady and tachy-
arrhythmias, car-
diac tumour, ped-
unculated left atrial
myxoma.
See also Chapter:
on “Cardiac
Arrest”
 Alimentary System
55
Gastro-oesophageal Reflux Disease

DIAGNOSTIC CLUES
Major features: Other symptoms: Complictaions:
Heart burn Chest pain Non-seasonal nocturnal asthma
Regurgitation Waterbrash Dysphagia (often signs of peptic ulcer or oesophageal cancer)
Chronic blood loss
Barret’s oesophagus (columnar lined oesophagus—
A precancerous condition)
⇓
Investigations to confirm the diagnosis:
a. Ambulatory pH monitoring
b. Barium meal showing complications of GOR such as stricture, ulcer
c. Endoscopy shows reflux changes

Management
Stepwise Approach:
Step 1 : a. Life style modification. See Table 55.1.
b. Antacids: Aluminium hydroxide, magnesium hydroxide and alginic acid
↓
If fails:
Step 2 : H2 receptor blockers (cemetidine, famotidine, ranitidine, roxatidine) with or without
prokinetic drugs (cisapride, domperidone, metoclopramide or mosapride citrate)
See Table 55.2.
↓
If fails:
Step 3 : Proton pump inhibitors (omeprazole, lansoprazole or pantoprazole). See: Drugs for
GER Or high dose H2 receptor blockers
↓
If fails:
Step 4 : Surgery.
338 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Table 55.1: Life style modification

Facts facilitating GER Management
a. Incompetent lower oesophageal sphincter i. Avoidance of prolonged Ryle’s tube intubation
ii. Avoid fatty food
iii. Elevate head of bed by 6-8 inches (important)
iv. Stop excess of caffeine
b. Raised intra-abdominal pressure Avoid lifting heavy weight
c. Impairment of oesophageal mucosal function Stop alcohol and smoking
d. Increased gastric content Avoid large meals. Avoid food and fluid for at
least 3 hours before bedtime.

Table 55.2: Drugs for GER

Preparations Dose Remarks
A. H2 receptor blockers:
Cemetidine Cemetidine (Cadila) 400 mg b.i.d. or 800 mg/day i. Exclude malignancy,
Cemetiget 200, 400 mg tab at bedtime for 4-8 weeks pregnancy, lactation
followed by 400 mg/day at ii. Side-effects: Diarrhoea,
bed time dizziness, headache

Famotidine Facid (Intas) 40 mg at bedtime or 20-40 mg — Do —

Topcid (Torren) b.i.d. for 6-12 weeks—
Famocid (Sun) maintenance dose 20 mg at
20 mg, 40 mg tab bedtime

Roxatidine Rotane (Hoest) 75 mg at bedtime or 75 mg — Do —

75 mg, 150 mg tab b.i.d.

Ranitidine Acelock (Cadila) 150 mg b.i.d. or 300 mg per — Do —

150 mg, 300 mg tab day for 4-8 weeks

B. Proton pump inhibitors:

Omeprazole Omez (Dr. Reddy) 20 mg/day for 4-8 weeks, if
Omizac (Torrent) symptoms persist, increase to
10 mg, 20 mg tab 40 mg/day for 8 weeks—
maintenance dose 20 mg/day

30 mg/day in morning, main-

Lansoprazole LAN (Intas) tenance dose 15 mg/day. In
Lanzap (Dr. Reddy) 15 mg, refractory cases 60 mg/day for
30 mg tab 8-12 weeks

Pantoprazole Pantoced (Sun) 40 mg/day for 4-8 weeks — Do —

Pantodac (Alidac) 40 mg

Rabeprazole Zenprazole 20 mg (Emcure) 10 mg t.i.d. before meals

Veloz 20 mg (Torrent)
contd...
contd...
Gastro-oesophageal Reflux Disease | 339

Preparations Dose Remarks

C. Prokinetics:
Cisapride Cisapro (Cadila) 10-20 mg every 4-8 hour Polonged Q-T interval,
Ciza (Intas) 10 mg tab 15-30 minutes before food arrhythmias
Domperidone Domstal (Torrent) with last dose at bedtime
Domperon (Alidac)
10 mg tab

Metoclopramide Perinorm (Ipca) 5-10 mg twice or q.d.s.

Reglan (CFL) 10 mg

Mosapride citrate Mosid (Torrent) t.d.s.

Moza (Intas)
Musapro (Emcure) 2.5 mg,
5 mg tab
D. Antacids specially
alginic
acid combination

E. Sucralfate

Motor Disorders of Oesophagus

Achalasia:
Due to obstruction of the lower end of oesophagus by a sphincter that will not relax.
Therapy to relieve the obstruction:
A. Medical therapy:
i. Isosorbide dinitrate
ii. Long acting nitrate
iii. Nifedipine
B. Dilatation therapy:
i. Dilatation with a large Hurst bougie: Gives temporary relief. A few patient gets prolonged relief
with weekly self dilation.
ii. Pneumatic bag dilatation under radiographic control by an expert because 5-15% risk of
perforation even in good hands. It is much more effective.
C. Surgery:
Indications:
a. If bag dilatation fails
b. Patient does not wish to be exposed to risk of perforation.
Type of surgery: Direct section of lower oesophageal sphincter muscle (myotomy) with sparing of
some gastric muscle fibres to prevent postoperative reflux (Hellar procedure).

Oesophageal Spasm
Treatment is unsatisfactory. Nitroglycerine or anticholinergic administration is disappointing. Occasionally
calcium channel blocker may help.
340 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Other Oesophageal Disorders

Rings and webs Diverticula Infection

Mechanical disruption If big, diverticulectomy Viral infection Fungal infection

with dilator or endoscope or diverticuloplexy requi- Herpes: Associated with imm-
red Acyclovir 250 mg/m2 IV, uno-deficient disorders
after improvement, orally (diabetes, chronic renal
200-400 mg 5 times/day failure and AIDS) and
Varicella zoster: Acyclo- patients taking steroids
vir and immuno-suppressive
Cytomegalo virus: Gan- drugs.
ciclovir a. Mild cases: 10-20
ml of oral nystatin
(100000/ml) 6 hrly
or oral clotrima-
zole (10 mg 6 hrly)
or ketoconazole or
fluconazole
b. Unresponsive
cases: IV ampho-
tericin B (10-15
mg for 6 hour/day
to a total of 300-
500 mg

Hiatus Hernia
A. Treatment of symptomatic sliding type hiatus hernia: Treat like gastro-oesophageal disease
B. Treatment of para-oesophageal type: Surgical correction.
 Alimentary System
56
Gastro-oesophageal Bleeding

Gastro-oesophageal bleeding is an emergency requiring immediate control and later long-term control
of bleeding. The first episode may be associated with a mortality of 30 to 80%. Long-term control is also
necessary because bleeding recurs in 70% cases and mortality rate increases with each recurrence.
Facts you can use for the management
Causes Common causes Less common causes Rare causes
Non-variceal Duodenal ulcer, Esophagitis, neoplasm Pancreatitis
bleeding gastric ulcer, gastric (gastric, lymphoma) Pancreatic cancer
erosion (due to NSAID, Blood dyscrasia
alcohol, stress in ICU, Uraemia vasculitis
neurological trauma)
Variceal a. Cirrhosis a. Extrahepatic portal vein a. Constrictive pericarditis
bleeding b. Extrahepatic portal obstruction (EHPVO): b. Tricuspid incompetence
vein obstruction i. Hypercoagulable states c. Schistosomiasis
(EHPVO) ii. Polycythaemia
i. Neonatal umbilical iii. Congenital portal vein
vein thrombosis obstruction
ii. Neonatal diarrhoea b. Primary biliary cirrhosis
and dehydration c. Budd-Chiari syndrome
c. Chronic pancreatitis d. Venocclusive disease
d. Non-cirrhotic portal e. Inferior vena cava obstruction
fibrosis d. Pancreatic cancer

Diagnostic Clues
Signs of bleeding: Haematemesis, melaena, low haemoglobin, shock (blood pressure below 100 mm +
rising pulse rate), blood urea elevated.
Aetiological diagnosis:
Clinical features Suggestive diagnosis
a. History of dyspepsia and pain abdomen ------------ Peptic ulcer
b. History of ingestion of NSAID, alcohol ------------ Gastric erosion
living in ICU, neurological trauma
c. Prior history of retching and vomiting ------------ Mallory-Weiss syndrome
d. Angioma of skin ------------ Hereditary haemorrhagic telengiectasia
342 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

e. Dilated abdominal wall veins + ------------ Portal hypertension

splenomegaly + spontaneous profuse
painless haematemesis + venous murmur
at umbilicus
f. Ascitis, testicular atrophy, gynaecomastia, ------------ Cirrhosis
palmer erythema, spider naevi with or
without hepatic encephalopathy
g. Dilated veins in flank and back, massive ------------ Hepatic venous outflow obstruction
hepatomegaly, absent hepatojugular reflux, Budd-Chiari syndrome
ascitis and oedema of feet

Investigations Abnormal findings Normal

a. Haemogram Anaemia
b. Liver function tests
i. Raised liver enzyme in active liver i. Non-cirrhotic portal
disease fibrosis (NCPF)
ii. Low albumin and elevated ii. Extrahepatic portal vein
globulin in cirrhosis obstruction (EHPVO)
c. Endoscopy i. Variceal bleeding in portal iii. Compensated cirrhosis
hypertension
ii. Non-variceal bleeding in peptic
ulcer and Mallory-Weiss tear
d. Ultrasonography i. Reveals evidence of portal
hypertension
ii. Suggests aetiology of portal
hypertension
e. Liver scan Points to cirrhosis i. Non-cirrhotic portal
f. Liver biopsy Cirrhosis, Budd-Chiari syndrome fibrosis (NCPF)
and reveals aetiology of liver ii. Extrahepatic portal vein
disease obstruction (EHPVO)
g. Portovenography Types:
i. Percutaneous splenoportography
ii. Arterioportography
Indication: When surgery of
portovenous shunt is contemplated
Management Medical Therapy
Drugs Mechanism of Dose Disadvantages Advantages
action
Vasopressin Constricts splan- IV bolus 20 U in Side-effects: Effective in 60%
chic arterioles 200 ml saline over Myocardial cases
↓ 20 minutes, follo- ischaemia, intesti-
Decreases portal wed by mainte- nal ischaemia
blood flow and nance dose of 0.2- (counteracted by
pressure 0.4 U/minute IV nitrate), extravasa-
contd...
contd...
Gastro-oesophageal Bleeding | 343

Drugs Mechanism of action Dose Disadvantages Advantages

infusion over 6-12 tion into subcuta-
hour. Combine neous tissue cau-
with nitroglycerine sing gangrene,
hypertension.
Needs ECG moni-
toring
Contraindicated in
coronary artery
disease
Glypressin A synthetic ana- 1 mg IV bolus Longer duration of
logue of vasopres- followed by 2 mg Expensive action and less
sin IV 6 hourly cardiotoxic effect
than vasopressin
Somatostatin Decreases splan- IV loading dose 250 Few side effects
chic blood flow, microgram follo-
decreases colla- wed by continuous
terals and variceal infusion of 250
blood flow microgram/hour,
continued for 3-
5 days
Octerotide A synthetic ana- 50 microgram IV
logue of somato- bolus, followed by
statin 50 microgram per
Metoclopramide Controls variceal hour as an IV
bleeding by increa- infusion
sing lower oesopha-
geal sphincter pres-
sure

BALLOON TAMPONADE:
Indications Types of tube Advantages Disadvantages
i. Torrential bleeding i. Sengastaken-Black- Controls in 70% cases i. Risk of aspiration
ii. Haemodynamically more tube (SB) with pneumonia in SB
unstable patient 3 lumen—one for tube because oeso-
iii. When urgent endo- gastric aspiration phageal secretion
scopic therapy not and two for inflation not aspirated
available of balloon. ii. Oesophageal
iv. If gastric lavage and ii. Minnesota tube rupture
vasopressin fail with 4 lumens, the iii. Oesophageal
fourth is for aspi- stenosis
ration of oesopha-
geal secretion
344 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

ENDOSCOPIC THERAPY
Procedure Advantages Disadvantages
Sclerotherapy (EVS) Sclerosant solution used: i. Safe and effective Complications:
i. Polidocanol ii. Can be performed i. Minor: Fever,
ii. Sodium decylsul- in the presence of chest pain super-
phate active bleeding ficial mucosal
iii. Absolute alcohol ulceration
EVS performed ii. Major: Pleural effu-
weekly for 4-6 ses- sion, pneumonia,
sions oesophageal stric-
ture
Endoscopic variceal Mechanical strangulation i. No systemic comp-
band therapy of varices. Needs 3-4 lications like EVS Suitable only for large
sessions ii. No local complica- varices
tion
iii. Faster elimination
of varices
SURGERY
Indications:
a. Emergency surgery:
i. Life-threatening bleeding
ii. Uncontrolled bleeding due to failure of sclerotherapy, balloon tamponade and variceal band
therapy.
b. Elective surgery for long-term management:
i. Recurrent bleeding after endoscopic sclerotherapy, balloon tamponade and band therapy
ii. Non-compliant patient
iii. Ectopic varices (e.g. jejunal varices)
iv. Diffuse gastric varices
v. Left sided portal hypertension
vi. Symptomatic massive splenomegaly

Types of Surgery
a. Portal decompressive procedures:
Anastomosing portal vein to systemic venous system (renal vein or inferior vena cava): Decreases
portal venous pressure
b. Non-decompressive procedures:
Ligation of varices
c. Liver transplantation:
Eliminates resistance to blood flow
 Gastro-oesophageal Bleeding | 345

Flow Chart of Management

⇓
Emergency resuscitation
⇓
Emergency endoscopy
⏐
Performed Not performed due
to non-availability
Oesophageal variceal Gastric varices of endoscope
Bleeding confirmed ⇓ ⇓
Glue injection Vasopressin or
glypressin or
Mild to Severe somatostatin or
moderate bleeding Failure Success octerotide
bleeding

Small varices Large varices Balloon tamponade with vasopressin

⇓ ⇓ Success Failure
EVS EVL 3-4 ⇓
Performed sessions Early EVS
weekly/4-6 ⇓
sessions Success
⇓ ⇓
i. Success i. Success
ii. Recurrence ii. Failure
⇓
Repeat EVS
iii Failure Elective Surgery for Emergency Surgery
long-term management

Key: EVS = Sclerotherapy

 Alimentary System
57
Peptic Ulcer Disease

Diagnostic Clues
Clinical features: Differential diagnosis:
Gastric ulcer Duodenal ulcer Non-ulcer dyspepsis
Pain:
a. Site:
Epigastrium +++ +++ +++
Right hypochondrium + + +
Left hypochondrium + + +
b. Radiation to back + + +
c. Severe +++ ++ +
d. Occurs at night ++ +++ +
e. Increased by food ++ + +
f. Relieved by food ++ +++ +
g. Nausea +++ ++ ++
h. Heart burn + ++
⇓
Investigations:
Radiography
Duodenal ulcer Gastric ulcer
If DU demonstrated radiographically no further If GU demonstrated radiographically, malignancy
diagnostic evaluation is necessary and treatment should be excluded particularly if following
can be started, since DU is rarely malignant. But if characteristics are demonstrated:
symptoms fail to subside with treatment, endoscopy i. Ulcer located completely within gastric wall
should be done to prove the diagnosis of ulcer ii. Nodularity of ulcer base
before considering surgery iii. No fold radiating to ulcer margin
iv. Large ulcer
Endoscopy essential with brush cytology and
6-8 punch biopsy specimens for histological exami-
nation
Treatment
Main therapeutic approach is ulcer healing drugs. For mechanism of anti-ulcer drugs (See Table 57.1)
and ulcer healing drugs (Table 57.2).
 Table 57.1: Mechanism of anti-ulcer drugs
Peptic Ulcer Disease | 347

Vagus releasing Stomach

ACH Parietal cells Mast cells of Gastrin cells of antrum

CAMP ⏐ lamina propria secrets gastrin which
H+/K+ ⎫ ↓ of gastric mucous secretes acid
ATPase ⎬⎭ Acid secretion secretes histamine

Acid H2 receptor Antacids Cytoprotectives: Antimuscarine Proton pump Prosta-

inhibitory antagonists sucralfate, colloid drugs inhibitors glandin
drugs bismuth, carbenolone

Table 57.2: Ulcer healing drugs

Preparations Dose Disadvantages Advantages
A. Antacids Aludrox, gelucil, 1-2 tabs t.i.d. M g . h y d r o x - c a u s e s Safe, if H2 receptor
Specially aluminium alucinol, gaviscon, 5-10 ml as often as diarrhoea. Mg trisill. antagonists not
hydroxide, mag. trisill, reflux liq. necessary causes constipation, tolerated
alginic acid may be combined to
minimise above side-
effects. Liquid is bet- ter
but not convenient
because taken in large
amount (upto seven
30 ml liquid in each 24
hours)
B. Anti-secretary
drugs:
a. H2 receptor antago-
nists:
i. Cemetidine Cemetidine (Cadila) 400 mg b.d. or 800 mg Mild sedation More convenient,
200 mg tab for 4-8 weeks at bed- taken once a day, less
time expensive than antacid
ii. Ranitidine Acilock 150, 300 mg 300 mg/day or 150 mg C/I gastric malignancy — Do —
tab b.d.
iii. Famotidine Facid (Intas) 40 mg at bedtime or C/I gastric cancer — Do —
Famocid (Sun) 20, 20 mg b.d.
40 mg tab
iv. Roxatidine Rotane (Hoest) 75 mg in evening or — Do — — Do —
75, 150 mg b.i.d.
b. Proton pump inhi-
bitors:
contd...
348 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Preparations Dose Disadvantages Advantages

i. Omeprazole Omez (Dr. Reddy) 20 mg/day for — Do — — Do —
ii. Lansoprazole Omizac (torrent) 10, 4-8 weeks
iii. Pantoprazole 20 mg LAN 30 mg/day
(Pantocid 40 LAN 30 Pantocid 40 mg/day
mg)
iv. Rabeprazole Zenprazole 20 veloz 20 mg/day Very fast, effective in
20 mg 10 minutes
C. Muscarine receptor
antagonists:
Anticholinergics: Atropine Inferior efficacy May be combined
Probanthine 15 mg t.i.d Unwanted side- with antacids or H2
Pirenzipine effects: Dry mouth, blockers for better
blurred vision, urinary effect
retention, arrhythmia

D. Cytoprotective: Sucralfate: Ulcerfate 1 gm t.i.d before each Interferes with absor-

(protects mucosal (Sun) 1 gm tab meal and at bedtime ption of tetracycline
defence) and phenytoin. Con-
stipation. Not conve-
nient because taken
more frequently on
empty stomach
Bismuth colloid: 1 tab q.i.d. or 2 tab Hastens healing like
Trymo (raptakos) b.i.d. before food for H2 blockers. Indicated
120 mg tab 4-8 weeks if H2 blockers not
tolerated
Licorice derivative:
Carbenoxolone Aldosterone like acti-
vity: Sodium and water
retention, hyperten-
sion, hypokalaemia.
Treated by thiazide
with potassium and
aldosterone antagonists
E. Antisecretary and Healing rate like H2
cytoprotective: blocker
Prostacyclin E1, E2
Misoprostol

F. Tricyclic anti-
depressant: Relieves stress
Trimipramine Perhaps helps healing

Diet
No specific diet is needed. Free choice is advised. But the following guidelines are reasonable:
a. Avoid fatty food, spicy and rich meals.
b. Exclude foods that produce pain.
c. Frequent small meals are advised because intragastric pressure rises after heavy meals.
Approach to Treatment
Peptic Ulcer Disease| 349

Aim of treatment:
i. Relief of symptoms like pain
ii. Healing of ulcer
iii. Prevention of recurrence
iv. Prevention of complications (bleeding, perforation, penetration)

Treatment of Duodenal Ulcer

A. Short-term management: First line drugs are cemetidine, ranitidine, famotidine or proton pump
inhibitors. They should be used in usual dosages (See Table: 57.2 Ulcer healing drugs) for
4-6 weeks
↓
If patients symptoms free, stop the drug
↓
If fails or complications ensue, choose the following options:
i. Change to a different drug
ii. Or increase the dosages of already used drug
iii. Or combination of two drugs
iv. Or admit in the hospital for treatment
↓
If fails, exclude Zollinger-Ellison syndrome by investigations:
↓
If ZE syndrome found If ZE syndrome not found
↓ ↓
Treat accordingly Resort to surgery
B. Long-term management in case of relapse:

Patient having 3-4 relapses only If patient having continuous symptoms:

Each year:
No need of continuous ulcer healing drug, Low dose ulcer healing drugs (cemetidine
when symptoms occur they should be treated 400 mg, ranitidine 150 mg, famotidine 20 mg,
with full dose of drug at least for 2 weeks after lansoprazole 15 mg) daily at bedtime. Some
symptoms abate. Thus, patient receives drugs express concern for risk of cancer due to long-
for 5-6 weeks every year. term exposure to these drugs but this is un-
founded. Nevertheless, in order to avoid conti-
nuous exposure, intermittent therapy is advised.
Other measures to prevent relapses:
i. Bismuth compound has lower relapse rate perhaps due to eradication of H. pylori
ii. A course for eradication of H. pylori may prevent relapse.

Treatment of Gastric Ulcer

Gastroscope at the start of the treatment. Biopsy also should be taken to be sure about the absence of
malignancy.
350 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Ulcer healing drugs should be taken for 8 weeks

85% ulcers heal 2-3% benign looking ulcer may harbour

malignancy (not a problem with DU)
↓
Endoscopic biopsy is taken
|

Ulcer benign: Ulcer malignant:

Continue medical Surgery
therapy for another
4-8 weeks in the same
dose or increasing
dose or antacid added
↓
If no healing, surgery
indicated

NSAIDs induced PU
Misoprostol 200 mg b.d. Least irritants are ibuprofen, daclofenac and nimesulide

H. Pylori induced PU
Treat H. pylori by the following combination of drugs:
H2 blocker + Clarithromycin + Tinidazole 500 mg b.d. or metronidazole 400 mg b.d. or t.d.s.

PU in Pregnancy
Antacid and sucralfate are probably safe.

Surgery:
Absolute indications:
Relative indications:
Duodenal ulcer Gastric ulcer
Continuous life-threatening compli- i. Complicated GU like DU
cations: Perforation, haemorrhage, ii. If cancer cannot be
penetration or pyloric stenosis confidently excluded
Uncomplicated DU with
i. Frequent severe recurrences that inter-
fere with social and professional life
ii. Poor response to ulcer healing drugs
iii. Poor compliance with drugs by patients
iv. Residence in remote areas where limited
access to medical and surgical facilities
If the patient does not favour prolonged
therapy due to frequent recurrences.
TREATMENT OF PU COMPLICATIONS
Peptic Ulcer Disease |351

Haemorrhage
Steps of Management
Arrange for laboratory studies: Blood should be drawn for the following tests:
Complete blood count, platelet count, prothrombin time, type and

⇓ cross-match, blood urea, electrolytes, blood sugar, serum amylase

calcium, liver tests and cardiac enzymes.
IV line instituted for saline infusion and blood transfusion. Blood transfusion indicated in shock, Hb
less than 10 gm/dl and if patient continues to bleed.
⇓
Pass a nasogastric tube if history of malena or vomiting blood. If the aspirate is clear or clears with
lavage the tube be removed. Removal of gastric contents will fascilitate subsequent endoscopy and
decompress stomach.
⇓
Some recommend IV H2 blocker
⇓
Diagnostic endoscopy is arranged if bleeding has not stopped

Locates site of bleeding Does not locate site of bleeding:

Angiography is indicated
Non-variceal bleeding Variceal bleeding: (see chapter on portal
hypertension)
PU bleeding: Gastric erosion: ↓
Endoscopic methods: H2 blocker, proton Sclerotherapy or band ligation
Sclerotherapy with pump inhibitor, ↓
1:10000 epinephrine antacids, sucralfate, If fails: TIPSS Surgery
(safe, effective and cheap) IV vasopressin or
or somatostatin also effective
Electrocoagulation
or
Thermal coagulation by heater probe
or
Nd-YAG laser therapy
↓
If fails:
a. Surgery
b. If patient is at high-risk for surgery: Angiography with embolisation
↓
Medical Therapy
1. Somatostatin and its analogue octreotide as well as vasopressin may be effective.
2. H2 blocker and proton pump inhibitor.
3. If test for H. Pylori is positive, treat it.
 Alimentary System
58
Gastric Cancer Management

Surgery
Curative Palliative
Wide section of stomach with its lymph nodes For relieving obstruction at gastro-oesophageal
and reconstruction of a passage for food junction and pylorus:
i. Bypass surgery: Gastrojejunostomy
ii. Endoscopic laser ablation
iii. Placement of plastic and expandable metallic
stents
iv. Injection of alcohol or sclerosants

Radiotherapy
Gastric cancer is radioresistant, hence used only for palliation of pain of advanced cancer.

Chemotherapy
Because of high recurrence rate chemotherapy is used only as adjuvant therapy.

Nutritional Support
A. Enteral support provided by:
i. Oral supplements
ii. Percutaneous endoscopic jejunostomy
B. Meals:
i. Frequent small feeds
ii. Avoidance of fatty and sugary meals
iii. Avoid drinking water with meals
C. Supplements: Ranitidine, vitamin B12, calcium

For Relieving Pain

i. Pain relieving drugs such as codeine, buprenorphine (norphin-unichem, tidigesic-Sun) ethyl morphine
(dionindon-indon), ketorolac (ketorol-Dr. Reddy)
ii. Liberal use of morphine
GASTRITIS
Gastric Cancer Management | 353

Diagnostic Clues
Acute gastritis Chronic gastritis
(Errosive or haemorrhagic gastritis) Types
i. Haematemesis or positive fecal occult blood a. Autoimmune associated with pernicious
anaemia
ii. Epigastric discomfort b. H. pylori induced gastritis
iii. Nausea, anorexia c. A premalignant condition progressing to gastric
cancer
Treatment:
I. Acute gastritis:
i. Avoidance and treatment of offending and causative agents:
a. Offending agents: Aspirin, NSAIDs, alcohol, bile reflux
b. Associated conditions responsible: Severe trauma, burn, sepsis, acute H. pylori infection
ii. H2 receptor antagonists
iii. Misoprostol only for prevention
iv. Sucralfate
II. Chronic gastritis
i. Treatment of pernicious anaemia with vitamin B12
ii. Treat H. pylori infection.
 Alimentary System
59
Ulcerative Colitis

DEFINITION
Ulcerative colitis is a chronic inflammatory disease of unknown aetiology, involving mucosa of rectum
and variable length of colon.

Diagnostic Clues
Clinical Features
Gastrointestinal Features: Constitutional Symptoms: Complications

Mild to moderate Severe case Mild case Severe case a. Local: Massive
case moderate case High fever, haemorrhage, colonic
Diarrhoea 3-5 Profuse diarrhoea Weight loss, low tachycardia, stricture, polyp, adeno-
stools/day, abdo- 6-20 motions/day grade fever, hypotension carcinoma, piles, anal
minal pain and rectal bleeding, fatigue, malaise dehydration, fissure, rectovaginal
rectal bleeding abdominal tender- progressive fistula, ischiorectal
ness, toxic dilatation anaemia, ano- abscess, acute dilata-
of colon (abdominal rexia, much tion of colon (toxic
distension + bowel raised ESR, megacolon)
sounds absent) leukocytosis b. Extraintestinal:
Pyoderma gangreno-
sum, erythema nodo-
sum-episcleritis, irido-
cyclitis, apthous ulcer
of mouth, clubbing,
⇓ ankylosing spondylitis

INVESTIGATION
Procto Stool Blood Rectal Radio- Colonoscopy
sigmoidoscopy culture biopsy graphy
Shows inflam- To exclude Anaemia, To exclude a. Plane X-ray Only indication
mation ulcera- infective leukocytosis, other forms of abdomen in in chronic cases
tion, bleeding of dysentery raised ESR colitis and standing and a. Reveals extent
contd...
Procto Stool Blood Rectal Radio- Colonoscopy
|
Ulcerative Colitis 355

sigmoidoscopy culture biopsy graphy

rectum and (Shigella, mucosal dys- supine position of disease
sigmoid Salmonella) plasia for cancer especially in b. Excludes
Stool surveillance severe cases, cancer, stricture
parasites shows dilated and pseudopolyp.
colon in toxic
megacolon
b. Double contrast
barium enema in
mild to moderate
cases (not in
severe cases).
Excludes Crohn’s
disease, cancer
colon. Shows
multiple ulceration
and abnormal
mucosal pattern in
ulcerative colitis.

Treatment
No medical therapy is curative but gives comfort. Only colectomy is curable but at a high price.

General Treatment
Dietetic Anaemia Anti-diarrhoeal agents Stress management
Low fibre content, Oral iron may be i. Diphenoxylate with i. Rest
nutritionally balanced poorly tolerated, atropine (2.5-5 mg) ii. Adequate sleep
with adequate calories. parenteral iron may ii. Codeine 15-30 mg iii. Tranquillizers,
In lactase intolerance be needed. Folic acid. iii. Loperamide 2-4 mg antidepressants
exclude dairy products Blood transfusion before meals and at
bedtime

TREATMENT BASED ON SEVERITY OF THE CASE

After confirming the diagnosis assess the severity of the case:

Severe and Acute Case

Hospitalise the patient.
Fluid and electrolyte Broadspectrum Corticosteroids Sulphasalazine
replacement: antibiotics
i. Give crystalloid, A little controversial. Hydrocortisone 300 mg Slow in acting,
plasma and blood. Antibiotic after stool, IV as continuous infusion hence not very
356 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Hypoalbuminaemia blood and urine culture. or 50-100 mg IV 6 hourly useful in severe

treated by albumin Combination antibiotics for 5-7 days cases
infusion. Anaemia recommended: IV Or
needs blood. ampicillin + gentamicin + ACTH 120 IU/day IM
ii. Nothing orally clindamycin Or
nasogastric suction Methylprednisolone
intensive parenteral 20-40 mg 12 hourly
feeding for 5 days
⇓
Response to Treatment

If responds If no response within 24-36 hours

Start oral feeding, oral corticosteroids. Prompt surgical intervention (colectomy with
Prednisolone 40 mg/day, tapered to reduce ileostomy) is needed particularly if toxic megacolon
5 mg/day every week to 20 mg/day given developed, perforation occurs and profuse
for 6-8 weeks and then gradually stopped haemorrhage
Sulfasalazine 2-4 gm orally/day added
⇓
Then treat like mild to moderate cases
⇓

Mild to Moderate Cases

General measures
Overcome dehydration,
electrolyte imbalance,
combat anaemia,
provide nutrition.
Sulfasalazine Corticosteroids
Start 1.5 gm/day, gradually Specially indicated if fails to respond
increased to 2-4 gm/day to sulfasalazine.
a. Topical:
i. Enema—Hydrocortisone 100 mg
given in 100 ml of saline for distal
ulcerative colitis given once or twice
daily until improvement, then tapered
to one enema at bedtime and then
alternate night and finally disconti-
nued.
ii. Steroid suppositories for rectal lesions
b. Oral prednisolone 30-60 mg/day for 7-
14 days and then tapered.
Indication: If topical steroids fail.
c. Corticosteroid has no prophylactic value
and hence discontinued after lesions
become quiescent
 d. Combination of topical and oral corti-
|
Ulcerative Colitis 357

costeroid more effective in producing

rapid remission
e. Sulfasalazine combined with cortico-
steroid is more effective

A simple regime: Combination treatment:

Prednisolone 5-10 mg q.d.s.
+
Sulfasalazine 0.5 gm q.d.s.
+
Topical steroid as enema nightly (in mild cases)
And morning evening (in moderate cases)

Drugs for Ulcerative Colitis

Drugs and Mechanism Dose Disadvantage Advantage
preparation
Sulfasalazine Compound of 5- 0.5-4 gm/day mild Side-effects: Rash, Mainstay of treat-
500 mg tab aminosalicyclic to moderate case: 3- headache, arthral- ment may be com-
acid (5-ASA) and 4 gm/day. To pre- gia, nephrotoxic. bined with steroid
sulphapyridine vent relapse as pro- Serious side-effe- for more benefit.
which is broken phylaxis: 1.5-2 gm/ cts: Rarely agranu- Prevents relapse. It
down by colonic day indefinitely locytosis (stop inhibits absorption
bacteria drug) exfoliative of folic acid, hence
dermatitis folic acid is helpful
especially if dose of
sulfasalazine above
3 gm/day. No evide-
Newer prep.: nce of foetal harm
i. Eudragrit L 5-ASA is the active
ii. Eudragrit S moiety and sulpha-
iii. 5-ASA micro- pyridine is res-
granule ponsible for side-
iv. 5-ASA atta- effects
ched to inert
carrier

Corticosteroid a. Topical: Facial mooning, Remarkable drug in

i. Prednisolone acne, echymoses, causing remission
Anti-inflammatory 20-40 mg dis- stria, hirsutism, both in acute and
solved in sal- infection, hyper- chronic cases
ine and used as tension, peptic
contd...
358 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs and Mechanism Dose Disadvantage Advantage

preparation
enema ulcer, bone abnor-
ii. H y d r o c o r t i - malities, emotional
sone 100 mg disturbance. These
enema complications res-
iii. Steroid foam olve after with-
iv. Suppositories drawal or reduc-
of predniso- tion of dose and by
lone 21 phos- specific treatment.
phate

v. Retention No prophylactic
enema of value in preventing
beta-metha- relapse
sone
vi. Toxocortical
pivalate
enema
vii. B u d e s o n i d e
enema
viii. F l u t i c a s o n e
propionate-
enema
b. Oral: Predni-
solone 30-
60 mg/day
c. IV: Hydrocor-
tisone 300 mg
In severe cas-
es
Methylpredni-
solone 20 mg
Azathioprine 12 hourly Side-effects: Indications:
Infection, pancre- i. When steroid
atitis and potential and sulfasala-
development of zine fail.
cancer ii. When chronic
steroid thera-
py needed
iii. Surgery is app-
ropriate
FLOW CHART FOR TREATMENT (SUMMARY)
Ulcerative Colitis | 359

First step: Find out the severity of disease after excluding any specific organism by routine stool
examination and stool culture:
⇓
Mild Moderate Severe Remission Chronic ulcerative
colitis with relapse
4-6 stools/day with 6-8 stools/day with
10 or more stools/ 2-3 motions/day
minimum rectal rectal bleeding, day with blood without blood and
bleeding and mucus, anorexia mucus, abdominal mucus
mucus. nausea. tenderness, tachy-
cardia
↓
Proctoscopy Proctoscopy Proctoscopy Once disease has i. Sulfasalazine in
↓ ↓ ↓ subsided, withdraw higher dose 6-
Finally granulated Same as mild case Spontaneous blee- steroid and sulfa- 8 gm/day
and friable red ding, prominent salazine continued ii. Steroid enema
mucosa Treatment same as ulceration, muco- in 1.5-2 gm/day iii. Oral predniso-
mild cases. sal sloughing lone if necessary
Treatment: Treatment:
A. Sulfasalazine i. Hospitalisation Refractory case
1.5 gm/day ii. IV fluid and i. Oral predniso-
slowly increa- electrolytes lone 20-40 mg/
sed to 3-4 gm/ iii. Antibiotic if day
day suppurative ii. Sulfasalazine
↓ complications suppository
If fails: suspected t.d.s. or toxo-
Topical steroid iv. If full diet is not cortal pivalate
as enema, sup- possible, paren- enema
pository or teral nutrition is
foam for distal instituted
colitis and v. Main drug: IV
proctitis hydrocortisone
↓ 300 mg or
ACTH 120 IU/
day for 7-10
days
↓
If fails: Once symptoms
Start oral pre- subside, stop IV ste-
dnisolone 30-60 roid and start oral
mg per day for prednisolone 30-60
contd...
360 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Mild Moderate Severe Remission Chronic ulcerative

colitis with relapse
7-14 days and mg/day and tapered
tapered over ↓
2 months

B. Symptomatic Once steroid tape-

treatment: red, and sulfasala-
Antidiarrhoeal, zine
anticholinergic, ↓
tranquillizer If no response to
and analgesic medical therapy:
Surgery
C. General treat-
ment: Avoid
lactose contai-
ning food and
raw vegetables,
proper nutri-
tion, vitamin,
iron adequate
rest and sleep

DESENSITIZATION
Desensitize the patient if uncontrollable side-effects occur. Stop the drug for 1-2 weeks resulting in
subsidence of side-effects. Then start sulfasalazine in gradually increasing dose: Starting with 0.25 or
0.5 gm/day and then gradually increasing the dose by half a tablet (250 mg) every week until the final
dose of 2-3 gm/day is achieved.
Contraindications for desensitisation: Agranulocytosis, hepatitis and frank haemolysis as side-effects.
Other drugs on trial:
FK-506; Fusidic acid; interferon alpha; monoclonial antibodies against CD4; antioxidant; sucralfate
enema; Chloroquine, revimisol; fish oil; nicotinic acid; ketotifen.
 Alimentary System
60
Irritable Bowel Syndrome

DEFINITION
Irritable bowel syndrome is characterised by:
i. Abdominal discomfort
ii. Alteration of bowel habits
iii. No demonstrable organic cause
Due to alteration of intestinal motility associated with altered electrical rhythm in the colon of unknown
aetiology.

FACTS (CLINICAL AND INVESTIGATIONAL)

YOU MAY USE FOR MANAGEMENT
Clinical Features
Personality Abdominal Altered bowel Stool Extraintestinal
symptoms habit
Rigid, obces- Left and lower Chronic inter- Small quantity, Urinary frequency,
sive compul- abdominal crampy mittent diarrhoea semisolid or liquid, headache, dysmeno-
sive, depressive pain related to and constipation hard pellet like, rrhoea, dysparaenia,
meals and relieved with feeling of mucus palpitation. No
by flatus and bowel incomplete physical deterio-
movement. Abdo- evacuation ration
minal distension. ↓

INVESTIGATIONS
The following investigations are done to exclude organic disease:
Stool Lab. investigations Proctosigmoidoscopy Barium enema
For occult blood, Haemogram, blood urea Anal fissure, piles
parasites and
pathogenic bacteria

MANAGEMENT
General Management
Sympathetic explanation of nature of disorder is essential. Patient should be assured that no organic
362 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

disease (especially cancer colon or inflammatory bowel disease) exists. Also reassure him that it is
incurable.

Drugs for Symptoms

Drugs should be avoided if at all possible. The aim should be to reduce symptoms to a tolerable level so
that patients’ normal activities are minimally disturbed.
a. Pain abdomen
i. Anticholinergic spasmolytics
ii. Pinavarium bromide: A new gut specific calcium channel blocker is now available.
b. Diarrhoea
i. Antimotility agents: Diphenoxylate (lomotil) or loperamide (Imodium) in the morning or if
necessary t.i.d. Imodium is better than lomotil because there is no risk of substance abuse with
imodium.
ii. Psyllium colloid also reduces diarrhoea.
c. Constipation
i. Hydrophillic colloid
ii. Unprocessed bran
iii. Occasional use of milk of magnesia or bisacodyl (dulcolax)
iv. Cisapride 20-30 mg/day.

Diet
Food to be avoided
Eliminate those food which produce symptoms.
Avoid legumes, cabbage, milk and spicy foods
for relieving gas bloat, prescribe simethicone or
methylpolyseloxone for gas
Fibre
i. Low residue diet has no place
ii. Increase fibre in the diet as follows:
a. Half cup of bran cereal/day
b. Ispaghula husk (refined) preparation
1-2 tsf with meals

Psychoneurosis
Should be treated. Depression should be treated by imipramine/amitriptyline at bedtime. Tranquillizer
should be avoided.

Biofeedback Therapy
Biofeedback techniques is a type of behavioural therapy. The particular abnormality for example increased
peristalsis is monitered by patient and therapist (e.g. by an electronic stethoscope to amplify the sounds).
This is immediate feedback, and after learning to recognise it the patient can then learn to identify any
change thus produced (e.g. a decrease in bowel sounds) and so become a conscious originator of the
feedback instead of a passive recipient. Relief of the symptom operantly conditions the patient to utilise
the maneuver that relieves symptoms (e.g. relaxation causing decrease in bowel sounds). With emphasis
on this type of learning, the patient is able to identify symptoms early and initiate the countermaneuvers,
thus decreasing the intensity of symptoms.
 Alimentary System
61
Crohn’s Disease

DEFINITION
Crohn’s disease is a chronic inflammatory disorder of unknown aetiology involving whole gastrointestinal
tract especially terminal ilium, jejunum and colon.

DIAGNOSTIC CLUES
Aim is to distinguish Crohn’s diseases from ulcerative colitis. See Table 61.1. For “Differential diagnosis
of Crohn’s disease and Ulcerative colitis”.

Table 61.1: Differential diagnosis of Crohn’s disease and ulcerative colitis

Clinical Ulcerative colitis Crohn’s disease
Bloody diarrhoea ++ +
Rectal bleeding ++ +
Abdominal pain + ++
Right lower quadrant pain Less ++ (mimicking acute appendicitis)
Palpable mass No +
(right lower quadrant mass
mimicking appendicitis)
Malabsorption Never Frequent
Fistula, stricture, fissure and perirectal abscess Less +
Small bowel involvement Less ++
Rectal involvement ++ (95%) + (50%)
Extraintestinal Complications
i. Joint: Arthritis, ankylosing spondylitis ++
ii. Skin: Erythema nodosum ++ + (10%; with colonic involvement)
Pyoderma gangrenosum ++ + (2%)
iii. Mouth: Apathous stomatitis + +
iv. Eye: Conjunctivitis, episcleritis, uveitis ++ + (10%; with colonic involvement)
↓
contd...
364

contd...
| Bedside Approach to Medical Therapeutics with Diagnostic Clues

↓
INVESTIGATIONS
Sigmoidoscopy and Vascularity, diffuse erythema Small ulcer, erosion, cobble
colonoscopy with biopsy and friability of mucosa. stone appearance (coarse
Uniformity of lesions irregularity of mucosal surface
Stricture
Segmental, discontinuous lesions
Radiological:
Meticulous air contrast
Barium enema:
Rectal involvement Invariable Spared
Distribution Continuous Segmental
Mucosa Fine ulceration Cobble stone appearance
Stricture Rare Common
Fistula Rare Frequent

Histological:
Distribution Mucosal Transmural
Cellular infiltrate Polymorph, plasma Lymphocytes, plasma cell,
cell, eosinophil macrophages
Gland Preserved Destroyed

MANAGEMENT
Diet
a. Well balanced diet
b. Low residue diet in case of stricture
c. Low fat diet for malabsorption
d. Lactose free diet in lactose deficiency
e. Avoid food causing symptoms
f. Avoid rubarb, tea, cola and grape fruit in hyperoxaluria.

MEDICAL TREATMENT

Vitamins Iron and Minerals Electrolytes Parenteral Alimentation

i. Vit. B12: 100 micro- i. Oral iron may not be Should be corrected Indications:
gram monthly IM in tolerated. Then IV i. Severe ill-patients
terminal ilium total dose infusion for giving rest to GI
resection. of iron is best. tract
ii. Vit. B complex. ii. Minerals should be ii. For preparing mal-
iii. Vit. C given. nourished patients
iv. Vit. D (50000 IU/ for surgery
week and calcium iii. Occasionally oral
1.5 gm/day to pre- feeding is not possi-
vent osteoporosis ble, then prolonged
contd...
 and osteomalacia.
Crohn’s Disease |
parenteral alimen-
365

v. Multivitamin tab. tation is needed at

vi. Vit. E: 200 mg twice home
daily in extensive
resection of intes-
tine.

SPECIFIC DRUGS FOR ACTIVE DISEASE

Corticosteroid Sulfasalazine Metronidazole Azathioprine and 6 Mer-
Indications: i. Effective for mild to i. Indicated in: captopurine:
First line drug for severe moderately active a. Bacterial infec- i. Indications: Chronic
disease disease with involve- tion severe disease refrac-
Preparation: ment of colon with or b. Perianal compli- tory to all other
Dose: without ileal involve- cations therapy or repeated
i. Prednisolone 20-40 ment. Not effective in c. Mild to moderate relapses after steroid
mg orally per day for only small bowel dis- disease with therapy
4-6 weeks tapered order active colitis or ii. Dose: 50-100 mg/
over further 4- ii. Dose: Start with 1 gm ileocolitis who day
6 weeks increased to 3-4 gm/ are intolerant to iii. Side-effects: Bone-
ii. In severe acute case: day sulfa salazine marrow suppression,
Pred. 30-60 mg IV + ii. Dose: 250-500 mg 3- fever, pancreatitis,
per day in divided Folic acid 1 mg/day 4 times/day, tapered risk of inducing
dosages until symp- orally as prophylaxis gradually to lowest malignancy
toms improve iii. Side-effects: Nausea, dose that control iv. Monitoring: Hb,
Or vomiting, headache symptoms WBC count, and
Hydrocortisone 200-400 which resolves on iii. Side-effects: Peri- platelet count moni-
mg per day in divided reduction of the dose. pheral neuropathy tored weekly.
dosages until symptoms iv. Monitoring: Comp- (burning paresthesia
improve lete blood count after in lower limbs) with
↓ one week of therapy prolonged treatment
When symptoms improve to look for leuko- but it resolves after
oral prednisolone started penia and thrombo- discontinuence of
↓ cytopenia treatment, although it
When symptoms subside v. 5-Aminosalicylic may take months for
i. Taper prednisolone acid (5 ASA) Mesal- full recovery.
over 2-3 months to the mine: Less side-
lowest dose that effects than sulfa-
control symptoms and salazine and as effec-
eventually disconti- tive as sulfasalazine.
nued
ii. Hydrocortisone enema
for distal colonic
disease: One enema at
bedtime.
366 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

TREATMENT DURING PREGNANCY

Sulfasalazine Corticosteroid Nutritional treatment
Not contraindicated Not contraindicated Should be prompt and aggressive
Only used in symptomatic Only used in symptomatic
patient patient

DRUGS FOR DIARRHOEA

Bulk Diphenoxylate Loperamide Cholestyramine
(imodium)
Agent: Late 2.5 mg + 1-8 tab/day 2-4 gm 2-4 times/day in a case
Psyllium 1-2 tsf once Atropine 0.025 mg of resection of intestine
or b.d. (lomotil) 1-2 tab 1-4 causing bile salt diarrhoea
times a day

TREATMENT OF EXTRAINTESTINAL COMPLICATIONS

Joint Skin Oral Eye Hepatobiliary
Arthritis: Sulfa- Erythema nodosum, Apathous stomatitis: Conjunctivitis, Cholesterol
salazine, NSAID pyoderma gangreno Resolves with control episcleritis, uveitis: gallstone:
sum: Relieved by of bowel symptoms Topical steroid eye Cholecystec-
sulfasalazine and drop tomy
steroid

FLOW CHART FOR MEDICAL TREATMENT

Decide the activity of the disease whether mild to moderate or severe. Also determine whether only
ileitis or ileocolitis or involvement of rectum is present:
Mild to moderate cases
Crohn’s disease Crohn’s disease Crohn’s disease
with ileitis with colitis with with rectal involvement
or without ileitis
i. Oral steroid Sulfasalazine, metronidazole Steroid enema
ii. Metronidazole Sulfasalazine Sulfasalazine
is not effective ↓ Metronidazole
If deteriorate: Oral prednisolone
Severe cases
Acute severe cases Chronic severe refractory cases not responding
Nothing orally except sips of water to other treatment
IV hydrocortisone or prednisolone Azathioprine
Antibiotics:
Metronidazole + gentamicin
Or ciprofloxacin or 2nd/3rd generation
cephalosporin.
The IV steroid and antibiotic
Regime continued for 5 days
 ↓
Crohn’s Disease| 367

IV steroid is substituted by oral steroid,

tapered and stopped.
Sulfasalazine may be added.

SURGERY
Indications: Type of Surgery
Fails to respond to medical therapy Resection of severely affected bowel and
Complications: end-to-end anastomosis
Stricture
Fistula
Local and abscess
Intra-abdominal abscess
Perforation
 Alimentary System
62
Malabsorption Syndrome
DEFINITION
Comprises both maldigestion and malabsorption.
CAUSES AND MECHANISM
Maldigestion
a. Deficiency or inactivation of pancreatic lipase:
i. Chronic pancreatitis
ii. Pancreatic cancer
iii. Cystic fibrosis
iv. Pancreatectomy
v. Zollinger-Ellison syndrome (excess gastric acid hydrolyses pancreatic lipase)
b. Reduced intestinal bile salt concentration:
Mechanism Causes
i. Reduced bile salt synthesis Parenchymal liver disease
ii. Defective bile salt delivery Biliary obstruction
iii. Abnormal bacterial proliferation in small bowel, Afferent loop syndrome, stricture, fistula,
which deconjugate bile salt blind loop
iv. Interrupted enterohepatic circulation of bile salt ileal resection, ileal inflammation
(Crohn’s disease)
v. Drugs precipitating bile salt Cholestyramine, neomycin
MECHANISM AND CAUSES
Malabsorption
Interrupted absor- Lymphatic obstruc- Mucosal absorptive Endocrine and Drug induced:
ptive surface: tion: defects: metabolic disor-
ders:
i. Intestinal i. Lymphoma i. Inflammatory Diabetes mellitus, Neomycin, colchi-
resection ii. Congenital and infiltra- carcinoid syndrome cin, irritant laxati-
ii. Mesenteric lymphangiec- tive disorders: rome, Addison’s ves, phenidione,
vascular tasia Crohn’s dis- disease, hypothy- methyldopa, met-
disease iii. Tuberculosis ease, amyloi- roidism, hyperthy- formin
iii. Jejunoileal iv. Retroperito- dosis, eosino- roidism, hyperpara-
bypass nial tumour philic enteritis thyroidism
contd...
 tropical sprue,
Malabsorption Syndrome | 369

infective ente-
ritis, giardi-
asis, collagen
disease
ii. Genetic abnor-
malies: Celiac
disease, disac-
charide defi-
ciency, hypo-
gammaglobi-
naemia, Hart-
nup disease,
cystinuria

DIAGNOSTIC CLUES CLINICAL FEATURES

Steatorrhoea: Diarrhoea: Other abdominal Features of nutritional deficiency:
symptoms:
Loose, pale, bulky, Volumenous, Pain, distension, Deficiency Protein
greasy and offen- watery, floating flatulence, borbory- Protein → Features
sive stool which is stool gmi Weight loss, oede-
difficult to flush out Iron, Vit. B 12 → ma, muscle wasting
from toilet pan. Oil folic acid Anaemia
seeping from rec-
tum Vit. K →
Bleeding
Calcium Vit. D →
Osteoporosis
Vit. A →
Night blindness
Vit. B
→ Neuritis, oral ulcer,
glossitis, skin pig-
mentation
Cobalamine, → Peripheral neuro-
INVESTIGATIONS pathy
Tests Procedure interpretation Comment
Carbohydrate absorption D-xylose absorption 5 gm xylose powder A good screening test
test orally, 5 hour urine
collected, normal above
25% excretion
Fat absorption 3 day fat collection Normal less than 6 gm/ – Do –
in stool day
contd...
370 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Protein absorption Estimation of stool for

alpha-1 antitrypsin (3 day Normally absent
collection)

Vit B12 Scilling test

Radio labelled Vit. B12
given orally, urine
collected for 24 hours.
Normal above 8% excre-
tion
Stool examination For pus cells, parasites, Giardiasis, culture orga-
blood culture nisms greater than 10 ×
5 per ml points to bac-
terial overgrowth

Serum cholesterol Normal value 150- Decreased

250 mg/dl

Serum carotene Normal value greater Decreased Fairly satisfactory scre-

than 100 IU/dl ening test for malabsorp-
tion
Haemogram For excluding anaemia

Serum chemistry For excluding renal and

liver diseases

PROCTOSIGMOIDOSCOPY
For excluding diffuse colonic diseases:
i. Ulcerative colitis ii. Crohn’s disease
iii. Microscopic colitis iv. Villous adenoma of rectum

SMALL BOWEL BARIUM SERIES

For excluding gross mucosal abnormalities:
i. Characteristic pattern of malabsorption syndrome:
a. Scattering of barium
b. Flocculation of barium
c. Dilated bowel loops with thickened folds
ii. Other disorders:
a. Blind loop syndrome
b. Congenital structural defects
c. Tuberculosis
d. Crohn’s disease
e. Lymphoma
SMALL BOWEL MUCOSAL BIOPSY
Malabsorption Syndrome | 371

1. Biopsy of diagnostic value:

a. Granulomatous lesions in tuberculosis,
b. Foamy macrophages and PAS—positive bacteria in Whipple’s disease,
c. Dilated lacteals in intestinal lymphangiectasia,
d. Flagelate forms of giardiasis,
e. Basophilic infiltrates in mastocytosis,
f. Eosinophilic infiltrates in eosinophilic gastroenteritis,
g. Amyloid material in amyloidosis
2. Biopsy is abnormal but not diagnostic:
a. Tropical sprue: Absence of major villous and mucosal abnormalities + Partial villous atrophy
b. Coeliac sprue: Shortened and flattened villi
c. Collagenous sprue: Subepithelial collagen bands
d. Scleroderma: Fibrosis around Brunner’s glands

FLOW CHART FOR INVESTIGATIONS

Quantitative test for stool fat + Serum carotene

Normal suggesting Abnormal suggesting steatorrhoea is present

steatorrhoea is not present (confirms in 85% cases)
↓ ↓
Perform tests to detect selective malab- Differentiate 2 groups of causes of steatorrhoea
sorption of single nutrient such as:
i. Serum folate
ii. Serum iron Pancreatic cause Small bowel disorder
iii. Serum vitamin B12 ↓
iv. Scilling test Perform D-xylase absorption test

Normal value suggests pancreatic Abnormal value suggests

cause i. Small bowel disease
↓ ii. Bacterial overgrowth
Perform tests of pancreatic function Perform C-xylose Breath test

Normal: Suggests small Abnormal: Suggests bac-

Take abdominal plane Measure serumtrypsin bowel disease. terial overgrowth
film level (normal 29-80) ng/ ↓ ↓
↓ ml) Take small bowel radio- i. Small bowel culture
Diffuse calcification of ↓ graph: showing number of
pancreas suggests If decreased below 20 ng/ a. Confirms causes of bacteria elevated points
80% damage to ml also suggests pancre- bacterial overgrowth to bacterial over growth
exocrine pancreas atic insufficiency such as diverticula, ii. Small bowel biopsy
↓ dilated small bowel, confirms Whipple’s
If these tests of pan- Crohn’s disease. disease, abetalipopro-
creatic function not b. Shows abnormal pat- tinaemia, amyloidosis,
diagnostic tern of malabsorption Chrohn’s disease,
↓ (scattering and floccu- giardiasis, eosinophilic
Perform secretin test lation of barium with enteritis, lymphan-
dilated bowel loop) giectasia, lymphoma,
mastocytosis.
372 |
TREATMENT
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Dealt under 3 headings:

i. Non-specific therapy for combating nutrient deficiency, (ii.) Symptomatic therapy, (iii.) Specific
therapy
Non-specific therapy:

Agents Preparations Oral Dosages IM IV

..................
Calcium Calcium gluconate 5-10 gm t.d.s. 10% soln., 10-30 ml
Calcium carbonate 2 gm/day in divided slowly
dosages
Iron Ferrous sulphate 325 mg t.d.s. Imferon

Magnesium Magnesium gluco- 1-4 gm/day in divi- 10 ml b.d. or t.d.s. Magnesium sulfate
nate ded dosages 0.5% soln., up to
1000 ml slowly
Vitamin B12 100 microgram per-
day for 2 weeks and
then 100 micro-
gram monthly

Folic acid 5 mg/day for 1

month, then mainte-
nance dose 1 mg/
day

Vitamin B complex Any multi-vitamin 2 tabs/day Available

or B complex tab
Vitamin A 100000-200000 IU
daily, maintenance
dose 25000-50000
IU/day

Vitamin D 30000 IU/day

Vitamin K Menandione 4-12 mg/day Acute bleeding:

Vitamin K 50 mg IV
slowly over
10 minutes

Medium Easily hydrolysed by pancreatic lipase IV 50-100 gm/day

and do not need bile salt for transport for 3-7 days
Chain triglyceride
(MCT)
SYMPTOMATIC TREATMENT
Malabsorption Syndrome | 373

Anti-diarrhoeal agents:
Oral:
a. Lomotil: 2 tabs (5 mg) initially and 1-2 tabs after each bowel movement (Maximum 8 tabs/day)
b. Imodium: 2 caps (2 mg) initially and 1-2 caps after each bowel movement (Maximum 8 caps/day).

SPECIFIC TREATMENT
A. Anti-parasitic drugs:
i. Giardiasis: Metronidazole 250 mg tab t.d.s. for 7 days
ii. Worms: Albendazole 1 tab
B. Others:
Diseases Drugs Dosages Comments
Pancreatic insufficiency a. Pancreatic extracts Large dosages 6-8 tabs/day
with each meal
b. Adjuvants:
i. H 2 blocker: Cem- 150-300 mg
etidine, ranitidine 30 mg
lansoprazole Cheap, effective and lack of
ii. Sodium bicarbonate 650 mg before and after each side-effects
meal
Drug induced Stop offending drugs

Bile salt malabsorption Cholestyramine 4 gm t.d.s. before food

Tropica sprue i. Broad spectrum anti- Short course (2-4 weeks) is Diarrhoea producing dehy-
biotic: Tetracycline usually recommended. dration needs hydration with
ii. Folic acid glucose-electrolyte solution.
iii. Vitamin B12 For stoppage of diarrhoea:
Lomotil or imodium are req-
uired

Coeliac disease i. Glutein free diet: a. Nutritional supple-

Wheat, barley or rye ments with vitamins
replaced by rice, maize/ (particularly fat soluble
corn vitamins: A, D, K, E)
ii. Refractory cases needs b. Haematinics
corticosteroid

Gastrointestinal lymphoma i. Low grade lymphoma: a. Chemotherapy:

Tetracycline Indication:
ii. Treat H. pylori with i. Low grade lym-
amoxicillin + met- phoma not res-
ronidazole + lanso- ponding to anti-
prazole biotic. Regime:
Cyclophospha-
mide + vincristine
+ prednisolone
contd...
374 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues
Bacterial overgrowth
Scleroderma
Whipple’s disease
Crohn’s disease
Eosinophilic enteritis
Zollinger-Ellison syndrome
Lymphangiectasia
Carcinoid syndrome
Tetracycline, ampicillin,
trimethoprim with sulpha-
methoxazole, quinolones
In few cases antibiotics help
to minimize bacterial proli-
feration
Trimethoprim with sulpha-
methoxazole
i. Sulphasalazine
ii. Corticosteroid
Corticosteroid
H2 blocker
Methysergide
A single course or inter-
mittent courses (2-3 weeks/
month)
Treated at least for one year
Prolonged therapy
High-dose
8-12 mg/day
ii. For intermediate
and high grade
lymphoma:
Cyclophospha-
mide + Adria-
mycin + Vincris-
tine + Predni-
solone gives 50-
70% remission
b. Radiotherapy: Lymph-
oma is radiosensitive.
Usually used as adju-
vant therapy after
surgery or with chemo-
therapy
c. Surgery: Specially indi-
cated in young
Calcium, B12 protein sup-
plement
i. Low fat diet
ii. Substituting medium
chain triglyceride for
long chain triglyceride
 Alimentary System
63
Intestinal Parasites

DIAGNOSTIC CLUES

Clinical Features Suggestive Parasites

a. Pain abdomen, diarrhoea, dysentery Suggests intestinal parasites
b. History of residence and travel Tropics—Amoebiasis, giardiasis, worm infection
c. Contact with pets, or farm animals and Non-typhoid salmonella infection, hydatid, tape
exposure to beef or pork meat worm infection
d. Children day care centre Giardiasis, cryptosporidium
e. HIV infection Associated with giardiasis, cryptosporidium,
isospora
f. Bleeding gastro-oesophageal varices Schistosomiasis
secondary to portal hypertension
g. Seizure Cysticercosis
h. Cough, transient pneumonitis Seen in migratory stage of round worm, hook worm
and strongyloides
i. Vitamin B12 deficiency anaemia D. latum infection
j. Extraintestinal manifestations (liver, lung, Amoebiasis
brain abscess)
k. Chronic travellers’ diarrhoea Due to giardiasis, amoebiasis, aeromonas, tropical
sprue
l. Upper gastrointestinal symptoms (bloating, Giardiasis, strongyloides
flatulence, cramps)
m. Lower intestinal symptoms Amoebiasis, Trichuris trichiura
376 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

INVESTIGATIONS
1. Stool examination: For eggs (tapeworm), cyst, segments of tapeworm
2. Urine examination: For eggs of schistosomiasis
3. Stool culture: For amoebiasis
4. Colonoscopy and sigmoidoscopy—To detect pathological lesions
5. Ultrasound for liver abscess
6. Serum analysis: For amoebiasis antibodies
7. Blood film examination: For trypanosoma
8. Chagas’ disease:
a. Blood film for trypanosomes
b. Complement fixation test, fluorescent antibody test and Elisa test
9. Trichinosis:
a. Muscle biopsy b. Serological test
10. Cysticercosis:
a. Plane X-ray of abdomen to show calcified cyst
b. Casoni skin test non-specific
c. Hydatid complement fixation test
d. Ultrasound and CT scan shows space occupying lesion
11. Schistosomiasis:
a. Urine examination for ova
b. Indirect fluorescent test, Elisa test
c. Plane X-ray abdomen and CT scan shows calcification in the wall of bladder and colon.

DRUGS FOR PROTOZOA

Parasite Clinical Drugs Dose Disadvantage Advantage

Balantidium coli i. Symptoms like Tetracycline 500 mg q.d.s. for
amoebiasis 10 days
ii. F u l m i n a t i n g or iodoquinole 650 mg t.d.s. for
dysentery 20 days
iii. Contact with or metronidazole 250 mg t.d.s. for
pig and its 5 days
excreta

Blastocystis Diarrhoea Iodoquinol See above Optic atrophy after Iodoquinol best
hominis or prolonged use treatment
Metronidazole See above

Cryptosporodium Severe protracted Spiramycin 3 gm/day in divided

diarrhoea in HIV dosages for 2-
infection 4 weeks

Dientamoeba Diarrhoea, abdo- Iodoquinol See above

fragilis minal pain or
Tetracycline See above
or 25-30 mg/kg in
contd...
Entamoeba his- Diarrhoea dysen- Paromomycin 3 dosages for
Intestinal Parasites| 377

tolytica tery a. Tissue amo- 7 days

ebicide against
invasive tro-
phozoites:
i. Metronida- Orally or IV 750 Nausea, metallic
zole mg t.d.s. for 10 taste, neuropathy
or days after prolonged use,
disulfiram like
reaction (abdomi-
nal pain, nausea,
vomiting) with
ingestion of alcohol

ii. Tinidazole 2 gm/day for 3-5 Less effective than Less side-effect
or days metronidazole

iii. Emetine IM or SC 1 mg/kg Nausea, diarrhoea, Most potent

or per day (maximum hypotension, arrhy-
60 mg/day) for thmia, tachycardia,
5 days chest pain, dysp-
noea. Monitored by
ECG. Contraindi-
cated in pregnancy
and heart disease.

iv. Dehydro- IM or SC 1-1.5 mg Contraindicated in As effective as

emetine per kg/day (maxi- pregnancy emetine and less
mum 90 mg per toxic
day)

v. Chloroquine Orally 600 mg base Only used in liver

per day for 2 days abscess. Now sel-
followed by 300 dom used
mg base/day for 2-
3 weeks

vi. Tetracycline 500 mg q.d.s. for 5-

10 days
vii. Paromomy- See above
cin
b. Luminal amo-
ebicide against
cyst:
i. Diiodohy 600 mg t.d.s. for i. Occasional
droxyquin 20 days optic neuritis if
or higher dose
given
ii. C/I children
contd...
378 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

ii. Diloxanide 500 mg t.d.s. for Anorexia, nausea, Less toxic than
furoate 10 days vomiting, flatus, diiodohydroxyquin
Entamizole forte pruritus
(DF + Metroni-
dazole) Amiclin
plus (DF + tinida-
zole)
Giardiasis Diarrhoea a. Quinacrine 100 mg t.d.s. for Dizziness, head- Drug of choice
(Atabrin) 5 days ache, vomiting,
Mepacrine yellow staining of
skin, Disulfiram
like reaction with
or alcohol. C/I
b. Metronidazole 250 mg t.d.s. for 5- psoriasis
or 7 days or
2 gm once daily for
3 days
Tinidazole 2 gm single dose
or 100 mg q.d.s. for Nausea, vomiting,
c. Furazolidine 7-10 days allergic reaction,
or disulfiram like
d. Secnidazole 2 tabs single dose reaction with
alcohol
Isospora Chronic watery a. Septran or 1 tab q.d.s. for
diarrhoea in AID bactrim 10 days followed
patients or by 1 tab b.d. for 3
b. Pyrimetha- weeks 50-75 mg/
minemine day
(daraprim)

DRUGS FOR INTESTINAL HELMINTHES

Parasites Clinical Drugs Dose Disadvantage Advantage

Ascaris lumbri- Pain abdomen irre- Albendazole 400 mg single dose C/I pregnancy
coides gular bowel or
Mebendazole 100 mg b.d. for Abdominal pain, Drug of choice:
3 days diarrhoea Mebendazole,
pyrantel pamoate
Intestinal flukes Praziquantel: (cisti- 25 mg/kg in 3 divi- Nausea, vomiting,
cide—Merc) ded dosages for diarrhoea, rash,
1 day sedation. C/I preg-
nancy

Liver flukes – do – – do – – do –

Schistosomiasis – do – – do – – do –
contd...
contd...
|
Intestinal Parasites 379

Tapeworm: Niclosamide Single dose 4 tab Autoinfection

i. T. solium (pork (Niclosan Biddle (2 gm) chewed See prevention
tapeworm) sawyer) thoroughly
ii. T. saginata 500 mg tab
(beef tape-
worm
iii. H. nana Niclosamide Single 2 gm (4 tab)
followed by 1 gm
(2 tab) daily for
Trichuris trichiura Mebendazole 6 days
Albendazole Same as ascaris
Pyrantel pamoate – do –
– do –
Strongyloides Occasionally no Thiobendazole
stercoralis symptom 20 mg/kg bd for
2 days (maximum
Mebendazole 3 g/day)
Albendazole Same as ascaris
– do –
Multiple Secnidazole (nitro- 2 gm single dose Nausea, metallic
Infection midazole) taste, stomatitis.
E. hist., Seczole (Intas): Avoid in pregna-
Giardiasis, Plain 500 mg tab ncy. Avoid alcohol
T. vaginalis DS 1gm tab (dilsulfiram reac-
B. fragilis tion)

Multiple infection: Albendazole i. Hookworm

Hookworm, round and round
worm, tapeworm, worm: 400 mg
St ro n g y l o i d e s , single dose
hydatid, ii. T. solium and
Trichuris trichiura T. saginata:
400 mg/day for
3 days
iii. Strongyloides:
400 mg/day for
3 days
iv. Hydatid: 600
mg/day (one
and half tab)
for 9 months
v. Neurocysticer-
cosis: 400 mg
b.d. for 30 days
Dracunculosis Mebendazole Round worm,
(guinea worm) hookworm, trichi-
nosis: 1 tab b.d.

contd...
380 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Thiobendazole for 3 days Only relieve symp-

25 mg/kg/day for toms but can cure
3 days worm
Metronidazole 250 mg t.d.s. for ↓
10 days
Extraction of worm by winding a centimeter of it round a
stick each day. Antibiotic for secondary infection.

Table 63.1: Drugs and parasites

Drugs Parasites
Albendazole Enterobiasis, ascariasis, trichuriasis, hookworm, hydatid disease
Ivermectin Onchocercaisis, filariasis, strongyloides, also effective against coexisting ascariasis, trichuriasis
and enterobiasis
Mebendazole Enterobiasis, ascariasis, trichuriasis, hookworm, hydatid disease
Niclosamide T. solium, T. saginata, D. latum, H. nana
Piperazine citrate Ascariasis, enterobiasis
Praziquantel Neurocysticercosis, intestinal tapeworm
Pyrantel pamoate Enterobiasis, ascariasis, hookworm, strongyloides
Metronidazole Amoebiasis, giardiasis, Blastocystis hominis
Thiobendazole Dracanculosis, strongyloidosis

TREATMENT OF AMOEBIASIS
Intestinal Amoebiasis

Asymptomatic cyst Symptomatic trophozoites passers

passers (amoebic dysentery)
(Carrier State)
Diloxanide furoate Mild to moderate Severe disease:
Or i. Metronidazole + D. i. Oral or IV metronida-
Iodoquinole furoate or iodoqui- zole + D. furoate or
Or nol iodoquinol + emetine
Metronidazole Or or dehydroemetine.
Or ii. Paromycin ii. Replacement of fluid,
Tinidazole electrolyte and blood.
Or Surgical treatment: Comp-
Secnidazole lication such as perforation,
Or toxic megacolon needs
Paromycin 8-12 mg/kg appropriate surgical treat-
t.d.s. for 7 days ment.
 Extraintestinal Amoebiasis
|
Intestinal Parasites 381

Simple uncomplicated liver abscess Large abscesses and those threatening to If for any reason metro-
Metronidazole + D. furoate rupture nidazole not used
No therapeutic aspiration needed i. Therapeutic aspiration required ↓
↓ ii. Metronidazole + emetine Emetine + chloroquine
When metronidazole fails perhaps, due iii. Metronidazole better
to large or multiple abscesses:
i. Oral or IV large dosages of metro-
nidazole + emetine
ii. Therapeutic aspiration may be
required

TREATMENT OF TAPEWORM INFECTION

1. D. latum, T. solium,
T. saginata, H. nana,
D. caninum
2. Cysticercosis
A. Drug of choice: Niclosamide:
a. For D. latum, T. saginata
A single 2 gm dose (4 tabs)
T. solium, D. caninum
b. H. nana and H. diminuta
2 gm/day for 7 days
B. Paromycin: Effective also in a. For H. nana—45 mg/kg
D. latum, Taenia species and once a day for 5-7 days
H. nana: b. For D. latum and Taenia
1gm every 15 minutes for
4 dosages
C. Mebendazole: Also effective 300 mg b.d. for 3 days
in taenia
D. Praziquantel: Also effective in Single dose 10-20 mg
taenia, H. nana and D. latum: per kg
E. Vitamin B12 for anaemia of D. latum
A. Praziquantel is effective in Dose 50 mg/kg/day in 3
cysticercosis of brain and sub- divided dosages for 14 days
cutaneous tissue
Steroid may be added to
prevent immunological
reaction.
B. Surgery: For accessible symptomatic Cyst may also be marsup-
E. granulosus cyst. ialised or cryosurgery
used.

Caution should be used in treating T. solium. Therapy with niclosamide or praziquantel results in the
release of eggs of T. solium from the proglottides, which are then passed as free eggs per rectum. In the
absence of strict enteric precaution. These eggs can inadvertedly be transmitted to the patients’ mouth
(external autoinfection) or that of others and ingestion can result in cysticercosis.
382 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

TREATMENT OF TRICHINESIS
Symptomatic treatment
a. Fever, myalgia and fatigue of acute stage:
Analgesic and antipyretic are used thiobendazole
b. Allergic manifestations (periorbital oedema,
and conjunctival haemorrhage: Give predni-
solone 40-60 mg/day)
Specific drugs
Any drug cannot alter the course of the disease
once the migratory phase has begun. Mebenda-
zole will stop further dissemination from
intestinal tract but have little effect on already
encysted larvae.

TREATMENT OF HOOKWORM, ROUNDWORM AND TRICHURIASIS

Adult worms Cutaneous larva migrans

Round worm: Hookworm and tri- (Creeping eruption due to wandering

curiasis: of larval nematodes)
A. Drugs without much side-effects: 1. Mebendazole 1. Topical application q.d.s. of 10%
1. Albendazole 400 mg single dose 2. Albendazole suspension of thiobendazole
divided 3. Pyrantel pamo- 2. Oral thiobendazole 25 mg/kg in
2. Mebendazole 100 mg b.d. for ate 2 divided dosages for 2-5 days
3 days
3. Pyrantel pamoate
B. Drugs with side-effects:
1. Levimisole 150 mg single dose
for adult and 50 mg for child
2. Piperazine salt. Now, abandoned
If with multiple infection, round worm
should be treated first because some will
induce migration of ascaris larva into
biliary and pancreatic tree.
TREATMENT OF TRYPANOSOMIASIS
African Trypanosomiasis American Trypanosomiasis
I. Before brain is involved (Chagas’ disease)

A. Gambiense B. Rhodsiense No satisfactory treatment available.

Infection (West African) (East African) a. Nifurtimox 10 mg/kg/day in 4 divided
↓ ↓ dosages for 3-4 months.
i. Suramin 20 mg/kg (prepared as Suramin Toxicity: Anorexia, nausea, vertigo,
10% solution in distilled water) IV arthralgia
every 3-5 days till a total dose of b. Future drugs at present being
5-10 gm is reached. Urine exami- evaluated:
ned for casts and RBC to check Benzinazole 5 mg/kg for 60 days
for nephrotoxicity before each Ketoconazole
injection Verapamil
ii. Pentamidine as in leishmaniasis Allopurinol
iii. Eflormithine Recombinant interferon
 II. After brain is involved:
|
Intestinal Parasites 383

Melarsoprol (Mel 1B)

For serious patient: 0.5 ml initially—maximum dose 3.6 mg/kg, i.e. 5 ml for a man of 50 kg
or
Eflormithine + Melarsoprol + prednisolone
or
Melarsoprol + Suramin
TREATMENT SCHISTOSOMIASIS (BILHARZIASIS)
Type of Infection Praziquantel Oxaminquine Metriphonate
S. mansoni Effective in all species 15 mg/kg 12 hourly Not useful
30 mg/kg twice in one day for 2 days
S. Japanicum 40 mg/kg once Not effective Not effective
S. haematobium 40 mg/kg Not effective 7.5 mg/kg every 2 or 3 weeks

Prevention
Personal hygiene: General measures:
Grooming of nails, hand washing before meal and after toilet.
Education, sanitation, efficient sewer disposal. Safe drinking water. All food handlers should have
their stool checked and treated.

Special Precautions
a. Chlorination of water does not destroy amoeba cyst, but adequate boiling and filtration of water
(boiling for 5 minutes) kill cysts.
b. Visitors to tropics: Boil water for 5 minutes. Cooked food should not be purchased from the market.
Fruits that can be peeled are safe. Salad vegetables can be soaked in dilute solution of sodium
hypochloride and then rinsed in boiled water.
c. Improvement in houses.
d. Don’t eat uncooked pork meat and beef to prevent tapeworm and trichinosis
e. For prevention of hydatid:
i. Prevention of infestation of dogs by their exclusion from slautering areas.
ii. Installation of deep offal pits or incineration system in slaughter houses
iii. Education of farmers
iv. Control stray dogs
v. Dog immunisation is a future measure
f. For prevention of hookworm:
i. Elimination of soil pollution by human excreta
ii. Wearing of shoes to avoid larva penetrating skin of foot
g. For prevention of trypanosomiasis:
i. African type: A single injection of pentamidine prevents gambience infection for 6 months.
Early treatment of patient is preferred.
ii. American type: Improvement in housing and killing of residual bugs by spraying of houses by
gamma BHC.
 Alimentary System
64
Constipation

DEFINITION
Constipation has the following characteristics:
i. Infrequent passage of stool
ii. Passage of hard stool
iii. Passage of small volume stool
iv. Straining to defecate
v. Sense of incomplete evacuation

FACTS RELEVANT TO TREATMENT

Causes
A. Intestinal:
i. Colonic disorders: Cancer colon, tuberculous bowel, volvulus, intussusception, intestinal
obstruction, Hirschprung’s disease, stricture (ischaemic, diverticulitis, postoperative) diverticulitis
ii. Rectal: Rectocele, rectal ulcer, haemorrhoids, rectal stricture (ulcerative colitis, postoperative)
rectal abscess, fissure, prolapse rectum
iii. Anal: Fissure, stricture
B. Neuromuscular:
i. Neurogenic: Multiple sclerosis, cerebrovascular accident, Parkinsonism, spinal cord lesion
Hirschprung’s disease, Chaga’s diseases, neurofibromatosis
ii. Muscular: Myopathy, amyloidosis, scleroderma
C. Endocrine and metabolic disorders:
Diabetes, hypothyroidism, panhypopituitarism, pregnancy, uraemia, hypercalcaemia, porphyria
D. Dietetic and habitual causes: Low fibre diet, lack of adequate fluid (dehydration), lack of exercise
prolonged travel, inadequate time for defecation, suppression of defecatory urge
E. Drugs: Anticonvulsants, calcium channel blockers, lead and mercury toxicity
F. Psychological: Anxiety, depression.

DIAGNOSTIC CLUES
Clinical features suggestive of aetiology:
Clinical features Probable aetiology
Constipation| 385

Symptoms beginning in childhood Hirschprung’s disease

Recent constipation in elderly or in adult with Malignancy

family history of colonic malignancy

Recent constipation in elderly Malignancy, ischaemic stricture, diverticulitis

Blood in stool, distension, vomiting, fever, weight Excludes functional disorders

loss

Recent intake of some drug Points to drugs as the aetiology of constipation

Recent surgery Colonic stricture

Recent reported constipation with occult Malignancy

blood and tenesmus

Stool of thin caliber Rectal or sigmoid colon stricture

Abdominal lump and dilated intestinal coils Intestinal causes

PR examination:
i. Rectal mass Malignancy
ii. Stool absent in rectum Hirschprung’s disease

INVESTIGATIONS

Barium enema Flexible sigmoidoscopy: Coloscopy: Rectal biopsy:

Reveals diverticuli, Reveals polyp, cancer of Indications are same as Confirms
stricture, malignancy, colon and rectum, colitis, barium enema. Shows Hirschprung’s disease,
Hirschprung’s disease sigmoid diverticular tumour, polyp, inflam- cancer, tuberculosis
constricted distal colon disease matory bowel disease,
with proximal dila- diverticular disease,
tation) volvulus
Indications for barium
enema:
i. Recent change in
bowel habits
ii. Stool positive for
occult blood
iii. Malignancy sus-
pected
386 |
MANAGEMENT
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Flow chart:
First educate the patient about colonic function and use of mild laxatives

Dietetic: Habit training Drugs

Adequate use of fibre sup- i. Regular defecation Mild laxative such as psyl-
plements: Unprocessed ii. Adequate time for defeca- lium hydrophilic colloids—
bran, fresh vegetables, tion bulk laxative (isogel, natu-
fruits, mucillages, cellulose, iii. Proper place for defecation rulax): 1 tsf (7 gm) t.d.s. until
corn, oats, they are contra- the result and then continue
indicated in gas bloating, that dose
obstructive cases.
↓
If no response to the above measures
Try potent laxatives (stimulant laxatives)
↓
If no response, think of organic causes and
If found treat them by medical treatment
↓
If medical treatment fails, resort to surgery
specially for Hirschprung’s disease and any
organic abnormalities

LAXATIVES
Types Preparations Dose Disadvantages Advantages
Bulk laxative: Increases Naturulax (intercare) 2 tsf with water at bed- i. Produces intesti- Totally harmless for
stool bulk Isogel (glaxo) time or twice daily nal obstruction if regular use
taken without
water
ii. Impaction above
stricture
iii. To prevent psyl-
lium bezoar drink
adequate amount
of water
+
iv. Contraindica-
tions: Abdominal
pain of unknown
aetiology, intes-
tinal obstruction,
gastrointestinal
bleeding and
faecal impaction
contd...
contd...
Constipation |387

Emolients: Anionic Docusates: Laxicon tab Up to 500 mg/day in Skin rash Useful for short-term
surfactant action. Pene- 100 mg (stadmed) divided dosages use (1-2 weeks) for
trates fluid into faeces Enema 0.25% Or avoidance of straining
Solution—50 ml 50-360 mg/day as in painful anal con-
ditions, AMI, after
abdominal and rectal
surgery or during preg-
Osmotic Laxative: nancy
a. Saline: Increases 1. Cremaffin (knoll) 7.5-15 ml at bedtime Sodium and magne-
intraluminal water containing milk of sium overload espe-
content magnesia + liquid cially in chronic renal
paraffin failure
2. Cremaffin pink
(milk of mag +
phenolphthalein)
b. Lactulose: Duphalac (duphar 10 gm b.d. Contraindication: Useful in patient whose
Retains fluid in interfran) Intestinal obstruction, colon is full of hard
intestinal lumen Side-effects: Gas blo- scybala because it sof-
ating, abdominal tens stool
cramps, flatus
Lubricant: Softens Agrol (warner) contai- 7.5-15 ml at bedtime i. Decreases absorp-
stool ning liq. paraffin + tion of fat soluble
phenolphthalein + agar vitamins (A, D, E,
K) if used chroni-
cally
ii. Paraffin pneumo-
nia
iii. Paraffinoma in
mesenteric nodes,
liver, spleen
Stimulants: a. Biscodyl dulcolax 5-10 mg nightly i. Contraindication:
Contact laxative (german reme- Acute surgical
stimulates colonic dies) 5 mg tab abdomen
motor activity b. Phenolphthalein: 7.5-15 ml at bedtime ii. Side-effects: Potent laxative
Cremaffin pink Abdominal cra-
(knoll) mps. Don’t give
c. Senna: Glaxenna 2 tabs at bed time antacid within
(glaxo) one hour of drug
produces electro-
lyte imbalance.
Antraquinone
laxative produces
benign melanosis
coli
Antispasmodic: Propantheline, mebe- 15 mg b.d. or t.d.s. Side-effects: Dry Mebeverine has more
verine, dicyclomine mouth, urinary specific effect on colon
retention and less side-effects
than propantheline and
dicyclomine
388

ENEMA
| Bedside Approach to Medical Therapeutics with Diagnostic Clues

Local Preparations
Large volume washouts with warm normal saline, oil retention enema (olive oil, arachis oil) and disposable
hypertonic saline enema, suppositories (glycerin, biscodyl). These agents are useful in:
i. Elderly
ii. Neurological deficits
iii. Constipation following abdominal surgery or prolonged bed rest.

LAXATIVE ABUSE
1. Major stimulant laxatives (senna, phenolphthalein, cascara, castor oil) can destroy intraluminal
nerve plexuses in the large bowel, causing “cathartic colon” (producing radiological appearance
similar to that of ulcerative colitis: A pipeline colon lacking haustrations + abnormal propulsive
activity).
2. Other disturbances:
i. Major electrolyte imbalance.
ii. Mild steatorrhoea.
iii. Protein loosing enteropathy.

SURGERY
Surgery is rarely required. Only indications are:
i. Hirschprung’s disease.
ii. Anatomical abnormalities such as stricture and obstruction.

FECAL IMPACTION
i. 150-200 ml of mineral oil retention enema followed by tap water enema and repeated as necessary.
ii. Occasionally manual evacuation necessary.
 Alimentary System
65
Diarrhoea

CLINICAL TYPES
1. Acute : Mild : 1-3 stools per day
Moderate : 4-5 stools per day
Severe : Above 6 stools/day
2. Chronic

Causes of Acute Diarrhoea

Lasting less than 3 weeks.
A. Osmotic diarrhoea: Due to large quantity of poorly absorbable osmotically active solutes:
Malabsorption, lactase deficiency, high carbohydrate diet.
Drugs: Laxative, antacids, lactulose
B. Secretary diarrhoea: Lymphoma, inflammatory bowel disorders, granuloma of intestine, Zollinger-
Ellison syndrome, hyperthyroidism, collagen vascular disease
C. Infective diarrhoea:
General Food poisoning AIDS
Bacterial E. coli, Clostridia Mycobacterium avium
Salmonella Salmonella intracellulare
Shigella Staph. aureus
Clostridia Vibrio
Shigella
E. coli
Yersina
Listeria
Parasitic: Giardiasis
E. histolytica
Tapeworm
Isospora
Viral Rota Cytomegalovirus
Norwalk Herpes simplex
Adenovirus
Fungal
390 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

D. Drug diarrhoea: Antacids, anti-arrhythmics, antibiotics, anti-neoplastic, antihypertensive,

theophylline, NSAIDs prokinetics, prostaglandin
E. Miscellaneous causes: Fecal impaction, intestinal ischaemia, acute diverticulitis.
Important causes of chronic diarrhoea:
i. Inflammatory bowel disorders (ulcerative colitis, Crohn’s disease)
ii. Infection: Bacterial, tuberculous, parasitic, fungal
iii. Malabsorption
iv. Ischaemic bowel disease
v. Drugs
vi. Colonic cancer
vii. Villous adenoma
viii. Diverticulitis
ix. Endocrine causes: Diabetes, Addison’s disease, hyper and hypothyroidism
x. Previous surgery: Gastrectomy, vagotomy, cholecystectomy, ileal resection
xi. Fecal impaction
xii. Irritable bowel syndrome.

Diagnostic Clues
Clinical features suggestive of probable causes are depicted below:
Clinical features associated with diarrhoea Probable diagnosis
A. Symptoms:
i. About diarrhoea:
a. Diarrhoea persisting for 1-3 days Viral diarrhoea
b. Prolonged watery diarrhoea Giardiasis
ii. Relation with contaminated food
a. History of shared contaminated food Food poisoning
b. Diarrhoea developing 12 hours of the meal taken Due to preformed
staphylococcal exotoxin
c. A lag period of 3 days after consumption of contaminated Food poisoning due to
food salmonellosis
iii. Lower abdominal cramp, abdominal tenderness, tenesmus, a. Bacterial diarrhoea
rectal urgency and in severe cases stool mostly bloody b. Inflammatory bowel
disorders
Right lower quadrant pain Crohn’s disease
Left quadrant abdominal pain Diverticulitis
B. Signs:
i. Fever Ulcerative colitis, Crohn’s disease, tuberculosis, amoebiasis,
lymphoma
ii. Marked weight loss Malabsorption, inflammatory bowel disorders cancer,
thyrotoxicosis
iii. Lymphadenopathy Lymphoma, Whipple’s disease, AIDS
iv. Neuropathy Diabetes, amyloidosis
v. Postural hypotension Addison’s disease, diabetes
 vi. Flushing Malignant carcinoid syndrome
Diarrhoea | 391

vii. Perianal disease with right Crohn’s disease

abdominal pain
viii. Hyperpigmentation Whipple’s disease, Addison’s disease celiac disease
ix. Emotional stress causing Irritable bowel syndrome
exacerbation of diarrhoea
in a case of chronic
recurrent diarrhoea
x. Oedema, ascitis anasarca Protein loosing enteropathy
C. Previous history of surgery Cholecystectomy, postgastrectomy, vagotomy
D. Response to therapy:
i. Corticosteroid responsive Ulcerative colitis, Crohn’s disease, Whipple’s disease,
diarrhoea Addison’s disease, pancreatic cholera eosinophilic enteritis
ii. Antibiotic responsive diarrhoea Bacterial overgrowth due to stasis in small intestine, tropical
sprue, Whipple’s disease, celiac disease
D. Association of certain disease with diarrhoea
i. Diarrhoea in anorexia nervosa Due to laxative abuse
ii. Arthritis Ulcerative colitis, Crohn’s disease, Whipple’s disease
iii. Peptic ulcer Zollinger-Ellison syndrome, gastrocolic fistula antacid
therapy
iv. Diarrhoea in male homosexual Due to giardiasis, shigellosis
E. About stools:
i. Large volume stool Site of diarrhoea in small intestine due to Crohn’s disease,
tuberculosis, fungal infection lymphoma, amyloidosis,
carcinoid tumour
ii. Small volume stools Site is left part of colon and rectum due to ulcerative colitis,
Crohn’s disease, amoebiasis diverticulitis
iii. Blood mixed with stool Inflammation rather than neoplasm
iv. Only mucus in stool without Irritable bowel syndrome
blood
v. Frothy stool and excessive flatus Putrifaction of unabsorbed aminoacids
vi. Visible fat or oil in stool Severe steatorrhoea
↓
Investigations
Interpretation of diagnostic tests is as follows:
Diagnostic tests Interpretation
A. Stool examination:
i. Large number of white cells Inflammation, colitis (Inflammatory bowel disorders, amoebic
colitis, tuberculous colitis, ischaemic colitis)
ii. White cells absent (white cells Antibiotic related colitis, giardiasis, viral diarrhoea, irritable
found rarely, only scattered is bowel syndrome, laxative abuse, E. coli
within normal limit)
iii. Occult blood in stool Suggests inflammation, has same significance as white cells
stool
392 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

iv. No pus cells in bloody stool Neoplasm of colon, heavy metal poisoning, ischaemic damage
of gut
v. Excess fat as shown as Sudan a. Steatorrhoea
stain b. Steatorrhoea in traveller’s diarrhoea suggests giardiasis
vi. Alkalinisation of stool results Phenolphthalein abuse
in pink colour
vii. Parasites Amoebiasis, giardiasis, worms
viii. Bacterial culture positive Infection
ix. Quantitative faecal fat estimation. Positive test suggests malabsorption
72 hour collected stool should
be quantitatively analysed for
fat content:
Indications:
a. When malabsorption suggested by
history and physical examination
b. When qualitative test of faecal fat
(Sudan stain positive) is positive
c. The patient has diarrhoea of
unknown origin

B. Blood count: Eosinophila Parasites, eosinophilic gastroenteritis

C. Urine examination: Proteinuria Amyloidosis, protein loosing enteropathy

Proctosigmoidoscopy
i. Shows presence or absence of mucosal inflammation in antibiotic associated diarrhoea. Normal
mucosa found in malabsorption
ii. Finding of solid stool in rectum suggests: Acute diarrhoea is subsiding
or
Irritable bowel syndrome
or
Diarrhoea secondary to faecal impaction
or
Diarrhoea is an illusion

Rectal Biopsy
May reveal:
(i) Amyloidosis, (ii) Whipple’s disease, (iii) Melanosis coli, (iv) Microscopic colitis

Therapeutic Tests
Good response to test substances Suggestive diagnosis
Pancreatic enzymes Pancreatic diarrhoea
Antibiotics Infective diarrhoea
Metronidazole Amoebiasis, giardiasis
Cholestryamine Bile acid malabsorption
Diarrhoea| 393

Indomethacin Prostaglandin induced diarrhoea

Various diets such as lactose free, carbohydrate free, low fat and avoidance of any specific food (food
allergy) may relieve diarrhoea (suggestive of offending diet.)

Treatment of Acute Diarrhoea

A. Correction of dehydration and electrolyte disturbances:
Mild to moderate cases Serious cases
a. Oral rehydration by oral rehydration solution (ORS). IV fluid is required
It is not contraindicated in presence of vomiting.
The only precaution is to give in small amount more
frequently. (See Table 65.1: ORS)
b. In children: 50-100 ml/kg over 4-6 hour—1-2 tsf every
10 minutes and after each hour fluid volume doubled
After patient is rehydrated:
ORS 100-200 ml/kg weight
every 24 hour until diarrhoea ceases

Table 65.1: ORS

Composition (WHO recommendation) mEq/L when diluted
Na K Cl HCO3 Glucose Form
90 20 80 30 20 g/L Powder
Making of ORS at home:
Items: Amount
Baking soda 1/2 tsf
Table salt 1/2 tsf
Table sugar 2 tablespoon
Or honey
Boiled water 1 litre

B. Addition of aminoacids to glucose based ORS or substitution of rice or grain gruel for glucose is
effective. Banana, rice, apple sauce and toast may be added after diarrhoea abates.
C. Antibiotics: Their use is controversial. Special indications for antibiotics are as follows:
a. Extremes age, malignancy, immunocompromised patients; Valvular, vascular or orthopedic
prosthesis.
b. Certain infections: Shigellosis, cholera, travellers’ diarrhoea, pseudomembranous enterocolitis
and parasitic disease (amoebiasis, giardiasis)
c. Combination of antibiotics: Most of the infections respond to quinolones (ciprofloxacin,
norfloxacin) + metronidazole or tinidazole.

Prevention
a. Ensure clean drinking water
b. Proper disposal of sewage
c. Strict personal hygiene should be maintained by food handlers
394 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

d. Travellers’ diarrhoea: Always drink boiled water. Avoid other drinks. Don’t eat raw vegetables raw
meat and sea food.
e. Breast feeding prevents infection in infants.

Treatment of Chronic Diarrhoea

A. Avoidance of milk and milk products and lactose containing food.
B. Nutritional supplements: Vitamins and mineral are prescribed.
C. Treatment of aetiology:
Aetiology Treatment
Secretory diarrhoea Diphenoxylate or loperamide. Contraindicated in
infectious diarrhoea and inflammatory bowel disorders
Diabetic diarrhoea Clonidine
Neuroendocrine tumours of pancreas, Octreotide (a synthetic somastatin analogue)
carcinoid tumour, short bowel
syndrome, HIV infection
Zollinger-Ellison syndrome Proton pump inhibitors
Bile salt malabsorption Cholestyramine

Travellers’ Diarrhoea
Diagnostic clues: Unformed stool, abdominal cramps, nausea, bloating, urgency, 5% cases: Fever, bloody
stool. Duration of diarrhoea above 1 week.
Treatment of Travellers’ diarrhoea: Mild cases:
Drugs Adult dosages Comments
Bismuth subsalicylate 30 ml every 30 mts for 8 dosages Liquid better than tablet.
Stool stains black.
Loperamide (Imodium) 4 mg stat, then 2 mg after each Contraindicated in bloody
loose stool. Maximum 16 mg/day stool and fever
Moderate to severe cases:
Bactrim DS 1 tab b.i.d. for 3-5 days Rash, contraindicated in near term
pregnancy
Norfloxacin 400 mg b.i.d. for 3-5 days Contraindicated in pregnancy, child
Ciprofloxacin 500 mg b.i.d. for 3-5 days – do –
Doxycycline 1st day 100 mg b.i.d., then
100 mg/day for 3 more days
For special circumstances:
Furazolidine 100 mg 6 hourly for 3 days For giardiasis
Tinidazole 500 mg b.i.d. for 3-5 days For giardiasis, amoebiasis
Metronidazole 400 mg b.i.d. for 3-5 days For giardiasis, amoebiasis and
pseudomembranous colitis
Preventive:
A. General: Boil water, peel fruit, cook properly
B. Chemoprophylaxis:
To be continued for 2 days after patient returns home.
Drugs Adult dosages Percent of protection Comments
Diarrhoea | 395

Bismuth i. 1 tab qds 40-60% i. Best

subsalicylate ii. 60 ml qds ii. Blackens tongue and stool
iii. Contraindicated if patient taking
anticoagulant, aspirin and
probenecid
Doxycycline 100 mg/day 60-80% Photosensitive reaction

Bactrim DS 1 mg/day 70-90%

Norfloxacin 400 mg/day 80% C/I child, pregnancy

 Oral Medicine
66
Oral Medicines

Dental Caries
Diagnostic clues Treatment
Early decay of tooth with pain. X-ray evaluation i. Proper hygiene to reduce dental plaque by
brushing, preferably with fluoride tooth paste,
flossing and vigorous mouth rinsing
ii. Diet: Reduce carbohydrate
Acute gingivitis: Acute ulcerative gingivitis:
vincent’s gingivitis:
Diagnostic clues Treatment
Pain, fetid odour, i. Improve oral hygiene
Gingival ulceration ii. Hydrogen peroxide mouth rinses (3% H2O2,
Smear shows spirochaetal and fusiform mixed with equal parts of warm water)
Bacilli iii. Penicillin or erythromycin if fever, lymph-
adenopathy present phenoxymethyl penicillin
250 mg q.d.s. for a week
iv. Metronidazole 200 mg t.d.s.
v. Warm saline gargle during acute phase
Candidiasis:
Diagnostic clues Treatment:
Creamy white fungal i. Treat underlying factors such as hyperglycaemia,
Colonies with erythema and mouth discomfort xerostomia and anaemia.
ii. Drugs: Acute condition:
a. Hydrogen peroxide—saline rinse (3% H2O2
diluted with equal parts of warm saline)
b. Sucking tablet of nystatin 50000 U q.d.s.
c. Clotrimazole tablet 10 mg dissolved orally
5 times a day
d. Ketoconazole 200 mg orally daily with flood
Chronic muco-cutaneous candidiasis:
No response to topical treatment. Clotrimazole or
miconazole may benefit. Amphotericin B is nephro-
toxic.
 Treatment of aetiology:
Oral Medicines | 397

Glossitis: i. Treat blood dyscrasias if present

ii. Treat malnutrition
iii. Treat anxiety and depression
iv. Find out if any drug reaction. Stop them if
present
v. Treat xerostomia and dehydration if present
vi. Treat candidiasis if present
vii. Treat hyperglycaemia if present
viii. Stop smoking
ix. Look for malignancy
Pharmacological approach:
i. Vitamins
ii. Tranquillizers and antidepressant
iii. Sialogogues such pilocarpine or bethanecol
may help occasionally
Alternative therapy:
If all the above treatment fails, hypnosis,
biofeedback may benefit.

Leukoplakia
Characterised by white and red patches occurring on oral mucosa which cannot be scraped off.

Flow Chart for Management

First, remove all irritants: Tobacco, ill fitting denture, poor hygiene, spicy and hot foods.

Lesion reversible Lesion not reversible

Take biopsy

Shows benign hyper-
keratosis and erythroplakia
due to epithelial atrophy
and inflammation
Indicates dysplasia due to malignant If lesion cannot be clas-
changes. Also strengthened by the sified as any specific
following features: Female, persis- disease
tence of lesions for some years, ↓
lesion on margin or base of tongue, Follow closely because
erosive lesions, speckled lesions of risk of malignant
(leukoplakia with small, red, velvety transformation
areas) and sublingual keratosis)
↓
Remove the lesion surgically.
Carbon dioxide, laser resection or
evaporation is also effective
398 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Apathous Ulcer
Diagnostic clues: Shallow, pseudomembrane-covered ulceration with a surrounding erythematous hallo.
May be associated with inflammatory bowel disease and Behçet’s syndrome.
Treatment
General measures: Bland mouth rinse, topical preparations, vitamins, mild sedatives and analgesics.
Specific measures: Steroids:
a. Prednisolone 40 mg orally daily for 2-3 days
b. Triamcinolone or hydrocortisone sodium succinate or betamethasone tablet kept in mouth or their
ointment applied t.d.s. until ulcer disappears
Other measures: Tetracycline mouthwash followed by application of emollient dental paste after
meals and at bed time.

Herpes Labialis: Cold sore:

Diagnostic Clues: Blisters on vermillion line of lips and adjacent skin. They are recurrent.
Treatment
a. Idoxuridine solution or ointment (1%) applied q.d.s.
b. Tetracycline (1%) or neomycin (1%) ointment applied q.d.s. for secondary staphylococcal infection.
c. Severe cases: Acyclovir IV 5 mg/kg every 8 hour.
Other steroid responsive oral lesions:
Bullous lesions of pemphigus, lichen planus.

Erythema Nodosum
Diagnostic clues: Red tender nodules on extensor aspect of lower limbs, often associated with arthralgia
or arthritis, usually seen in children and young adult.
Treatment
a. Oral lesions: Topical tetracycline and minocycline capsule dissolved in water and applied q.d.s.
b. Extra-oral manifestations: Corticosteroids.
Xerostomia:
a. Eliminate causes if any
b. Frequent sips of water
c. Meticulous oral hygiene
d. Treatment or prevention of candidiasis by topical nystatin
e. Glycerine
f. Methylcellulose as lubricant.
Inflammation of Salivary Glands:
a. Acute: Treat infection with antibiotics. Oral hygiene
b. Chronic sialadenitis: Remove obstruction such as calculus.
Haliostosis (Bad breath):
Remove and treat causes: Chronic tonsillitis, atrophic rhinitis, respiratory tract infection, gastrointestinal
disorders.
Tonsillitis
Acute tonsillitis
Characterised by sore throat, fever, dysphagia.
Tonsil swollen exuding pus (easily wiped away)
Treatment: Bedrest, ample bland fluid to drink,
semi-solid diet, mild purgative.
Severe cases: Penicillin for 1 week
Pharyngitis
Acute pharyngitis
Characterised by tickling sensation or a lump in
the throat, severe dysphagia, husky voice, cervical
gland may be enlarged with red and swollen
pharynx.
Treatment: Avoidance of smoking, talking, alcohol
and irritant foods. Aspirin may help.
Oral Medicines | 399
Chronic tonsillitis
Characterised by frequent attacks of acute
tonsillitis and chronic sore throat without much
systemic reaction
Treatment: Appropriate treatment for dental and
sinus infection, smoking, alcohol and dusty
atmosphere avoided. Mandl’s paint applied to fauces
and tonsils twice daily for two weeks.
Chronic pharyngitis
Characterised by aching, feeling of a lump, voice
has dead tone, pharyngeal mucosa thickened, uvula
elongated posterior wall filled with mucus traversed
by enlarged venules.
Treatment: Eradication of infection in mouth or
nose, avoidance of alcohol, smoking, excessive use
of voice, a warm alkaline saline gargle may help
and allay the anxiety of cancer.
 Liver, Gall Bladder and Pancreas
67
Acute Infective Hepatitis

DEFINITION
Acute infective hepatitis denotes inflammation of liver by haptotropic viruses: A, B, C, D, E, Non-A,
Non-B and recently described virus G.

Aetiological, Clinical, Investigational Facts you can use in the Management of Acute
Infective Hepatitis:
Aetiology
Causative agents Characteristics of liver disease
A. Acute hepatitis viruses: Damages liver with prodromol ‘flue like’ illness
A, B, C, D, E, Non-A, Non-B
B. Cytomegalovirus Rare. Sometimes seen in immunosuppressed patients
Herpes simplex virus
Herpes zoster virus
C. Drugs: a. Acute and chronic hepatitis
Halothane
Methyldopa
Antituberculous drugs
Phenylbutazone b. Granulomatous hepatitis
Allopurinol
D. Chemicals: Alcohol Hepatitis

Clinical Clues
A. Mild to moderate hepatitis:
Symptoms Signs
Prodromol symptoms of ‘flue-like’illness for
a few days to two weeks followed by jaundice. Hepatic: Extrahepatic:
Enquire about drugs, alcohol, exposure to Tender hepato- Arthralgia, arthritis, and
industrial toxins, travel, contact with jaundiced megaly urticaria in hepatitis B
patient, male homosexual and blood and non-A and non-B
transfusion hepatitis
B. Fulminant hepatic failure associated with
cerebral oedema
Course of hepatitis:
Acute Infective Hepatitis | 401

HBV infection Acute HAV infection

Drug induced hepatitis
Subclinical Icteric Chronic 10% ↓
65% 25% Complete recovery
99% recovery 99% recovery Healthy carrier Chronic hepatitis
1% death 70%-90% 10%-30%
↓
Cirrhosis hepatic
cancer

INVESTIGATIONS
A. Liver function tests:
AST, ALT Alkaline Prothrombin Gama- Low albumin
↓ phosphatase: time glutamil points to
Elevated in icteric transferase:
Phase of acute ↓ ↓ ↓ ↓
hepatitis elevated in Persistently Much elevated alcoholic
cholestasis elevated, in alcholic hepatitis,
found in alco- points to hepatitis and chronic
Level falls slowly Persistently holic and drug fulminant autoimmune hepatitis
in three months in elevated level induced hepa- hepatic hepatitis and
uncompleted even after titis failure and cirrhosis
recovered cases 3 month points ↓ severe
to chronic a. Ultrasound cholestasis
hepatitis of liver done to
exclude extra-
hepatic biliary
obstruction by
showing no
dilated intra-
hepatic biliary
duct.
b. ERCP may also
be needed
B. Virology and serological studies: See Table 67.2: “Serological Patterns in Infective Hepatitis”
Table 67.1: Life history of serological marker of viral infection
When appears in blood When disappears from Interpretation Immunity
blood
I. Hepatitis
A. virus: Early first appearance Persists for several Diagnostic of recent No
i. IgM antibody in acute illness with months (6 months) and infection
anti HAV elevated ALT then disappears
contd...
402 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

ii. Ig G anti-HAV Appears during conva- Detected throughout Diagnostic of past Confirms
lence in 2-6 weeks life and used as epi- infection
demiological tool to
assess frequency of
II. Hepatitis infection
B. virus:
i. Hbe Ag Appears transiently in Disappears in 2-6 It persistence for more
all patients weeks than 8 weeks points to
carrier state

ii. Anti-HBc First appears in blood Disappears after seve- Not found if patient
antibody during 2nd month ral months immunised

iii. Anti-Hbe Appears after appear- Persists for several Suggests good reco-
antibody ance of anti-HBc months very
during 3rd week

iv. IgM anti-HBc Appears with onset of Persists for 3-6 months Diagnostic of recent
symptoms HBV infection

v. IgG Anti-HBc Appears later Persists in blood for

several years

vi. Serum anti- Appears 4 months after Persists throughout life Indicates complete
HBs onset of symptoms recovery Lifelong immunity

Table 67.2: Serological patterns in infective hepatitis

Abnormal Patterns Interpretation

1. HBs Ag Present Acute HBV infection. High infectivity
IgM anti-HBV Present
HBe Ag Present
Anti-HBs Absent
Anti-Hbe Absent

2. HBs Ag Present Chronic HBV infection. High infectivity

Ig G anti-Ag Present
HBe Ag Present
Anti-Hbe Absent
Anti-HBs Absent

3. HBs Ag Absent Remote past infection of HBV

Anti-HBS Absent
Ig G anti-Hbc Present
Hbe Ag Absent
contd...
contd...
Acute Infective Hepatitis | 403

4. Ig M anti-HAV Present Acute HAV infection

5. Anti-HAV Present Past infection of HAV. Immune to reinfection
with HAV with HAV
6. HBe Ag Present a. Chronic carrier of HBV
b. Chronic infection with HBV
7. Anti-HBe antibody Present Complete recovery
8. Ig antibody anti-HEV Present Chronic infection with HEV
9. Ig M antibody Anti-HEV Present Acute infection with HEV
10. HCV antibody Present Infection with HCV
(Third generation ELISA test)
11. Anti-HDV and IgM Present Acute infection with HDV
Anti-HDV
12. Antinuclear antibody Present Autoimmune hepatitis
Anti-smooth muscle antibody Present
Anti-liver-kidney microsomal Present
(LKM) antibodies

MANAGEMENT OF ACUTE VIRAL HEPATITIS

It is described under three headings:
1. Management of acute viral hepatitis A, B, Non-A and Non-B
2. Management of acute hepatitis C
3. Fulminant hepatic failure

MANAGEMENT OF ACUTE HEPATITIS A, B, Non-A, Non-B and E:

Majority of hepatitis A and E recover completely without therapeutic intervention. No specific treatment
exists.
A. General management:
Conventional old recommendation Recent recommendation
1. Bedrest: Does little to speed resolution 1. Strict bedrest is not essential. Vigorous exercise
detrimental. Restricted physical activity is advised.
2. Diet: Low fat diet 2. Low fat diet is not advised unless presence of
nausea and vomiting. High caloric diet is advised.
IV glucose is needed if patient has persistent
vomiting. If severe vomiting sips of fluid
is allowed.
3. Corticosteroids 3. Only indicated in rare cases of prolonged
cholestasis. It relieves itching and reduces serum
bilirubin relapses common after cesation of
corticosteroid.
B. Treatment of aetiology: Withdraw causative drugs and alcohol.
C. Symptomtic treatment:
a. Severe pruritus : Cholestyramine, antihistaminic.
b. Severe vomiting : Prokinators
c. Sedative and hypnotic is not prescribed
404 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

D. Convalescence: The period of convalescence should be approximately twice (2-4 weeks) the
symptomatic period (2-3 weeks). Follow-up of biochemical studies (bilirubin and transaminases)
should be performed initially at weekly and then at monthly intervals until recovery is complete
when patient becomes asymptomatic with normal bilirubin and transaminases.
If HBs Ag remains positive even after three months or transaminases elevated, chronic hepatitis is
suspected.
E. Isolation: For hepatitis A isolation is not necessary except in fecal incontinence because they excrete
little virus in normal bowel conditions, but gloves should be worn while handling faeces. In cases
with hepatitis B, Non-A and Non-B hepatitis, avoid direct contact or ungloved hand contact with
blood and other body fluids.

SPECIFIC MANAGEMENT OF ACUTE HEPATITIS C

Action Dose Disadvantages Advantages Monitoring

Interferon alpha: Immuno- SC 3 times a Side-effects: 50% patients Regular blood
modulatory week for fever, myalgia, show favou- tests and platelet
and antiviral 6 months arthralgia, loss rable response, count every
of hair, hypothy- of whom 50% 2-4 weeks.
roidism relapse on If platelet count
stopping drug drops below
5000/cmm or
WBC below
3000/cmm
interferon injec-
tion should be
stopped.
Patients with poor response, should be
treated by combination of ribavarin
1gm/day + interferon

MANAGEMENT OF FULMINANT HEPATIC FAILURE

A. Basic life support
B. Nutritional support:
Glucose infusion: Up to 3 litre of 10% dextrose solution given daily by monitoring blood glucose
level regularly.
Hypoglycaemia should be avoided. Hypoglycaemia aggravates encephalopathy.
C. Treatment of complications:
1. Coma:
Dietary protein: Lactulose: Treat hypokalaemia
Withdrawn Given orally to produce two soft motions and hyponatraemia:
daily and not diarrhoea. Neomycin may be used
2. Gastrointestinal haemorrhage:
Factors promoting bleeding Management
i. Acute erosion in stomach and oesophagus i. Acid is reduced with H2 blocker
with excess acid production and antacid
 ii. Coagulation disorder ii. Determine the need for replacement
|
Acute Infective Hepatitis 405

therapy with fresh frozen plasma, clotting

factor concentrate or platelet.
3. Respiratory complications:
Airway should be protected from aspiration of blood and gastric content by early intubation and
ventilation
4. Cerebral oedema: Mannitol infusion often reduces intracranial pressure promptly.
D. Corticosteroid: Use of corticosteroid is controversial. It should not be used if increased intracranial
pressure is present.

TREATMENT OF CHRONIC HEPATITIS

Aetiology
Viral Chemical Miscellaneous
(Chronic drug hepatitis)
Chronic HBV Methyldopa Autoimmune hepatitis
Chronic non-A, non-B Isoniazid Metabolic causes:
Chronic B hepatitis Nitrofurantoin Wilson’s disease
with superimposed Oxyphenacetin Alpha-1 antitrypsin deficiency
Chronic hepatitis D Amidarone Biliary disorders:
Chronic hepatitis C Phenytoin Primary biliary cirrhosis
Cholangitis

Diagnostic Clues for Clinical Types of Hepatitis:

Clinical: Chronic persistent Chronic lobular Chronic active
hepatitis hepatitis hepatitis
i. Onset like acute 70% 90% 30%
hepatitis
ii. Recurrent acute Rare Common Common
episode
iii. Extrahepatic Rare Common Common
features (arthralgia,
arthritis, nephrosis
erythema nodosum)
iv. Jaundice Persistent
v. Prognosis Good Good Variable
Serology:
HBs Ag present HBs Ag present i. HBs Ag in 20-30 cases
ii. Anti-HCV+
iii. HDV positive
Autoimmune hepatitis:
i. Hypergamaglobinaemia ii. AMA positive
iii. ASMA positive iv. ALKM positive
406 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

LABORATORY AND OTHER INVESTIGATIONS

Chronic persistent Chronic lobular Chronic active
hepatitis hepatitis hepatitis
i. Serum protein Serum albumin reduced
in advanced disease
ii. Ultrasound of liver:
To exclude space
occupying lesion
iii. Liver biopsy:
Necrosis • Rare • Rare • Present
Site of inflammation • Portal • Portal/lobular Portal inflammation
spilling over liver
parenchyma
Lobular architecture Preserved Preserved Distorted
Fibrosis Slight Slight Common
Progression to cirrhosis Rare Rare Common
Therapy No specific No specific Anti-viral and
therapy therapy corticosteroid
Table 67.3: Clinical syndromes of hepatitis
Subclinical infection Acute hepatitis with recovery Fulminant hepatitis

Acute hepatitis
(10% cases)

Normal histology Chronic persistent Chronic active Chronic lobular

(Carrier) hepatitis hepatitis hepatitis
cirrhosis
↓
Primary hepatocellular
carcinoma

MANAGEMENT OF CHRONIC HEPATITIS B, C, AND D

Drugs Action Dose Advantages Disadvantages

Interferon Antiviral, antiproli- a. Chronic hepa- 50% cases bene- Side-effects:
ferative and imm- titis B: 5 mil- fited Myalgia, headache,
uno-modulation lion units of nausea, diarrhoea
alpha 2b sub- anorexia, alopecia
cutaneously depression
per day for
16 weeks
b. Chronic hepa-
titis C: 3 mil-
contd...
 lion units sub-
Acute Infective Hepatitis| 407

cutaneously
3 times per
week for 6-
Thymosine 24 months
Lamivudine
Investigational drugs:

Ganciclovir, famciclovir, GMCSF, ARAM

MAYOCLINIC DRUG REGIME FOR CHRONIC ACTIVE HEPATITIS

Drug combination Dose Advantages Monitoring Remarks
Corticosteroid plus 30 mg prednisolone Reduces symptoms, Liver biopsy and Before starting this
low dose azathio- + suppresses inflam- liver function test regime, the follo-
prine 50 mg azathioprine mation, decreases checked periodi- wing factors should
↓ morbidity and early cally. If normalcy be considered:
Tapering gradually mortality and dec- achieved, treatment i. Steroid is not
over several weeks reases progression should be discon- indicated in
to months to a daily to cirrhosis tinued chronic hepa-
maintenance dose titis B
of 10 mg of predni- ii. It is also not
solone plus 50 mg indicated in
of azathioprine chronic persis-
↓ tent hepatitis
If no favourable res- because it does
ponse within 2- not progress to
3 months, treatment cirrhosis or
should be disconti- liver failure
nued iii. There is no
evidence that
corticosteroids
benefit asymp-
tomatic chro-
nic active hep-
atitis
PROPHYLAXIS

Hepatitis A Hepatitis B Delta Hepatitis

A. General: Clean and safe A. General: Vaccination against hepatitis B is
water supply. Hygienic food a. Separate toilet facility; effective
preparation bedding and clothing
B. Vaccination: should be laundered;
contd...
408 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
i. Passive: Immune serum
globulin before exposure
or during early incu-
bation period: 0.02 ml/kg
IM
ii. Active: Two formalin
inactivated hepatitis A
vaccine used in deve-
loped countries but its
role is little in developing
countries.
Hepatitis A
Hepatitis B
program of continuing
education regarding
hepatitis transmission (See
Table 67.4); regular
serological survelience;
avoid spilling of blood
during collection, storage
and transport; hospital staff
at risk must be screened for
HBs Ag
b. RIA or ELISA method;
patient requiring multiple
transfusion should be
immunised with vaccine if
anti-HBs is negative and
routine screening for HBs
Ag in the last trimester of
pregnancy.
B. Vaccination:
i. Pre-exposure prophylaxis to
health workers, handi-
capped, IV drug users,
homosexual, haemophilic.
ii. Postexposure prophylaxis:
Combined hepatitis B
vaccine (3 IM Injections at
0, 1, 6 months) + HBIG
(0.06 ml/kg).
iii. All infants born to HBs Ag
positive mother should be
given HBIG (total dose
0.05 ml) within 24 hours of
birth followed by active
vaccination.
Table 67.4: Transmission of hepatitis
Route of transmission Incubation period
Enteric or faeco-oral route. Average 28 days
Person-to-person spread common.
Contamination of water following rains
and flood is important.
HBs Ag present in blood, semen, vaginal 6 weeks to 6 months
secretion, saliva, breast milk, ascitic
contd...
contd...
|
Acute Infective Hepatitis 409

Route of transmission Incubation period

fluid.
Routes: Parenteral, percutaneous
(blood, plasma injection with contami-
nated needle, dental extraction, opera-
tion, tattooing, ear piercing, rajor, nail
clipping, tooth brushes); vertical
transmission (from mother to foetus)
and oral-oral spread as in deep kissing
(virus in saliva).
Hepatitis C
Transmitted by blood and blood pro-
ducts. Common in drug users.
Hepatitis D
Parenteral through blood transfusion
and IV drug users.

TREATMENT OF AUTOIMMUNE HEPATITIS

Drugs Dose Advantages

Corticosteroid Prednisolone 1-1.5 mg/kg. After Controls clinical condition and
remission tapered off but conti- prolong life
nued for next 2 years on mainte-
nance dose.

Azathioprine 50-100 mg/day. Steroid sparing effect and thus

Used combined with steroids. lessened side-effects of steroids.

Cyclosporin Used in steroid resistant cases.

 Liver, Gall Bladder and Pancreas
68
Cholelithiasis and Cholecystitis

CHOLELITHIASIS (GALLSTONE IN GALLBLADDER)

Diagnostic Clues
A. Asymptomatic: 60-80% are asymptomatic according to one survey in USA
B. Symptomatic:
Pain
At right hypochondrium
occasionally referred to the
back near scapula. Biliary
colic quickly reaches to plateux
and after 30 minutes to several
hours subsides.
GI symptoms Complications
Dyspepsis, intolerance to Acute cholecystitis, obstructive
fatty food, flatulence, jaundice, calcification of gall-
belching, heartburn bladder (occasionally responsible
for cancer gallbladder), common
bile duct stone and cholangitis,
gallstone ileus

Investigations
A. Laboratory investigation:
Liver function tests WBC count Blood culture
Alkaline phosphatase elevated Polymorphonuclear leukocytosis Done repeatedly during
in biliary obstruction. points to biliary infection fever to isolate organisms
Prothrombin time may be
prolonged due to inadequate
absorption of vitamin K
B. Imaging: (See flow chart 68.1)

Management
Medical:
i. Dietary change: Fatty food avoided.
ii. Antispasmodic and analgesic for pain.
Surgical:
A. Asymptomatic patients:
Past recommendations Present recommendations
Cholecystectomy 1. Cholecystectomy:
a. Not advised in majority of patients. Keep under observation.
 b. Cholecystectomy advised:
|
Cholelithiasis and Cholecystitis 411

i. If patient is diabetic (due to coexisting complication

especially cardiac)
ii. Calcified gallbladder (because frequent association with
cancer gallbladder)
iii. Large gallstone
iv. Young patient who may develop complications due to many
years of life ahead.
2. Oral bile salt treatment.

B. Mild symptomatic cases with infrequent pain

a. Cholecystectomy not recommended
b. Medical dissolution by bile salt may be considered.
C. Symptomatic patients:

IMAGING FOR DIAGNOSIS OF GALLSTONE (FLOW CHART 68.1)

Plane X-ray abdomen:
Low cost but low yield
May reveal enlarged liver, calcified gallstone or air in biliary tract
↓
Next, ultrasound:
Rapid; not limited by pregnancy and jaundice.
May reveal small gallstone. May detect gallstone in above 95% cases; dilated biliary duct; site of
obstruction by stone in biliary tree; simultaneous screening of liver and pancreas is possible.
Followed by the following investigations
↓ ↓
In non-jaundiced patient; In jaundiced patient and patients with poor liver function
Oral cholangiography:
Cheap. Detects gallstone in Determine whether bile duct is dilated or not
90-95% cases
↓ ↓ ↓
If unsatisfactory: IV If intrahepatic If non-dilated:
Cholangiography bile duct dilated:
↓ ↓
Percutaneous transhepatic Endoscopic retrograde
cholangiography (PTC) preferred cholangiopancreatography
best for showing duct stone
If PTC and ERCP shows normal biliary system:
A. Magnetic resonance reveals gallstone
B. Liver biopsy
Cholecystectomy with exploration for gallstone. Its advantages:
i. Mortality is only 0.5% ii. No recurrence of gallstone
iii. No risk of developing cancer gallbladder
↓
412 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

POSTCHOLECYSTECTOMY SYNDROME
Ten percent patients continue to have significant abdominal symptoms after cholecystectomy.

Suggestive Causes
Overlooked gallstone during surgery, pancreatitis, peptic ulcer, oesophageal diseases, small bowel disorder,
irritable bowel syndrome, biliary dyskinesia, stenosis of sphincter of oddi.

Management
i. Endoscopic sphincterectomy
ii. If recurrent pancreatitis occur, pancreatic septectomy is advised
iii. Biliary dyskinesis: Nitrate, calcium channel blocker and anticholinergics are helpful.

ACUTE CHOLECYSTITIS
Diagnostic Clues
Symptoms
Pain right hypochondrium
or epigastrium, referred to
back at scapular level.
Signs Complications
Right hypochondrium tender. Secondary bacterial infection
Distended gallbladder in less producing empyema,
than 25% cases. In 20% cases perforation, gangrene
jaundice may be present. and cholangitis

Investigations
WBC count Serum bilirubin Abdominal X-Ray IV cholangiography Ultrasound
Moderate poly- 1-4 mg/dl Shows gallstone in i. Opacification of May detect stone
morphonuclear 10% cases gallbladder rules
leukocytosis out diagnosis of
cholecystitis
ii. Opacification of
bile duct without
opacification of
gallbladder points
to cystic duct
blockage

Treatment
Medical
Most cases subside in a few days with conservative treatment.
i. Admission in hospital
ii. Nasogastric suction
iii. Oral feeding stopped
iv. Antibiotics: Ampicillin + gentamicin or 2nd or 3rd generation cephalosporin. Clindamycin added
in resistant cases.
 v. Pentazocin or pethidine and atropine for analgesia
Cholelithiasis and Cholecystitis | 413

vi. Look for gangrene (leukocytosis will increase).

Surgical
New Recommendations
a. Cholecystectomy should be done within
48 hours of the onset. Operative cholangio-
graphy should be performed at the time of
operation to determine whether bile duct
stone is present. About 10% patients of
acute cholecystitis also have stones in
common bile duct.
b. Acute cholecystitis with acute medical
conditions such as acute myocardial
infarction, cholecystostomy should be done
and later cholecystectomy is done under
favourable conditions.
Old Recommendations
When acute cholecystitis resolve on
conservative line of treatment, after 4-6 weeks
later elective cholecystectomy is done.
Points against the above regime:
i. 25% cases do not resolve needing emergency
surgery with high mortality.
ii. Many patients have recurrent cholecystitis.
iii. Delay in surgery invites complications.

Types of Surgery
a. Cholecystectomy
b. Cholecystostomy in seriously ill patients.
c. Endoscopic sphinterectomy can be performed to remove ductal stone.

Non-Surgical Treatment of Gallstones

A. Oral Bile Salt Therapy:
Chenodeoxycholic acid (CDCA)
Ursodeoxycholic acid (UDCA)

Dose Mode of action Indications Essential require- Disadvantages Monitoring

ments
Dose of CDCA: i. CDCA: i. Cholesterol i. Patency of i. Drugs are i. Oral cholecy-
13-15 mg per kg. Downgrades gallstone in a cystic duct as non-defini- stogram every
For obese 18-20 cholesterol functioning shown by tive. 6 months.
mg per kg. synthesis in gallbladder oral chole- ii. More patie- ii. L i v e r
hepatocytes. as judged by cystography. nts are not function tests.
ii. UDCA: oral cholecy- ii. Gallbladder cleared of
Suppresses stography. able to con- stone comp-
absorption of ii. Reserved for centrate mat- letely.
dietary chol- mild or asy- erial given iii. Significant
esterol from mptomatic orally morbidity
intestine and patients. iii. Gallstone iv. Gallstones
preventing iii. Patients in should not be recur in 30%
biosynthesis whom risk of above 1.5 cm cases.
contd...
414 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Dose Mode of action Indications Essential require- Disadvantages Monitoring

ments
of choleste- cholecystec- in size. v. Only effective
rol. tomy is high. iv. Gallstone in non-calci-
iv. Elderly and should pre- fied or radio-
very obese ferably be lucent stone
patient. less than 100 in presence of
v. Patients who household functioning
refuses sur- unit density gallbladder.
gery. on CT scan. vi. Dissolves
v. Drugs which stone in 6-
increase 24 months.
cholesterol vii. Side-effects:
saturation of Diarrhoea
bile (oestro- Elevated tra-
gen, oral nsaminase.
con- viii. UDCA has
traceptive, less side-
clofibrate) effect than
should be CDCA.
avoided.
B. Percutaneous transhepatic puncture of gallbladder and instillation of either compound directly into
gallbladder:
Advantages Disadvantages
a. Dissolves gallstone in significant Gallstones recur unless lifelong treatment with
number of cases CDCA or UDCA
b. Rapid dissolution in 6-7 hours in 95% cases
C. Extracorporeal laser shock therapy and lithotripsy
Action Advantage
Fragments stone to allow spontaneous When combined with oral bile salt treatment for
passage out of the gallbladder into 2 weeks before lithotripsy and for a prolonged period
common bile duct. after a stone-free state can be achieved by
12 months in up to 85% cases.

CHRONIC CHOLECYSTITIS
It is a common condition due to gallstone characterised by chronic inflammation and thickening of
gallbladder wall.

Diagnostic Clues
Symptoms
Pain in right hypochondrium
referred to right shoulder and
back. Intermittent biliary colic.
Nausea, flatulence, intolerence
of fatty food.
Signs
Tender right hypochondrium,
Murphy’s sign positive.
Complications
Acute cholecystitis, bile
duct obstruction, gallbladder ileus,
hydrops of gallbladder and cancer
gallbladder.
Investigations
|
Cholelithiasis and Cholecystitis 415

Flow Chart 68.2

Plane X-ray of abdomen may reveal calcified stone
↓
Ultrasound: Detects gallstone, liver, bile duct and pancreatic disorders
↓
Oral cholecystogram:
i. May show gallstone
ii. Gallbladder may not opacify pointing to gallbladder disease
↓
If fails: Next perform IV cholangiogram which will opacify gallbladder and bile duct
(unless stone obstructs cystic duct)
↓
Radioisotope scan: Confirms cholecystitis
↓
If above tests fail:
Perform PTC or ERCP to establish diagnosis before surgery is undertaken.

Treatment
Cholecystectomy

CHOLEDOCHOLITHIASIS (STONE IN COMMON BILE DUCT AND CHOLANGITIS)

Diagnostic Clues
Symptomatic patient Asymptomatic
Biliary colic, jaundice, pancreatitis, cholangitis 30% patients are asymptomatic.
(intermittent pain, fever, chill, jaundice),
gallbladder not distended

Investigations
Flow Chart 68.3
Ultrasound
Advantages: i.Initial procedure in investigation of biliary obstruction
ii.Rapid and cheap
iii.Not limited by jaundice and pregnancy
iv. Simultaneous scanning of liver, pancreas and bile duct
Disadvantage: Limited by massive obesity and ascitis
↓
Cholangiography:
Contraindicated in jaundice and pregnancy, misses 40% of duct stone
↓
If fails: CT scan
416 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Disadvantage Advantages
Costly i. Not limited by jaundice, obesity and ascitis
ii. Accurate identification of dilated bile duct
iii. Simultaneous scanning of hepatic and pancreatic masses.
↓
Assess bile duct patency by above investigations

↓ ↓
If bile duct dilated: If bile duct not dilated:
Perform percutaneous transhepatic Endoscopic retrograde cholangiopancreatography (ERCP)
Cholangiogram (PTHC):
Contraindication: Contraindications: Pregnancy
Pregnancy and massive ascitis Complications: Pancreatitis, cholangitis, sepsis
Complications: Advantages:
Bleeding, bile peritonitis, sepsis i. Best visualisation of distal biliary tract
Advantages: ii. Simultaneous pancreatography
i. Best visualisation of proximal biliary tract iii. Visualisation of ampulla and duodenum
ii. Bile cytology and culture iv. Bile and pancreatic cytology
iii. Percutaneous transhepatic drainage v. Endoscopic sphinterectomy and stone removal

Treatment
Medical
Aminoglycoside + Ampicillin for mild cases and for severe attack add clindamycin. Response is within
48-72 hours.
↓
If no response, emergency surgery is undertaken or endoscopic sphincterectomy is done.

Surgery
Cholecystectomy Endoscopic sphincterectomy
If gallbladder present, cholecystectomy Only in selected patients
with removal of stone from duct is done
 Liver, Gall Bladder and Pancreas
69
Acute Pancreatitis

Causative Factors
I. Common causes: 80%
a. Alcohol
b. Biliary tract disease (gallstone)
II. Less common causes:
Postoperative Metabolic Viral Infection Drugs Miscellaneous
Abdominal surgery • Hyperglycaemia • Mumps • Azathioprine • SLE
particularly involving • Hypercalcaemia • Hepatitis • Thiazide • Penetrating peptic
pancreas, biliary tract • Renal failure • Coxsakie • Frusemide ulcer
and stomach • Estrogen • Pancreatic tumour
• Steroid • Metastasis
• Ascariasis

Clinical Clues
Symptoms
• Epigastric and umbilical pain;
constant, mild to severe,
relieved by crouching
• Nausea, vomiting and
abdominal distension
Signs
a. Mild to moderate cases: Low a. Early complications:
grade fever, tachycardia,
hypotension, epigastric mass
in 10-20% cases
b. Severe cases:
• Bluish discolouration (echy-
moses) around umbilicus
(Cullen’s sign)
• Bluish discolouration in the
flank (Grey Turner’s sign)
• Shock, hypoxia
• Abdominal distension due
to ileus
Complications
• Organ failure: Cardiac,
respiratory and renal
• GI Bleeding
• Haematological:
Disseminates intravascular
coagulation, haemorrhage
and thrombosis of portal
and splenic veins
• Ileus
b. Late complications:
• Pseudocyst
• Pancreatic abscess
• Stricture of pancreatic duct
• Diabetes mellitus
418 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Diagnostic Investigations
Biochemical
i. Serum amylase: Elevated for i. Leukocytosis from 15000 to
48-72 hours. Also raised in
non-pancreatic conditions
(mumps, renal failure,
cancer lung, pregnancy,
biliary tract disease, perfora-
ted peptic ulcer) 20-40%
false negative.
ii. Serum bilirubin: Elevated in
10% cases.
iii. Serum lipase: Elevation is
virtually diagnostic. It is
normal in non-pancreatic
hyper-amylasaemia.
iv. Hyperglycaemia common.
v. Hypocalcaemia in 25% cases.
vi. Blood urea may be raised.
vii. Electrolyte disturbed.
viii. Liver function may be
abnormal.
Haematological Imaging and X-ray
i. Plane film of abdomen
20000/cmm abnormal in 50% cases.
ii. C-reactive protein may be ii. Upper GI X-Ray: Widening
raised of duodenal loop or displace-
ment of stomach points to
pancreatic mass. Superceded
by ultrasound and CT scan.
iii. Ultrasound detects inflam-
mation oedema, calcification,
gallstone, pancreatic mass
and pseudocyst.
iv. CT scan: Detects pancreatic
calcification, pancreatic mass
and enlargement. Also shows
pancreatic calcification and
abscess. Calcification sugge-
sts pre-existing chronic
pancreatitis.
v. Radioisotope scanning:
Evaluates gallbladder and
biliary tree.

Management of Acute Pancreatitis

1. Supportive measures : Fluid replacement:
Mechanism of fluid loss Assessment of fluid loss Types of fluid replacement
Fluid loss is a hallmark. i. By pulse rate, drop in blood i. Crystalloid
It is due to copious fluid loss pressure, urine output, blood ii. One unit of human albumin
from inflammed pancreas. urea and haematocrit level. (12.5 gram) given if volume
ii. Urinary output is maintained deficit exceeds 3-4 litres.
30-50 ml per hour by replace- iii. Blood or frozen plasma.
ment of fluid.
2. Symptomatic treatment: Pain is treated by meperidine or buprenorphine. Morphine is contraindicated
because it produces spasm of sphincter of oddi and biliary tract.
3. Reduction of pancreatic secretion:
Oral feeding H2 receptor antagonists Anticholinergics Nasogastric suction
Stopped 150 mg ranitidine X2 or Useless. Incidence of Controversial. Only
40 mg famotidine X2 or tachycardia, ileus and indicated in ileus with
proton pump inhibitor hypotension increases. abdominal distension
daily if upper GI
bleeding occurs.
 Acute Pancreatitis|
4. Antioxidants: Oxidants are released overwhelmingly in acute pancreatitis. Hence antioxidants are
419

helpful.
5. Prophylactic antibiotics: Its value is uncertain. A recent controlled trial with imipenem showed
reduction in the rate of sepsis. Imipenem is a third generation cephalosporin.
6. Feeding: Once pain has subsided, small feeds of clear liquid rich in carbohydrate but low in protein
and fat is advised. After a few days regular but small feeds are given.

Additional Measures in Severe Pancreatitis

a. Fluid loss: Often fluid loss is 10-15 litres which is required in first 24 hours to maintain adequate
urinary output 30-50 ml per hour.
b. Refractory shock: Dopamine drip, plasma specially frozen plasma or blood if haematocrit falls.
c. Hypocalcaemia: IV calcium (calcium chloride or gluconate) if signs of tetany present.
f. Severe hyperglycaemia: Small dosages of regular insulin is prescribed.
g. Acute respiratory distress syndrome: Intubation with positive pressure respiration and humidified
oxygen. Monitored by blood gas analysis.
h. Renal failure: Haemodialysis or peritoneal dialysis when urinary output remains persistently less
than 30 ml/hr.

Management of Complications of Acute Pancreatitis

1. Infected pancreatic necrosis
Medical treatment Surgical treatment
Antibiotics: It is fatal without prompt surgical drainage
i. Best: IV ciprofloxacin + metronidazole
ii. Others: Cefotaxime, ceftazidime, rifampicin,
clindamycin
2. Acute pancreatic pseudocyst:
Half of them resolve spontaneously in 6 weeks
↓
If fail to resolve, many types of drainage procedures are available. Early drainage is required if the
cyst is above 5 cm in size or enlarging.

Types of Drainage Procedures

Percutaneous catheter drainage Endoscopic cystoduodenostomy Endoscopic transcapillary
Or cystogastrostomy drainage
65-95% resolve Advocated if pseudocyst adheres
to gastric or intestinal wall
↓
If the above procedures fail, surgical
open drainage is the only option left
3. Pancreatic abscess: Initially, percutaneous drainage under antibiotic cover is attempted. Only 50%
cases are cured.
↓
If fail, surgical debridement with open packing should be done with further debridement as the
packing is changed.
420 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

4. Gastrointestinal bleeding:
Antacids and H2 blockers
↓
If fail, selective mesenteric angiography with embolisation of the bleeder
↓
If fails, or fistulisation of abscess or pseudocysts in stomach, duodenum and colon present with
major bleed:
Surgical intervention is launched
5. Gallstone pancreatitis:
A. Cholecystectomy: There are two views regarding this procedure:
↓ ↓
Treat all patients medically till they Cholecystectomy done on all
improve patients within 48-72 hours once the pain subsides
↓
Next, early cholecystectomy performed
B. Endoscopic papillotomy:
Indications:
i. Patients who deteriorate in 48 hours of medical treatment
ii. Patients who do poorly with surgical treatment
C. Gallstone pancreatitis can be prevented by elective surgery of the disease of biliary tract, e.g.
gallstone.

Prognosis of Acute Pancreatitis

50% resolve with medical treatment
40% cases are quite ill but survive the attack
10% cases succumb despite the best therapy.

Adverse Prognostic Signs in Acute Pancreatitis

• Age over 55 year • Leukocyte count above 16000/cmm
• Blood glucose above 200 mg/dl • Haematocrit decrease above 10%
• BUN rise • Serum calcium below 8 mg/dl
• Arterial PO2 below 60 mmHg • LDH over 250 units/L
• AST over 250 units/L • Organ failure: Shock, respiratory failure, renal failure
• High C-reactive protein

CHRONIC PANCREATITIS
It is sequelae of acute pancreatitis:
↓ ↓
Recurrent pancreatitis Recovery. No further attacks
Chronic relapsing pancreatitis
↓ ↓
Mild recurrent Severe recurrent
pancreatitis pancreatitis
Aetiological Consideration
Acute Pancreatitis| 421

Primary aetiology: Other causes:

Alcohol i. Congenital pancreatitis (uncommon)
ii. Idiopathic pancreatitis
iii. Stricture of pancreatic duct (e.g. following trauma)
iv. Protein—caloric malnutrition (Tropical pancreatitis)
v. Cystic fibrosis
vi. Haemachromatosis

Clinical Consideration
Symptoms and signs
a. Chronic pain in epigastrium and left hypo-
chondrium, aggravated by food, relieved by
forward flexion of trunk and radiates to back. ii. Obstruction of duodenum due to cicatricial
b. Anorexia and weight loss. Depression
c. Deficiency syndromes:
i. Exocrine insufficiency: Malabsorption,
diarrhoea and steatorrhoea
ii. Endocrine insufficiency: Diabetes
mellitus
Complications
i. Obstructive jaundice due to constriction of
common bile duct
stricture
iii. Pseudocyst
iv. Pancreatic abscess and calcification
v. Transverse colon obstruction (rare)
vi. Haemorrhage and thrombosis of splenic or
portal vein with portal hypertension
vii. Massive bleeding from oesophageal varices

Diagnostic Investigations
Flow Chart
First arrange for plane X-ray of abdomen:
It shows pancreatic calcification which is diagnostic of chronic pancreatitis.
If calcification is not detected:
↓
Next step: Ultrasound or CT scan:
i. Rules out solid pancreatic mass suggesting cancer
ii. Shows calcification if not shown in abdominal X-ray
iii. May detect ductal dilatation
iv. May detect pseudocyst
↓
If the diagnosis is not confirmed by the above investigations:
Lastly ERCP is performed which is virtually diagnostic of chronic pancreatitis by showing common bile
duct and pancreatic duct stricture with intervening areas of ductal dilation (“Chain-of-lake” appearance).
↓
Other supportive investigations:
i. Endocrine insufficiency: Blood sugar for detecting diabetes
ii. Exocrine insufficiency: Tests for pancreatic function:
a. Secretin test: It is gold standard. It invovles estimation of volume, bicarbonate and enzyme
secretion in duodenal aspirate after injection of secretin and pancreozymin. In chronic pancreatitis
they all are reduced.
422 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. Tubeless pancreatic function test (NBT-PABA test): In chronic pancreatitis the test substance
given orally is reduced in urine.
c. Glucose tolerance test
iii. Liver function tests done if common bile duct is obstructed
iv. Upper gastrointestinal barium meal shows duodenal obstruction.

Treatment of Chronic Pancreatitis

Pain
Medical treatment of pain is unsatisfactory.
Approach to pain management:
First try salicylate, acetaminophen, pentazocin or pethidine. Morphine is contraindicated because it
produces spasm of sphincter of oddi and duodenum
↓
Next, exclude other causes of abdominal pain (peptic ulcer, gallstone).
↓
If other causes of abdominal pain is excluded, arrange for ultrasound of pancreas to exclude any pancreatic
mass. If mass is not present:
A 3-4 week trial of 3-8 capsule or tablet of pancreatic enzyme taken at meal and at bed time
↓
If no relief, ERCP is performed to show a localised ductal obstruction. Appropriate surgery should be
considered.
↓
If no surgical remedial lesion is present and severe pain continues, subtotal pancreatic resection advised.

Steatorrhoea
Low fat diet, pancreatic enzyme and H2 blocker are prescribed.

Osteomalacia
If clinical evidence of osteomalacia (tetany) present, then only vitamin D given by injection.

Diabetes Mellitus
i. Treatment of steatorrhoea helps diabetes.
ii. Each patient should have a supply of glucagon injection to combat hypoglycaemia because glucagon
secretion is defective.

Pancreatic Lithiasis
It has been recently suggested that administration of citrate in the form of citric acid (2.6 gm), potassium
dihydrogen citrate (4 gm) and sodium dihydrogen citrate (4 gm) t.d.s. with meals

Surgical Treatment of Chronic Pancreatitis

I. Surgical treatment of pain
Types of Surgery
|
Acute Pancreatitis 423

Lateral pancreato- Pancreatic resec- Total pancreatec- Partial pancreat- Splanchiectomy

jejunostomy: tion tomy ectomy Relieves some
Duct is opened and Mortality rate less See partial pan- Done in selected types of pain
all strictures divi- than 5% createctomy patients.
ded and drainage of Causes diabetes
entire pancreas is mellitus
achieved. Pain reli- Disadvantages:
eved in 60-80% • Infection such as
cases subphrenic
abscess
• Fistula
• Prolonges morbi-
dity with steator-
rhoea and diabetes

II. Surgical treatment of complications:

Pseudocyst Obstruction of common bile duct Obstruction of duodenum Abscess
Resection and drainage Some form of bypass surgery. Gastrojejunostomy Drainage.
It also relieves pain Choledochojejunostomy Also relie-
Also relieves pain. ves pain
III. Newer surgical modalities:
i. Endoscopic cystogastrostomy
ii. Endoscopic cystojejunostomy
iii. Pancreatic stenting
iv. Extracorporeal shock wave lithotripsy
 Endocrinology
70
Diseases of Hypothalamus and Anterior
Pituitary Gland

PHYSIOPATHOLOGICAL CONSIDERATION

Hormones secreted by anterior pituitary Regulation of hormone production

Trophic hormones Other hormone A. Hypothalamus stimulates production

• Corticotrophin (ACTH)
• Thyrotropin (TSH)
• Gonadotropins:
Luteinizing hormone (LH)
Follicle stimulating hormone (FSH)
• Trophic hormones of specific target
organs (thyroid, adrenal and gonads)
producing target gland hormones
• Prolactin (PRL) of all pituitary hormone except
• Growth hormone prolactin which is inhibited by
(GH) hypothalamic dopamine production
B. Secretion of trophic hormones is
also regulated by negative feedback
by their target gland hormones

Disease Produced
Failure of target gland Failure of pituitary gland due to damage
or removal of pituitary
↓ ↓
Rise of respective pituitary hormones as a Loss of trophic hormones resulting in secondary
result of loss of negative feedback inhibition hypothyroidism, adrenal insufficiency and hypo-
gonadism. Loss of PRL deficiency may also occur

AETIOLOGICAL CONSIDERATION
Anterior pituitary dysfunction can be caused by disorders of either the hypothalamus or pituitary:

Common disorders of pituitary Other pituitary and hypothalamic disorders (Less common)
Pituitary adenoma:
↓ ↓
 Pituitary adenoma
Diseases of Hypothalamus and Anterior Pituitary Gland |
425

Size Clinical manifestation due to

1. Microadenoma Hormone production Mass effect

less than 10 mm a. Clinical features No mass a. Head trauma, pituitary surgery
in diametre: produced if they effect. or radiation may cause hypopitui-
produce excess tarism
hormone b. Disorders causing hypopituitarism
b. No feature of hypo- i. Other tumours of pituitary
pituitarism or hypothalamus:
2. Macroadenoma • Craniopharyngioma
greater than 10 mm • Metastasis
in diametre: ii. Inflammatory disorders:
a. Secretary
macroadenoma→ ⎧ May produce
combination
• Sarcoidosis
• Histocytosis X
b. Non-secretary ⎨ of pituitary iii. Infection:
macroadenoma: ⎩ hormone excess • Tuberculosis
Hypopituitarism→ Mass effect due
to pressure on
adjacent structures

Table 70.1: Causes of hypopituitarism

Primary Secondary
• Pituitary tumour: • Destruction of pituitary stalk:
Adenoma, craniopharyngioma Trauma
• Ischaemic necrosis of pituitary: Tumour
Postpartum (Sheehan’s disease) Aneurysm
• Vascular disease: Surgery
Carotid aneurysm • Hypothalamic other CNS diseases:
Cavernous sinus thrombosis Inflammatory: Sarcoidosis
• Inflammatory disease: Infiltrative: Lipid storage disease
Haemochromatosis Hypothalamic tumour: Primary,
Amyloidosis metastasis leukaemia, lymphomas
• Idiopathic Idiopathic: Congenital or familial
• Immunogenic: anorexia nervosa
Lymphocytic hypophysitis
• Iatrogenic:
Irradiation to nasopharynx or sella
Surgery
426 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Diagnostic Clues
A. Clinical manifestations of hypopituitarism
I. Features of hormone deficiency:
Gonadotrophin TSH ACTH GH deficiency Other
deficiency deficiency deficiency in adult features
Men Women Child (Secondary hypo- (Secondary Obesity, asthenia, Dry, pale
• Loss of • Loss of Congenital: thyroidism cau- adrenal failure reduced cardiac finely textured
axillary axillary and • Micropenis sing thyroxin causing cortisol output skin
hair pubic hair • Cryptorchism deficiency) deficiency)
• Dimini- • Amino- • Sense of Fatigue, weak- Weight loss,
shed rrhoea smell decr- ness, weight asthenia,
beared eased change, hyper- hypotension
growth lipidaemia
• Low libido
• Infertility

II. Mass effect due to pressure on adjacent structures:

i. Pressure on optic chiasma: Headache, loss of visual field or acuity
ii. Hyperprolactaemia
iii. Pituitary apoplexy due to sudden enlargement of pituitary tumour
III. Asymptomatic pituitary adenoma
Microadenoma found on imaging for Macroadenoma: Incidental discovery.
another purpose: Evaluate them for hormone excess (Hyper-
Asymptomatic: prolactaemia, acromegaly and Cushing’s disease.
Evaluate for evidence for hyperprolactaemia. If pituitary hormone excess is not present,
Cushing’s syndrome or acromegaly therapy is not required
B. Laboratory investigations for hypopituitarism
1. Biochemical findings:
• Fasting blood glucose low
• Hyponatraemia
2. Evaluation of target hormone function to determine whether target gland dysfunction is primary:
Thyroid Gonads Adrenal
Free T4 low TSH normal Sex steroids (testosterone, Ser. cortisol low
estradiol low)

If target hormone is deficient, its trophic hormone is measured to determine whether target gland
dysfunction is secondary to hypopituitarism. There are certain tests which help in this direction:
Dose Blood sample Result
a. ACTH stimu- 250 microgram Serum cortisol Serum cholesterol does not
lation test: synacthen IV or IM rise in secondary hypoadrena-
lism due to hypopituitarism
↓
If ACTH stimulation
test normal
Diseases of Hypothalamus and Anterior Pituitary Gland | 427

↓
Perform Metyra- Metyrapone 1.5 gm Serum for 11-deoxycortisol concentration
pone test: orally at 11 PM 11-deoxycortisol under 7 microgram/L in
and cortisol primary hypoadrenalism
collected at 11 AM
next morning
b. Insulin hypogly- 0.15 U/kg regular Plasma for cortisol Low in hypopituitarism
caemia test: insulin IV and growth hormone
Anatomical localisation of pituitary gland and hypothalamus:
MRI: Provides best visualisation of parasellar lesion.

TREATMENT OF HYPOPITUITARISM
Medical Treatment
Aim is to replace multiple hormones but cortisol replacement is most important substitution therapy
which are given lifelong.
Drugs Dosage Indications Precautions Monitoring
A. Hydrocortisone:
1. Hydrocortisone 15-25 mg orally in divi- Dose doubled or tripled
ded dosages: 15 mg orally during mild
morning, 5-10 mg late stress
afternoon
2. Prednisolone 3-7.5 mg/day Some patients feel – do –
better with predni-
solone
3. Dexamethasone: 0.25 mg/day – do – – do –
4. Hydrocortisone 75 mg 6 hourly Severe stress e.g.
IM/IV trauma, surgery, infec-
tion
B. Thyroid hormone:
Levothyroxin Maintenance dose: Glucocorticoid repla-
0.125 mg/day (Range cement preceed thyro-
0.05-0.3 mg/day) xin therapy to prevent
C. Sex hormones: adrenal crisis
1. Androgen Long acting testoste- Male hypogonadism
rone enanthate 200 mg
IM every 3-4 weeks for
many months
2. Estrogen: See Table 70.1: “Estro-
gen Replacement
Therapy”
3. Chorionic gona- 2000-3000 U IM three To improve spermato-
dotrophin (hCG) times weekly genesis in males
Dose of hCG adjusted
to normalise testoste-
rone level
contd...
428 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs Dosage Indications Precautions Monitoring

If after 6-12 months
sperm count remains
low add injection of
FSH (Fallopian beta or
urofollitropins)
4. Leuprolide Intermittent injection If pituitary is intact to
improve spermato-
genesis; an alternative
therapy is leuprolide
5. Clomiphene in 25-50 mg orally daily An alternative therapy
males to improve spermato- Dosages increased until
genesis. Clomiphene response or side-effect
stimulates a man’s own occur by 0.1 mg (0.3 IU)
pituitary gonadotro- every 3-4 weeks up to
phin (when pituitary is 0.7 mg daily. It is further
intact) and thus inc- increased by 0.1 mg/0.3
reases testosterone and IU) at monthly intervals
sperm production. to a maximum of about
1 mg (3 IU) daily.
Clomiphene in 50 mg/day for 5 days For fertility induction If desired effect (imp-
female every two months in female, clomiphene roved energy, muscle
induces ovulation. strength) are not
D. Human growth Somatotropin SC Severe growth hor- Side-effects: achieved within about
hormone (hGH- starting 0.2 mg/(0.6 IU) mone deficiency • Oedema 3 months at maximum
somatorophin) three times weekly or • Arthralgia tolerated dosages,
daily somatotropin is discon-
tinued.
E. Other drugs: Reverses hypogona-
a. C a b e r g o l i n e , dism seen in hyperpro-
bromocriptine lactinomas and hypopi-
or quinagolide tuitarism resulting from
pituitary tumour

Table 70.2: Oestrogen replacement therapy

Premenopausal women
Aim is to maintain secondary sex characteristics
and to prevent osteoporosis:
a. Ethinyl estradiol 5-20 microgram/day or conju-
gated oestrogen (Premarin 0.6 to 1.25 mg/day).
b. For inducing cyclic bleeding, oestrogen should be
given for 25 days each month accompanied on
the last 5 days by medoxyprogesterone 5-10 mg
per day. Alternatively an oral contraceptive
preparation can be used.
Postmenopausal women
Oestrogen (premarin or evalon) corrects dyspareunia
+
Long acting testosterone enanthate 50 mg IM every one
to two months for improving libido (diminished libido
due to absence of adrenal androgen)
SURGICAL AND IRRADIATION TREATMENT
Diseases of Hypothalamus and Anterior Pituitary Gland |
429

1. Transphenoidal removal of pituitary tumour will sometime reverse hypopituitarism.

2. Growth—hormone secreting tumour:
Radiation therapy with X-ray, gamma knife or heavy metals but may increase the likelihood of
hypopituitarism.
 Endocrinology
71
Acromegaly and Gigantism

Acromegaly is due to excess growth hormone which is due to pituitary adenoma.

DIAGNOSTIC CLUES
Clinical
CNS Skin Extremities and jaw Joint
• Vision loss Thickened Enlargement of hands, feet and jaw • Arthritis
• Headache and forehead. Protrusion of lower jaw • Carpal tunnel syndrome

LABORATORY INVESTIGATION
A. Plasma somatomedins C:

Markedly elevated Moderate elevation

↓ ↓
Confirms acromegaly Perform Glucose test: Measuring
GH after giving 75 mg of glucose
orally every 30 minutes for 2 hour
↓
Failure to suppress GH to less than
2 ng/ml confirms the diagnosis of
acromegaly

After the establishment of the diagnosis of acromegaly,

pituitary should be imaged by CT scan and MRI to detect pituitary adenoma

B. Other investigations:
Blood Examination X-ray
• Hyperglycaemia a. Of skull: Enlarged sella turcica and thickened skull
• Prolactinaemia b. Hand: Tufting of terminal phalanges
TREATMENT OF ACROMEGALY
Acromegaly and Gigantism | 431

A. Drugs
Disadvantages Advantages
Octreotide • Costly • Indicated in patients who do not
• Side-effects: respond to surgery or dopamine
Dopamine agonist: Injection site pain, loose agonist
alcoholic stools, abdominal • Benefits also ectopic acromegaly
discomfort, cholelithiasis
Cabergoline 1-1.5 mg/kg Side-effects: Nausea, headache, About one-third of adenoma
orally hypotension shrinks by 50%

B. Surgery and radiotherapy

1. Transphenoidal resection of pituitary adenoma:
Types of adenoma Disadvantage:
a. Macroadenoma—Complete cure not possible Side-effects:
b. Microadenoma—Cure possible In 10% cases CSF leak,
hypopituitarism, hyponatraemia
Advantage:
• Treatment of choice
• GH level falls immediately
• Well-tolerated
2. Radiotherapy: Macroadenoma: Measure somatomedins and if it is elevated radiotherapy is used to
prevent regrowth of the tumour.
The full effect of radiotherapy on growth hormone secretion may take up to 10 years. The somatostatin
analog octreotide in depot form 10-30 mg IM monthly given to suppress GH secretion while the effect
of radiation is being awaited.
 Endocrinology
72
Hyperthyroidism (Thyrotoxicosis)

Hyperthyroidism refers to the clinical manifestations produced by excess of circulating thyroxine (T4)
and triiodothyronine (T3).

Causes of Hyperthyroidism
A. T4 and T3 induced hyperthyroidism
Graves’ disease: Nodular hyperthyroidism Other unusual aetiologies
Most common specially i. Multinodular goitre: i. Subacute thyroiditis
in young women. Exoph- Common in elderly ii. Iodine induced hyperthyroidism
thalmos and pretibial ii. Solitary toxic nodule/adenoma usually precipitated by excess
myxoedema only found in iodine in diet, radiographic
this type. Mechanism: Due material and amiodarone
to presence of antibodies (contains iodine)
against thyroid (an auto- iii. Struma ovarii: Thyroid tissue
immune disorder) which present in ovarian dermoid
binds TSH receptors in tumour and teratoma responsible
thyroid and stimulate for thyroid hyperfunction
thyroid to hyperfunction. iv. Transient hyperthyroidism:
Hashimoto’s thyroiditis, preg-
nancy, irradiation
B. TSH induced hyperthyroidism:
Rare
i. Pituitary adenoma
ii. Pituitary hyperplasia: Due to diminished feedback effect of T4 upon the pituitary. It may be
familial or caused by prolonged untreated hypothyroidism especially in youth.

DIAGNOSTIC CLUES
Clinical
Symptoms Signs
General: ———————→ Anxiety, weakness, heat intole- Restlessness, weight loss, swea-
rance, palpitation, diarrhoea, ting, hyperactivity, warm moist
oligomenorrhoea skin
contd...
Cardiovascular:
Hyperthyroidism (Thyrotoxicosis) |433

Raised pulse rate, ectopics, atrial

fibrillation, cardiac failure
Central nervous system: Fine tremor, brisk tendon reflexes
Special signs in Graves’ disease: i. Lid retraction, lid lag,
chemosis, infiltrative oph-
thalmopathy
ii. Thyroid: Diffuse non-tender
goitre often with bruit
iii. Pretibial myxoedema
Signs in elderly: May present only atrial fibril-
lation, heart failure and weight
loss
Diagnostic features of thyroid Features Diagnosis
gland in hyperthyroidism: Diffuse non-tender Graves’ disease
enlargement
Multiple thyroid nodule Toxic multinodular
goitre
Single thyroid nodule Thyroid adenoma
Tender painful goitre Subacute thyroiditis
Normal thyroid gland Graves’ disease
Investigations
1. Plasma TSH estimation (most reliable first line test)
Higher than 0.1 U/ml Lower than 0.1 U/ml
↓ ↓
Excludes clinical Measure plasma T4
hyperthyroidism
↓ T4 elevated: T4 normal:
Plasma T4 estimation Diagnosis of clinical Euthyroid Measure T3
hyperthyroidism or ⏐
confirmed Subclinical ↓
Elevated T4 hyperthyroidism
↓
TSH induced Elevated T3
hyperthyroidism a. Clinical hyperthyroidism
b. T3 thyrotoxicosis (rare)
2. Twenty-four hour radioiodine uptake estimated in confirmed case of hyperthyroidism:
Elevated Low
Suggested hyperthyroidism Points to:
due to multinodular goitre a. Postpartum thyroiditis
b. Iodine induced hyperthyroidism
c. Factitious hyperthyroidism
3. Nuclear scanning: Employed if the presence of an autonomous nodule is suspected.
4. MRI and CT scanning: Indications:
434 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

a. Severe cases of thyrotoxicosis

b. Euthyroid exophthalmus: Visualises Graves’ ophthalmopathy affecting extraocular muscles.
5. Thyroid antibodies: Present in Hashimoto’s disease.
If titre is significant: Only reversible measures for control of hyperthyroidism should be followed.
Surgery and radiotherapy should be avoided.
6. Antithyroglobulin or antimicrosomol antibodies elevated in Graves’ disease.

TREATMENT OF HYPERTHYROIDISM
Treatment varies according to the cause of hyperthyroidism. See aetiological consideration in the beginning
of this chapter.
I. Drugs: Graves’ Disease:
Dose Indications Advantages Disadvantages
Propranolol: i. Propranolol: i. For symptomatic Promptly relieves tac-
Started 10 mg per relief hycardia, tremor, dia-
day 20-40 mg ii. Initial treatment of phoresis, anxiety, and
q.d.s. choice for thyroid periodic paralysis
ii. Atenolol 25-50 storm
Verapamil: mg/day Used if contraindica-
Isoptin 40-80 mg t.i.d. tion to beta blocker
exists
Carbimazole: Inhibits Neo-mercazole Nicho- i. Younger patient i. Restores normal i. Remission rate
thyroxin synthesis los) thyrozole Cadila) ii. Small diffuse size only 40-50%
anti-thyrox (Macleod) gland and mild ii. Better response in ii. Side-effects: Rash,
5, 20, 100 mg disease areas of deficiency agranulocytosis,
Started 30-40 mg/day, than in the west serum sickness,
maintenance dose 15- cholestatic jaun-
20 mg per day. Conti- dice, nephrosis,
nued for 12-24 months. hypoglycaemia
Monitoring: At 4 week iii. Recurrence of
interval assess clini- hyperthyroidism
cally and free T4. If T4 within 6 months
does not fall, increase after therapy is
dose. Patient advised to stopped.
stop drug immediately
if jaundice, fever, chill
and sore throat deve-
lops.
Propylthiouracil: Initial dose 300-600 Drug of choice during Reduces symptoms Arthralgia, lupus ery-
mg/day in 4 divided breast feeding or preg- thromatosus, aplastic
dosages. During preg- nancy Brings TSH level to anaemia, thrombocyto-
nancy 200 mg/day normal penia
Iodinated contrast Telepaque: First start i. Patient intolerant
agents: carbimazole and then to carbimazole or
telepaque added 500 propylthiouracil
mg b.d., continued for ii. Newborn thyro-
8 months toxicosis
iii. Severe hyperthy-
roid symptoms
contd...
 II. Radioactive Iodine (131 I) Therapy
Hyperthyroidism (Thyrotoxicosis) | 435

Action Dose Indication/contra- Advantages Disadvantages

indication
Destroys overac- 8-10 mCi i. Not given in i. Controls 90% Hypothyroidism
tive thyroid tissue pregnancy patients develops after
Follow-up: Clini- ii. Can be added to ii. No risk of several years in
cal evaluation and propranolol but cancer or 30% patients
plasma T4 assessed not with pro- leukaemia or
at 4-6 weeks inter- pylthiouracil so foetal malfor-
vals propylthio- mation
uracil stopped
for 2 weeks
If normal Symptomatic S y m p t o m a t i c before RAI
Then yearly hypothyroidism hyperthyroidism therapy insti-
follow-up Treat with thy- Repeat RAI tuted. RAI
roxine therapy treatment fail-
ure occurs due
to propylthio-
uracil treatment
iii. Severe thyro-
toxicosis
iv. R e c u r r e n c e
after antithy-
roid drugs or
surgery
v. Systemic ill-
ness preven-
ting other
methods of
treatment
III. Thyroid Surgery (Subtotal Thyroidectomy)
Procedure Indications Advantages Disadvantages
Preoperative: i. Pregnancy when i. Effective in the i. Vocal cord para-
Carbimazole and propranol given till T3 normal. thyrotoxicosis not hands of expert lysis due to dam-
Telepaque 500 mg b.d. or Lugol’s iodine 2-3 controlled with low surgeon age to recurrent
drops daily for several days given to reduce dose of carbima- laryngeal nerve
vascularity of thyroid. Drugs are stopped zole. Usually sur- iii. Hypoparathyroi-
postoperatively. gery done in midtri- dism. Check serum
Follow-up: Patients evaluated at 4-6 weeks after mester calcium postopera-
surgery by determining T4 and TSH ii. Large multinodular tively
goitre iv. Hypothyroidism in
iii. If high suspicion of 50% cases eventu-
Thyroid func- Development Determine serum malignancy ally
tion normal of sympto- calcium to exc- iv. Pressure symp-
Patient seen matic hypo- lude hypopara- toms
at 3-6 months thyroidism thyroidism v. Retrosternal goitre
and then Treated with vi. Recurrence of hy-
annually thyroxin perthyroidism after
drug and radioac-
tive iodine therapy
436 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

TREATMENT OF COMPLICATIONS
1. Ophthalmopathy

131-th I therapy for ophthalmopathy Carbimazole

i. Worsens 15% and improves none Worsens 3% and improves 20%
ii. 131-th I therapy + prednisolone: Prednisolone
given for 3 months after 131-I therapy:
Worsens none and improves 67%

2. Thyroid Crisis or Storm

Diagnosis:
Clinical Investigations Prognosis
Severe manifestation of hypothy- Serum T3, T4 high, baseline Mortality 20-40%
roidism, fever, abdominal pain, WBC count, serum calcium,
persistent diarrhoea, delirium, plasma cortisol
psychosis.
Precipitating factors:
Stress, infection, metabolic upset:
Uncontrolled diabetes, electrolyte
imbalance. Sudden interruption of
antithyroid drugs, thyroid surgery

Management
1. Supportive treatment:
Oxygen, IV fluid with or without electrolytes, multivitamin
2. Treatment of precipitating factors:
Infection, stress
3. Drugs:
Propylthiouracil: Iodine Propranolol Hydrocortisone
400 mg every 6 hour a. Sodium iodide 250 mg 10-40 mg every 50 mg IV 6 hourly
(by nasogastric tube if every 6 hour orally or 4-6 hour orally or and then tapered
necessary) or IV (1 gm) slowly IV 1 mg/mt
Carbimazole 15-25 mg b. Lugol’s solution
6 hourly 10 drops t.d.s.
4. Symptomatic treatment: Acetaminophen for hyperthermia. Atrial tachycardia and CCF: Digoxin

3. Cardiac Complications
Sinus tachycardia Auricular fibrillation CCF
i. Propranolol i. Treat thyrotoxicosis Digoxin
ii. Treat thyrotoxicosis ii. Cardioversion fails Frusemide
 Hyperthyroidism (Thyrotoxicosis)

iii. Digoxin and propranolol reduces fast

| 437

ventricular rate. Beta blocker used

carefully. Reduce dose of digoxin if
beta blocker used
iv. Anticoagulant is used to prevent
arterial thromboembolism

4. Dermopathy (Pretibial myxoedema)

Topical glucocorticoid and nocturnal plastic occlusive dressing.
1 2 3
TREATMENT OF OTHER AETIOLOGIES OF HYPERTHYROIDISM
Toxic solitary nodule Toxic multinodular goitre Subacute thyroiditis
i. Symptomatic treatment: i. Symptomatic treatment: i. Propranolol
Propranolol Propranolol ii. Telepaque 500 mg/day
ii. Definitive treatment: ii. Definitive treatment: orally, continued for 15-60 days
• 131-I therapy in over age • 131-I therapy better than until T4 normal
of 40 year patient surgery iii. Antithyroid drugs or 131-I are
• Surgery in patients under • Surgery ineffective
age of 40 iv. If hypothyroidism develops,
iii. 95% recurrence with anti- treat with thyroxin
thyroid drugs resorted for
4 pressure symptoms or 5
cosmatic indication

Hashimoto’ thyroiditis TSH hypersecretion

with hyperthyroidism induced hyperthyroidism
Rare
i. Treated with propranolol Tumerogenic Non-tumerogenic
ii. If hypothyroidism develops, Surgery Antithyroid drugs
treat with thyroxin

HYPERTHYROIDISM AND PREGNANCY

Diagnosis Complications Drugs Surgery
Clinical features Thyroid crisis, • Carbimazole in smallest Reserved for:
not helpful because eclampsia, CCF, dose possible i. Patients allergic
pregnancy also produces premature delivery • Breast feeding safe only to antithyroid drugs
tachycardia, tremor, with propylthiouracil ii. Resistant to antithyroid
sweating, warm skin, drugs
palpable thyroid iii. Large goitre
Laboratory tests: T4
high (greater than 20 gm/dl
TSH low
438 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

INVESTIGATIONS
Acute thyroiditis Subacute thyroiditis Chronic thyroiditis
T3, T4 resin uptake: Elevated Markedly elevated Normal or low
Radio-iodine uptake: a. May be high but low
in atrophic variety of
Very low in initial Hashimoto’s thyroiditis
hyperthyroid phase b. Low in Riedel’s thyroiditis
Titre of thyroid Very high in Hashimoto’s
autoantibodies: thyroiditis
T3, T4, TSH When thyrotoxic T3, T4
raised and TSH normal.
ESR Normal in silent variety Markedly raised

TREATMENT
Specific treatment Treatment of hypo- Treatment of hyper- Symptomatic treatment
thyroid phase thyroid phase
Acute suppurative thy- i. Parenteral anti-
roiditis: biotic instituted
immediately
↓
Followed by app-
ropriate antibio-
tics according to
bacteriological
culture of the
aspirate of the
affected area
ii. Localised abscess
Subacute thyroiditis: drained Hypothyroid phase Propranolol 20-40 mg Anti-inflammatory
treated with thyroxin 8 hourly analgesics
0.05-0.1 mg/day and a. Coated aspirin
discontinued after 3- 600 mg 6-8 hourly
6 months monitored by for 7-10 days
thyroid function test. b. D e x a m e t h a s o n e
8 mg/day started
and gradually
halved by 7-10 days
and then tapered
Postpartum thyroiditis Thyroxin Propranolol
(Silent thyroiditis)
Chronic autoimmune Thyroxin suppresses
thyroiditis (Hashimoto) goitre growth, corre-
cts hypothyroidism
and normalises TSH.
Smaller dose if asso-
ciated with IHD.
Riedel’s thyroiditis: Oral tamoxifen for Short-term steroid for
1 year. Remarkable painful compressive
partial to complete symptoms
remission
THYROIDITIS
Hyperthyroidism (Thyrotoxicosis) | 439

Aetiological consideration and classification

Pathology Causes Frequency
1. Chronic thyroiditis: Chronic lymphocytic thyroi- i. Iodine supplementation Most common in USA
a. Hashimoto’s thy- ditis ii. Drugs: Amiodarone,
roiditis alpha-interferon, inter-
b. Riedel’s thyroiditis Invasive fibrous leukin-2 Rarest
(Riedel’s struma) Thyroiditis. May be asso-
ciated with multifocal
systemic fibrous synd-
rome (retroperitonial fib-
rosis, fibrous mediastinitis
and sclerosing cervicitis)

2. Subacute thyroiditis Granulomatous and giant cell i. Viral infection Fairly common
(Quervain’s thyroiditis) thyroiditis ii. Postpartum

3. Acute suppurative thy- Inflammatory cells Pyogenic infection, rarely Rare

roiditis fungal or tuberculous infec-
tion
DIAGNOSTIC CLUES
Clinical
Sex Thyroid gland Functional status Other features
Hashimoto’s thyroiditis Six times more com- a. Diffusely enlarged, a. Usually progresses a. Depression,
mon in women than in firm, finely nodu- to hypothyroidism chronic fatigue,
men lar, or b. Uncommonly dry mouth and
b. Atrophic in 10% hyperthyroidism eye (mild)
cases b. Sometime associa-
ted with:
i. Adrenal insuffi-
cient (Schmidt’s
syndrome)
ii. Other endocrine
deficiencies:
Polyglandular
autoimmunity
and other auto-
immune con-
ditions (inflam-
matory bowel
disorder or
celiac disease)
Riedel’s thyroiditis Middle aged or elderly Asymmetric enlarge- Normal
women ment of thyroid, stony
hard and adherent to
neck structure produ-
contd...
440 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

cing pressure symp-

toms (dysphagia, dysp-
noea, pain, hoarseness
Subacute thyroiditis: Young and middle aged a. Painful diffuse May be associated with Upper respiratory
women enlargement, ten- thyrotoxicosis or hypo- catarrh preceding
der thyroidism or euthyroid 7-10 days, fever
Acute thyroiditis b. Occasionally pain-
less enlargement
(Silent thyroiditis).
Severe pain, ten-
derness, redness,
fluctuation

HYPERPROLACTINAEMIA
Physiological Consideration
• Serum prolactin rises during pregnancy and reaches maximum by the time of delivery.
• Prolactin + Estrogen + Progesterone develops breast and forms milk in the acinii.
• After parturition, estrogen is suddenly withdrawn results in the onset of lactation.
• Dopamine inhibits prolactin and lactation is inhibited.
• Sucking constitutes a powerful stimulus for continued production of prolactin and oxytocin and milk
production.

AETIOLOGICAL CONSIDERATION
Physiological Drugs Diseases
• Pregnancy Estrogen, opiates, dopamine receptor • Pituitary adenoma
• Puerperium antagonists (metoclopramide, • Craniopharyngioma of hypothalamus
• Sucking phenothiazine) and dopamine— • Primary hypothyroidism
• Stress depleting agents (reserpine, methyldopa) • Cirrhosis
• Renal failure

DIAGNOSTIC CLUES
Clinical
Male Female
• Erectile dysfunction • Oligomenorrhoea
• Diminished libido • Amenorrhoea
• Gynaecomastia • Galactorrhoea
• Infertility • Osteoporosis
• Infertility

LABORATORY INVESTIGATIONS
A. Investigation of conditions causing hyperprolactinaemia:
Conditions Investigations
• Pregnancy Measure serum hCG
• Hypothyroidism Measure serum free thyroxin and TSH
 • Renal failure BUN, creatinine
Hyperthyroidism (Thyrotoxicosis) | 441

• Cirrhosis Serum bilirubin, liver enzyme

B. Serum prolactin level:
Greater than 250 ng/ml Lower than 100 ng/ml
Diagnostic of prolactinoma in the Any other cause of hyperprolactinaemia
absence of renal failure and late pregnancy
C. Imaging: MRI and CT scan of pituitary and hypothalamus
Detects macroadenoma and microadenoma (difficult to visualise)
If no imaging abnormality detected, suggests idiopathic hyperprolactinaemia.

TREATMENT OF HYPERPROLACTINAEMIA
I. Microadenoma
A. Non-prolactin secreting microadenoma:
Symptomatic Asymptomatic
Usually treated for infertility and oestrogen deficiency by Treatment not required.
dopamine agonists: Periodic follow-up of
prolactin level and assess-
ment of symptoms should
be done.
Drugs Dosage Monitoring Advantages Disadvan-
tages
Bromocriptine: Started 1.25- Plasma prolactin Restores normal Nausea, diz-
2.5 mg orally level at 2-4 menses and fer- ziness, ortho-
q.h.s. with food at weeks interval tility. Reduces static hypo-
bedtime. Maxi- measured till prolactin level tension
mum dose normal and then
2.5 mg t.d.s. every 6-12 months

Cabergoline Started 0.25 mg - Do - Best tolerated

twice a week.
Maximum dose
1.5 mg twice a week
B. Prolactin secreting microadenoma: Transphenoidal resection of microadenoma is done only in
the rare patients who do not respond to bromocriptine or cabergoline or do not tolerate them.
II. Macroadenoma: Prolactin secreting:
A. Medical Therapy:
Drug Dose Monitoring Advantages
Bromocriptine See above Prolactin level estimated Restores prolactin level,
Cabergoline Dose is higher if mass every 4-6 weeks; pituitary reduces tumour size
effect is present imaging repeated every 3- and improves visual field
4 months. If satisfactory
drug continued indefinitely
B. Surgery Therapy
Transphenoidal surgery is indicated to relieve mass effect, to prevent further tumour growth, if
tumour does not shrink or visual field do not improve during medical therapy.
442 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

C. Radiotherapy
Indication: Macroadenoma growing in spite of medical therapy
Risk: Hypopituitarism

Special Precaution in Women Patient

A. Women patients with microadenoma:
i. Patients who wants to become pregnant, should be managed by an endocrinologist.
ii. Patient who do not wants to be pregnant, medical therapy indefinitely measuring prolactin level
every 6-12 months and then every 2 years plasma prolactin should be measured after
bromocriptine therapy has been withdrawn for several weeks to determine whether the drug is
still needed.
B. Women patients with macroadenoma secreting prolactin:
She should not become pregnant unless the tumour has been resected surgically, as the risk of
symptomatic enlargement during pregnancy is 15-35%. Barrier contraception is essential during
dopamine agonist treatment.
 Endocrinology
73
Hypothyroidism

Hypothyroidism refers to the clinical manifestation associated with deficiency of thyroid hormone.

AETIOLOGICAL CONSIDERATION
Primary hypothyroidism Secondary hypothyroidism
A. Due to diseases of thyroid: Due to TSH deficiency associated with
a. Idiopathic myoxoedema—commonest (90%). disorders of pituitary and hypothalamus
Middle aged women. Non-goitrous
b. Autoimmune thyroiditis
(Hashimoto)—common cause of goitrous
hypothyroidism
c. Endemic goitre due to iodine deficiency or
naturally occurring goitrogens harming thyroid
d. Congenital of childhood:
• Environmental iodine deficiency
• Hormonal biosynthetic defect
• Maldevelopment (cryptothyroidism)
B. Iatrogenic
• Thyroidectomy
• Radioactive iodine therapy
• Drugs: Iodine, lithium, interferon alpha, interferon-2, amiodarone, phenylbutazone

Diagnostic Clues
Clinical
Symptoms Signs Complications
Cold intolerence, fatigue, som- a. Usual signs: Bradycardia, goitre, Coronary artery disease, CCF,
nolence, poor memory, consti- slow tendon reflex relaxation, psychosis, myxoedema coma
pation, myalgia, hoarseness, facial and periorbital oedema, (coma + severe hypothermia +
history of radioactive iodine dry skin, non-pitting oedema, hypoventilation + hypotension)
therapy, or thyroid surgery myxoedema precipitated by infection, drug
b. Rare signs: Deafness, carpal or cold exposure
tunnel syndrome
444 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

LABORATORY FINDINGS
• Hyponatraemia • Elevated cholesterol, ECG: Other findings: Antibodies
• Hypoglycaemia triglyceride and creatine Low voltage, T wave against thyroperoxidase and
• Anaemia Kinase abnormalities thyroglobulin elevated in
Hashimoto’s thyroiditis

THYROID FUNCTION
A. Non-goitrous hypothyroidism
Primary hypothyroidism Secondary hypothyroidism
TSH Suggested by normal
TSH +
Normal Elevation • Evidence of pitui-
or tary or hypothalamic
low Marked elevation Moderate elevation disease
(above 20 U/ml) (less than U/ml) • Evidence of mass
lesion of pituitary or
Excludes primary Confirms primary hypothalamus
hypothyroidism hypothyroidism

TRH Test Measure Free T4

Blunted or flat Normal or delayed Low free T4 Normal T4

response response Confirms clinical Sub-clinical
hypothyroidism hypothyroidism
Pituitary Hypothalamic (Primary) which develops into
hypothyroidism hypothyroidism clinical hypothyroi-
dism at a rate of 2.5%
per year
B. Goitrous hypothyroidism
Measure free T4

Normal or high Low

Arrange for microsomal Arrange for urine I2

antibodies (24 hour)

Positive Negative Less than 50 μg Above 100 μg

Autoimmune Drug induced Severe iodine Biosynthetic

thyroiditis hypothyroidism deficiency defect
(Hashimoto)
TREATMENT OF HYPOTHYROIDISM
Hypothyroidism | 445

Drug of choice is thyroxine (T4) which is converted to T3, more active thyroid hormone.
Preparation Action Contraindication Side-effects Drug interaction
Eltroxin (glaxo) Increases BMR and Acute myocardial Aggravates angina, Enhances effect of
100 mcg tab metabolism of CHO, infarction, thyrotoxi- tremor, tachycardia, oral anticoagulant.
Thyronorm (knoll) protein and fat cosis insomnia, headache, Aspirin, amiodarone,
25 mcg, 100 mcg sweating and phenytoin
enhances effect of
thyroxin
Dosages of thyroxine:
A. Initiation of therapy:
In young patient below 60 yr In elderly above 60 yr In cardiac patient
100 mcg/day and continued for 50 mcg/day Starting 25 mcg/day, monitoring
several weeks to reach steady carefully for exacerbation of
state of plasma T4 level taken cardiac symptoms
in morning with water in
empty stomach
B. Dose adjustment and follow-up: Treatment continued for life.
In primary hypothyroidism In secondary hypothyroidism In coronary artery disease
Measure plasma TSH level Measure T4 level. Maintain Dose should be increased
after 2-3 months of thyroxine plasma T4 level near normal carefully and slowly keeping
therapy. Dose adjusted in or near the middle range. Dose in mind worsening of angina,
12-25 μg increment at intervals of thyroxin should be adjusted heart failure or arrhythmia
of 6-8 weeks until TSH at 6-8 weekly intervals until the
becomes normal goal is achieved
↓ ↓ ↓
Thereafter annual TSH Thereafter annual T4 measure- If cardiac symptoms worsen
measurement is adequate to ment is suffice for adjusting the inspite of medical therapy,
monitor therapy. Over treatment dose coronary revascularisation surgery
precipitates auricular fibrillation should be considered. Bypass
and osteoporosis. Usual mainte- surgery is safe in hypothyroidism
nance dose: 100-200 μg/day
Note: Don’t rely entirely on TSH and T4 level. The goal is to keep the patient euthyroid and symptom
free.

Treatment of Sub-clinical Hypothyroidism

Indications for thyroxin treatment:
i. Symptoms of hypothyroidism is present
ii. Goitre present
iii. Hypercholesterolaemia
iv. Serum TSH level increases to more than 20 μg/ml
446 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Management of Hypothyroidism not Responding to Standard Thyroxine Therapy

Arrange for serum TSH determination

Elevated serum TSH level Suppressed

In patients receiving standard replacement serum TSH
dose of thyroxine but not responding. It is level (less
due to increased thyroxine requirement under than 0.1 U/L)
the following conditions:

Interference to Drugs
intestinal absorption:
Malabsorption Drug interfering Drugs increasing Drugs blocking Pregnancy
interfering thyroxin absorption: thyroxin clearance: conversion of Thyroxin
absorption of Cholestyramine, Rifampicin, carba- T4 to T3: requirement
thyroxin sucralfate, aluminium mazepine, phenytoin Amiodarone increases
hydroxide, soya milk,
calcium supplement

1 2 3 1, 2, 3 Some patient’s
May exhibit May not exhibit Drugs suppres- If are not present: complain of
hyperthyroidism hyperthyroidism sing TSH: Low-dose of T4 hypothyroid
Dose of T4 should Determine whether NSAID, opioids, given unless hyper- symptom
be reduced hypopituitarism nifedipine, vera-, thyroidism Look for con-
present. If present pamil, steroids current illnes-
treat used ses, e.g. adrenal
insufficiency
hypogonadism,
anaemia or dep-
ression
⇓
If the above conditions ruled out or treated adequately
and still hypothyroid symptoms persist:
Determine T3 level, if it is low, such patients may
benefit from a careful increase in thyroxin dose.

MANAGEMENT OF MYXOEDEMA COMA

1. Replacement therapy:
IV T4 400-500 microgram stat followed by 100 microgram daily IV for several days when the
patient is comatosed, followed by 0.1 to 0.15 mg daily orally in the morning in empty stomach.
2. Supporting treatment:
a. Blankets used to reduce heat loss. Active warming is not helpful and may lead to vasodilatation.
b. IV fluid and blood transfusion for shock
c. Ventilatory assistance with intubation or tracheostomy for CO2 retention.
3. Hydrocortisone:
Hypothyroidism |447

As the adrenal reserve is not known, hydrocortisone 150 mg IV should be given on the first day,
gradually tapered over 5-7 days as the patient improves.
4. Treatment of precipitating factors:
Attend to trauma infection.
 Endocrinology
74
Thyroid Enlargement

Determine by palpation (not by ultrasonogram or thyroid scan) two types of thyroid enlargement:
I. Diffuse enlargement:
A. Endemic: Mechanism: Causes:
a. Intrinsic enzyme defect in thyroid hormone synthesis
b. Idiopathic
Decreased thyroid hormone production
TSH production increases
Thyroid stimulated and enlarges
B. Sporadic: Mechanism:
Lack of iodine in diet or presence of goitrogens
Decreased thyroid hormone production
Excess TSH production
Thyroid stimulation and enlargement
Sporadic cretinism: Characterised by growth failure, mental retardation, myxoedema, signs of
hypothyroidism with T4 low and TSH high
Treatment: Thyroxin
II. Nodular enlargement:
Single nodule Multinodular
Adenoma, colloid nodule or cyst a. Usually benign
Usually malignant: Characterised by rapid enlargement, b. Hyperthyroidism may supervene in long-
irregular margin, hard, fixed, cervical adenopathy standing case (Toxic multinodular goitre)

EVALUATION OF SINGLE NODULE

Low degree of suspicion of cancer
History and physical Family history of goitre, residence in
examination: area of endemic goitre, older women,
soft nodule
High index of suspicion of cancer
Risk of malignancy:
Previous irradiation of head, neck, chest
in childhood, hoarseness due to vocal
cord paralysis, family history of medul-
lary thyroid carcinoma, multiple endo-
crine neoplasia syndrome, young adult-
men, firm nodule, enlarged lymphglands,
fixed, recent growth of nodule.
 Thyroid Enlargement

Occasional patient develops cancer

| 449

without the above risk, hence all

patients should be evaluated by
investigation specially by needle
aspiration
Laboratory evaluation:
Fine needle Normal cells Colloid nodules Hypercellular Suspicion of cancer
aspiration and ↓ or adenoma aspirate a. 131-I therapy or
cytology: Treated by b. Surgery
TSH suppression Benign
by thyroxin
131-I thyroid Hyperfunction Hypofunctional
scan: (hot nodule): Surgery (Cold nodule):
131-I therapy or
surgery
Ultrasono- Cystic lesion: Solid lesion:
gram: Usually benign Cyst yielding High index of sus-
bloody fluid: picion of malig-
↓ nancy
Malignant suspicion
Roentogeno- Shell-like calci- Punctate calcification:
gram: fication: Usually benign Suspicion of malignancy
Hormonal T3 may be high
evaluation: T4 may or may not increase
TSH usually subnormal
Toxic autonomous nodule
Thyroxin Regression after 0.05-0.1 mg/day Increase in size of
therapy: for 6 months or more goitre: Malignancy

TREATMENT OF NODULAR ENLARGEMENT OF THYROID

Multinodular goitre Single nodule
i. Asymptomatic patients: i. If high suspicion of malignancy as
No treatment is required revealed by needle biopsy:
ii. Symptomatic patients: Nodule is resected
a. Measure TSH ii. Solitary nodule with hyperthyroidism:
Low TSH points to hyperthyroidism Treated with radioactive iodine
and treated accordingly iii. Hot nodule is usually benign but
b. May produce pressure symptoms is resected to cure hyperthyroidism
(dyspnoea, dysphagia) by pressure
on oesophagus and trachia if goitre is large:
• Radioactive iodine therapy relieves pressure symptoms
• Subtotal thyroidectomy
c. In some patients nodule enlarges disproportionately
Needle biopsy needed for evaluation of cancer
 Endocrinology
75
Treatment of Hyperparathyroidism

AETIOLOGICAL CONSIDERATION
Primary
• Parathyroid adenoma (Commonest)
• Parathyroid hyperplasia (Less common)
• Carcinoma (Rare)
Secondary
i. Physiological: Lactational
ii. Pathological:
• Chronic renal failure
• Bone diseases: Rickets and osteomalacia
• Drugs: Lithium poisoning, lead poisoning,
• Pseudohypoparathyroidism
• Intestinal malabsorption

PHYSIO-PATHOLOGICAL CONSIDERATION
Primary hyperparathyroidism:
Produces excess PTH leads to

Hypercalcaemia Hypercalciuria Chronic bone reabsorption

Responsible for 5% Diffuse demineralisation

renal stone of bone

Secondary Hyperparathyroidism: Pathogenesis:

Chronic renal failure
Hyperphosphataemia
Decrease in production of 1, 25 (OH) D3
↓
Decrease in ionised calcium
↓
Parathyroid gland stimulated resulting in secondary hyperparathyroidism

DIAGNOSTIC CLUES
Clinical
Asymptomatic : Common
Symptomatic : Bones, stones, abdominal groans and psychotic moans
Bones Stones and kidney Abdominal groans
Treatment of Hyperparathyroidism

Psychotic moans Other

| 451

• Pain • Calcium stones • Pain, nausea, vomi- • Psychosis • Fatigue

• Arthralgia (18%) ting and constipation • Coma • Paresthesia
• Demineralisation • Nephrocalcinosis • Peptic ulcer • Depression • Hypertension
resulting in patho- • Renal failure • Pancreatitis in 3% • Increased sleep • Band keratopathy
logical fracture, cys- • Nephrogenic diabe- cases • Confusion • Pruritus
tic bone lesion (ostei- tes insipidus (poly- • Deafness
tis fibrosa cystica) uria and polydipsia) • Soft tissue calcifi-
cation

LABORATORY INVESTIGATIONS
Biochemical
• Persistent hypercalcaemia (Ser.
calcium above 10.5 mg/dl)
• Hypophosphataemia (Less than 2.5
mg/dl). In secondary hyperthyroidism
due to renal failure ser. phosphate is
high
• Alkaline phosphatase elevated only if
bone disease is present
Hormonal
• Inappropriate elevation of PTH by i. CT scan, MRI, ultrasonography and
immunoradiometric assay (IRMA).
This test is specific and differentiate
primary hyperparathyroidism from ii. X-ray of bones:
other causes of hypercalcaemia
• Non-suppressibility of PTH by
calcium infusion
• Cortisol 150 mg/24 hours for 10 days
bring down the hypercalcaemia due to
primary hyperparathyroidism unlike
that of secondary hyperparathyroidism
Imaging
scintography: Can detect 90% of
adenoma
• Skull: Pepper-pot appearance in
osteitis fibrosa
• Vertebra: Osteoporosis, comp-
ression fracture of vetebral body
• Long bones: Erosion of distal one-
third of clavicle; erosion of distal
end or medial surface of neck of
femur
• Deformities and pathological
fracture
• Hands: Subperiosteal bone in
radial aspect of phalanges
• Teeth: Loss of lamina dura
• Ectopic calcification: Around
joint or in soft tissue in osteo-
dystrophy.

TREATMENT OF HYPERPARATHYROIDISM
A. Treatment of hypercalcaemia:
a. Hydration:
i. Mild cases: Ensure large fluid intake orally
ii. Severe cases: Hospitalise the patient and hydrate with IV fluid
b. Bisphosphonate:
Preparation Action Dose Advantage
Pamidronate Inhibits bone Pamidronate: 30-90 mg Relieves bone pain,
Alendronate reabsorption in 0.9% saline IV over lowers calcium level
⇓ 4-12 hours gradually over several days
Monitoring
i. Check serum calcium and albumin twice yearly
ii. Check renal function and urine calcium once yearly
iii. Check bone density every 2 years
452 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

B. Asymptomatic hyperparathyroidism:
i. Observe closely medically
ii. Advised to keep active, avoid immobilisation and drink adequate fluid
iii. Avoid thiazide diuretics, large amount of vitamin D and A and calcium containing antacids.
C. Oestrogen replacement:
Oestrogen is given to postmenopausal women. Avoid digitalis to prevent its toxic effects
D. Propranolol:
Propranolol is useful for preventing adverse cardiac effect of hypercalcaemia
E. Renal osteodystrophy due to secondary hyperparathyroidism during renal failure:
Osteodystrophy may be prevented by avoiding hyperphosphataemia.
Calcium acetate is given with meal to bind phosphate. Calcitriol is given orally or IV after dialysis,
also suppresses parathyroid hyperplasia.

SURGICAL THERAPY
A. Parathyroidectomy:
Indications:
i. Symptomatic hyperparathyroidism
ii. Patients with hypercalcaemia, hypercalciuria, low cortical bone density, young patients
iii. Pregnancy
iv. Difficulty ensuring medical therapy and follow-up
B. Subtotal parathyroidectomy:
Indicated in parathyroid hyperplasia associated with chronic renal failure.
 Endocrinology
76
Hypoparathyroidism

Physiological Consideration of Parathyroid

Parathyroid gland
Synthesises and secretes parathyroid hormone (PTH)
↓
PTH regulates skeletal and mineral metabolism
↓
Effect of PTH on bone, tubule and kidney

Bone Renal tubule Kidney

Increases osteoclastic Increases tubular Inhibits absorption Stimulates synthesis
activity and mobilises reabsorption of of phosphate and of 1, 25-dihydroxy-
calcium from bone calcium bicarbonate by cholecalciferol by
renal tubule kidney

Results in increased serum ionised

Calcium

In hypoparathyroidism due to decreased In hyperthyroidism due to increased

serum PTH hypocalcaemia and hyper- serum PTH, hypercalcaemia occurs
phosphataemia occurs

HYPOPARATHYROIDISM AND PSEUDOHYPOPARATHYROIDISM

Aetiological Consideration
Causes of three types of hypoparathyroidism:
Primary Functional Pseudohypopara-
hypoparathyroidism hypoparathyroidism thyroidism
i. Thyroidectomy or radiotherapy Magnesium deficiency Due to renal resistance to
for hyperthyroidism due to malabsorption PTH caused by mutation
ii. Parathyroidectomy for primary and chronic alcoholism involving PTH receptor
hyperparathyroidism
iii. Autoimmunity:
a. Sporadic contd...
454 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. As a part of polyglandular autoimmune syndrome—Familial

iv. Congenital absence of parathyroid and thymus (Di George syndrome)
v. Other causes:
Heavy metals, haemosiderosis due to transfusional haemochromatosis, granulomas, infection (HIV)
and drugs (INH, rifampicin, propylthiouracil).

DIAGNOSTIC CLUES
Clinical
Symptoms Signs

Acute Chronic Acute Chronic

• Tetany • Lethargy • Convulsion • Chvostek’s signs
• Muscle cramps • Personality change • Carpopedal spasm (Facial contraction on
• Irritability • Anxiety tapping facial nerve
• Tingling of circumoral • Blurring of vision in front of ear)
area, hand and feet due to cataract • Trousseau’s signs
• Mental retardation (Carpal spasm after
application of a cuff)
• Nail thin and brittle
• Skin dry and scaly
• Defective teeth
• Cataract

LABORATORY INVESTIGATIONS
Blood Urine Test
• Calcium low Calcium low Teripartid (Parather 1-34 synthetic
• Phosphate high parathyroid hormone) IV infusion
• Alkaline phosphatase normal test can differentiate pseudohyper-
• Magnesium low parathyroidism type 1A, 1B and II
• PTH
a. Hypocalcaemia + Low PTH
↓
PTH deficiency hypoparathyroidism
b. Hypocalcaemia + Normal or elevated PTH
↓
Target organ resistance in pseudohypoparathyroidism

TREATMENT HYPOPARATHYROIDISM
Treatment of hypoparathyroidism is lifelong.
Aim: Improvement of calcium status of the patient.
PTH is not replaced because it is less effective, expensive and likely to fail in the long-run due to
antibody generation.
Treatment of Hypocalcaemia of Hypoparathyroidism
Hypoparathyroidism | 455

Medical Therapy
I. Treatment of hypocalcaemia:
Acute hypocalcaemia: Chronic hypocalcaemia of hypoparathyroidism
• Ensure adequate airway Aim is to increase gut absorption of calcium and
• Calcium administration: depleted phosphate.
i. Calcium chloride or calcium gluconate A. Calcium is given to maintain serum 8-9 mg/dl:
0.5 to 2 mg/kg body weight/hour IV i. Vitamin D:
ii. Calcium gluconate 10% solution 10-
Preparation Dose Comment
20 ml slowly IV
Vitamin 1, 25 1-2 mcg per Ideal, onset
iii. Calcium gluconate infusion:
(OH) 2 D3 24 hour and off set
10-50 ml 10% calcium gluconate may be added
quick
to 1 litre of 5% glucose in water or saline given
Vitamin 1-alpha 0.5 to 3 mcg Effective in
slowly IV drip
per 24 hour small dose
Calciferol 0.25 to 20 mg Effective only
After parenteral calcium oral calcium 1-2 gm/day
/24 hour in large dose
should be given as soon as possible. Liquid calcium
B. Verapamil
carbonate (500 mg/ml) 1-3 gm/day especially useful.

II. Decreasing phosphate level

Treated by antacid (aluminium hydroxide), thiazide and ammonium chloride.
III. Treatment of magnesium deficiency if present
Magnesium deficiency results in hypocalcaemia, hence should be treated.
IV. Treatment of hypercalciuria:
Respond to only oral thiazide given with potassium.

SURGICAL THERAPY
Transplantation of cryopreserved parathyroid tissue restores normal calcaemia in about 23% cases.
 Endocrinology
77
Osteomalacia

Osteomalacia is characterised by decreased mineralisation of bone associated with increased thickness

of osteoid bones.

PATHOPHYSIOLOGY
Types of vitamin D

D2 D3
Derived from plants Synthesised in skin under the influence
of ultraviolet radiation

Action of vitamin D
Main action of vitamin D is to increase absorption
of calcium and phosphate from intestine
↓
Deficiency of vitamin D results in hypocalcaemia
and hypophosphataemia which in turn causes
defective mineralisation of bone causing:

In adult In a child
Osteomalacia Ricket

AETIOLOGICAL CONSIDERATION
A. Vitamin D deficiency and resistance:
• Insufficient sunlight exposure
• Malabsorption
• Nephrosis (Renal loss of vitamin D binding protein)
• Chronic renal failure
• Vitamin deficient ricket (due to genetic defect in renal synthesis of 1, 25 (OH) 2D
B. Dietary calcium deficiency:
• Malnutrition
• Housebound elderly
 C. Phosphate deficiency:
Osteomalacia | 457

• Congenital
• Acquired: Malabsorption, phosphate binding antacid (aluminium hydroxide) and renal tubular
acidosis
D. Disorder of bone matrix: Hypophosphatasia
E. Inhibitors of bone mineralisation:
• Aluminium
• Bisphosphonate

DIAGNOSTIC CLUES
Clinical
Bone Muscle Skin Skeletal deformities
• Diffuse skeletal pain • Proximal muscle • Pruritus due to Osteodystrophy
• Pathological fracture (pelvic girdle) deposition of calcium
weakness resulting in skin in uraemia
in waddling gait • Ischaemic necrosis
due to vascular calci-
fication causing
lesion of toes and fingers

Children: Adult:
• Bowing of tibia • Lumbar scoliasis
and femur • Thoracic kyphosis
• Growth retardation • Aseptic necrosis of
head of femur after
renal transplant

LABORATORY INVESTIGATION
Blood
• Alkaline phosphatase high if
bone involved
• Serum phosphorus : Low
• Serum calcium : Low
• Serum 25-hydroxy vitamin
D: Low
Radiography of Bone densitometry
chest, pelvis and hip
• Osteopenia Determines degree of osteopenia
• Radiolucent bands
perpendicular to bone
surfaces (pseudofracture
or looser’s zone)

If blood examination and radiography are not diagnostic

⇓
Bone biopsy is done which reveals increased thickness of
osteoid seams and decreased mineralisation of bone

TREATMENT OF OSTEOMALACIA
I. Treatment of osteomalacia with vitamin D and calcium (based on aetiology):
458 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Drugs preparation Nutritional vitamin Vitamin D malab- Anticonvulsant Vitamin D resistant Chronic renal
D deficiency sorption induced induces osteo- rickets failure
osteomalacia malacia
25 (OH) D3 —— 100-300 mcg/day Usually not requi- a. Type I: 50-100 50-100 mcg/day
Calciferol: 20 mcg red mcg/day
or 50 mcg capsule b. Type II: 200
mcg or more/
day
1.25 (OH) D3 —— 1-2 mcg/day 0.25-0.5 mcg a. 1-3 mcg/day in 0.25-3 to 4 mcg/
Calcitriol: 0.25 twice a day Type I day
mcg or 0.5 mcg b. 5-20 mcg/day
capsule in Type II
a. 1-2 gm/day in 1-2 gm/day 800-1000 mg/day —— 1000 mg/day
Elemental calcium: children
i. C a l c i u m b. 800-1000 mg
carbonate: per day in
Suspension adult
12.5 ml = 1 gm
calcium: Tab 6
= 1 gm – do – – do – – do – —— – do –
calcium
ii. Calcium glu-
conate
Tab 650 mg
1gm = 17 tab ——
Tab 1000 mg – do – – do – – do – – do –
1 gm = 11 tab
iii. Calcium
lactate Tab
325 mg 1gm
= 24 tab Tab
650 mg 1 gm
= 12 tabs
II. Control of Phosphate
• Restrict phosphorus intake in diet
• Use of phosphate binding antacids (aluminium hydroxide)
• Calcium carbonate 1-3 gm with each meal
III. Fluoride induced osteomalacia:
• Supply of normal drinking water
• Treated with calcium and vitamin D
IV. Hypoparathyroidism induced osteomalacia:
Treated with calcium and vitamin D
V. X-linked hypophosphataemia causing osteomalacia
Treated with:
• 0.25 mcg calcitriol twice a day up to 3-4 mcg/day
• Elemental calcium 1-4 gm/day in 4-6 divided dosages
MONITORING
Osteomalacia | 459

a. Biochemical monitoring:
The initial response to treatment is an increase in alkaline phosphatase (if bone is not involved) and
rise in urine and serum calcium. PTH may fall as secondary hypoparathyroidism is ameliorated.
b. Radiological monitoring:
Improvement in skeletal mineralisation takes months.
c. Bone density monitoring:
Density improves within a few weeks.

PREVENTION
• Adequate sunlight exposure
• Vitamin D supplement for prophylaxis: 400/day as in sunlight deprived individuals (living at high
altitude, veiled women, confined patients).

SURGERY
Parathyroidectomy:
Indications:
• Severe secondary hyperparathyroidism associated with any of the following:
• Persistent hypercalciuria
• Persistent hypercalcaemia (Ser. above 11-12 mg/day)
• Progressive extraskeletal calcification
• Pruritus not responding to medical treatment
• Ischaemic ulcer and necrosis.
 Endocrinology
78
Metabolic Bone Diseases

Metabolic bone disease is characterised by diffusely decreased bone density and diminished bone strength.
It is of two types:

Both bone matrix and mineral decreased Bone matrix intact but mineral decreased
↓ ↓
Osteoporosis Osteomalacia

OSTEOPOROSIS
Pathogenesis
Ageing Menopause Malnutrition Alcohol and tobacco

Increased bone loss

↓
Decreased bone density
Diminished bone strength
↓
Pathological fracture of bone

AETIOLOGICAL CONSIDERATION
A. Primary osteoporosis:
1. Postmenopausal
2. Senile
3. Idiopathic: Juvenile osteoporosis
B. Secondary osteoporosis
1. Endocrine disease:
• Hypogonadism
• Ovarian agenesis
• Glucocorticoid excess
• Hyperthyroidism
• Hyperparathyroidism
2. Gastrointestinal and liver disorders:
• Malabsorption
 • Biliary cirrhosis
Metabolic Bone Diseases | 461

• Chronic obstructive jaundice

3. Bone marrow disorders:
• Multiple myeloma
• Disseminated carcinoma
4. Connective tissue disorders:
• Osteogenesis imperfect
• Homocystinuria
• Marfan’s syndrome
5. Others:
• Tobacco
• Alcohol
• Immobilisation

DIAGNOSTIC CLUES
Clinical
A. Asymptomatic: Common
B. Symptomatic:
• Backache from vertebral fracture
• Loss of height due to spontaneous fracture

LABORATORY INVESTIGATIONS
Blood examination Imaging bone demineralisation Bone densitometry
Serum calcium, phosphorus, PTH Usual sites: Spine, pelvis, CT and X-ray absorptiometry:
and alkaline phosphatase normal femoral head and neck Shows osteopenia

TREATMENT OF OSTEOPOROSIS
I. Drugs:
Preparations Dose Indication Precaution Advantage Disadvantage
I. Sex hormones: Evalon 2 mg/day Hypogonadism in post- • Raises HDL • Endometrial hyper-
Estrogen: Premarin 0.625 mg per menopausal osteo- • Reduces hot flushes plasia
day porosis • Relieves vaginal dry- • Uterine bleeding
ness • Breast cancer
• Fluid retention
• Pulmonary embolism
Testosterone -------- Male hypogonadism

II. Bisphosphonate: Taken in empty sto- Patient must remain Prevents also cortico- Oesophagitis
Inhibits osteoclast mach with 8 oz of water upright after taking the steroid induced osteo-
induced bone re- 90 minutes before con- drug to prevent oeso- porosis
abruption sumption of food for phagitis
ensuring intestinal
absorption
contd...
462 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Preparations Dose Indication Precaution Advantage Disadvantage

Alendronate: 10 mg/day orally If hypocalcaemia is • Esophagitis
or produced, treat with • Gastritis
70 mg orally once vitamin D • Anorexia
weekly is more con- • Weight loss
venient • Hypocalcaemia

Etidronate 40 mg/day for 2 weeks Less expensive and Less effective than
every 3 month better tolerated than alendronate
alendronate
Pamidronate 60 mg by slow IV infu- Indicated in patients
sion in normal saline who do not tolerate oral
every 3 month bisphosphonate

III. Raloxifene: 60 mg/day orally Postmenopausal • Reduces LDL Does not raise
Selective estrogen women can use in • Does not produce • HDL unlike oestro-
receptor modu- place of oestrogen endometrial hyper- gen
lator (SERM) plasia and breast • Does not reduce hot
cancer unlike oestro- flushes unlike oestro-
gen gen
• Teratogenic hence
contraindicated in
premenopausal
women
• Increases risk of
thromboembolism

IV. Calcitonin acts by A nasal spray is avai- Reduces vertebral frac- • Rhinitis
decreasing bone lable: 1 puff/day ture and bone pain • Epistaxis
reabsorption Parenteral preparation. • Allergy
Calcium preparation • Flue like symptoms
must be given to pre- • Arthralgia
vent secondary hyper- • Headache
parathyroidism • High cost
• Parenteral prepara-
tion

V. Calcium and • Given for whole life Indicated in patients Also prevents osteo- Hypercalcaemia devel-
vitamin D • Given with meals to with high risk of osteo- porosis and osteo- ops if patients on glu-
reduce calcium oxal- porosis malacia cocorticoids or thiazide
ate nephrocalcinosis
Calcium carbo- 1-1.5 gm elemental
nate: calcium/day
Calcium citrate: 0.4-0.6 gm/day
Vitamin D2 400-1000 I.U. daily

VI. Anabolic steroid Used with oestrogen,

calcium and vitamin D
II. General and Symptomatic Management
Metabolic Bone Diseases | 463

1. Exercise: Advised regular exercise:

• Walking or running
• Weight training
• Balance exercise can reduce risk of fall
• Bedridden patients should be given passive and active exercises.
2. Avoidance of falls:
• Adequate lightning facility
• Hand rails on staircase should be provided
• Hand holds in bathroom
• Use of cane or walker.
3. Avoidance of tobacco and alcohol.
4. Nutrition: Diet should be adequate in proteins, total calories, calcium (calcitriol 0.25 mcg/day
and vitamin D (400-800 IU/day).
5. Glucocorticoids: Dose should be reduced or discontinued.
6. Hypercalciuria: Treated by thiazide diuretics.
7. Treatment of backache:
Acute Chronic
• Analgesics • Orthopaedic brace
• Heat • Back extension exercise
• Gentle massage • See also General management above
• Sometimes brief period of bedrest
 Endocrinology
79
Diabetes Insipidus

It is caused by deficiency of vasopressin or resistance to vasopressin.

AETIOLOGICAL CONSIDERATION
I. Deficiency of vasopressin
(Central diabetes insipidus-CDI):
A. Primary : Familial
B. Secondary :

Damage to hypothalamus-pituitary stalk by: Vasopressinase induced

• Tumour of hypothalamus and pituitary (this enzyme destroys vasopressin)
• Trauma: i. Surgical Seen in last trimester of pregnancy
ii. Accidental, head injury and in puerperium
• Infection: Encephalitis, tuberculosis, syphilis
• Sarcoidosis
• Histocytosis “X”
• Metastasis
II. Resistance to vasopressin: Nephrogenic diabetes insipidus (NDI):
(Failure of kidney to respond to vasopressin)
Congenital Acquired
Familial • Renal: Pyelonephritis, renal amyloidosis, renal multiple myeloma
• Potassium depletion
• Sjögren’s syndrome
• Sickel cell anaemia
• Chronic hypercalcaemia
• Drugs: Democycline, lithium, methicillin

DIAGNOSTIC CLUES
Clinical
Intense thirst with increased water intake; polyuria (2-10 litre urine/day); nocturia, dehydration
Causes of polyuria: Differential diagnosis:
• Solute polyuria: Diabetes mellitus, diuretic, hypercalciuria
• Renal failure
 • Diabetes insipidus: CDI, NDI
Diabetes Insipidus |
465

• Compulsory water drinking (CWD)

DIAGNOSTIC APPROACH
First determine whether polyuria and polydipsia exist or not by recording fluid intake and urine volume
⇓
Then, differentiate different causes of polyuria:
i. Renal disease by urine analysis and estimation of blood urea, creatinine and electrolytes.
ii. Hypercalcaemia by serum calcium estimation
iii. Diabetes mellitus by estimation of urine and blood glucose
⇓
Finally differentiate CDI, NDI and CWD:
Central DI Nephrogenic DI Compulsory Normal
water drinking
Onset of polyuria: Sudden Variable Variable
Urine volume: Large Moderate Variable
Nocturia: ++++ ++ ++
Preference for iced water: ++++ + +
Water deprivation and
vasopressin injection test:
Urine osmolality: Rises above Unchanged after Like normal Rises below 9%
9% after vasopressin people after vasopressin
vasopressin injection injection
injection

TREATMENT OF DIABETES INSIPIDUS

1 2 3
Central diabetes insipidus Partial diabetes insipidus Nephrogenic diabetes insipidus
Hormone replacement (Some residual vasopressin • Solute restriction
remaining) • Hydrochlorthiazide
Acute: Chronic: • Chlorpropamide (diabetese) • Indomethacin
Aqueous Desmopressin • Clofibrate • Indomethacin + Desmopressin
vasopressin or lypressin • Carbamazepine

4
Compulsory water drinking (CWD)
• Psychotherapy
• Avoid thioridazine and
lithium because these cause polyuria
466 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Table 79.1: Agents used in diabetes insipidus

Drugs Dose Indications Duration of action Advantage Disadvantage

(Hrs)
1. Hormonal
agents
Desmopressin i. Aqueous vaso- Used in acute CDI 3-6 (SC) Antidiuretic effect • IV injection rai-
acetate pressin 5-10 but not in nephro- ++++ in aq. prep. ses blood pres-
IU S.C. (Pit- genic DI sure
ressin) 20 U/ Vasopressor
ml Treatment of Antidiuretic efect effect ++++ in
Short half-life, choice in central ++++ Aq. prep.
repeated dos- DI. Also useful DI Vasopressor effect • Contraindicated
ing with preg- nancy 12-24 (Intranasal) + in liver disease
ii. Intranasal pre- and puer- perium Hence blood pres- • Side-effects: GI
paration: 10- Chronic therapy in sure does not rise symptoms, asthe-
20 mcg CDI nia. Intranasal
Best given at prep. causes
night to find nasal irritation
lowest dose
that will pre-
vent nocturia. 12-24
iii. Parenteral pre-
parations: S.C.
or IV 2-4 mcg 24-72
iv. In oil: 5 IU IM Pain at injection
site
Lypressin (LVP) 2-4 IU IV 4-6

2. Non-Hormonal
agents Used in central DI,
Chlorpropamide: 200-500 mg/day not used in nephro- 24-48 Hypoglycaemia
(diabenese) genic DI. Only
used in partial
central DI

Partial CDI
Clofibrate 500 mg q.d.s. Not recommended
Carbamazepine 400-600 mg/day routinely due to
Partial CDI many side-effects
Hydrochlorthiazide 50-100 mg/day Nephrogenic DI 24-48 hours

Nephrogenic DI
Indomethacin 100-150 mg/day 6-8
PATHO-PHYSIOLOGY OF DIABETES INSIPIDUS
Diabetes Insipidus |
467

Hypothalamus synthesises

Vasopressin Oxytocin

Migrate to posterior pituitary

↓
Vasopressin and oxytocin released in blood in
response to normal physiological stimulus

Vasopressin: Oxytocin:
Concentrates urine and conserves Stimulates uterine contraction
water under the influence of and ejects milk
thirst centre

Failure of vasopressin release due Failure of diseased kidney to

to damaged pit. and hypothalamus respond to vasopressin
↓ ↓
Absence of vasopressin causes no Lack of vasopressin effect
concentration of urine and no water ↓
conservation No concentration of urine nor
↓ water conservation
Resulting in central diabetes ↓
insipidus Causing nephrogenic diabetes
insipidus
 Endocrinology
80
Diabetes Mellitus

CLASSIFICATION
(Modified from WHO Study Group 1985)
A. Diabetes Mellitus
1. Insulin-dependent diabetes (IDDM) : Type 1:
2. Non-Insulin dependent diabetes (NDDM) : Type 2:
a. Non-obese b. Obese
3. Malnutrition - Protein deficient diabetes mellitus (PDDM)
4. Other types of diabetes mellitus:
a. Pancreatic disease Fibrocalculous pancreatic diabetes mellitus (FCPD)
b. Drug induced:
• Thiazide • Phenytoin
• Corticosteroid • Analgesic
c. Abnormalities of insulin or its receptors:
• Congenital lipodystrophy • Acanthosis nigricans
• Autoimmune
d. Genetic syndromes:
• Glycogen storage disease • Huntington’s chorea
• Lawrence-Moon-Biedl syndrome
B. Impaired glucose tolerance (IGT)
a. Non-obese b. Obese
C. Gestational diabetes mellitus

DIAGNOSTIC CLUES: CLINICAL

Diabetes mellitus: IDDM (Type 1) NIDDM (Type 2) PDDM (Protein defi- FCPD (Fibro-calcu-
cient) lous pancreatic dia-
betes mellitus)
Polyurea and thirst ++ +

Weakness ++ +

Polyphagia ++ +

Weight loss ++ –
contd...
contd...
Diabetes Mellitus | 469

Peripheral neuropathy + ++
(Cramp, paresthesia)

Recurrent blurred + ++
vision
Vulvovaginitis + ++

Pruritus + ++

Often asymptomatic – ++

Age (Yr) 5-30 35-50 10-30 10-30

Sex M:F = 1 : 1 In Indian M>F M >F M> F

Prevalence: More in west; 1% in 90% of all diabetics Tropics Tropics

India, Japan
Genetic i. Hereditary + Hereditary ++ Not established Not established
ii. Strong HLA asso- No HLA, Islet cell
ciation antibodies absent
iii. Islet cell anti-
bodies present
Nutrition Non-obese Often obese or may be Emaciated Lean, emaciated
non-obese specially in
India

Ketosis Prone Not prone Not prone Not prone

Ketosis only in severe
stress

Insulin lack: ++++ +– ++ ++

Insulin secretion: Insulin absent Measurable quantity

of insulin present

Insulin resistance Rare +++ particularly in +++ ++

obese

Insulin requirement Low-to-moderate Low, moderate-to-high High Moderate

Sulphonylurea Unresponsive Responsive Unresponsive Rarely responsive

Common cause of Nephropathy, CHD, CHD, nephropathy, Infection, lack of treat- Lack of treatment
death: ketoacidosis, hypo- stroke, gangrene ment
glycaemia

Special features of Stunted growth, rave-

PDDM: nous hunger, derma-
contd...
470 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

titis, paresthesia, cramp

and amenorrhoea in young
patient hailing from poor
socioeconomic strata of
rural population, severe
hyperglycaemia, no res-
ponse to sulphonylurea,
pancreas normal. Progres-
sive

Special features of Recurrent attacks of

FCPD: abdominal pain, indi-
gestion, bulky stool
and skiagram of abdo-
men shows calcifica-
tion, moderate hyper-
glycaemia, responds to
sulphonylurea, abnor-
mal pancreatic func-
tion, may improve after
pancreatic surgery

B. Impaired glucose tolerance (IGT): Likely to be obese. Macrovascular disease.

C. Gestational diabetes mellitus: Associated with pregnancy. Blood glucose findings same as IGT.

COMPLICATIONS OF DIABETES MELLITUS

Microangiopathy: Retinopathy, nephropathy, neuropathy.
Macroangiopathy: Coronary artery disease, stroke, atherosclerosis, impotency.

LABORATORY INVESTIGATIONS
Biochemical Normal Impaired glucose Diabetes mellitus
(mg/dl) intolerance (mg/dl) (mg/dl)
A. Blood glucose
Fasting plasma glucose: Less than 110 110-120 Above or equal to 126
Random: 200 or above
Oral glucose tolerance Less than 140 140 mg or above 200 or above
test 2 hour after 75 gm but less than 200
of glucose load
B. Other tests for glucose
Glycosylated haemoglobin Serum fructosamine
• High with diabetes with • Reflects the state of hyperglycaemia over
chronic hyperglycaemia preceding 2 weeks only
• It reflects the state of hyperglycaemia over • Normal value: 1.5-2.4 mmol/L
preceding 8-12 weeks
• Useful in monitoring the progress of disease
 • Value:
Diabetes Mellitus |
471

Good Fair Poor

5.5-6.5 Upto 8.5 Above 9
C. Lipoprotein abnormalities
In obese type 2 diabetes (Insulin resistance syndrome):
a. High serum triglyceride: 300-400 mg
b. Low HDL: Less than 30 mg/dl
c. Qualitative change in LDL
D. Urine examination for glucose and ketones
Glucose Ketones
Method: Tested by paper strip impregnated Nitroprusside test
by glucose oxidase
Comment: A normal renal threshold for glucose Should be monitored during febrile illness,
as well as reliable bladder emptying is persistent hyperglycaemia, nausea, vomiting or
essential for interpretation abdominal pain

TREATMENT OF DIABETES MELLITUS

Goal:
i. Allevation of symptoms
ii. Metabolic control:
Good Acceptible Poor
Blood glucose (mg/dl) 80-120 Less than 140 Above 140
Lipoprotein: Ser. cholesterol Less than 200 Less than 255 Above 255
Ser. triglyceride Less than 150 Less than 200 Above 200
LDL 130 upto 160 Above 180
HDL 50 upto 40 Less than 35
Glycosylated haemoglobin Less than 8 Less than 10 Above 10
(Normal 6-8%)
Body mass index:
Men: Less than 25 Less than 27 Above 27
Women: Less than 24 Less than 26 Above 26
Blood pressure: Less than 140/90 Less than 160/90 Above 160/95
iii. Prevention for acute and long-term complications

DIET IN DIABETES
Goals
Blood glucose Calories Characteristics of food
Maintenance of Provision of adequate calories for maintaining i. Proper fibre content of food
normal blood reasonable weight in adult, proper growth and ii. Proper glycaemic index of food
glucose development in children and to meet increa- iii. Proper consistency and physical
sed metabolic need during pregnancy and form of food
lactation or recovery from catabolic illness
472 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Ascertain calories required based on body weight for diabetes:

First find out the ideal body weight:
Medium frame Small frame Large frame
a. Ideal weight for adult men of 5 ft Substract 10% Add 10%
height: 105 lb. Add 6 lbs for every
one inch height
b. Ideal weight for adult women of 5 ft
height: 100 lbs. Add 5 lbs for every
one inch height
Next, calculate calories required based on body weight:
Overweight (Large frame) .......20 kCal/kg/day
Under weight (Small frame) .......40 kCal/kg/day
Ideal weight .......30 kCal/kg/day
(Carbohydrate, protein and fat)
Distribution of nutrients in the diet of a diabetic
% Total calories Cal/gram
Carbohydrate ... 60-65% 4
Protein ... 15-20% 4
Fat ... 15-25% 9

CARBOHYDRATE IN DIABETIC DIET

Classification of Carbohydrate
Starch Sugar
(Complex sugar) a. Monosacchrides: Orange, carrot, honey, ripe fruit
• Cereals b. Disaccharides: Sugarcane, beet root, milk
• Potato c. Polysaccharides: Cereals, roots, pulses, liver, muscle, cellulose, pectin
• Root vegetables

Ideal Carbohydrate for Diabetes

i. Types:
Complex CHO—Cereals, pulses
Advantages of complex CHO:
• Slowly digested and absorbed producing slow rise in blood sugar
• Also rich in fibres
• Rich in vitamins and minerals
• Reduces risk of atherosclerosis and hyperlipidaemia
ii. Glycaemic index:
• Carbohydrate of high glycaemic index is rapidly absorbed and raise blood sugar faster and not
ideal for diabetics. For example: Glucose, cornflakes, honey, carrot, rice (white), potato.
• Carbohydrate of low glycaemic index is ideal for diabetics. For example: Brown rice, banana,
raisin, peas, beans, orange, milk, yoghurt, lentil, soyabean, peanut.
iii. Consistency, physical form and processing of CHO: The consistency of food (liquid, puree or solid,
raw or cooked) affects the digestibility of starch and blood glucose response.
Form of food not suitable for diabetics
Diabetes Mellitus

Form of food suitable for diabetics

| 473

Foods with greater glucose response due
to quick digestion and absorption:
i. Ragi taken in the form of kanjee (gruel)
ii. Wheat kanjee
iii. Cooked food is more hyperglycaemic
iv. Apple juice is more hyperglycaemic
v. Ground rice more hyperglycaemic
vi. Beans which were ground first and
cooked is more hyperglycaemic
vii. Chopped food more hyperglycaemic
Foods with lesser glucose response:
i. Ragi taken as chappati
ii. Wheat chappati needs more chewing
resulting in prolongation of digestion and
delay in rise of blood glucose level
iii. Raw food less hyperglycaemic
iv. Whole apple less hyperglycaemic.
v. Whole cooked rice is less hyperglycaemic
vi. Beans first cooked and then ground
less hyperglycaemic
vii. Whole food less hyperglycaemic

Fibres
Classification:
Water soluble Water insoluble
Pectin, gums, mucilage, fruits, oat, barley, Cellulose, hemicellulose and lignin
legumes, psyllium and fenugreek seeds (methi)
Fibre requirement in diabetic diet:
i. 25 gm/1000 KCl or 40 gm/day
ii. Fenugreek seeds: 10-20 gm taken
5-10 minutes or along with meals
Comment on fibres Advantages Disadvantages
Water soluble fibres: Effective in controlling blood Do not contribute to faecal fat
sugar and serum lipids
Water insoluble Decreases intestinal transit time,
increases faecal bulk and thus
reduces constipation

Protein
Requirement: 30 gm (0.5 gm/kg/day) per day
Classification:
First class protein Second class protein Third class protein
Containing all essential Lacking in one or more Cereals, oat, barley,
amino acids with high essential aminoacids: ragi, rice and wheat
biological value: soyabean, grams, pulses,
i. Non-vegetarian: Egg, mutton, peas, beans, nuts
fish, pork, chicken
ii. Vegetarian: Milk, curd, paneer
At least one-third of the dietary requirement must be from first class protein. Leucine and arginine
also stimulate insulin secretion.
474

Fat
| Bedside Approach to Medical Therapeutics with Diagnostic Clues

Serum lipid abnormalities produce atherosclerosis. Maintenance of serum lipids is essential in diabetics.
Cholesterol is found in foods of animal origin.

Classification of Fat
1. Unsaturated
Liquid at room temperature. Usually from vegetable source, free from cholesterol:

Polyunsaturated Monounsaturated
fatty acid (PUFA) fatty acid (MUFA)
↓
Lowers blood cholesterol and LDL:
2. Saturated
Solid at room temperature, usually from animal source. Contains cholesterol and atherogenic: Meat,
milk, ghee, butter, cheese
3. Vegetable oils
↓
Fatty acid contents of vegetable oils
A. Saturated fat Percent of fatty acid
• Coconut oil (Does not contain cholesterol) 80%
• Palm oil 50%
• Rice bran oil 25%
B. Unsaturated fat Percentage of monosaturated Percentage of polyunsaturated
fatty acid fatty acid
• Groundnut oil 48% 34%
• Sunflower oil 20% 70%
• Safflower 12% 75%
• Mustard oil 55% 33%
Disadvantages and advantages of unsaturated fat
Advantages Disadvantages
PUFA Lowers blood cholesterol and LDL Excess intake may promote carcinogenesis,
suppresses immunity and may reduce HDL
MUFA Lowers LDL without decreasing HDL.
Reduces risk of CAD
4. Essential fatty acids:
Linoleic (n-3) and alpha linolenic (n-3) acid are essential fatty acids and are important for diabetics.
They are important and precursors of prostaglandins and other biologically active log chain PUFA.
⇓
Omega-6 and Omega-3 fatty acids are derived from linoleic acid. They are good for diabetics for
preventing complications. Omega-6 fatty acid are found in many foods and omega-3 fatty acids are
found in plant foods (but not in all vegetable oils) fish and shellfish. Eicosapentanoic acid (c20:5) and
docosahexanoic acid are derived from fish oil
⇓
Advantages Disadvantages
Diabetes Mellitus |475

• Lowers plasma cholesterol, Lowers HDL

triglyceride and LDL
• Reduces diabetic retinopathy particularly by
omega-3 found in fish oil
• Eicosapentanoic acid and decosahexanoic
acid reduces CAD risk in diabetics
• Lowers blood pressure, prolongs platelet
aggregation and bleeding time
Requirement of fatty acid for diabetic diet:
a. Ratio of n-6: n-3 fatty acid should not exceed the ratio of 5:1
b. Essential fatty acid should provide 3% of energy
c. Ratio of saturated fat; MUFA: PUFA should be 1:1:1
d. Calories provided by saturated fat is less than 10%, PUFA 8% and MUFA 12% of total calories of
30% derived from fat.

Artificial Sweetening Agents

Classification:
Caloric sweetening agents
Fructose, sorbitol, manitol, xylitol
Provides 4 calories/gm
Non-caloric sweetening agents
Saccharine, aspartame saccharine
300 times sweeter than sugar and aspartame
180 times sweeter than sugar
Can be used to sweeten coffee, tea or juice
Maximum permitted consumption 2-4 mg/kg/day

Alcohol
Alcohol should not be used at all. It is an additional source of calories. Each ml provides 7 calories.

Disadvantages
a. Supplements calories
b. Excessive consumption of alcohol by a person who is fasting and skipping meals can lead to
hypoglycaemia via inhibition of gluconeogenesis, and poses serious risk for persons who are taking
insulin and oral agents
c. Exacerbates neuropathy, dyslipidaemia, obesity
d. Cannot recognise symptoms of hypoglycaemia

Vitamins and Minerals

Indications for these micronutrients:
a. People on weight reduction diet
b. Strict vegetarians
c. Pregnant and lactating women
d. Elderly
476 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

e. Those taking medicines

f. Patients in ICU
g. Patients with poor metabolic control
Vitamin E is supplemented for the antioxidant benefit.

Flow Chart for Determining the Ideal Diet for Diabetics

First ascertain the weight of the patient.
Determine ideal calories requirement according to weight.
Determine distribution of nutrition (CHO, protein and fat) in the diet.
Ideal diet recommended: For diabetics of ideal weight without any complication.
i. In obese diabetic (Type 2) focus on weight reduction more
ii. Carbohydrate 60% (Recently American Diabetic Association recommended considerable reduction
of CHO because high CHO diet causes hyperglycaemia, hypertriglyceridaemia and lowers HDL)
of total calories and most of it is given as complex carbohydrate with lower glycaemic index.
iii. Fibres 40 gm/day
iv. Protein: 0.5 gm/kg/day. Poultry and fish are better than red meat
v. The remaining calories (roughly 30%) distributed as follows:

FAT
PUFA Saturated fat MUFA
6-8% Less than 10% Remaining calories
vi. Cholesterol less than 200 mg/dl
vii. No alcohol

Diet in other Special Situations

A. Children and Elderly Pregnancy
Adolescents
Based growth and development Weight reduction is not recom- Maintenance of adequate
monitored by weight and height mended because body weight maternal and foetal nutrition
measurement on standard growth declines after 60 years of age.
chart.
B. Catabolic Illnesses
In severe catabolic states additional nutritional support is necessary.
In stressfull situations 1.5 gm of protein per day per kg is needed.
C. Nephropathy
Low protein intake (0.5 gm/kg/day is recommended and first class protein is advised. Increased
calcium intake and restricted sodium and potassium is necessary.
D. Dyslipidaemia
Weight reduction, increasing physical activity, low fat, low saturated diet and high in fibres is
recommended.

Exercise and Yoga

“Vigorous exercise like wrestling, sports, horse riding, long walks and digging wells in obese diabetics,
the thin diabetics were not allowed such vigorous exercises”. —Charak
Advantage of Exercises
Diabetes Mellitus | 477

a. Increases number and sensitivity of insulin receptors.

b. Improves glucose tolerance.
c. Exercise first breakdown muscle glycogen, followed by hepatic glycogenolysis and hepatic
neoglucogenesis, followed by generation of free fatty acids for muscle fuel requirement.
d. Increases counter hormone level (glucagon, cortisol, epinephrine and norepinephrine decreases
insulin level. Fall in insulin level increases hepatic glycogenolysis. Rise in glucagon promotes
hepatic glucogenesis and fat oxidation.
e. Breaks down muscle glycogen followed by lactate formation, followed by gluconeogenesis. Increases
insulin in working muscle.

Precautions for Exercise

Before prescribing exercise a thorough clinical examination should be carried out and complications
like IHD, neuropathy, retinopathy trophic ulcers should be noted and exercise modified accordingly
(Table 80.1).

Advantages of Yoga
Changes in Heart Metabolic Hormone Well-being
muscle changes
Increases oxygen Augments stroke Reduction in blood Raises insulin Development
uptake volume. Reduction lipids, reduction receptors, reduces of sense of
in both systolic in fasting and post- insulin resistance well-being
and diastolic prandial blood and increases
blood pressure glucose, reduction insulin sensitivity
in fatty acids (resul-
ting in better insulin
utilisation), LDL, VLDL,
cholesterol

Some Specific Yoga Practices in Diabetics

Yoga Pranayam
• Dhanurasan (most effective) Reduces fasting and
• Ardh-Matsendrasan postprandial blood
• Halasan glucose level
• Paschimotasan
• Vajrasan
Table 80.1: Energy expenditure in different types of exercises in 58 kg body weight
Calorie consumption per hour on the job
Driving 204 Swimming 270
Telephone conversation 198 Tennis 618
Teaching 204 Walking (3.3 km/hr) 108
Writing 102
Badminton 312 Showering 180
Running (9 km/hr) 594 Watching TV 78
478 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Oral Antidiabetic Drugs

Classification
I. Sulfonylureas
A. First generation:
1. Tolbutamide 2. Chlorpropamide 3. Acetohexamide
B. Second generation: (All drugs start with “G”)
1. Glibenclamide 2. Glipizide 3. Gliclazide
C. Third generation:
Glimepiride
II. Biguanides
1. Phenformin 2. Metaformin
III. Newer drugs:
A. Insulin secretagogues
1. Glimepiride 2. Ripaglinide
B. Insulin sensitisers:
1. Trioglitazone 2. Rosiglitazone 3. Pioglitazone

Classification based on Mechanism of Action

I. Insulin secretagogues:
1. Sulfonylureas 2. Ripaglinide 3. Glimepiride
II. Insulin sensitisers:
1. Biguanides 2. Rosiglitazone 3. Pioglitazone
4. Trioglitazone 5. Anti-obesity drugs-
III. Inhibitor of glucose absorption:
1. Acarbose 2. Miglitol
IV. Insulin mimetic drugs:
1. Insulin analogues 2. Vandelium salt

Pharmacology of Drugs
Name of drugs: Prepa- Onset and duration Available strength Dosing Advantages
rations
Tolbutamide, Rastinon Quick onset and short 500-1000 mg tab Starting 0.5 gm after • Less prone to hypo-
(Hoest) duration of action— first main meal, increa- glycaemia
6-12 hours sing upto 3 gm in 2- • Suitable for elderly
3 divided dosages
Chlorpropamide, Dia- Rapid onset, long half- 100 mg, 250 mg tab 100-500 mg/day in • Avoided in elderly
benese, chlorformin life (36 hours) single dose in morning and renal insuffici-
(Cadila) ency
• Very potent drug
• Prone to hypogly-
caemia
Glibenclamide, Dionil 2.5 mg Starting 2.5 mg/day 30 • Most potent, widely
(hoest) 5 mg tab minutes before meal, used drug.
Eglucon (boeh) increased gradually to • Controls secondary
contd...
contd...
Diabetes Mellitus | 479

Name of drugs: Prepa- Onset and duration Available strength Dosing Advantages
rations
20 mg/day failure to first genera-
tion drugs. Incidence
of secondary failure is
very low.
Glipizide. Glynase Rapid and short dura- 2.5-5 mg 2.5-30 mg/day. Multi- • As potent as gliben-
(USV) tion of action ple dosing clamide
• Can be used in renal
impairment
Patient on insulin can
be transferred to glipi-
zide, those receiving
less than 20 U, stop
insulin stopped strai-
ghtway and glipizide
given in usual dose, if
on more than 20 U half
insulin dose + usual
dose of glipizide given.

Gliclazide. Half-life 10-20 hours 80 mg tab 80-120 mg/day in • Favourable influence

Dimicron (serd), 2 divided dosages over platelet aggrega-
Reclide (Dr. Reddy) tion and fibrinolysis.
• Protects from vas-
cular complications.
• No hyperinsulinae-
mia
• No weight gain un-
like SU and insulin.
Glimepride. Glypride Quick onset and pro- 1 mg, 2 mg tab 1-6 mg/day in a single • No hyperinsulinae-
(SUN) longed duration of dose mia
action • No significant hypo-
glycaemia
• Safer in elderly and
renal impairment
Metformin 7-12 hours 500 mg, 850 mg 1-2.5 gm per day in Stimulates insulin
2 divided dosages secretion
15 minutes before each • Controls postprandial
meal blood glucose peak
• Less hypoglycaemia
• Reduces triglyceri-
daemia
• Useful in renal imp-
airment and elderly

Proglitazone Half-life up to 24 hours 15 mg, 30 mg 15-30 mg/day • Used as monotherapy

or with SU, metafor-
min or insulin
contd...
480 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Name of drugs: Prepa- Onset and duration Available strength Dosing Advantages
rations
Rosiglitazone – do – 2, 4, 8 mg 4-8 mg/day as a • Insulin sensitiser
Result (SUN) single dose or in • No weight gain
divided dose (b.d.) • Lowers triglyceride level
• Insulin sensitiser
• No hypoglycaemia
• Used as monotherapy, with
SU, metformin or insulin.
Acarbose — 50-100 mg 75-300 mg in • Weight gain
3 divided dosages
with first bite of • Used as monotherapy, with
food SU, metformin and insulin

Indications of Oral Antidiabetic Drugs

Sulfonylureas
• Non-obese NIDDM not
controled by diet alone.
• Glibenclamide used at the
onset or in secondary failure
to first generation SU.
Biguanides Proglitazone, rosiglita acarbose
• Obese NIDDM not controlled by • In type 2 diabetes
diet alone • As monotherapy, with SU, met-
• Can also be used in non-obese formin or insulin
patient
• Secondary failure to SU
• Reduces insulin requirement in
insulin taking NIDDM
• Reduces insulin resistance
• Brittle diabetes (marked labile
blood glucose)

Disadvantages of Anti-diabetic Drugs

A. Adverse Effects and Complications
Sulfonylureas Biguanides Acarbose Newer Drugs
• Gastrointestinal: • Anorexia, nausea, Gas, flatulence, loose • Troglitazone: Liver fai-
nausea, vomiting, vomiting motion. These side- lure, withdrawn in USA
heart burn • Lactic acidosis usually effects can be reduced by • Roziglitazone piogli-
• Hepatitis, cholestasis with phenformin (but gradually increasing the tazone do not raise liver
• Rashes challenged by many dose. enzymes but it is better
• Blood dyscrasias authorities) specially Hypoglycaemia may to estimate liver
• Disulfiram like reaction associated with liver occur specially with SU. enzymes and if ALT is
(flushing of skin) with failure, renal failure, raised slight, stop strai-
alcohol intake with only cardiac failure and ghtway.
first generation SU alcohol intake.
(chlorpropamide).
• Hypoglycaemia—pro-
longed hypoglycaemia
contd...
contd...
Diabetes Mellitus |481

in chlorpropamide. Risk of hypoglycaemia

more in old age, renal and hepatic insuffi-
ciency and concurrent use of non-selective
betablockers.
• Weight gain
• Chlorpropamide less used now due to pro-
longed hypoglycaemia, dilsulfiram like
reaction, progressive retinopathy, water
retention and hyponatraemia.

B. Contraindications
1. C/I to SU
• Insulin dependent diabetes
• Pregnancy
• Allergic to SU
• Patient with severe kidney and liver disease
• On the day of major surgery or postoperatively
• Chlorpropamide contraindicated in renal insufficiency and in old age
2. C/I to Biguanides
• Renal failure, liver failure, cardiac failure
• Arteriography and IV urography
• Alcoholism
• Diabetes mellitus with complications
• Pregnancy
• Old age above 70 years
• COPD with hypoxia (risk of acidosis)
C. Drug Interactions with SU
Increase in hypoglycaemia Worsening of glycaemic control:
Aspirin, fibrate, alcohol, H2 blockers, Barbiturates, rifampicin, thiazide, loop diuretic,
anticoagulants, probenecid, allopurinol, phenytoin, corticosteroids, estrogen, growth
beta-adrenergic blockers, sympatholytic drugs. hormone, catecholamine.
D. Anti-diabetic Drug Failure
Primary failure Secondary failure
About 20% patients do not respond About 3-5% of initial responders gradually loose
to SU and needs insulin from the onset. their response to continued SU therapy.
This is termed primary failure. This is termed secondary failure.
Its causes:
Dietary indiscrition, lack of physical activity,
intercurrent illness, stress, concomitant therapy
with diabetogenic drugs, decreasing beta cell
function, increasing insulin resistance.
482 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

INSULIN THERAPY
Parentarily Available Insulins in India
Types of insulin Boots Novo-Nordisk Elily USA Hoechst Sarabhai
Rapid acting Soluble Actrapid: Huminsulin: Insuman: Rapidica 40:
(short acting) insulin 40 • Procine 40 R-40 Rapid Procine
• Human 40 Human Human Human

Intermediate NPH 40 a. Monotard: Humainsulin Insulin Zimulin 40:

acting: NPH Lente 40 HM 40/100 N 40 basal 40 Procine
Isophane b. IZS: Lentard 40 L 40 Human
c. Insulatard: NPH 40
Premixed Mixtard: Procine 40 Huminsulin 40 Insuman: Rapimix:
NPH + Regular Human: NPH: Regular NPH: Regular NPH: Reg
(Biphasic) NPH: Regular 30 70 25 75 30 70
30 70 50 50 50 50 procine
40 100 20 80 Human
50 50 40 60
10 90
Ultracting insulin
⎧ 75:25,
Humalog Mix:
a. Lispro
⎨ Prefilled100insulin
⎩ 15 ml
b. Ultralente, Human, 100
Long acting Insulin protamine zinc (PZI)
Insulin purified Bovine 40

Classification of Insulin Based on Time-course of Action

Insulin Onset of action Peak activity Total duration of action
preparation (hr) (hr) (hr)
Short acting
Regular 0.5-1 2-4 4-6
Semilenate 1-2 3-6 8-12
Intermediate acting
NPH 3-4 10-16 20-24
Lente 3-4 10-16 20-24
Long acting
PZI 6-8 14-20 32
Ultralente 6-8 14-20 32
Premixed
NPH + Regular 0.5 2-10 12-18
Characteristics of Insulin Preparations
Diabetes Mellitus |
483

Species Purity Concentration of Insulin types

Human • Purified insulin of all
Procaine species are available.
Bovine • In purified insulin conta-
minated precursors pro-
ducing anti-insulin anti-
bodies is reduced or
eliminated.
insulin
40/100 units/ml dispensed • Lispro injected 20 mts
in 10 ml vials. before meals. Regular
insulin 30 mts before
meals.
• IV insulin used for DKA,
hyperglycaemic emergen-
cies and acute infection.

Insulin Administration
Syringe Sites of Stability of Insulin delivery
injection insulin dosing systems
Plastic disposable Abdomen, thigh, Judicious balance • Insulin infusion pump: SC, IM, IV,
syringe may be upper arm, flanks of diet, regular intraperitonial
reused by recap- and buttocks. Sites moderate exercise • Subcutaneous injection
ping until blun- are rotated. can stabilise insulin • Continuous subcutaneous infusion
ting of needle. dosage. (CSII)
Strenuous exercise • Pen-sized injecture with cartridge
precipitates hypogly- (eliminate need for carrying syringe
caemia. Increase the and insulin bottle)
dose of insulin in • Nasal, oral, rectal insulins
anticipation of • Pancreas transplantation
strenuous activity

Standards of Laboratory Control of Diabetes Mellitus

Good Fair Poor
Capillary blood (venous)
Fasting (mg/dl) 70-115 up to 140 above 140
2 hr postprandial 100-150 up to 180 above 180
Serum lipids (mg/dl)
Total cholesterol 200 up to 240 above 260
HDL cholesterol 50 up to 40 less than 35
LDL cholesterol 130 up to 160 above 180
Triglyceride 150 up to 250 above 250
GHB:
Hb A (%) 8-8.5 up to 10.5 above 11
Hb C(%) 5.5-6.5 up to 8.5 above 9
Fructosamine
(mmol/L) 2.8 up to 3.5 above 4
484 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Indications of Insulin Therapy

Definite indications Relative indications
• Type 1 • Microangiopathic complications
• Ketosis prone IDDM • Liver and renal disease
• Pregnancy • Diabetic on steroids
• Acute metabolic decompensation • Failure of oral antidiabetic agents
• Major stress: • It is preferable to give insulin for a short period if
Surgery the patient is highly symptomatic or with periarthritis
Sepsis shoulder, balanoposthitis, pruritus vulva or painful
neuropathy.

Problems of Insulin Therapy

Insulin allergy Insulin lipodystro- Insulin lipoatrophy Insulin resistance Hypoglycaemia
phy Common in young
i. Local allergy: Prevented by rota- women. Treated by Insulin injection if Due to delay in
Itching and ting the sites of injecting purified required 100-200 taking meals or
induration at injection or purified insulin in the mar- U, termed insulin unusual physical
injection site insulin. gin of atrophic site. resistance caused exertion. See below
ii. Systemic by formation of “Hypoglycaemia”.
allergy: insulin antibodies.
Angioedema, Overcome by puri-
laryngospasm, fied human insulin.
hypotension.
Treated by
antihistamine,
purified insu-
lin or desensi-
tization

Therapy with Insulin

Clinical Trials (DCCT, UKPDS)
They established the following facts: Conventional Treatment with Subcutaneous
Intensive Insulin Therapy (Multiple Insulin Injection once or twice daily
Injections or Insulin Pump) Treatment of choice for Type 2 diabetes.
1. In Type 1: More hypoglycaemia and weight Severe hypoglycaemia and macrovascular
gain occurs but fatal hypoglycaemia does not complications occur more than Type 1 in long-
occur. Moderate control of glycaemia is as standing diabetics.
effective (Hb A/C: no higher than 2% above
upper limit of normal) in reducing compli-
cations as tight control. Reduces 60% micro-
vascular complications than conventional
treatment.
contd...
 Diabetes Mellitus |485

2. In Type 2: Type 2 diabetes with insulin resistance and visceral obesity treated intensively by SU +
metformin with or without insulin decreases microvascular complications more than conventional
therapy. Intensive therapy with metformin also reduces macrovascular complications (stroke, acute
myocardial infarction) but do not reduce microvascular complications (neuropathy, nephropathy,
retinopathy).
Metformin is superior to insulin or SU in diabetic related end points in obese patient.

Recommendation of American Diabetic Association

i. Vigorous treatment of hyperglycaemia
ii. Vigorous treatment of hypertension and blood pressure should be reduced to 144/80.

Regimens of Insulin Therapy

Type 1 Type 2
Once daily injection 0.5-1 U/kg/day by one injection of 0.2 U/kg per day of intermediate
intermediate insulin with or without insulin before dinner in the evening
addition of small amount of regular or
insulin in the morning or evening Intermediate insulin in evening +
OHA in day time
Twice daily injections 2 injections/day of intermediate Split mixed regimen:
insulin with or without addition Premixed insulin twice daily: Two-third
of small amount of regular insulin of total daily dose half hour before
or premixed insulin twice daily breakfast and one-third of total daily dose
half hour before dinner in the evening.
Three injections daily Mixture of regular + NPH in
morning
+
Regular at dinner in evening
+
NPH at bedtime
Four injections daily Regular insulin before breakfast,
lunch and dinner
+
Intermediate insulin before bed time

Algorithm of Management of Diabetes Mellitus

Diagnostic clues
a. History and Physical Examination:
Note obesity, age of onset, family history of
diabetes, whether on insulin, peripheral pulses
whether diminished or not, smoking, hyperten-
sion, use of oral contraceptive, abnormalities
on ophthalmic examination and neurologic
examination
Patient education
Explain to patients regarding nature of diabetes,
hazards, complications and also advise for regular
check for glucose by self monitoring, adjustment
of insulin dose, personal hygiene (foot care) for
stopping smoking. Also tell how to manage
hypoglycaemia.
↓
486 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. Laboratory Investigation
• Fasting blood sugar
Suggesting diabetes: Above 126 mg/dl
• Postprandial blood sugar
Suggesting diabetes: Above 200 mg/dl
• Also note ketonuria, glycoHb, lipid profile, serum creatinine.
↓
Treatment of Type 2 Diabetes Mellitus by OHA Drugs
Obese patient Non-obese patients
• Weight reduction by diet and increased
physical activity
• Hypoglycaemic agents: Mild cases Severe case
Start monotherapy with metformin or alpha- FBS 120-less than 200 mg:
glucosidase inhibitor (Acarbose) Occasionally controlled by
↓ multiple feedings limited in
If fails, add SU sugar and caloric content-
↓ restriction of saturated fat
If fails, add thiazolidine or pioglitazone and cholesterol also advised
↓ ↓
If metformin + SU + thiozolidine fail Not controlled, start SU
↓ ↓
Different insulin regimens started Not controlled, add metformin
↓
Not controlled, add thiozolidine or pioglitazone
↓
Not controlled, combine or
substitute insulin

Insulin regimens
A. Insulin Therapy: Type 2
Insulin (soluble) requirement per day: 0.2 U/kg/day
or according to
Fasting blood sugar – 50
10
For example: If fasting blood sugar is 200 mg% the insulin requirement would be 200 minus 50 divided
by 10 which works out to be 15 U of intermediate (or) long acting insulin.

1. Single injection
Asymptomatic type 2 patients Symptomatic type 2 patients with polyuria,
polydipsia, polyphagia and marked loss of weight
50% of the dose calculated by the above The above calculated dose can be started as inter-
formula can be starting dose as intermediate mediate insulin in the morning.
type in the morning (about 25-30 U).
Gradually increased by 4 units every 4th day.
 ↓
Diabetes Mellitus | 487

Check fasting blood sugar next morning

If FBS under control, continue If FBS is high, add a small dose of

the same dose of insulin intermediate insulin 50% of morning
↓ dose before dinner time in the evening
↓ ↓
Check postdinner blood sugar and if high, a small Check also prelunch blood sugar, if high:
dose of regular insulin added before dinner regular insulin needed in the morning
or
2. Two injections split dose insulin regimen with premixed insulin (NPH 70 + Regular 30): 2/3rd of
total daily dose of premixed insulin in the morning before breakfast and 1/3rd of total daily dose in
the evening before dinner.
Advantage: Relatively convenient.
Disadvantage: Fasting hyperglycaemia common.
If with above regimens fasting hyperglycaemia persist the intermediate insulin has to be given at
bedtime instead of before dinner.
Increased gradually based on target blood glucose at 7 AM and 5 PM.
↓
If the above regimens fail to control hyperglycaemia and insulin needed above 50.
3. Resort to four-injection insulin therapy:
Small dose of regular insulin One injection of intermediate
+
t.d.s. before meals insulin at bedtime
Advantage of four injections: • More convenient with pen-injector
• Gives greater flexibility regarding meal patterns
Disadvantages of four injections: Less convenient
↓
4. Occasionally three injection insulin therapy more convenient than the split dose
therapy and four injections therapy:
Regular + NPH before breakfast
Regular (8-10 U) before dinner in evening
NPH small dose (6 U) at bedtime
B. Insulin Therapy of Diabetes Type 1
Various insulin regimens Advantages Disadvantages
Two Injections: Split doses of • Relatively convenient • Prebreakfast hyperglycaemia
premixed insulin (Regular + • Controls postprandial glycaemia common
NPH) at breakfast and dinner in eve- • Increased risk of nocturnal
ning hypoglycaemia due to tight
control of prebreakfast hyper-
glycaemia
Three injections: Premixed insulin • Controls postprandial hyper- • Less convenient
in AM + regular at dinner + NPH glycaemia at breakfast and • Lunch schedule is relatively
at bedtime. dinner inflexible as to time and quantity
contd...
488 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

• Can prevent prebreakfast hyper- to avoid hypoglycaemia from

glycaemia with less risk of noc- morning NPH
turnal hypoglycaemia • Dinner schedule cannot be
delayed without extra feeding
Four injections: Regular or • Relatively inconvenient
Lispro* • Controls PP glycaemia • Pumps expensive and less con-
insulin before meals • Allows flexibility of meals venient than multiple injection
+ • Tight glycaemic control possible • Risk of skin infection and pump
Long acting insulin to maintain with least risk of hypoglycaemia failure
basal insulin levels.
*Role of insulin Lispro in place of regular insulin in intensive insulin therapy type 1 and 2 diabetes mellitus

Type 1 and 2 Diabetes Mellitus

Advantages Disadvantages Insulin regimens At bedtime
• Safer Due to very short Prebreakfast Prelunch Predinner
• More convenient duration (3-4 hour), a. Insulin 5U 4U 6U
• Improves post- it requires small lispro + 12U 12U
prandial glucose dosages of multiple Ultralente 5U 4U 6U
control than injections b. Insulin 3U 3U 2U
regular insulin lispro + 8-14 U
NPH

Early Morning Hyperglycaemia in Type 1 Diabetes Mellitus

Causes Mechanism Blood Glucose (mg/dl) Therapy
Samogye effect Development of noctur- 10 PM 3 AM 7 AM Reducing inappropria-
nal hypoglycaemia 90 40 200 tely high dosages of
Stimulates surge of coun- administered insulin imp-
ter-regulatory hormones roves morning hyper-
(Samogye effect) glycaemia
Produces hypoglycaemia
at 7 AM

Down syndrome Reduced tissue sensiti- 110 110 150 Dosages of intermediate
vity to insulin between insulin can be divided
5 AM to 8 AM. This is between dinner time and
evoked by growth hor- bedtime
mone released hours
before at the onset of
sleep.

Waning of circulating The most common cause 110 190 220 Either increasing the
insulin level: or of fasting hypergly- evening dose or shifting
contd...
Waning of insulin dose caemia due to waning of
Diabetes Mellitus

it from dinner time to

|
489

plus Down syndrome circulating insulin level. bedtime or both, can be

Fasting hyperglycaemia effective. A bedtime pork
is more severe NPH insulin provides
more sustained overnight
insulin levels than human
NPH or human ultralente
insulin. If this fails,
insulin pump is required.

Waning of insulin dose Highest fasting hypergly- 110 40 380 – do –

plus Down phenomenon caemia
plus Somogye effect

Management of Chronic Complications of Diabetes Mellitus

Microvascular complications Macrovascular complications
• Diabetic retinopathy • Coronary artery disease
• Diabetic nephropathy • Stroke
• Diabetic neuropathy • Peripheral vascular disease

Diabetic Retinopathy
Types
Background or “Simple” retinopathy Progressive retinopathy
Characterised by micro-aneurysms, Characterised by newly formed
haemorrhages, exudate and retinal vessels near optic disc with blindness
oedema without vision loss
⇓
Treatment
⇓
Prophylaxis Therapy Treatment
• Intensive insulin therapy 1. Drugs: • Argon photocoagulation
delays onset and progress Affecting viscosity and • Vitrectomy for vitreous haemor-
• Stop smoking coagulation: Aspirin, rhage traction detachment
• Treat hypertension dipyridamol,
• Ophthalmological exami- and aldose reductase
nation annually in inhibitors
Type 2 at onset and after 2. Macular oedema:
5 year of diagnosis Argon photocoagulation
of Type 1
490 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Other Ocular Complications

Glaucoma Cataract Extraocular palsy Optic neuropathy
Usual treatment Usual treatment

DIABETIC NEPHROPATHY
Preceded by microalbuminuria (30-300 mg albumin/24 hour) which is reversible.

Treatment of Diabetic Nephropathy

1. Early diabetic nephropathy with microalbuminuria
a. Outcome of persistent microalbuminuria:
• Blood pressure rises
• Increase in cardiovascular
deaths even in the absence
or renal failure
II. Progressive diabetic nephropathy
A. Outcome:
• Nephrotic syndrome with oedema
• Increase in proteinurea
• Renal failure
• Hypertension
• Coronary and cerebral atherosclerosis
seems to be accelerated
b. Management of early nephropathy:
• Tight glycaemia control
• Low protein diet (8 gm/kg/day)
• Antihypertensive therapy:
ACE inhibitor is the drug of choice:
Captopril 50 mg b.d. even in normotensive
patients
Other drugs: Ramipril 10 mg/day
Enalapril 2.5-20 mg/day
ACE inhibitor empedes progression of
proteinuria.
B. Management:
• Antihypertensive drugs
ACE inhibitors. Stop ACE inhibitor if
persistent hyperkalaemia (above 6 mEq/L)
and high serum creatinine (above 2 mg dl)
• Dialysis has been of limited value
• Renal transplantation is more promising

Diagnostic Clues
Early phase Late phase
GFR: Increased Decreased
Kidney size: Increased Decreased
Microalbuminuria: Increased Increased
Proteinuria: Increased
Ser. creatinine: 0.8-1 mg 2-10 mg
Blood urea: 10-15 mg Greater than 30—greater than 100 mg
Diastolic blood pressure: Normal High
Fluid retention, oedema and Nil Present
hypoalbuminaemia
Retinopathy, neuropathy and arterial Present
disease (CAD, stroke)
Prognosis: Better
Diabetes Mellitus

• 10 years survival in 20% cases

| 491

• 2 years survival in nephrosis in 50% cases

• If serum creatinine above 2-3 mg percent
• Poor prognosis in presence of hypertension
and infection

DIABETIC NEUROPATHIES
Pathological Types Diabetic Neuropathy
Types Structure involved Main part affected
Radiculopathy Nerve root
Mononeuropathy Mixed spinal and cranial nerve Single dermatome
Nerve terminal Arm, leg, 3rd and 6th nerve
Polyneuropathy Nerve terminal and muscle Face, quadriceps, glutitis, hamstring
Autonomic neuropathy Sympathetic ganglia CVS, gastrointestinal tract, bladder,
impotency

Peripheral Neuropathy
Clinical (Sensory-Motor)
Stocking-glove Involvement of Multiple nerve Diabetic amyotro- Painful diabetic
pattern of sensory one nerve (femo- involvement. phy: Weakness of neuropathy:
loss in the distal ral and cranial thigh muscles. Hyperesthesia-
parts of limbs, with diplopia and severe burning
neuropathic ophthalmoplegia. pain at night.
planter ulcer (due
to repeated
“silent” trauma).

Treatment
Drugs Advantages Disadvantages
Amitriptylin Often dramatic relief • Morning drowsiness but improves with
25-75 mg at bedtime within 48-72 hours time or lessened by giving it several
hours before bedtime
• Stop it if no improvement after 5 days
of therapy
Desipramine Same efficacy as amitriptyline
25-150 mg/day
Gabapentine Indicated if tricyclic fails Giddiness, ataxia
900-1800 mg/day in
3 divided dosage
Capsicum cream: 2-4 Reduces local nerve pain Glove should be worn for application to
times daily avoid eye and genitalia contact
492 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

(produces burning sensation)

Carbamazepine: Blood dyscrasias
100-400 mg orally b.d.
Other new drugs for diabetic neuropathy:
• Methylcobalamin: 1 amp. IM/day for 10 days or 500 mcg-1500 mcg/day for 1-2 months
• Alpha lipoic acid 100 mg/day
• Evenly primrose oil (primosa-universal) 1000 mg/day for 1-2 months.

Autonomic Neuropathy
Clinical
Cardiovascular
• Postural hypotension
• Decreased cardiovascular
response to valsalva’s manoeuvre
Gastrointestinal Genitourinary
Gastroparesis: Intractable nausea, • Inability to empty bladder
vomiting and bouts diarrhoea and • Impotency
constipation particularly nocturnal

Treatment
A. Gastroenteropathy:
• Frequent small meals (6-8 meals per day) low in fat and low in fibres
• Occasional parenteral nutrition required due to vomiting and diarrhoea
• Drugs:
Metoclopramide Erythromycin Cisapride Anti-diarrhoeal drugs
10-20 mg IM or IV t.d.s. 120-500 mg 10 mg t.d.s. but use Diarrhoea responds to
or orally. Limited use q.i.d. limited due to cardiac • Broad spectrum antibiotics
due to extramedial arrhythmias and (azithromycin, tetracycline,
side-effects prolonged cephalosporin
QT interval • Clonidine
• Loperamide
• Amitriptyline 25-50 mg
for cyclic vomiting
B. Atonic bladder
Bethnechol Catheter decompression
10-15 mg t.d.s. occasionally of distended bladder helps
improves emptying of bladder
C. Orthostatic hypotension
• Use of compressive garments
• Sodium chloride 1-4 gm q.i.d.
• Fludrocortisone 0.1-0.3 mg q.i.d.
Side-effects: Hyperkalaemia, supine hypertension and congestive cardiac failure
D. Erectile dysfunction
Sildenafil (viagra) 50-100 mg one hour before coitus.
C/I of sildenafil: Nitrate therapy
Side-effects: Transient headache, flushing, dyspepsia
See chapter on “Impotency”
Macrovascular Complications
Diabetes Mellitus |
493

Coronary artery disease

Stroke
Peripheral vascular disease.

Risk Factors for above Diseases

Insulin resistance, hyperglycaemia, hypertension, hyperlipidaemia, smoking, obesity.

Treatment
Management of risk Aspirin ECG Management of diabetic acute myocardial
factors infarction
• Glycaemic control 80-325 Yearly • Glycaemic control: Initial insulin infusion
mg/day 1-4 U/hour + Dextrose infusion of 5 gm/hour to
• Hypertension control maintain plasma glucose 100-150 mg/dl
to 130/85 or lower • Potassium chloride 10-20 mEq can be added
• Hyperlipidaemia control to low to each litre of insulin-glucose infusion
density lipoprotein 100 mg/dl or lower

Diabetic Foot Ulcer

Causes: • Neuropathy
• Vascular insufficiency
• Infection

Prophylaxis for Foot Ulcer:

a. Daily foot examination for redness, blisters, abrasions and lacerations.
b. Wash foot daily with mild soap and lukewarm water and dry it between toes by pressure and then
rub well with vegetable oil upwards from tips.
c. If foot becomes too soft and tender, rub with alcohol once a week.
d. Toe nail: If brittle and dry, soften them by soaking for one-half hour each night in lukewarm water
containing one tablespoonful of powdered sodium borate (borax), followed by rubbing with vegetable
oil. Long nails are filed with emery board and file them straight without cutting the corners of the
nails.
e. Shoes: Low healed of soft leather with wide base should be prescribed.

Treatment
A. Corns and Calluses:
• Use of well fitting shoes
• Soak feet in lukewarm water (not hot) using a mild soap for ten minutes and then rub off excess
tissue. Do not cut corns or calluses.
B. Cold feet with impaired circulation:
Stop smoking. Keep warm with warm stockings. Do not sit with legs crossed. Do not apply hot
water or hot water bag. Change shoes and stockings daily. Prescribe cholesterol lowering agents.
Don’t use non-selective beta blockers.
494 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

C. Abrasions:
Should be treated by a doctor. Avoid irritating tincture of iodine. Apply sterile gauze. Elevate limb.
D. Foot ulcer:
• Use cholesterol lowering agents.
• Consult vascular or orthopedic surgeons and pediatrist.
• Debridement with antibiotics.
If fails: Platelet derived growth factor should be applied locally. Don’t use non-selective beta blockers.

Coma in Diabetics: Differential Diagnosis

Hypoglycaemic DKA Hyperosmolar Lactic acidosis Non-metabolic
coma non-ketotic stroke, SAH
coma (HONC)
Clinical: Palpitation, Dehydration, Dehydration, Nausea, vomiting, SAH: Neck stiff
sweating, air hunger, elderly, stupor, epigastric pain, transient hyper-
anxiety, tremor, sweet breath, polyuria, thirst, deep and laboured glycaemia, neu-
hunger, fatigue, vomiting, rapid rapid respiration breathing, stupor, rological deficit
confusion, coma low vol. pulse, coma, phenformin
hypotension therapy
Investigations
Blood glucose Low, often less 350-850 mg/dl 800-1600 mg/dl 180-300 mg/dl Transient hyper-
than 50 mg/dl glycaemia
Plasma ketone Negative ++++ + + Negative
25-100 mg/dl
Bicarbonate: Normal Less than 10
Blood pH: Normal Less than 7.3 Normal Less than 7.3 Normal
Osmolality Normal Less than 330 340-350 Less than 310 Normal
(mOsm/l)
Blood urea Normal + ++ + Normal
Haematocrit Normal +++ ++++ ± Normal
(dehydration)
Anion gap (eEq/ ⇓ Greater than 12 10-12 Greater than 16
L) ⇓ ⇓ ⇓
Treatment: i. 20-40 ml i. Repletion of i. Normal i. Hyperlatae-
50% glucose volume with saline 2-3 L mia acidosis
ii. G l u c a g o n water and in 2-3 hour corrected by
mg IV sodium, —followed rapid and
electrolytes by 0.5% massive dose
(potassium, NaCl — of IV bicar-
phosphate) followed by bonate 500-
and rarely 5% dextrose 850 mmol
bicarbonate. when plasma may be req-
ii. Insulin for glucose falls uired.
correction of to
contd...
contd...
Diabetes Mellitus | 495

hyperglycaemia and 300 mg/dl or lower. ii. Dichloroacetate also red-

ketogenesis. ii. Potassium supplement uces lactate.
iii. 5% glucose solution for required more urge-
nutrition and free water. ntly than DKA.
iv. Care of precipitating iii. Insulin requirement
factors. lower than DKA: IV
insulin 5 U/L mortality
30-50%.

Monitoring Methods
Urine tests Blood tests
Glucose Glucose
Ketone Glycated Hb
Albumin Fructosamine

Diabetic Ketoacidosis (DKA)

Mechanism
DKA results from following biochemical disturbances

Insulin Deficiency Glucagon Catechol- Cortisol

Lipolysis Diminished Hyperglycaemia excess amine excess excess
utilisation of ↓ ↓ ↓
glucose causes: ↓
FFA increases Osmotic diuresis Gluconeo- Results Causes:
↓ ↓ genesis in: i. Preven-
Accelerates i. Increased Polyuria i. Glycog- tion of
betaoxidation of protein enolysis utilisa-
FFA in peripheral breakdown and glucon- tion of
tissue and liver ii. Diminished eogenesis amino
↓ utilisation of ii. Lipolysis acid for
Excess ketone aminoacids in protein
bodies formation peripheral tissue synthesis
(Normally ketones ↓ ii. Gluconeo-
oxidised by cardiac Rise in plasma Dehydration and genesis
and skeletal muscle aminoacids electrolyte increases.
to produce energy. imbalance
When production
of ketones exceed
the take up capacity
of cardiac and skeletal muscle, ketones accumulate in blood and spell out in urine).
496 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Diagnostic Clues
Clinical
Polyuria, polydipsia, marked fatigue, nausea, vomiting, mental stupor and coma. Hypotension, itching,
dyspnoea (hurried breathing).
Precipitating factors:
Interruption of insulin therapy, sepsis, trauma, surgery, acute myocardial infarction and pregnancy.

Laboratory Investigations
Glucose Acetone Bicarbonate and pH
Urine: ++++ ++++ Low bicarbonate less than 15 mEq/L pH
less than 7.3
Plasma: Greater than 300 mg/dl ++++
Blood: Leukocytosis
often elevated
Serum potassium:

Investigations for Monitoring

Glucose, BUN, creatinine, pH, bicarbonate, potassium, calcium, phosphorus.
ECG with long strip of Lead II.

Management of DKA
Aim:
i. Correction of dehydration by fluid and electrolytes
ii. Correction of hyperglycaemia by regular IV or IM insulin
iii. Correction of acidosis
iv. Correction of hypopotassaemia and hypophosphataemia
v. Treatment of infection.

General Measures
• Rhyle’s tube aspiration of stomach is started routinely to prevent vomiting and gastric dilatation
• Bladder catheterisation is done if no spontaneous flow of urine
• Start intake and output chart
• Start IV line
• Oxygen started if PO2 less than 80 mmHg.

Flow Chart
A. Fluid and Electrolyte Replacement
Total fluid deficit is about 10% body weight
Nature of infusion fluid:
a. Isotonic saline (0.9%)
b. 0.45% saline
Initial fluid replacement:
Diabetes Mellitus | 497

Isotonic saline: Hypotonic (0.45%) saline:

0.5 litre in first 30 minutes Indicated if serum sodium is
↓ more than 155 mEq/L
1 litre in next hour
1 litre in next 2 hour
↓
1 litre in next 4 hour
↓
1 litre in next 8 hour and so on (in children one-fourth of the
above schedule) till the volume deficit is corrected.
If fluid volume replacement is low, satisfactory recovery
is hampered. If excess fluid volume is replaced respiratory
disturbance and cerebral oedema occurs.
↓
Next, rest of the fluid volume deficit is corrected by
0.45% saline infusion at the rate of 150-500 ml/hour
depending on degree of dehydration and cardiac status.
B. Insulin Therapy
1. Intravenous insulin therapy
Start IV regular insulin by adding 50 U to 500 ml isotonic saline with 16 drops per minute and
the dose adjusted as follows:

Based on weight of the patient Based on blood glucose level

0.15 U/kg or 10-15 U initially, followed by Blood glucose 300-400 mg---4 U/hour
continuous infusion at the rate of 5-10 U/hour Do – 400-500 mg---5 U/hr
till blood glucose falls to 250 mg% Do – 500-600 mg---6 U/hr

If decrease in blood glucose of 50-75 mg%/hour does not

occur, the insulin dose should be doubled because of insulin
resistance by increasing the drip rate to 24 and then 32 drops/
minute depending on the response. Half-life of IV insulin is only
3-5 minutes, hence continuous infusion is advocated.
⇓
If blood glucose declines to less than 250 mg%, stop insulin
IV infusion and start 5% dextrose saline with 5U insulin per
pint of saline to prevent dangerous hypoglycaemia and cerebral oedema.
2. Intramuscular insulin therapy
If regular insulin infusion not possible, resort to IM insulin:
First hour 0.5 U/kg
↓
Each hour 0.1 U/kg till blood glucose reaches 250 mg%
thereafter and every two hour later or less
498 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

3. Subcutaneous insulin therapy

Once oral intake is started, SC insulin is given about 30 minutes before meals stopping IV infusion
of insulin.
Comments on Insulin Therapy:
Advantages Disadvantages
• Corrects hyperglycaemia • Excessive rapid correction of hyperglycaemia by insulin
• Corrects acidosis infusion produces osmotic encephalopathy
• Reduces hyperosmolarity
C. Potassium Replacement
Dose
i. Based on serum K level:
Ser. K less than 3 mEq/L Infuse 0.6 mEq/kg for one hour. For example, patient weighing
60 kg, add 36 mEq of K in one pint of saline in one hour. Potassium
is available as chloride salt in 10 ml ampoules, each ml containing
2 mEq of K.
Ser. K 3-4 mEq/L Infuse 0.4 mEq/kg/hour
Ser. K 4-5 mEq/L Infuse 0.3 mEq/kg/hour
Ser. K 5-6 mEq/L Infuse 0.2 mEq/kg/hour
Ser. K above 6 mEq/L Withhold K
If insulin is not infused reduce the dose of K to half the above dose.
ii. Usual dose: Potassium infused 20-30 mEq/hour within 2-3 hour after beginning of therapy or
sooner if initial serum K is very low.

Monitoring of Potassium
• By serum potassium level: Checked every 2 hour if serum K less than 4 or above 6 mEq/L.
• By ECG: Rhythm strip of lead II taken every 1-2 hour. Progressive loss of T-waves or formation of
U-waves suggest hypokalaemia and should prompt start measurement of serum K.

Oral Potassium Rich Food

When oral intake starts, give K rich food such as tomato juice and grapefruit.
D. Bicarbonate Replacement
Disadvantages
Bicarbonate replacement
may cause: Hypokalaemia,
tissue hypoxia, cerebral
acidosis, worsening of
hyperosmolarity and much
clinical benefit not
demonstrated.
Indications
Hurried respiration, pH less than
7.1, hypotension and shock,
severe hyperkalaemia, coma,
plasma bicarbonate less than
5 mEq/L and cardiac dysfunction.
Dose
1 ml/kg of 8.4% NaHCO3 added
to a bottle of hypotonic saline
is infused slowly over a period
of 10 minutes and repeated after
30 minutes if hurried respiration
persists (respiratory rate above
36/minute). It is safer to infuse
10 mEq of potassium with each
infusion of bicarbonate unless
hyperkalaemia is present.
 E. Phosphate and Magnesium Replacement
Diabetes Mellitus |
499

Both decline in DKA and further declines on insulin therapy. Severe phosphate deficiency (less
than 0.35 mmol/L, i.e. less than 1 mg/dl) develops during insulin therapy and may cause lysis of
RBC and muscle weakness and letharginess.
Phosphate replacement Magnesium replacement
Indication Indication
Seldom required in the treatment of DKA and not Ventricular arrhythmia
routinely given. In severe hypophosphataemia a
small amount of phosphate should be given.
Dose Dose
IV infusion at a rate not to exceed 3 mmol/hour Magnesium can be given as magnesium
sulphate (50%) in dosages of 2.5-5 ml
(10-20 mEq) IV.
F. Antibiotics
Appropriate IV antibiotic should be given for infection and started routinely because infection is
the commonest precipitating factor.

Complications Occurring during DKA Therapy

1. Complications developing
at the onset of therapy
• Hypoglycaemia
• Hypokalaemia
• Vascular thrombosis
• Cerebral oedema resulting in
brain herniation and death
2. Other complications
Lactic acidosis
Suspected if refractory
metabolic acidosis,
dehydration, shock and
infection occur
↓ ↓
Treated by adequate volume
replacement, control of sepsis
and judicious use of bicarbonate
Cause
Excessive insulin treatment
Due to excessive correction of acidosis by bicarbonate
Due to dehydration
Reason unknown
Arterial thrombosis Cerebral oedema
Manifested as stroke, acute Manifested as features of inc-
myocardial infarction or reased intracranial pressure
ischaemic limb (headache, papilloedema
and altered mental status)
with fall in serum sodium
Treated by aspirin provoked by rapid correction
of hyperglycaemia by insulin
and overhydration
↓
Treated by IV 20% mannitol

Prevention of DKA
Education and awareness of diabetic patients is essential.
• Self management during prodromol sick days. More insulin required during such illnesses.
• More insulin during infection
• Testing of urine for ketones
• Testing for blood glucose.
 Endocrinology
81
Phaeochromocytoma

Phaeochromocytoma is a tumour of adrenal and located in either or both adrenals or anywhere along
sympathetic chain.

DIAGNOSTIC CLUES
Clinical
Attacks Cardiovascular Central nervous GI tract Others
system
Of headache, • Hypertension • Anxiety • Nausea • 10% cases not associated
perspiration (paroxysmal) • Visual • Pain abdomen with hypertension
and palpitation • Anginal pain disturbance • Vomiting • 10% with extra-adrenal
and dyspnoea • Tremor phaeochromocytoma
• Heat • 10% cases involve both
• Intolerance adrenals
• Syncope • 10% have metastasis
• Psychosis
• Irritability

Laboratory Investigations
A. Biochemical
↓ ↓ ↓
Assay of urinary catecholamines, Direct assay of epinephrine and ESR high, leukocytosis
metanephrine, vanillylmandelic norepinephrine in blood and urine
acid (VMA) during attack during or following an attack
↓ ↓
Elevated Elevated
B. Imaging
CT scan of adrenal A whole body scan MRI
Detects phaeochromocytoma with 123-I MIBG Visualises suspected
in 90% cases Can localise tumour with bone metastasis
↓ sensitivity of 85% and a
If no adrenal tumour found, CT scan of specificity of 90%
abdomen, pelvis and chest is done to detect
tumour located along sympathetic chain
Treatment of Phaeochromocytoma
Phaeochromocytoma | 501

Surgical Resection of Tumour

a. Type of surgery and indications:
i. Laparoscopic removal in case of small-to-moderate size tumour.
ii. Very large tumour needs open laparotomy.
b. Preoperative measures:
i. Phenoxybenzamine 10 mg orally every 12 hours and increase the dose every 3rd days till blood
pressure is controlled. Calcium channel blocker can also be effective and better tolerated than
phenoxybenzamine.
ii. After control of hypertension, propranolol is given 10-40 mg q.d.s. to control tachycardia and
other arrhythmias.
iii. Monitor with ECG till cardiac status becomes stable which takes about few weeks.
c. Intraoperative measures:
i. Hypertensive crisis if occurs, treated by nifedipine 10 mg sublingually. In severe cases IV infusion
of nicardipine 2-6 mcg/kg/minute or nitroprusside 0.5-10 mcg/kg/minute IV prescribed.
ii. If tachyarrhythmia develops, IV atenolol (1 mg bolus) or esmolol or lidocaine given.
d. Postoperative measures:
i. If shock develops due to volume depletion, IV saline or colloid and high dosages of epinephrine
given.
ii. If hypoglycaemia develops, treated by 5% dextrose.
iii. Due to metastasis catecholamines may increase. Re-check urinary catecholamines level
postoperatively. Also re-check blood pressure and symptoms.
e. Inoperable and metastatic tumours:
i. Metyrosine 250-500 mg four times daily, increased daily by increment of 250-500 mg to a
maximum of 4 gm/day given. It reduces catecholamine synthesis.
ii. Phaeochromocytoma may be treated with combination chemotherapy (e.g. cyclophosphamide,
vincristine, and dacarbazine) or with high dosages of 131-I MIBG.
 Endocrinology
82
Hyperaldosteronism

AETIOLOGICAL CONSIDERATION
A. Primary aldosteronism:
i. Unilateral adrenocortical adenoma (Conn’s syndrome) 78%
ii. Bilateral cortical hyperplasia 27%
B. Secondary aldosteronism: Due to stimulation of adrenal by extra-adrenal factors.
Physiological Water and electrolyte imbalance Renal
• Pregnancy • Excessive potassium intake • Renal artery stenosis
• Menstruation • Salt loss • Profound renal vasoconstriction
• Volume depletion • Severe arterial nephrocalcinosis

Diagnostic Clues
Clinical
• Hypertension and sodium retention
• Polyuria and polydipsia
• Muscular weakness

LABORATORY INVESTIGATIONS
Flow Chart
Hypertension
↓
Determine plasma potassium
↓ ↓
Low Normal or high
↓ ↓
Suggests aldosteronism Hyperaldosteronism excluded
↓
Then determine plasma renin activity

Low (less than 5 mcg/dl) Normal or high

↓ ↓
Suggests primary aldosteronism Primary aldosteronism excluded
Then determine 24 hour urine aldoste- Suggests secondary aldosteronism
 rone and plasma aldosterone
Hyperaldosteronism |503

↓
↓ ↓
High Low or normal
↓ ↓
Suggests primary aldosteronism Undetermined diagnosis
To find out the aetiology of aldoste-
ronism determine plasma aldosterone
and 18 hydroxy-corticosterone levels
with posture studies

Plasma aldosterone level assessed

at 8 A.M. (after overnight sleeping)
and again after 4 hours
↓ ↓
Plasma aldosterone level with Plasma 18 hydroxy-corticosterone level
posture studies
↓ ↓
High plasma aldosterone level High (above 18 mcg/dl)
with no response to upright posture Suggests adrenal neoplasma
(less than 10 mcg/dl which does
not rise during upright posture)
Suggests adrenal adenoma

ANATOMICAL LOCALISATION
CT scan detects 60-80% adrenal adenoma but cannot detect 20% hyperplasia.
Hence adrenal scan is done with either adrenal vein catheterisation or isotope scanning with
iodocholesterol.

TREATMENT OF HYPERALDOSTERONISM
Unilateral adrenal adenoma
Treated by laparoscopic
adrenalectomy
or
Life long spironolactone
therapy
Bilateral adrenal hyperplasia Hypertension
a. Best treated by spironolactone Treated with antihyper-
100-400 mg/day tensive drugs
b. Sometimes respond well
to dexamethasone suppression
therapy
 Endocrinology
83
Cushing’s Syndrome
(Hypercortisolism)

Chronic Cushing’s syndrome refers to manifestations of excess corticosteroic.

AETIOLOGICAL CONSIDERATION
Due to excessive ACTH secretion
(ACTH-dependent Cushing’s syndrome) 85% cases
a. 70% cases due to hyper-
secretion by very small
(microadenoma) benign
pituitary adenoma 5 times
more common in women
than men.
b. Glucocorticoid adminis-
tration.
Due to excessive cortisol secretion
(non-ACTH dependent) 15% cases
1. By adrenal tumour:
a. Small adenoma producing
15% cases due to non- excess cortisol.
pituitary neoplasm b. Large carcinoma producing both
(ectopic) e.g. small cell excess cortisol and androgens
lung carcinoma which resultant hirsutism and with
produces excess ACTH. virilization.
Hyperpigmentation and 2. Bilateral adrenal nodular hyperplasia
hypokalaemia commonly due to excess ACTH production by
associated. adenoma of anterior pituitary.

DIAGNOSTIC CLUES
Clinical
Head : Emotional disturbance, depression, fatigue
Face : Moon face, plethoric face
Trunk : Trunchal or central obesity with sparing of limbs, “Buffalo hump”
(excess fat over upper part of back)
Skin : Easy bruising, purple striae
Bone : Osteoporosis, pathological fracture, vertebral collapse
Muscle : Proximal muscle weakness
Women : Acne, amenorrhoea, hirsutism
Age/sex : Common in middle aged women
Blood pr. : Hypertension
Blood sugar : Hyperglycaemia
INVESTIGATIONS
Cushing’s Syndrome (Hypercortisolism) | 505

Flow Chart

Suspected Cushing’s syndrome : Obesity 90%

Facial plethora, hirsutism : 80%
Menstrual disorders : 70%
Muscle weakness, back pain, striae : 60%
Emotional disturbances, acne, bruise : 40-50%
Three stage diagnosis:
First, establish the diagnosis of hypercortisolism (Cushing’s syndrome)
↓
Next, aetiological diagnosis of Cushing’s syndrome
↓
Lastly, anatomical localisation of tumour

Urinary free cortisol Overnight low dose dexamethasone Metapyrone test 750 mg
suppression test (1 mg dexame- given orally every 4 hours
thasone at 11 PM; serum cortisol for 6 dosages
Normal Abnormal:
measured at 8 AM next day)
↓ High above
Excludes 160 mcg/day Normal: Abnormal: Ser. High urinary 17-hydroxycorticoid
↓ ↓ cortisol fails to and cortisol level lacking a normal
Cushing’s Points to Excludes decrease to less circadian rhythm
syndrome Cushing’s Cushing’s than 5 mcg/dl ↓
syndrome syndrome (serum cortisol Suggests Cushing’s syndrome
regardless of above 5 mcg/dl) regardless of aetiology and type
aetiology ↓
or type Suggests Cushing’s
syndrome regardless
of aetiology and type
↓
Investigations to differentiate different aetiologies
and types of Cushing’s syndrome

a. Plasma ACTH level Corticotrophin releasing: Hormone

b. High dose dexamethasone suppression test (CRH) given IV (1 mcg/kg)
Stimulates plasma ACTH
a. ACTH low a. ACTH high a. ACTH high and cortisol production
(Less than (70-100 pg/ml) b. Suppression
50 pg/ml) less than 50% Positive No
b. No suppression b. No suppression baseline level response response
↓ ↓
Cushing’s Ectopic
↓ ↓ ↓ disease ACTH syndrome
506 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

↓ ↓ ↓
Suggests non-ACTH Suggests ectopic Suggests ACTH
dependent adrenal ACTH syndrome dependent Cushing’s
tumour syndrome

OTHER LABORATORY INVESTIGATIONS

Glucose tolerance WBC count Serum potassium
Impaired • Leukocytosis Hypokalaemia especially
• Granulocytosis in ectopic ACTH syndrome
• Lymphopenia

ANATOMICAL LOCALIZATION OF TUMOUR

A. CT scan/MRI
CT/MRI of sella turcica: CT scan of chest, CT scan of adrenal
abdomen and pelvis
Positive in 50% of cases Shows ectopic tumour Shows adrenal tumour
pituitary microadenoma
B. Adrenal scintigraphy

Provides image of adrenal gland Provides information about

adrenal function
↓
Detects adrenal adenoma Bilateral increase of Fails to show uptake
iodocholesterol of iodocholesterol
↓ ↓
Suggests bilateral Suggests adrenocortical
adrenocortical hyperplasia carcinoma

TREATMENT OF CUSHING’S SYNDROME

Different approaches of treatment of different aetiologies of Cushing’s syndrome:

ACTH dependent Adrenal tumour Ectopic tumour

Cushing’s syndrome (Non-ACTH dependent)
i. Pituitary microsurgery i. Surgery i. Surgical removal of
pituitary microadenoma ii. Drug therapy ectopic tumour
(Treatment of choice) ii. Adrenalectomy
ii. Pituitary irradiation iii. Drug therapy
iii. Drug therapy
iv. Adrenal surgery
Surgery and Irradiation Therapy
Cushing’s Syndrome (Hypercortisolism) | 507

Procedure Advantages Disadvantages Indications

1. Cushing’s
disease due to
microadenoma
a. Pituitary Selective transphe- i. After adenomec- i. Normal cortico- Treatment of choice
microsur- noidal resection of tomy rest of prt- trophin suppres-
gery adenoma uitary function sed and require
returns to nor- 6-36 months to
mal recover normal
ii. Method of choice function. Hydro-
for initial therapy cortisone rep-
iii. Surgical morta- lacement needed
lity rare in the meantime.
ii. Diabetes insipi-
dus, CSF rhinor-
rhoea, haemor-
rhage in less than
2%.
b. Bilateral By laparoscopic • When pituitary
adrenalec- method surgery fails
tomy: • Advanced Cushing’s
syndrome
c. Pituitary i. Cure rate 23% • Young patient
irradiation: ii. Panhypopitui- • When surgery fails
tarism seldom
develops
iii. Steroid replace-
d. Stereotoxic ment not needed
radiosurgery
(gamma
knife)
2. Adrenal tumour: Surgical removal Unilateral adenoma In unilateral adrenalec-
a. Adrenal ade- removal has high remi- tomy contralateral
noma: ssion rate adrenal is suppressed,
so post-operatively
hydrocortisone rep-
lacement required until
recovery occurs.
b. Adrenal car- Surgical removal Surgical cure only in
cinoma: few cases
3. Ectopic synd- a. Surgical removal
rome: of ectopic tum-
our followed by Indolent inoperable
irradiation and tumour due to advan-
chemotherapy ced malignancy and
b. Adrenalectomy metastasis
508 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Medical Therapy
The effect of drug therapy is temporary, lasting while the drug is administered. Recurrences occur after
interruption of drugs.
Drugs Dose Action Side-effects moni- Indications
toring
I. Cushing’s Ketoconazole 200 mg 6 hourly Inhibits biosynthe- Liver enzymes Patients who are
disease: sis of cortisol and monitored for not surgical candi-
ACTH secretion progressive eleva- date
tion
Mitotane 2-4 gm/day – Do – Side-effects:
Anorexia, nausea,
diarrhoea,
somnolence,
pruritus

II. Adrenal neo- – Do – Side-effects:

plasm: Metyrapone
a. Adenoma: Mitotane exacerbates
or virilization in
Ketoconazole female
or
Metyrapone

b. Carcinoma: Mitotane – Do – Only drug effective

in metastatic adre-
nocarcinoma
III. Ectopic Ketoconazole Octreotide given Octreotide supp-
ACTH or parenterally several resses ACTH
secreting Metyrapone time daily secretion in one-
tumour: or third cases
Ketoconazole
+
Metyrapone
or
Octreotide (Soma-
tostatin analog)

Nelson’s Syndrome
Cause Clinical features Treatment
Occurs after bilateral adrenalec- Increasing hyperpigmentation, i. Pituitary adenomectomy and
tomy headache, visual disturbances, irradiation is the treatment of
plasma ACTH level as high as choice.
1000-10000 pg/ml ii. Cyproheptadine, bromocrip-
tine and valproic acid may be
used in minority of patients
to reduce the level of ACTH.
 Endocrinology
84
Addison’s Disease
(Adrenocortical Insufficiency)

AETIOLOGICAL CONSIDERATION
1. Primary: (With deficiency of cortisol and aldosterone and elevated plasma ACTH):

Incidence Causes and Mechanism Remarks

A. Autoimmune: 80% cases in USA. Defect in T-cell mediated
Age: Child, adult immunity. Inherited as an
autosomal recessive trait.
50% cases have anti-adrenal
antibodies.
Associated with other endo-
crine diseases, e.g. autoim-
mune hypothyroiditis and
antibodies against para-
thyroid, gonads or pancreas.

B. Infection: Tuberculosis common in Histoplasmosis, tuberculosis

underdeveloped countries destroys adrenal.

C. Bilateral adrenal Anticoagulant therapy during Often with abdominal pain

haemorrhage: open heart surgery, major and fever. Diagnosed by CT
trauma, sepsis. scan.

D. Adrenoleuko 30% cases. Due to accumulation of very

dystrophy: Any age long chain fatty acids in
adrenal cortex, testes, brain
and spinal cord.
E. Adrenal hyper- a. Congenital: Defect in Mineralocorticoid and corti-
plasia: adrenal enzyme for sol deficiency with excess
• Congenital cortisol synthesis resul- androgens.
• Acquired ting in excess ACTH
production which stim-
ulates adrenal to
become hyperplastic.
b. Acquired: Drugs
2. Secondary to pituitary a. Most often due to
disorder: glucocorticoid
therapy with sup-
pression of ACTH
contd...
510 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. Due to pituitary disea-

ses suppressing ACTH
production.
Deficient ACTH and CRH
3. Tertiary due to hypo- production resulting in sup-
thalamic disorders: pression of hypothalamus-
pituitary-adrenal axis

Diagnostic Clues

A. Clinical General GI tract Cardiac Skin and Hair Other Features

1. Chronic: Weakness, fatigue, Anorexia, nausea, Hypotension ortho- i. Pigmenta- a. Addison’s
weight loss, mental vomiting, diar- static, small heart tion of crea- disease may
irritability rhoea and abdomi- ses, pressure be associa-
nal pain areas, nip- ted with
ple, knuck- ovarian
les, elbows. failure, testi-
ii. Sparse axil- cular failure
lary and pernicious
pubic hair anaemia,
especially in hypothyroi-
women. dism.
b. Hyperkalae-
mia and vol-
ume deple-
tion (due to
aldosterone
deficiency)
only in pri-
mary disease.
c. Adrenoleu-
kodystrophy
characterised
by neuropsy-
chiatric sym-
ptoms and
hypogona-
dism.
2. Acute adrenal failure (Adrenal crisis):
Triggered by illness, injury or surgery. Characterised by shock.
B. Laboratory Investigations:
Flow Chart
Suspect adrenal failure in presence of hypotension, weight loss,
pigmentation, hyponatraemia and hyperkalaemia
↓
Measure plasma cortisol, urinary cortisol (17 hydroxycorticoid, 17 ketosteroid) at 8 AM
↓
 Addison’s Disease (Adrenocortical Insufficiency)

↓
|
511

Normal Low
↓ ↓
Excludes Addison’s disease Diagnostic of Addison’s disease
↓
One hour rapid ACTH
stimulation test performed

↓ ↓
Serum cortisol Serum cortisol less than 20 mcg/dl
above or equal to 20 mcg/dl
↓ ↓
Excludes Addison’s disease Diagnostic of Addison’s disease
↓
To differentiate primary from
secondary type of Addison’s disease:
Note the following differentiating
characteristics

Secondary Addison’s disease due to Primary Addison’s disease

pituitary and hypothalamic disorders
Characterised by: Characterised by
i. Deficiencies of other i. Hyperkalaemia and volume
pituitary hormones depletion
ii. Symptoms of pituitary or ii. Hyperpigmentation
hypothalamic mass lesions iii. Other autoimmune
(headache, visual field loss) endocrine deficit
iii. Known pituitary or
hypothalamic diseases
↓
If distinction is still not clear: Measure ACTH level

Low High
↓ ↓
Suggests secondary type Suggests primary type
↓ ↓
Test for other pituitary Other investigations
hormone deficiency A. Autoimmune Addison’s Disease
i. Anti-adrenal antibodies found in
serum in about 50% cases. Anti-
bodies against thyroid may also
be present.
ii. CT scan of adrenal: Non-calcified
adrenal.
512 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

B. Non-autoimmune Addison’s Disease:

i. Chest X-ray: Evidence of tuber-
culous, fungal infection or cancer
as possible cause.
ii. CT scan:
a. Adrenal gland enlarged in 85%
cases due to metastasis or
granulomatosus disorders.
b. Calcification in tuberculosis
(50% cases), haemorrhage
fungal infection, pheochromo-
cytoma and melanoma.

Treatment of Addison’s Disease

I. Primary Addison’s disease
A. Specific Treatment: Replacement therapy should include both glucocorticoid and
mineralocorticoid.
1. Glucocorticoid plus mineralocorticoid
2. Dehydroepiandrosterone (DHEA).
Glucocorticoid: Mineralocorticoid:
Hydrocortisone (Drug of choice) Fludrocortisone acetate (potent salt retaining effect)
15-25 mg orally in two divided dosages, two-third 0.05-0.3 mg orally daily or every other day.
(15-20 mg at 8 AM) in the morning and one-third Monitoring:
(5-10 mg in evening) in the late afternoon or early
evening with milk, meal or antacid. If postural If oedema,
Or hypotension, hypokalaemia or
Prednisolone (some patient responds better to hyperkalaemia hypertension ensues
prednisolone) 5 mg in the morning and 2.5 mg in or weight loss occurs
the evening. ↓ ↓
Monitoring: Dose adjusted according to weight Raise the dose Lower the dose
gain, hypertension, diabetes mellitus, active
tuberculosis.
Dehydroepiandrosterone (DHEA)
50 mg orally each morning given to some women for better well-being, mood and sexuality.
B. General Management:
Stressful situations
Infection Mild (due to vomiting, diarrhoea, endoscopy,
Treat vigorously raising the dose of hydrocortisone arteriography) and severe stress (due to severe
at the same time. trauma, surgery):
a. Severe stress: Hydrocortisone 50 mg IV or IM
6 hourly
b. Lesser stress: Prednisolone orally
↓
When stress subsides lower the dose to normal
The patient should wear a medical alert bracelet,
“Adrenal insufficiency, takes hydrocortisone”.
Addison’s Disease (Adrenocortical Insufficiency) | 513

C. Adrenoleukodystrophy:
a. Lorenzo’s oil therapy normalises serum long chain fatty acid concentration but ineffective
clinically.
b. Haemopoetic stem cell transplantation from normal donors, improves neurologic
manifestation.
II. Secondary Addison’s Disease
a. Glucocorticoid therapy instituted like primary disease. Mineralocorticoid is usually not necessary.
b. Other pituitary hormones may also have to be replaced.

Treatment of Adrenal Crisis

Supportive Treatment
5% glucose saline immediately a. Hydrocortisone 100-200 mg
till hypotension is corrected.
Specific Treatment Precipitating Factors
Gastrointestinal upset, trauma,
IV every 4-6 hour. surgery and infection managed.
↓
If IV not possible, IM
cortisone acetate 50 mg
given.
↓
Once the patient improves,
oral steroid started and then
tapered.
b. Mineralocorticoid not requi-
red initially until the dose of
hydrocortisone is less than
100 mg per day.

Prophylaxis
1 2 3 4 5
Minor illness Vomiting Severe illness Surgery During excessive
Double the dose Immediate IV fluid Hydrocortisone Hydrocortisone exercise, sweating,
of glucocorticoid 50 mg IV 8 hourly 50 mg given pre- hot weather and
for 3 days and tapered accor- operatively g a s t ro i n t e s t i n a l
↓ ding to response ↓ upset
When illness resol- Dose reduced 3-4 Add salt to the diet
ves, resume the days after uncomp-
maintenance dose licated surgery
 Arthritis and Musculoskeletal Disorders
85
Arthritis
CLASSIFICATION OF ARTHRITIS
Characteristics Representative Diseases
Inflammation characterised by redness, warmth,
swelling morning stiffness:
• Present Rheumatoid arthritis, SLE, gout, dermatomyositis,
polymyalgia rheumatica
• Absent Osteoarthritis

Number of joints involved:

• Monoarticular Gout, septic arthritis, trauma, Lyme disease
• Polyarticular Rheumatoid arthritis, SLE
• Oligoarticular Reiter’s disease, psoriatic arthritis, inflammatory
bowel disorders.
Site of joint involved:
• Distal interphalangeal joint Osteoarthritis, psoriatic arthritis.
• Metacarpophalangeal joint and wrist Rheumatoid arthritis, SLE
• First metatarsal and phalangeal joint Gout, osteoarthritis

Extra-articular manifestations: Rheumatoid arthritis

Nodules, pericarditis, pleural effusion, lympha-
denopathy with leukopenia

Joint fluid findings:

• Non-inflammatory Osteoarthritis, trauma, neuropathic arthropathy
• Inflammatory Rheumatoid arthritis, Reiter’s disease, ankylosing
spondylitis, psoriatic arthritis, inflammatory bowel
disease.
• Purulent with leukocytosis with positive culture Septic arthritis
• Haemorrhagic Haemophilia, trauma, neuropathic joint, haeman-
gioma, other benign neoplasm
• Sodium urate crystal Gout

contd...
Findings of laboratory investigations:
|
Arthritis 515

ESR:
• High Polymyalgia rheumatica, rheumatoid arthritis, SLE
• Low Osteoarthritis

Serum uric acid: High (above 7.5 mg/dl) Gout

Autoimmune findings:
• Rheumatoid factor Rheumatoid arthritis (positive in 85% cases)
• Antinuclear factor (ANF) Rheumatoid arthritis (20% cases)
Sjögren (positive in 20% cases)
SLE, scleroderma and dermatomyositis (positive
in 90-100% cases)
• HLA-B27 Ankylosing spondylitis (positive in 90% cases)
Inflammatory bowel disorder (+ 50%) Reiter’s
disease (+ 80%)
Investigations for infections:
• Positive blood culture Septic arthritis
• Leukopenia Rheumatoid arthritis (Felty’s syndrome)
• Leukocytosis Septic arthritis
Gonococcal arthritis
Imaging:
• Radiograph not diagnostic Gonococcal, infective arthritis, myalgia rheumatica,
collagen disorders, Sjögren arthritis
• Radiograph diagnostic a. Reiter’s disease: Progressive joint lesion in
sacroiliac and peripheral joint.
b. Ankylosing spondylitis: Erosion and sclerosis
of sacroiliac joint, calcification of annulus
fibrosus, calcification of anterior and lateral
ligaments and squiring of vertebrae (“Bamboo
spine”).
c. Rheumatoid arthritis: Narrowing of joint
space, juxta-articular osteoporosis, erosion of
ulnar styloid and juxta-articular margin.
d. Gout: Punched out erosion with overhanging
rim of cortical bone (“rat bite”).

Rheumatoid Arthritis
Diagnostic clues
Clinical:

General Special types

• Systemic symptoms: Fever, malaise, weight loss.
• Symmetrical inflammatory polyarthritis.
• Extra-articular manifestations: Nodules, vasculitis, pulmonary fibrosis.
516 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Felty’s syndrome Sjögren’s syndrome

RA + splenomegaly, granulo-
cytopenia, risk of recurrent
bacterial infection and non-
healing leg ulcer.
Laboratory investigations
See classification of arthritis.
Dry mouth, dry eyes,
parotid gland enlargement,
dental caries and recurrent
tracheobronchitis.

Treatment of RA
Aim:
• Relief of pain and inflammation
• Preservation of muscle strength and joint function and return to normal life style
• Pharmacotherapy: Minimising side-effects, NSAIDs for pain relief, steroids and DNARDs for immune
modulation and checking of inflammation and disease modification (arrest or retarding disease process)
• Surgery
• Physiotherapy.

Pharmacotherapy
Non-steroid anti-inflammatory drugs (NSAIDs)
Classification

Salicylates Non-Salicylates
a. Aspirin
b. Buffered Acetic acid Propionic acid Fenamic Enolic acid Newer
aspirin a. Phenyl acetic • Ibuprofen acid a. Pyrazolone: NSAIDs
c. Enteric acid: • Naproxen • Mefenamic • Phenyl- • Nimesulide
coated • Diclofenac • Flubiprofen acid butazone • Cox-2
aspirin b. Indoles: • Ketoprofen b. Oxicam: inhibitors:
• Indomethacin • Peroxicam • Celecoxib
• Sulindac • Rofecoxib
• Valdecoxib
Characteristics of Individual Drugs of NSAID Group
Indole Salicylates Propionic Acid Fenamic acid Pyrazolones Oxicam Newer NSAIDs
Indomethacin Cheap, effective Side-effects Useful but Phenylbutazone Effective, safe GI friendly, spe-
very effective but more gastric much less. Pre- weak. Diarrhoea more gastric and long-life. cially celecoxib,
particularly if irritation. ferred drug to only side-effect. irritation, fluid rofecoxib and
used at night, start with. retention and valdecoxib. No
but more dys- bone marrow coagulation
pepsia, peptic depression. abnormalities,
ulcer and fluid Rarely used hence not C/I in
retention. now. thrombocytope-
nia, haemosta-
tatic defects and
chronic coagu-
lation.
Dosages, Advantages and Disadvantages of NSAIDs
|
Arthritis 517

NSAIDs inhibit cyclo-oxygenase (Cox-1 and Cox-2) that converts arachidonic acid to prostaglandins
which promote inflammation. Celecoxib and rofecoxib selectively inhibit only Cox-2 producing anti-
inhibitory effect but spares Cox-1 which protects gastric mucosa.

Drugs Dosages Advantages Disadvantages General Remarks

1. Propionic acid deri- a. Ibuprofen 200, 400, Side-effects: i. Make a small
vatives: 600 mg tab. • GI: Dyspepsia, nau- selection.
600 mg q.d.s. sea, vomiting, blee- ii. Prescribe estab-
b. Ketoprofen: 50, ding lished drugs with
100 mg tab. 75 mg • Renal: Renal failure, proven efficacy
b.d. or t.d.s. nephrosis and less side-
c. Naproxen: 250, 500 • Haematological: effects.
mg tab. Bleeding with anti- iii. Avoid usage of
250 mg b.d. or t.d.s. coagulant or surgery older aspirin, phe-
d. Flurbiprofen: and blood dyscrasias nylbutazone and
Froben 100 mg tab. with phenylbutazone, indomethacin.
100 mg once daily indomethacin iv. Prescribe one drug
or b.d. • Ear: Deafness and at a time.
tinnitus with higher v. Prescribe for a
dose of salicylates limited time.
• Fluid retention with vi. If one drug is not
indomethacin and effective during
high dose of rofeco- 2-3 weeks, try
xib another drug .
C/I: Renal failure, vii. Don’t use aspirin
pregnancy, lactation. with other
Other disadvantage: NSAIDs. More
Can’t prevent erosion analgesic effect is
and progression of joint produces if
disease. NSAIDs combi-
ned with paraceta-
mol, dextroproxy-
phene (proxyvon)
or muscle relaxa-
0nts (baclofen,
chlorzoxazone).
2. Phenylacetic acid: Diclophenac: 50 mg, – do –
100 mg SR tab
25 mg/ml amp.
50-100 mg/day, increa-
sed maximum
200 m/day. SR tab
100 mg b.d.
IM 75 mg once or twice
daily.
3. Indole Indomethacin: 25, 50 – do –
mg cap. 25 mg b.d. or
t.d.s.
contd...
518 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

4. Oxicams: Piroxicam: 10-20 mg 20 mg/day Long life –do –

Mefenamic acid
5. Fenamic acid: Ponstan 250, 500 mg cap 250-500 mg
t.d.s.

100-200 mg b.d.
6. Phenylbutazone: – do –
a. Celecoxib: 100-200 mg cap:
7. Cox-2 inhibitors • Osteoarthritis: 200 mg/day or
100 mg b.d.
• Rheumatoid arthritis: 100-
200 mg b.d.
b. Rofecoxib: 12.5, 25, 50 mg cap,
valdecoxib 10, 20 mg/day
• Osteoarthritis: 12.5 or 25 mg/day
• Acute pain: 50 mg/day upto
5 days
8. Nimesulide: 100 mg tab
100 mg b.d.

Glucocorticoids
They are anti-inflammatory and immune modulators.
Drugs Dosage Advantages Disadvantages
Prednisolone: 5, 10 mg tab. Side-effects:
5-20 mg/day. Once See Table: “Side-effects
symptom is controlled, of glucocorticoids”
take twice the daily dose
on alternate days
Methylprednisolone IV: 500 mg IV b.d. for 3-5
days
Intraarticular triam- See Table 85.1: Intra-
cinolone articular glucocorticoid

Table 85.1: Intra-articular glucocorticoids

Dosage Indications Contraindications
10-40 mg/joint if one or two joints are • When one or two joint involved • Uncertain diagnosis
only involved • Tendinitis • Proven or possible infection in joint
• Capsular and ligamentous invol- • Severe joint damage since steroids
vement will be ineffective and may increases
• A temporary measure for nerve joint damage.
compression
 Table 85.2: Side-effects of glucocorticoids
Arthritis| 519

1. Disease process: Do not retard progression of disease and after stopping disease reappears
2. Adrenal suppression: Prevented by low dose of steroid prescribed in the morning
3. Immunosuppression: Prone to infection
4. Endocrine abnormalities: Cushing syndrome, hyperglycaemia
5. Musculoskeletal: Osteoporosis, steroid myopathy (hip and shoulder muscles weakened).
Ischaemic aseptic bone necrosis of femoral head and humeral head.
6. Central nervous system: Euphoria, insomnia

IMMUNOMODULATORS AND IMMUNOSUPPRESSIVE DRUGS

See Table 85.3.
Table 85.3: Dosage, indications and clinical features of immunomodulators and immunosuppressive drugs
Drugs Indications Dosage Advantages Disadvantages
Methotrexate: Myositis, synositis 2.5 mg tab • Easily available Side-effects
(Folic acid antagonist) 7.5 mg weekly • Rapid onset of action • GI intolerance
Maximum daily dose • Better compliance in • Alopecia
25 mg long-term treatment • Headache
If no response after as compared to other • Bone marrow depres-
6 weeks, increase the DMARD drugs sion. Toxicity reduced
dose by 2.5-5 mg every • Can be combined with by folic acid 1-2 mg/
2-4 weeks to maximum sulfasalazine and day.
of 25 mg/week. hydroxychloroquine

Sulfasalazine: Synovitis 500 mg tab. Effective and faster Side-effects:

Start 500 mg, action Nausea, allergic errup-
increased by 500 mg tions, occasionally apla-
weekly till maximum stic anaemia, reversible
2000-3000 mg in azoospermia.
divided dosages (b.d.)
given after food.
Hydroxychloroquine: Mild synovitis 200 mg tab C/I: CI: Sulpha, glucose-6-
200 mg b.d. (6 mg/kg) Porphyria, glucose-6- phosphate dehydro-
Maximum 400 mg/day phosphate dehydro- genase deficiency
genase deficiency, sig- Side-effects: Pigmen-
nificant liver and renal tary retinitis, rash, GI
impairment. upset.

Leflunomide: 10, 20 mg tab CI: Pregnancy, signifi-

20 mg/day cant liver impairment,
rifampicin
Side-effects:
Diarrhoea (reduce
dose), if much eleva-
tion of serum transa-
minase—stop drug,
treat with cholestria-
mine, rash, alopecia
contd...
520 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Gold salt: Aurothio- • Synovitis when met- 20 mg test dose follo- C/I: Impaired renal and
glucose (IM prep) hotrexate not tole- wed by 50 mg IM hepatic function, rash
rated weekly for 20 weeks, Side-effects:
• Erosive disease then 50 mg once in Nausea, vomiting, diar-
2 weeks for 3 months rhoea, dermatitis sto-
and then 50 mg once matitis, albuminuria,
3 weeks for an indefi- cytopenia with IM gold.
nite period. Side-effects more with
IM gold than oral gold.
Auranofin: Oral prep. – do – 3 mg tab.
3 mg b.d.
Maximum 9 mg/day

D-Pencillamine Synovitis 125, 250 mg tab. C/I: Pregnancy

Start 250 mg/day for Side-effects: Derma-
6 weeks, increased by titis, haematological
125 mg every 4-8 toxicity
weeks.

Azathioprine: Refractory synovitis or 50 mg tab. 1 mg to 1.5 Steroid sparing agent Side-effects: Infection,
myositis mg/kg/day, increased at nausea, hepatic toxicity,
8-12 weeks interval. oncogenecity after long
Maximum 2.5-3 mg/kg/ term use.
day.

Cyclophosphamide: 25, 50 mg tab 1-1.5 mg/ Vasculitis Side-effects: Infection,

Oral: kg/day, increased to nausea, vomiting, steri-
maximum 2.5-3 mg per lity, alopecia, oncoge-
kg/day necity

IV: 0.5-1gm/m2 monthly – do –

Cyclosporine: 25, 50, 100 mg tablet. Synovitis Side-effects: Renal toxi-

2-3 mg/kg/day city, hirsutism, anaemia

Tumour necrosis factor a. Entanercept: SC Side-effects: Infection,

(TNF): 25 mg biweekly. Ste sepsis
roid and NSAIDs
and methotrexate
can be continued
during treatment.
b. Infliximab: 3 mg/kg
IV with weekly
methotrexate.
APPROACH TO TREATMENT OF RA
|
Arthritis 521

Flow Chart
Initial Therapy for Mild Disease:
NSAIDs, hydroxychloroquine, sulfasalazine or minocycline. Chloroquine less favoured.
⇓
If fails or side-effects occur, switch on to glucocorticoids: Indications of steroids:
|

Symptomatic relief. C/I to methotrexate Persistent synovitis Severe constitutional

Used short-term to tide or DMARD drugs refractory to NSAIDs symptoms (fever, weight
over acute disabling loss) or extra-articular
episode manifestation
⇓
If fails, immunomodulatory and immunosuppressive drugs are indicated:

Indications

Active synovitis not responding Rapidly progressive arthritis To relieve dependence on

to NSAIDs and DMARDs clinically and radiologically. steroids for control of symp-
Significant extra-articular toms.
manifestations.

Selection of drugs
Methotrexate is the initial drug of choice for moderate to severe RA
↓
If fails, leflunomide, tumour necrosis factor inhibitors or azathioprine
↓
If partial response to the above agents and if disease is severe, combination thereby is indicated:
a. Methotrexate + hydroxychloroquine or sulfasalazine or both
b. Methotrexate + Leflunomide or azathioprine or cyclosporine
c. Etanercept with methotrexate or infliximab with methotrexate

Current Suggestions
Maximum joint damage occurs early in the disease. Aggressive use of combination drugs (DMARDs)
reduce joint damage and deformities early in the disease. After stability by combination therapy slowly
withdraw one by one depending on the response.

Management of Drug Toxicity

A. NSAIDs
a. To reduce GI toxicities:
• NSAIDs taken with food and antacids
• Change to buffered aspirin or enteric coated aspirin
522 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Change to GI friendly celecoxib or rofecoxib

• Concomitant use of omperazole (not ranitidine) or famotidine (40 mg b.d.)
• Concomitant use of misoprostol (prostaglandin E but causes diarrhoea and it is an abortifacent)
b. Stop NSAID 5-7 days before surgery.
c. Stop NSAID in pregnancy and lactation.
B. Glucocorticoids
a. During surgery: Increase the dose of steroid before, during and after surgery.
b. Steroidal osteoporosis prevented and treated by calcium 1-1.5 gm/day, vitamin D 800 U/day.
For menopausal osteoporosis oestrogen or bisphosphonate or calcitonin are prescribed with
judicious exercise.
c. For steroidal myopathy reduce the dose of steroid and advise exercise.
C. Immunomodulatory and Immunosuppressive Drugs
(Disease modifying and slow acting anti-rheumatic drugs DMARD)

When to stop toxic drug? When to continue for prolonged Monitoring

Gold: Discontinue if proteinuria
above 1-1.5 gm/24 hour, if no
improvement even after taking
1000 mg of gold, rash, pancyto-
penia and thrombocytopenia.
Chloroquine: Stop if visual
deterioration and ophthalmo-
logical abnormalities occur.
Pencillamine: Stop if skin rash.
Desensitise.
Methotrexate: Stop if persistent
elevation of hepatic enzyme and
persistent cough and dyspnoea.
Leflunamide: Stop if much
increase in liver enzymes and treat
with cholestyramine
period?
Gold: If response occurs without
side effects continue for long
period.
Pencillamine: If response favour-
able, continue for prolonged
period.
a. Urine analysis for protei-
nuria:
• Gold: Urine examination
done before each injection
• Pencillamine: Urine exa-
mination done for pro-
teinuria monthly
b. Blood count and platelet
count:
• Gold: Before each gold
injection done.
• Pencillamine: Monthly
blood and platelet count.
• Sulphasalazine: Count
done since risk of aplastic
anaemia.
c. Ophthalmological exami-
nations
Gold: Done every 6 month
due to risk of retinal toxicity
Chloroquine: 6 monthly
d. Liver function tests
Methotrexate: Frequent LFT
required because of risk of
hepatic fibrosis.
 Table 85.4: Classification of DMARDs
|
Arthritis 523

Drugs of proven value Newer effective drugs Experimental drugs

Methotrexate, azathioprine, gold salt,
D-pencillamine, cyclophosphamide,
sulfasalazine
• Leflunomide
• Tumour necrosis factor inhibitors:
a. Etanercept (SC twice weekly
25 mg)
b. Infliximab (IV 10 mg/kg)
• Plasmapheresis
• Thoracic drug drainage
• Total body irradiation
• Interferon

PHYSIOTHERAPY
Rest
Essential indications Other requirement during rest
Active disease with acute inflammation. • Proper posture
Rest reduces pain, muscle spasm, • Firm mattress
wasting and deformities. • Back rest
• Splints; see below

Exercise
Once inflammation has settled, a programme of simple graduated active exercise is essential. Exercise
may be done in heated pool since it reduces effect of gravity and muscle spasm. The application of ice,
heat and ultrasound fascilitates exercise.

Splints and Walking Aids

Splints should be light, durable and inexpensive. Splints are used in acute phase till inflammation subsides
in one or two weeks. Avoidance of flexion deformity is essential. Many patients require sticks, crutches
or frames for walking.

Domestic Activities
Patients’ access to routine activities, e.g. dressing, combing, bathing, cooking, ironing, etc. should be
aided by aids available. Furnitures should be moved to provide a clear floor area for walking. Careful
selection of wheel chair is done for indoor and outdoor activities.
Appliances to assist daily activities are selected, e.g. comb with handle, dressing stick, raised toilet,
high back chair.

Occupational Therapy
Prescribed for daily activities and job orientation.

ORTHOPAEDIC SURGERY
Aim
i. Relief of pain so that patient can sit or sleep without pain.
ii. Improvement in function.
524 |
Procedures
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Surgical procedures
• Carpal tunnel, tarsal tunnel and ulnar nerve Decompression for release of entrapped nerve
entrapment
• Ruptured tendons at wrist and achilles Repair surgery
• Persistent synovitis leading to joint damage Synovectomy
• Pain in acromioclavicular joint and metatarsalgia Excision orthoplasty
• Pain relief and improvement of function of wrist, Arthrodesis
ankle and subtarsal joints
• Persistent pain and dysfunction of hip, knee, Joint replacement
elbow and shoulder
• Atlanto-axial subluxation Fixation
 Arthritis and Musculoskeletal Disorders
86
Other Arthritis

DIAGNOSTIC CLUES
Clinical

Aetiological Features Symptoms and Signs Precipitating Features

Non-gonococcal infective • Occurs in previously dama- Mono-articular arthritis,
arthritis: ged joints occasionally polyarthritis due
to haematogenous spread
• Staphylococcal infection
60% Streptococcal more
common
Viral
Fungal
Microbacterial

Gonococcal infective In 50% cases joints are heal- Migrating arthralgia, teno-
arthritis: thy sinovitis, arthritis of wrist and
ankle

Gout: 90% cases due to under excre- Clinical types:
tion than overproduction of
uric acid resulting in hyper-
uricaemia. Asymptomatic
hyperuricaemia also occurs.
Secondary gout due to renal
disease, diuretic, low dose
aspirin, cyclosporin, myelo-
proliferative disorders, hae-
molytic anaemia, polycythae-
mia, cyanotic congenital
disease.
a. Primary gout:
• Acute gout of single
joint of foot (first
metatarsal joint) and
ankle.
• Chronic gout: Repea-
ted acute gouty arthri-
tis with chronic joint
deformities and tophi.
b. Secondary gout asso-
ciated with causative
disorders.
c. Pseudogout: Present as
acute monoarthritis or
oligoarthritis or chronic
polyarthritis.
Acute gout: Surgery, dehydra-
tion, fasting, alcohol, meat.
Secondary gout: Dehydra-
tion, eclampsia, diabetic
ketoacidosis, starvation.
Pseudogout: Old age, osteo-
arthritis, neuropathic joint
disease hyperparathyroidism,
haemochromatosis, diabetes
hypothyroidism.
contd...
526 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues
Spondyloarthropathies
Osteoarthritis: Characterised by deteriora-
tion of articular cartilage with
reactive new bone formation
at articular surface especially
as a sequal of trauma, chronic
inflammatory arthritis or
congenital malformation.
Spinal stenosis.
Spondylitis, sacroiliitis, infla-
mmation of tendon insertion
sites, asymmetric oligo-
arthritis + Extra-articular
manifestations: Inflammatory
eye disease, urethritis and
mucocutaneous lesions.
Types:
a. Ankylosing spondylitis:
Found in adult. Inflam-
mation and ossification
of spinal and sacroiliac
joint, hip and shoulder,
fusion of apophyseal
joints of spine (bamboo
spine). Low back pain.
b. Arthritis of inflammatory
bowel disorders (ulcera-
tive colitis and Crohn’s
disease) characterised by
colitis, spondylitis, sac-
roiliitis and arthritis of
knee and ankle.
c. Reiter’s disease:
Common in young men,
associated with HIV
infection, Chlamydia
infection, asymmetric
oligoarthritis, urethritis,
conjunctivitis and skin
mucosal lesions.
d. Dysenteric arthritis: Like
Reiter’s syndrome.
Common in elderly
Joint involved: Distal and
proximal interphalangeal
joints of hand, hip, knee,
cervical and lumbar spine.
Coarse crepitation felt on
moving joint of knee.
DIAGNOSTIC CLUES: LABORATORY FINDINGS
Other Arthritis | 527

Routine Investigations
CBC High Rheumatoid arthritis
ESR Do Ankylosing spondylitis
CRP Do Infective arthritis
VDRL + Syphilis

Specific Investigations
A. Biochemical:
1. Rheumatoid Factor ... Positive in 70-80% of rheumatoid arthritis.
Positive in connective tissue disease and Sjögren arthr.
2. Anti-nuclear antibody (ANB) ... Present in acute and chronic polyarthritis, SLE.
3. HLA B27 ... Positive in ankylosing spondylitis.
4. Uric acid ... High above 8 mg in male and above 7 mg in female in
gout. Normal in 30% patients of gout.
B. Culture
Blood culture ... Positive in septic arthritis.
Bacterial culture ... Throat, urethral, prostatic and rectal culture for
gonococcal arthritis.
C. Joint Fluid Examination:
Appearance: Viscosity Mucus clot WBC count Pre- Protein Sugar
dominant cells
Normal Clear High Good Above 200 Less than 2- Equal to blood
Monocytes 3 g/dl sugar

Non-inflamma- Clear High Good 200-5000 – do – – do –

tory: Monosite
• Osteoarthritis
• Trauma
• Neuropathic

Inflammatory: Cloudy, yellow Low Poor 5000-50000 Above 3 gm 25% less than
• Rh arthritis Urate crystal in Poly above 60% BS
• Gout gout
• Ankylosing S.
• Reiter, psori-
atic, inflamma-
tory vowel dis-
eases
• SLE
• Tuberculous

Purulent: Turbid Variable, usually Poor Above 50000 – do – Above 50% less
low Poly above 80% than blood sugar
contd...
528 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

D. Biopsy:
Joint biopsy Positive in gout
...
Synovial biopsy Monoarthritis
...
Tissue biopsy Vasculitis, poly-
... myositis, sclero-
derma

E. Imaging
X-ray, CT scanning, MRI and Isotope scanning
Symmetrical shadows Asymmetrical shadows Para-articular soft tissue Soft tissue atrophy and
calcification bone reabsorption
1. Soft tissue • Bursal swelling Gout, scleroderma, Raynaud’s phenomenon,
changes: • Soft tissue deposits as osteoarthritis scleroderma, leprosy
Inflammatory in gout
arthritis • Periarticular micro-
crystal deposit in gout
2. Joint space Narrowing due to carti- Ankylosis Loose bodies
widening lage destruction
Early stage of arthritis i. Symmetrical: Infla- End stage of arthritis • Osteoarthritis
with joint distension due mmatory arthritis usually seen in ankylo- • Neuropathic joint
to effusion like Rh. arthritis sing spond. and infective
ii. Asymmetrical: arthritis
Osteoarthritis of
knee
3. Changes in articulating bones
Juxta-articular osteo- Juxta-articular sclerosis Osteophytes Erosion
porosis (Eburnation)
Inflammatory arthritis • Osteoarthritis • OA • Inflammatory and
• Neuropathic joint • Neuropathic infective arthritis
• Psoriatic arthritis • Sharpened articular • Gout
margin and lipping in • Tumour
OA

4. Changes in vertebral column

• Narrowing of intervertebral disk
` space in disk prolapse
• Disk calcification ... Ochranosis, AS
• Osteophytes ... Degenerative arthritis
• Bamboo spine ... Late stage of AS
• Joint fusion ... AS
 • Ligamentous calcification ... AS
Other Arthritis |
529

and ossification
• Demineralisation of vertebral column ... AS
with squaring of vertebral bodies
5. Changes in sacroiliac joint:
Erosion and sclerosis ... AS
6. Cortical bone
Punched out erosion with overhanging rim
of cortical bone ... Gout

TREATMENT OF OTHER ARTHRITIS

General Therapy
Education and emotional factors Rest Special
Explain the disease and fluctua- • Bedrest for inflammed joint at • Osteoarthritis: Mild to moderate
tion. Tell about prognosis. Edu- least for 2 weeks case: Supervised walking prog-
cation of families essential • Gradual increase of activity ramme prescribed.
• Correction and/or prevention of
causative/predisposing factors.
• Weight reduction advised.
• Kneeling, squatting (for knee
arthritis) and heavy weight lifting
(for lumbar spine arthritis)
avoided.
Physical Therapy
Pain relief Exercise Support
Hot compress, immobilisation of • Ankylosing spondylitis: To main- • OA: Cane, crutches and walker
joint by splint or traction or by tain mobility and prevent flexion can support weight bearing joint.
elevation. Hot water bottle or bath, deformity. Regular spinal exten- Wearing soft sole shoe, cervical
paraffin wax bath, infrared and sion exercise in prone position; collar and lumbar corset help.
ultrasound therapy specially in breathing exercise, jogging, • Non-gonococcal infective
OA. cycling, swimming and brea- arthritis: Keep joint in optimal
thing in warm water. position to prevent flexion
• Osteoarthritis: Muscle streng- deformities by slints, slings or
thening exercise. even casts.
• Non-gonococcal infective arthri-
tis: Muscle tightening exercise to
prevent atrophy.
• Tuberculous arthritis: Muscle
strengthening exercise.
530 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

OCCUPATIONAL THERAPY AND REHABILITATION

Physiotherapist should strive for gainful employment and social rehabilitation.

Drugs and Surgical Therapy

Drugs Surgical Therapy
Non-gonococcal Antibiotics prescribed based on smear and culture of joint fluid, • Frequent local aspiration when
infective arthritis blood, urine or other sites of infection. If organisms cannot be synovial fluid rapidly reaccumu-
determined by culture gram staining may help: late.
Bactericidal antibiotics are chosen against staphylococci, • Surgical drainage reserved for
pneumococci and gram negative organisms given IV for 2 septic arthritis of hip because the
weeks, followed by oral therapy for 1-2 weeks. site is inaccessible for repeated
Gram positive cocci Cloxacillin 2 gm t.i.d. or 100 mg/ aspirations when medical therapy
kg per kg per day IV fails.
Gram negative cocci Penicillin 50,000 U/kg 4h IV
Gram negative bacilli → Gentamicin 1.5 mg/kg 8h IM/IV
If no organism detected Piperacillin 50 mg/kg 4h IV
+ Gentamicin
Gonococcal arthritis 5 to 20% cases resistant to penicillin. Usually no joint aspiration needed.
Ceftriaxone 1 gm/day IV or cefotaxime 1 gm IV 8 hourly or
spectinomycin 2 gm IM 12 hourly

When improves, switch on to oral cefixime 400 mg b.d. or

ceprofloxacin 500 mg b.d. for 7-10 days.

Polymyalgia rheuma- Prednisolone 60 mg/day for 1-2 months, then tapered guided
tica by ESR.

Giant cell arthritis: Prednisolone 60 mg/day for 1-2 months and then tapered guided
by ESR.

Reiter’s syndrome: • NSAIDs Bowel resection helpful when

If fails: peripheral joint involved (hip,
Sulfasalazine knee)
• Antibiotics for non-gonococcal sexually transmitted infection.
Tetracycline 250 mg q.d.s. for 3 months for C. trichomatis.
Enteric Reiter’s syndrome do not respond to antibiotics.
If fails to antibiotics: Sulfasalazine 1000 mg b.d.

Arthritis of inflamma- NSAIDs often effective

tory bowel disease If fails: Prednisolone or NSAID + sulfasalazine

Gout I. Acute attack

First treat acute attack, then treat hyperuricaemia.
However, if patient is taking already hypouricaemic drugs,
the same should be continued during acute attack.
A. NSAIDs:
i. Indomethacin : 25-50 mg t.i.d. for 5-10 days.
C.I. Active PU, impaired renal function and
history of allergic reaction
contd...
contd...
Other Arthritis | 531

ii. Ibuprofen : 800 mg 8 hourly, reduced to 400 mg

8 hourly.
iii. Diclofenac : 50 mg 8 hourly, reduced to 25 mg
8 hourly.
iv. Naproxen : 500 mg 8 hourly, reduced to 250 mg
8 hourly after 1-3 days.
v. Piroxicam : 40 mg/day, reduced to 20 mg daily
after 1-3 days.
B. Cox-2 inhibitor, if GI complications occur.
C. Colchicine : 0.5 to 0.6 mg orally every hour till pain
subsides or until nausea or diarrhoea occurs. Usual
total dose 4-6 mg, maximum dose 8 mg.
IV dose reduces GI side-effects. Initial dose 2 mg in
20-50 ml saline given through IV catheter. Two
additional doses of 1 mg each can be given at 6 hour
intervals. Total maximum dose 4 mg and additional
colchicine not given orally for 3 weeks. IV dose C/I
in combined lesions of liver and kidney.
Oral colchicine not used in inflammatory bowel
disease.
D. Corticosteroids: Dramatic improvement in acute
attack. Best reserved for patients unable to take
NSAID.
i. Polyarticular: Methylprednisolone 40 mg/day
tapered off over 7 days or orally prednisolone
40-60 mg/day tapered off over 7 days.
ii. Monoarticular: Intra-articular triamcinolone 10-
40 mg depending on the size of joint.

Psoriatic arthritis: a. NSAID sufficient for mild cases

b. Disease modifying drugs: Methotrexate 7.5 mg per week
in 3 divided dosages with monitoring blood count monthly
and LFT bimonthly. Sulfasalazine, gold, pencillamine,
azathioprine, cyclosporin A, somatostatin, psoralen,
PUVA and fumaric acid.

Ankylosing spondy- a. NSAIDs : Indomethacin 25-50 mg t.d.s., after improve-

litis: ment dose reduced to minimum effective dose.
Side-effects: Headache, giddiness, nausea, vomiting, P.U.,
renal insufficiency, depression, psychosis. Naproxen and
diclofenac also effective.
b. Sulfasalazine 1.5-2 gm/day monitored by blood count and
LFT monthly.
Side-effects: Rash, nausea, vomiting. Only effective in
peripheral arthritis type without spondyloarthritis. If
improvement occurs, continue for 1-2 years.
c. Synovitis of a single joint: Intra-articular steroid bene- End stage deformities needs
ficial. surgery.
contd...
532 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

d. No cure. Avoid steroid and smoking.

a. Acetamenophen (paracetamol) 2.6 to 4 gm/day with or

Osteoarthritis: without dextropropoxyphene 65 mg t.d.s. with or without Indications for surgery:
muscle relaxants (methocarbamol, diazepam) less toxic • Relief of pain
and as effective as NSAID. • Relief of severe disability
If fails: NSAIDs: Ibuprofen 400 mg t.d.s., diclofenac 50 • Failure of conservative therapy
mg t.d.s., piroxicam 20 mg/day. • Correction of mechanical dis-
If fails or GI side-effects: Cox-2 inhibitors . ability
Reduce the dose of NSAID, acetaminophen or Cox-2
inhibitor or given only during exacerbation. Procedures:
b. Intra-articular triamcinolone 20-40 mg in osteoarthritis • For Knee: Osteotomy arthro-
of knee is effective 2-3 times a year may obviate use of desis, arthroscopy debridement,
analgesics. total knee replacement
c. Capsaicin cream 0.025% applied b.d. can reduce knee pain • For Hip: Osteotomy excision
without NSAID. arthroplasty, arthrodesis, total
hip replacement
• Lumbar spinal stenosis: Decom-
pressive laminectomy
• Severe pain: Laminectomy and
• Artificial tears (0.5% hydroxymethylcellulose) spinal fusion
Sjögren’s syndrome: • Oral soothing gel (1% methyl cellulose of glycerine)
• Special tooth paste
• Saline/steroid nasal spray
• Topical vaginal gel
• Oral hygiene to prevent infection
• NSAID
Disease modifying drugs: Steroid, chloroquine, cyclophos-
phamide, azathioprine, methotrexate, cyclosporin.
 Arthritis and Musculoskeletal Disorders
87
Connective Tissue Disorders

DIAGNOSTIC CLUES
Clinical
Systemic lupus Scleroderma Dermatomyositis Polyarteritis nodosa
erythematosus polymyositis
Systemic features: Fever, anorexia weight Fever, malaise Low grade fever, anore- Fever, malaise, weight
loss xia, fatigue and weight loss, limb pair
loss.
Skin and mucosa: • Malar flush (butterfly Thickened skin, pig- Dusky red rash over Palpable purpura, cuta-
rash) mentation, depigmen- malar area like SLE, neous vasculitis livedo
• Discoid rash tation, telengiectasia, erythema over face, reticularis, subcuta-
• Oral ulcer Raynaud’s phenomena neck shoulder, upper neous nodule, skin
in 90% cases, subcu- chest and back. ulcer, digital gangrene
taneous oedema, digital Periorbital oedema,
ischaemia purplish (heliotrope)
suffusion over eyelid

Muscle: Muscle weakness due Proximal muscle weak- Myalgia

to disuse atrophy and ness, occasional tender
myositis and late atrophy

Sex/Age: Female more than male Female more than male Female more than male Female more than male
Adult
Joint: Arthritis Arthralgia Arthralgia Arthralgia

Drugs: Possible association:

Chlorpromazine, hyd-
ralazine, isoniazid,
methyldopa, procaina-
mide, quinidine, beta-
blocker, cemetidine.

CVS: Cardiac failure, arrhy- Heart block, pericardi- AMI, myocarditis, CCF
thmia, hypertension, tis, myocardial fibrosis,
pericarditis right heart failure
contd...
534 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Respiratory system: Pleurisy, pleural effu- Pulmonary fibrosis Aspiration pneumonia Capillaritis, haemo-
sion, bronchopneumo- due to nasal regurgita- ptysis
nia, pneumonia tion

GI tract: Dysphagia, hypomoti- Dysphagia Abdominal pain, nau-

lity of GI tract sea, vomiting

Renal: Glomerulonephritis Renal lesion rare in Haematuria, proteinu-

Indian patient. Renal ria, RBC cast, renal
hypertension, protei- hypertension
nuria

Nervous system: Seizure, psychosis Peripheral neuritis, Seizure, stroke, peri-

carpal tunnel syndrome pheral neuritis

Haematological: Anaemia, leukopenia, Mild anaemia ESR always raised leu-

thrombocytopenia kocytosis

Renal: Proteinuria Proteinuria

Haematuria Cylindruria

Immunological: • LE cell + • ANA 80-95% cases • ANA present in 80- • ANCAs +

• Antibody to native • Rheumatoid factor in 95% cases • Serological tests for
DNA present in 50% 25-33% cases • Rheumatoid factor in hepatitis B or C in 20-
cases • Scleroderma antibody 33% 30% cases
• Antinuclear antibody (SCL 70) present in
(ANA) present in 95- 30% cases
100% cases
• False positive serolo-
gical test for syphilis
• Rheumatoid factor
present in 20% cases

Muscle enzyme: Creatinine phospho-

kinase and aldolase +

Muscle biopsy: Biopsy of clinically

involved muscle show
specific histology

Electromyograph: Abnormal

Biopsy of other tissues: Biopsy of muscle,

nerve, lung, kidney
when involved.

contd...
contd...
Connective Tissue Disorders | 535

Angiography: Aneurysmal dilatation

in renal, mesentery or
hepatic arteries
Cancer scanning: • Search for occult malignancy
not very cost effective
• Ultrasonography of pelvis
occasionally helpful to locate
ovarian malignancy.

TREATMENT OF CONNECTIVE TISSUE DISORDERS

General Supportive Measures
• Adequate sleep
• Adequate bed rest for fatigue
• For depression low-dose tricyclic antidepressant
• Avoid exposure to sun in SLE. Use sun-protection cream. Don’t go to hill station to avoid ultraviolet
light
• To avoid infection dental and urogenital procedure done under antibiotic cover
• Avoid indiscriminate use of antibiotics
• Normal balanced diet with low salt
• Educate about pregnancy and birth control

Physical Therapy
For arthralgia and arthritis in SLE and scleroderma for contracture in scleroderma physical therapy is
required.
Bed rest with assisted active range of movement during active disease is prescribed. More active
exercise prescribed for improving strength once inflammation has subsided.

Symptomatic Treatment

SLE Scleroderma Polymyositis Polyarteritis nodosa

dermatomyositis
Photosensitive rash: • Sun cream
• Protective clothing
• Avoid exposure to sun

Skin lesions: Topical glucocorticoid Pencillamine and

methotrexate

Arthralgia, arthritis and • NSAIDs Periarticular changes:

serositis: • Selective cox-2 inhi- Pencillamine, metho-
bitor trexate
• Avoided in active
nephritis
contd...
536 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Raynaud’s phenome- • Avoid exposure of

non:Due to reversible entire body to cold.
vasospasm: Protect hands and feet
from cold and trauma
• Stop smoking
• Avoid stress
• Avoid drugs causing
vasospasm (Adrena-
line, beta blocker)
Drugs:
See under “Specific
drugs” on page 537
GI complications: • For reflux oesopha-
gitis: H2 receptor
blockers, proton
pump inhibitors and
promotility drugs
(metoclopramide,
bethanochol).
• For oesophageal stric-
ture: Mechanical dila-
tation.
• GI hypomotility: With
bacterial overgrowth:
i. Advise sleeping
with head end of
bed elevated.
ii. Broad spectrum
antibiotics (terra-
mycin and metro-
nidazole).

Local complications: • Rash: Topical cream

• Obstinate ulcer:
hydrocortisone pellet
orally
• Intranasal prep. for
discoid lupus and
local flare of disease

Pulmonary complica- • Standard therapy • Standard therapy

tions: • Steroid for interstitial
pulmonary fibrosis

Cardiac involvement: Standard therapy Standard therapy

SPECIFIC DRUGS
Connective Tissue Disorders | 537

Hydroxychloroquine Steroids Immunosuppressive Drugs for Raynaud’s

drugs syndrome

Dose and preparations: 400 mg/day for 4-6 • Prednisolone 1-2 mg/ i. C y c l o p h o s p h a - • Calcium channel
weeks—then 200 mg kg/day orally (60-80 mide oral or IV. blocker such as nife-
alternate day for pro- mg/day)—tapered by ii. Azathioprine: Ste- dipine (side-effects:
longed period. no less than 10% roid sparing agent. Constipation, gastro-
every 7-10 days. iii. IV immunoglobu- esophgeal reflux).
Indication SLE: Rapid reduction pro- lin for thrombo- • Prazosin (side-effect:
Rash, photosensitivity, duces relapse. cytopenia. orthostatic hypoten-
arthritis, alopecia and • IV pulse of methyl- iv. Plasma exchange sion).
malaise. Not useful in prednisolone 500 mg and plasma-phere- • Sympathetic ganglion
fever, renal, CNS and infusion given over sis against circula- blockade with long
haematological compli- 30 mts 12 hourly for ting immuneco- acting anaesthetic
cations. 3-5 days—then revert mplexes. benefits progressive
to oral drug. Indicated v. Dehydroepiandos- digital ulcer or surgi-
life-threatening glo- terone (DHEA): A cal digital sympathec-
merulonephritis, CNS new agent for mild tomy.
disorders, haemato- to moderate SLE. • Nitroglycerine oint-
logical complications. ment can be applied
• Steroids indicated in along course of digital
patients not respon- artery.
ding to conservative
treatment, rash and
fatigue.
Scleroderma Scleroderma
Benefit only in arthral- For periarticular
gia, myositis and peri- changes: Pencillamine,
carditis. methotrexate.
Dermatomyositis Dermatomyositis
Dosages same as in • IV infusion benefits
SLE, once muscle dysphagia.
enzyme level normali- • Methotrexate or aza-
ses taper dose to main- thioprine given if no
tenance level of 10-20 response to steroid or
mg/day. cannot tolerate side-
Polyarthritis effects of steroid.
Same as in SLE. • Steroid + cyclophos-
phamide initially—
followed by cyclo-
phosphamide only.

Side-effects: Neuropathy, myopathy, Hypertension, oedema, Myelosuppresion, leu-

retinal changes etc. Steroid induced kaemia, CCF, alopecia
myopathy and hypo-
kalaemia in derma
tomyositis.
 Blood
Anaemia
CLASSIFICATION
I. Diminished Production
A. Microcytic
1. Iron deficiency
2. Thalassemia
a. Alpha thalassemia
b. Beta thalassemia
3. Anaemia of chronic infection •
B. Macrocytic
1. Megaloblastic:
a. Vitamin B12 deficiency •
b. Folic acid deficiency
c. Normocytic
2. Nonmegaloblastic
a. Scleroblastic anaemia
b. Aplastic anaemia: Pancytopenia
88
Causes
• Deficient diet
• Decreased absorption
• Increased requirement in pregnancy and lactation
• Blood loss: Gastrointestinal, menstrual
• Haemoglobinuria
Hereditary
Chronic infection or inflammation
• Cancer
• Liver
Pernicious anaemia
• Gastrectomy
• Blind loop syndrome, surgical resection of ileum
• Fish tapeworm
• Pancreatic insufficiency
• Crohn’s disease
• Dietatic insufficiency
• Decreased absorption in tropical sprue, drugs (phenytoin,
sulphasalazine, septran)
• Increased requirement in pregnancy and chronic haemolytic
anaemia
Myelodysplasia, chemotherapy, liver disease myxoedema
• Chronic alcoholism
• Drug toxicity (anti-TB drugs, chloramphenicol)
• Lead poisoning
• Idiopathic
 • Acquired:
Anaemia | 539

• SLE
• Chemotherapy, radiotherapy
• Toxins: Benzene, toluene, insecticides
• Drugs: Chloramphenicol, phenylbutazone, gold salt,
sulphonamides, phenytoin, cabamazepine, tolbutamide
• Pregnancy
• Paroxysmal nocturnal haemoglobinuria
II. Increased destruction
Morphologic changes Other abnormalities Types of haemolytic
in RBC anaemia
• Microspherocytes RBC osmotic fragility Hereditary spherocytosis
• Elliptocytes increased Hereditary elliptocytosis
• Sickel cells Haemoglobin S Sickel cell anaemia
• Target cell Haemoglobin C Haemoglobin C disease
• Fragmented RBC Macroangiopathy (Disseminated intravas-
cular coagulation, haemolyticuraemic synd-
rome, thrombotic thrombocytopenic purpura)
• Spherocytes, Positive Autoimmune haemolytic anaemia
reticulocytosis Coomb’s test • Idiopathic
agglutinated RBC • Acquired: SLE, chronic lymphatic leukaemia,

DIAGNOSTIC CRITERIA OF ANAEMIA:

Microcytic Anaemia
Iron deficiency anaemia
Clinical: • Usually caused by bleeding from Known chronic disease • Geography: Alpha thalassaemia in
GI tract-ulcer, cancer
• Responds to iron therapy
• Smooth pale bald tongue, angular
stomatitis
• Plummer-Vinson syndrome:
dysphagia due to oesophageal
web + koilonychia +
splenomegaly
• Thin and brittle nail
Peripheral blood: • Pica
Microcytic hypochromia
Bone marrow:
Specific lab. Absent bone marrow iron store
findings: And
other findings • Serum ferritin less than
12 microgram/L
• Elevated TIBC
• Low transferrin saturation
Anaemia of chronic Anaemia with haemoglobin defect
infection (Thalassaemia)
southern Asia and China. Beta-
thalassaemia in mediterranean
area (Greek, Italian)
• Splenomegaly, growth failure,
bony deformities (frontal bossing
and prominent cheek bones)
Positive family history
Acanthocytes, target cell tear drop
cells, nucleate RBC abundant
Normal or increased Hypercellular marrow
iron store
• Normal or elevated • In beta thalassaemia HbA or HbF
serum ferritin elevated
• TIBC normal or low • RBC survival diminished
• X-ray skull: Hot-cross-appeara-
nce, widened diploic space and
hair-on-end appearance
540 | Beside Approach to Medical Therapeutics with Diagnostic Clues

MACROCYTIC ANAEMIA
Megaloblastic

Vit. B12 deficiency Folic acid deficiency Non-megaloblastic

Clinical: Glossitis, peripheral neu-
ritis, posterior column
signs, mild icterus
Peripheral blood: Macro-ovalocytes,
hypersegmented neutro-
phils, megaloblasts seen
Bone marrow: Hypercellular, mega-
blasts, giant metamyelo-
cytes
Biochemical abnormali- • Elevated LDH
ties: • Ser. Vit B12 less than
100 pg/ml
• Specific for PA: Hista-
mine fast achlorhydria,
anti-intrinsic factor and
anti-parietal cell anti-
bodies present, gastric
atrophy (stomach
biopsy)
HAEMOLYTIC ANAEMIA
Similar to Vit. B12 defi- • Alcoholics (target cell
ciency except neurologi- present
cal signs absent • Hypothyroidism: Also
associated with perni-
cious anaemia
• HIV treated with zido-
vudine
• Myelodysplasia
Similar to B12 deficiency (bleeding splenome-
gally) cytopenia,
hypercellular marrow,
promyelocyte and
blast cell in peripheral
blood
• Reduced folate level in • Liver disease
RBC or serum • Haemolytic anaemia
• Serum bilirubin inc- • Cytotoxic drugs
reased • Multiple myeloma
• Pregnancy

Sickel cell disease Acquired haemolytic anaemia

Clinical: Growth failure. Acute crisis a. Autoimmune:
(acute pain in chest, abdomen and long
bones). Veno-occlusion leading to splenic
infarct, acute myocardial infarction,
stroke, organ failure (cardiac, kidney)
Investigations: Features of haemolytic
anaemia. Sickel cells: Of 5-50% of RBC.
Howel-Jolly bodies, target cells. Leuko-
cytosis, thrombocytosis. Haemoglobins
85 to 95%.
i. Warm antibody type: Above age
40 yrs; mild jaundice. Positive
direct antiglobulin test
ii. Cold antibody type:
1. Cold haemagglutinin disease
(CHAD): Raynaud’s pheno-
menon; RBC agglutination
occurs while collecting
blood as the temperature is
lowered in the syringe. IgM
antibody present.
 Table 88.1: Summary of abnormalities of RBC in haemolytic anaemia
Anaemia| 541

Abnormalities Congenital haemolytic anaemia Acquired haemolytic anaemia

Sickle cells Sickel cell anaemia

Schistocytes Microangiopathy
Acanthocytosis Abetalipoproteinaemia Severe liver disease
Spherocytes Hereditary spherocytosis Immune warm body type
Target cells Thalassaemia
Haemoglobinopathy (HbC)
Agglutinated cells Cold agglutinin disease

2. Paroxysmal cold haemoglobinuria (PCH): Children acute episode precipitated by exposure

to cold with haemoglobinuria and jaundice.
b. Non-immune: Secondary to infection, drugs (penicillin, cephalosporin, quinine, rifampicin, PAS,
methyldopa), Pb, burn injury.
c. Paroxysmal nocturnal haemoglobinuria (PNH): Adult; nocturnal episode of red urine related to
sleep; mild jaundice, splenomegaly; venous thrombosis, haemolytic anaemia, thrombocytopenia,
leukopenia, decreased leukocyte alkaline phosphatase, aplastic marrow; positive acid HAM test.

TREATMENT OF ANAEMIA
Approach to Treatment
Examine peripheral blood smear:
Hypochromic- Macrocytic- Normochromic-
microcytic normochromic normocytic

Hypochromic-microcytic anaemia: Look for the following:

a. Middle aged females with history of several pregnancies or heavy menstrual loss usually due to
iron deficiency and treated with iron.
b. In males and young adults or postmenopausal females usually due to blood loss with iron loss and
treated with iron.
c. History of bleeding peptic ulcer, gastric cancer, piles and hookworm infection should be treated
with iron. Aetiology should be treated.
d. Patients showing koilonychia, cheilosis pica points to iron deficiency and treated.
e. Dysphagia with koilonychia suggests Plummer-Vinson syndrome and treated with iron.

If there is doubt about a hypochromic anaemia due to iron deficiency arrange for iron studies: Serum
iron level, TIBC, transferrin saturation and bone marrow iron store:

Abnormal Normal or high

Suggests iron deficiency Suggests:
542 | Beside Approach to Medical Therapeutics with Diagnostic Clues

Anaemia of chronic infection Thalassaemia Sideroblastic anaemia

Associated conditions treated and
eleminating aggravating factors,
e.g. marrow suppressing drugs and
steroid used if polymyalgia or
arteritis suspected.
Macrocytic Anaemia
Normochromic-macrocytic
Examine bone marrow
Treated by blood trans- Genetic type needs no treatment.
fusion, splenectomy and Acquired type: Causes are treated;
bone marrow transplant pyridoxin in high dosages (25-100 mg
t.d.s.), folic acid if deficient, treated;
blood transfusion and if iron load
detected, treated with iron chelating
agents.
With reticulocytosis, normoblastic,
hyperbilirubinaemia
Haemolytic anaemia

Megaloblastic marrow Non-megaloblastic Congenital Acquired

Due to vit. B12 and folic (normoblastic) due Suggested by family Due to identifiable
acid deficiency to alcohol abuse, history of anaemia, jaun- underlying disease such
Investigated for the haemolysis dice, gallstone, spleno- as SLE, chronic lympho-
aetiology and treated megaly and history of cytic leukaemia (with
accordingly. therapeutic splenectomy lymphadenopathy) and
Treated according to cold agglutinin disease
causes. (painful acrocynosis)
Treated according to
causes.
Table 88.2: Schilling test
Done by giving IM B12 and radio labelled B12
Conditions accusing megaloblastic anaemia
1. Pernicious anaemia: Giving concurrently B12 + Intrinsic factor, corrects Vit B12 deficiency
2. Bacterial overgrowth in blind loop: Giving antibiotic corrects B12 deficiency
3. Pancreatic insufficiency: Giving pancreatic enzymes corrects B12 deficiency
4. Fish tapeworm: Giving anthelmintic corrects Vit B12 deficiency.
Normocytic Anaemia (Broad type)
Sideroblastic anaemia Haemolytic anaemia Aplastic anaemia

Clinical: Refractory anaemia Pallor, icterus, splenomegaly, a. Pancytopenia without aplastic

a. Hereditary: Child, young adult
b. Acquired: Middle aged and elderly.
Associated with myeloproliferative
disorders and, rheumatoid arthritis and
due to drugs (isoniazid, cycloserine,
chloramphenicol, lead). Bleeding.
↓ b. With reticulocytosis
Investi- • Hypochromic + microcytosis
gations: • Ring sideroblasts, a few target cells
haemolytic facies, ankle ulcer,
pigment gallstones
a. Without reticulocytosis: Due
to haemolytic anaemia asso-
ciated with other disorders:
Infection, folate deficiency
↓ b. Pancytopenia with aplastic
marrow: Due to aleukaemic
leukaemia, myelodysplasia,
hypersplenism (Tropical,
cirrhotic), bone marrow infil-
tration by cancer, lymphoma,
multiple myeloma, myelo-
fibrosis, osteopetrosis, SLE
bone marrow:
contd...
contd...
Anaemia | 543

Sideroblastic anaemia Haemolytic anaemia Aplastic anaemia

stippled RBC, siderocytes in peripheral
blood.
• Bone marrow: Hyperplastic with
predominant macronormoblasts
Specific Haemolytic Anaemias
a. Evidence of excessive RBC
destruction: Raised indirect
bilirubin, urinary urobili-
nogen increased, serum
haptoglobin decreased,
serum LDH raised.
b. Features of increased RBC
production: reticulocytosis,
erythroid hyperplasia of
bone marrow, basophilic
stippling in Pb,
thalassaemia, Heinz bodies
in G-6-PD deficiency.
c. Change in RBC: Sickel cell
in Sickel cell disease, target
cell in thalassaemia, sphero-
cytes in hereditary sphero-
cytosis, elliptocytes in
hereditary elliptocytosis,
Schistocytes (fragmented
RBC) in microangiopathic
disease.
d. Features of intravascular
haemolysis: Haemoglobi-
naemia, haemosiderinuria,
methemalbuminaemia.
↓
i. RBC indices: Normochro-
mic normocytic
ii. Peripheral blood: Reticulo-
cytopenia; pancytopenia,
thrombocytopenia
iii. Bone marrow: Markedly
hypocellular, megakaryo-
cytes, iron store normal.
↓
Certain other aplastic anaemias
a. Fanconis anaemia:
Abnormalities:
• Skeletal (hypoplastic or
absent thumb)
• Neurological (micro-
cephaly, micropthalmia and
mental retardation)
• Renal malformation
• Patchy hyperpigmentation
of skin.
b. Red cell aplasia:
• Congenital
• Acquired: Associated with
thymoma.

Hereditary spherocytosis G-6-PD deficiency Sickel cell disease Acquired haemolytic anaemia
Clinical: Jaundice, Acute haemolytic
splenomegaly, pigment gallstone. anaemia
Inherited as autosomal dominant

TREATMENT OF INDIVIDUAL ANAEMIAS

Iron Deficiency Anaemia
I. Correction of iron deficiency and replenishing body iron store:
Iron Preparations
Oral Parenteral
Indications: Majority of cases respond to oral Very few indications of parenteral therapy:
iron therapy i. Patient not tolerating oral iron
ii. Refractory to oral iron
iii. Patient needing repeated periodic parenteral
iron due to excess chronic blood loss not
preventable by oral iron therapy
544 | Beside Approach to Medical Therapeutics with Diagnostic Clues

iv. Patients with GI diseases (P.U., ulcerative

Forms: Ferrous form (ferrous sulphate,
ferrous gluconate, ferrous
fumarate) better than ferric form.
Iron in the form of haemoglobin is
not more advantageous and more
expensive.
Dose: Ferrous sulphate 25 mg t.d.s. given
at bedtime better in a single dose
after food. Better absorbed if given
with vit. C and fructose but vit. C
is expensive.
Duration of Haemoglobin normalises in about
therapy: 6-8 weeks. To replenish body iron
store therapy has to be continued
for 6 months.
Advantage: Oral iron safer and cheaper
colitis) which may be aggravated by oral iron.
Iron dextran (imferon)
a. IM: Given by “Z” track technique to prevent
staining of skin at injection site. Before giving
IM a test dose (small dose) should be given
imferon (50 mg/ml) 2.5 ml injected IM into
each buttock (Total 5 ml = 250 mg of iron)
daily
b. IV: IV iron dextran 1:20 dilution in saline (not
in dextrose), total dose given 20 drops/minute
after 5 minutes if no side-effect then the rate
is increased to 40-60 drops per minute
Calculation of total dose:
Iron to be injected (mg) = (15–patient’s weight
in gm/dl) × 3
Parenteral iron has more side-effects and
costilier.
Anaphylaxis (rare), fever, joint pain, nausea,
vomiting, diarrhoea, abdominal pain,
backache, skin rash, lymphadenopathy

Disadvantage: Nausea, vomiting, epigastric

side-effects discomfort, constipation, diar-
rhoea, anaphylaxis rare. GI side-
effects lessened by starting with
smaller dose with gradual increase
in the dose or given after meals.
Failure of: Causes:

Response to i. Non-compliance
oral iron ii. Non-absorption of iron (rare)
iii. Prolonged GI bleed exceeding rate of new erythropoesis
II. Treatment of underlying causes: Hookworm infestation, PU, pile and other causes of occult blood
should be treated.
III. Prevention:
i. Fortification of food item such as salt with iron
ii. Mases treatment of hookworm infestation in endemic areas.
iii. Iron supplement is essential for first 3 year of life and during pregnancy.
APLASTIC ANAEMIA: TREATMENT
Anaemia | 545

I. Specific Treatment
A B
Mild to moderate cases with slow progression Severe cases with rapid progression (Neutrophil:
• RBC transfusion and platelet transfusion given Less than 500 platelets: Less than 20000 reticulo-
as necessary. cyte: Less than 1% bone marrow cellularity: Less
• Antibiotic for infection. than 20%)
• Identification and removal of causative agent. 1. When compatible donor (HLA mediated
• Androgen (oxymetholone, fluoxymesterone, sibling) not available and patient is above
nandrolone decanoate): Oxymetholone (2-4 50 years:
mg/kg per day orally. Injectable form of a. IV antithymocytic globulin (ATG) 15 mg/
testerone enanthate (5-8 mg/kg once weekly). kg/day for 8-10 days + cyclosporin A
5-10 mg per kg per day orally. ATG must
Disadvantages Advantages be used in combination with corticosteroid
side-effects (prednisolone 1-2 mg/kg/day initially with
Masculinisation with • Improves haematocrit rapid tapering).
hirsutism, acne, fluid • Lessens transfusion
b. Antilymphocytic globulin (ALG) with or
retention, hepatocellular requirement
without androgen or high dose of cortico-
carcinoma and clitoral • Stimulates bone
steroid (Methylprednisolone 100 mg/kg
enlargement. Oral agent marrow within 3-6
per day over one or two week period).
can cause cholestatic months
c. Granulocyte-macrophage colony stimu-
jaundice also.
lating factor or granulocyte colony stimu-
lating factor given as continuous infusion
for two weeks in aplasia due to myelotoxic
drugs or aplastic anaemia in children or
with predominant neutropenia.
d. Aplastic anaemia due to SLE:
Prednisolone + plasmapheresis
2. When compatible donor is available and the
patient is young adult:
a. Allogenic bone marrow transplant
b. Blood transfusion
c. ALG

II. General Measures

• Suppression of menses by drugs
• Avoidence of aspirin and anti-platelet drugs
• Low dose prednisolone (10-15 mg) decreases capillary bleeding in severly thrombocytopenic
patients
• Strictly follow aseptic technique in IV infusion. Avoidance of IM injection.
546 | Beside Approach to Medical Therapeutics with Diagnostic Clues

Hereditary Spherocytosis
Moderate to severe cases Very mild cases
• Splenectomy: Eliminates site of haemolysis Splenectomy not necessary
• Unsplenectomised patient should receive folic acid
mg/day for sustain erythropoesis
• Pneumococcal vaccine given prior to splenectomy and oral
penicillin prophylaxis given postsplenectomy to avoid sepsis

Paroxysmal Nocturnal Haemoglobinuria

Mild to moderate cases Severe case
a. Erythropoesis enhanced by: • Allogenic bone marrow transplant
• Iron • Saline washed RBC given through leukocyte filter
• Folic acid • Folic acid supplement and iron replacement
• Androgen: Oral oxymesterone 5-50 mg • Androgen, steroid and antithrombotic drugs are
or IM nandrolone decanoate 25-200 mg occasionally used.
once weekly.
b. Prednisolone alternate day reduces haemolysis. Prolonged administration
with low dose required.

G-6-PD Deficiency
No specific treatment available.
• Stoppage of offending drugs specially sulpha, primaquine, pamaquin, nalidixic acid,
chloramphenicol, nitrofurantoin, dapsone, etc.
• Maintenance of high urine output and, if required haemodialysis.
• Jaundice in neonatal patient if severe may need phototherapy and exchange transfusion.

TREATMENT OF SICKEL CELL DISEASE

No specific treatment available.
A. Management of specific complications
Infection Transfusion Pain management Management of crisis
Acute painful crisis Acute vasospastic
crisis
Prophylactic penicillin • Used to treat all com- • Analgesic • Elimination of preci- • Exchange transfusion
Immunisation: Against plications. • Ensure fluid sup- pitating factor • Cytotoxic drug
pneumococci, H. influ- • Suppresses HbS plement • Infection treated hydroxyurea (500-
enzae and hepatitis B Disadvantages: • Identify aetiology • Ensure hydration 700 mg/day)
recommended a. Transmission of especially infection. • Oxygen: For Increases HbF by
Proper management of viral disease hypoxia (due to stimulating
febrile patient. b. Iron overload chronic pulmonary erythropoesis (HbF
c. Allo-immunisa- disease) monitored milder than HbS)
tion. by arterial PO2.
Hence take advice of a
haematologist
B. General management
Anaemia | 547

• Treatment of pain
• Prevention of dehydration
• Treatment of fever and infection
• Supplements: Adequate caloric intake, folic acid, vitamin C and vitamin E, zinc.
C. New therapies
• Hydroxyurea: Induces HbF synthesis which is a milder form of sickel disease. Decreases
frequency of vaso-occlusive episodes
• Benefitted by erythropoetin or butyric acid
• Bone marrow transplant
• Gene therapy.
D. Prevention
a. Genetic counselling: Can alert the couple at risk about the possibility of having affected offspring.
b. Prenatal diagnosis: Alert the couple for pregnancies at risk.

I. Treatment of Congenital Haemolytic Anaemia

A. Congenital
• Hereditary spherocytosis • Acquired autoimmune haemolytic anaemia
• Hereditary elliptocytosis • Cold agglutinin disease
• Paroxysmal nocturnal haemoglobinuria • Paroxysmal cold haemoglobinuria
• G-6-PD deficiency • Immune haemolysis due to drugs
• Sickel cell disease • Microangiopathic haemolytic disease

II. Treatment of Acquired Haemolytic Anaemia

A. With warm antibody: Initial treatment: Prednisolone 1-2 mg/kg/day in divided dosages. Monitored
by haematocrit (raised), haemoglobin (raised) and reticulocyte count (decreased) and if satisfactory
taper the dose 5-15 mg/day or 10-30 mg alternate day.
If prednisolone ineffective:
Splenectomy advised if reduced RBC survival found in spleen
If ineffective: Refractory cases:
a. Azathioprine 50-200 mg/day or cyclophosphamide 60-150 mg/day
b. Or IV gammaglobulin 500 mg/kg/day for 1-4 days
Advantage Disadvantage
Highly effective in controlling haemolysis • Benefit is short lived
• Very expensive
c. Or Danazol
d. Blood transfusion: Reserved for life-threatening anaemia or significant hypoxia.
Difficulties
• Transfused RBC may be rapidly destroyed
• Both grouping and cross matching difficult due to presence of antibodies.
Slow administration of least incompatible blood is advised.
548 | Beside Approach to Medical Therapeutics with Diagnostic Clues

B. Cold agglutinin disease:

Severe cases Mild cases
a. Steroids and splenectomy often ineffective Avoidence of cold exposure.
b. Chlorambucil is effective: 2-4 mg/day Protective clothing in cold weather, use of
c. High dose immunoglobulin (2 gm/kg may be leather glove and stocking or moving to a
effective temporarily temperate climate is advised.
d. Interferon may be effective for some patients
e. Blood transfusion: Rarely necessary. Indicated in critically ill patients with tachycardia, angina,
CCF, cerebral hypoxia with confusion and responding to bed rest and oxygen
C. Paroxysmal cold haemoglobinuria:
• Avoid cold exposure
• If chronic: Steroid and cyclophosphamide may benefit.
D. Microangiopathy
• Withdraw offending drugs
• Treat infection with antibiotics
• RBC transfusion or platelet pack needed
Vigorous plasma exchange induces dramatic remission.

Treatment of Thalassaemia
Moderate to severe case

Hb H Severe case Thalassaemia Mild case

intermedia
With microcytosis: • Folate supplement. a. Regular blood Most difficult (Alpha thalas-
Supplemental iron • Avoid oxidative transfusion to to treat. Needs saemia trait, beta
drug such as sulpha maintain Hb at careful judgement thalassaemia
10-14 gm/dl regarding trans- minor)
Iron chelation for fusion, iron
iron overload chelation and
splenectomy
↓
Iron chelation:
Desferrioxamine:
Advantages Disadvantages Dose
• Free of serious • Must be given • Subcutaneously:
side-effects, permanently. By using an infusion
cardiac disease • Very short pump over 8-10 hrs/day,
delayed, reversal half-life 5 days a week. Forms
of CCF standard chelation
therapy.
• IM: 1.5-2 gm b.d. or t.d.s.
• IV in CCF
Treatment of Megaloblastic Anaemia
Vitamin B12 deficiency
General management: Severe anaemia (Less than 4 gm/dl) Same as vit B12
treated by packed RBC given slowly
(15 drops to 30 drops/minute). Before
transfusion collect sample for Vit B12
and folic acid estimation.
Preparations and dose: a. Vit. B12 IM or deep subcutaneous:
100 microgram/day: 1st week
100 microgram weekly for first
month
100 microgram monthly for life
indicated if patient not wanting
parenteral
b. Oral cobalamine: 1000 microgram
per day and continued indefinitely.
Response to therapy: i. Haematological improvement
occurs
ii. Neurological features of short
duration (6 months) also
improve. Neurological features
do not improve if persist for
beyond 12 months.
Treatment of cause: i. Expulsion of tapeworm
ii. Improvement of vegan diet
iii. Surgical correction of intestinal
stagnant loop
Prophylaxis: Vit. B12 given from time of operation i.
after total gastrectomy or after ileal
resection if B 12 absorption test ii.
postoperatively point to malabsorption
of vit. B12
Precautions: In severe anaemia in whom there is
no clear indication as to which
deficiency present, it is better to give
both B12 and folic acid.
Anaemia | 549
Folic acid deficiency
Folic acid 1 mg/day for 2 months.
Large dose (5 mg t.d.s.) in severe
malabsorption
Indications for long-term folic acid
therapy:
i. Severe haemolytic anaemia
(Sickel cell, thalassaemia major)
ii. Myelosclerosis
iii. Gluten-induced enteropathy
when gluten-free diet not effec-
tive.
Haematological improvement occurs.
Response delayed if there is infection
or the patient has already received
blood transfusion.
To all pregnant women: Folic
acid + iron
Patient undergoing regular
haemodialysis
iii. Premature infants (less than
1.5 kg)
iv. Parenteral nutrition
Folic acid should not be given alone
in megaloblastic anaemia until vit B12
excluded since folic acid precipitate
neurological change by aggravating
methionine deficiency in the brain.
 Blood
89
Leukaemias

DIAGNOSTIC CLUES
Clinical Laboratory Findings
Acute leukaemia Symptoms: Short duration of symp- Cytopenia or pancytopenia, more than
toms including fatigue, fever, and 30% blast cells in bone marrow and
bleeding (from skin, mucosa, epistaxis blast cells in peripheral blood is 90%
or menorrhagia) and infection
Signs: Purpura, petechiae, variable
enlargement of liver, spleen and lymph
nodes. Sternal tenderness.

Chronic myelogenous Symptoms: Fatigue, night sweats and • Strikingly elevated WBC above
leukaemia: low grade fever 150,000/L
Signs: Splenomegaly (often markedly • Markedly left-shifted myeloid series
so, sternal tenderness) but a low percentage of promyelo-
cytes and blast cell (less than 5%)
• Leukocyte-alkaline phosphatase
low (in leukocytosis due to infection
leukocyte-alkaline phosphatase
increased)
• Presence of philadelphia chromo-
some
• Bcr-abl gene found in peripheral
blood by molecular technique.

Chronic lymphocytic Symptoms: • Lymphocytes above 5000/L

leukaemia: • Older patients • Elevated WBC
• Fatigue • Bone marrow infiltrated with small
Signs: lymphocytes
• Lymphadenopathy • Immunophenotype of CLL is unique
in that it co-expresses B lymphocyte
lineage markers such as CD19 with
T lymphocyte marker CD5.
• Pancytopenia
Hairy cell leukaemia: Clinical symptoms:
Leukaemias

• Hairy cell present on blood smear

| 551

• Middle aged men and bone marrow biopsy

• Fatigue
Signs:
Splenomegaly (often massive)

TREATMENT OF LEUKAEMIA
Chronic Myeloid Leukaemia
Treatment is based on the three phases of the natural history of disease:
1. Chronic phase with leukocytosis
2. Accelerated phase (Leukocyte count resistant to control with busulphan and hydroxyurea; more
than 5% blast cells in peripheral blood, more than 20% blast cells plus promyelocytes in marrow;
persistent or increasing splenomegaly and unexplained fever)
3. Blastic or terminal phase (Blast cells more than 30% in peripheral blood and marrow).
1. Chronic phase:
a. Drugs
Single drug therapy
Drugs Dose Monitoring Response Side-effects and Comment

Hydroxyurea: Started at 2 gm/daily Adjusted to keep WBC WBC count decreases, Side-effects rare but
PO, usual maintenance count near 5000/L. spleen becomes smaller, includes rashes, mouth
dose 1.0-1.5 gm daily symptoms disappear. ulcer, GI symptoms. Does
Given without inter- not eradicate cells with Ph
ruption because WBC chromosome. Also useful
count rises within days in patients who cannot
after discontinuation. tolerate interferon alfa.
Busulfan: 4 mg/day WBC count monitored Clinical improvement, • Pancytopenia, if treat-
In the early stage give weekly and never allow Hb rises, WBC count ment not stopped, bone
allopurinol 400-600 mg to fall below 15 × 109/L falls within a few weeks irreversibly damaged
daily with copious fluid and maintain near of starting treatment. • Pigmentation in patients
to avoid hyperuricae- normal count by giving on busulphan more than
mia. 1-2 mg on alternate day. two years
• Amenorrhoea
• Interstitial pulmonary
fibrosis, reversible if
recognised early and
steroids help.

Recombinant Normalisation of blood Early side-effect: Influ-

alpha interferon: 5 million units/m2 count and marrow in 35- enza-like febrile reaction
85% of patients. suppressed by paracetamol.
Late side-effects: Anorexia,
weight loss, neurotoxicity,
Parkinsonian syndrome and
immune thrombocytopenia
occurs in 10% cases.
552 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

b. Combination Therapy
i. Combination of interferon with low dose cytarabine may be more effective than interferon
alone.
ii. Many haematologists start with hydroxyurea, then switch to interferon alfa once symptoms
relieved and WBC count restored.
iii. Intensive combination therapy: It has been used in an attempt to induce Ph-negative haemopoiesis
and in the hope of eradicating the Ph-positive clone which has been achieved in about one-third
of patients by using cycles of combination chemotherapy similar to those used in acute leukaemia.
However, the effect is usually transient and intensive therapy delay blast transformation or
prolong survival.
c. Leukopheresis: It has been used in reduction of leukocyte count, symptomatic improvement and
reduction in splenomegaly. But this treatment has not been shown to have any effect on long-term
survival.
d. Splenic irradiation or splenectomy
Indications
Refractory cases or terminally ill patients with marked splenomegaly
Disadvantages
No significant effect on survival, nor the quality-of-life
e. Bone marrow transplant: The only available curative therapy is allogenic bone marrow
transplantation.
Requirement
Allogenic HLA matched donor
HLA matched sibling: HLA matched unrelated donor:
Young adult (under 60-yr) Young adult (under 60-yr)
60% have long-term Results are inferior to those achieved
disease free survival in sibling transplant
following BMT
Beneficial response
• Cures by initial cytoreduction followed by long-term immunologic control mediated by donor’s
immune system
• The chronic phase disease which has recurred after allogenic transplantation can usually be
reversed without additional chemotherapy by the infusion of T lymphocytes from the initial
donor (“Donor lymphocyte infusion”)
• Probability of 3 year survival is 50% for recipients in chronic phase.
f. Recent drugs: Experimental oral agent: STI 571 has recently been reported to produce remarkable
results in chronic myeloid leukaemia. This inhibits the tyrosine kinase activity of the bcr-abl oncogene.
It has excellent tolerability, low toxicity and excellent control of the disease even in advanced form.
2. Accelerated Phase
• Responds temporarily to oral hydroxyurea or busulphan
• Splenectomy only fascilitates treatment in patients with thrombocytopenia and progressive
myelofibrosis.
• The result of BMT is poor.
3. Blastic or Terminal phase: Highly resistant to treatment and usually fatal.
The result of acute myeloid leukaemia is poor. Response rate ranges from 10-30%.
Prognosis
Leukaemias | 553

Therapies Survival rate

Past treatment 3-4 years
Interferon based 5-6 years
STI 571 Further increase in survival rate.

TREATMENT OF CHRONIC LYMPHOCYTIC LEUKAEMIA

Asymptomatic patients warrant therapeutic interference. Complete remission is rare and aim is to control
symptoms and improve the quality-of-life rather than cure the disease.
Indications for treatment:
Symptoms Signs Investigation Complications
Systemic symptoms Increasing Marrow failure Haemolytic
Progressive fatigue lymphadenopathy anaemia and
immune thrombocytopenia
I. Early indolent asymptomatic stage: Treatment not needed
II. Late stage I, II, III, IV (Progressive and symptomatic stage):
A. Drugs
Drugs Dose Monitoring Advantages Disadvantages Comment
Chlorambucil 0.6-1 mg/kg PO Regular blood Convenient, effec- 80% respond less May be combined
every 3 weeks for count every 2-3 tive and well-tole- well immunosup- with steroid.
6 months week rated. pression. Intermittent treat-
Stopped tempo- In 20% good result ment produces
rarily if low platelet lymph node impal- less immunosup-
count and reintro- pable and blood pression: Given
duced at a lower count normal. 0.2 mg/kg/day in
rate cycles of 10-14
days, followed by
a two week
interval.
Fludarabine IV 5 days a week Higher response No improvement
once month for 4- which is long in survival. Second
6 months lasting line therapy.
Long lasting imm-
unosuppression.
Chemotherapy + New experimental
antibody directed treatment
against antigen
expressed by CLL

B. Bone marrow transplant: The rare young patient with aggressive CLL may require allogenic bone
marrow transplant.
C. Splenectomy: Indications
i. Autoimmune haemolytic anaemia and immune thrombocytopenia resistant to steroid
ii. For controlling resistant symptoms.
iii. Gross splenomegaly may be dominant feature of the disease.
554 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

D. Radiotherapy: It may be useful to control localised lymphadenopathy/which has not responded

to chemotherapy.
E. Treatment of complications:
Autoimmune haemolytic anaemia and
immune thrombocytopenia
• Steroid: If needed prolonged steroid treatment
for control, splenectomy should be considered,
if the general condition is fit for operation
• RBC and platelet transfusion
Infection
• Should be treated promptly
• Regular intravenous infusion of normal
human immunoglobulin (400 mg/kg
3 weekly for one year) has been shown to
reduce minor bacterial infection

Hairy Cell Leukaemia (Indolent cancer of B lymphocytes)

Diagnostic Clues
Clinical Laboratory investigations
• Splenomegaly, often massive • Pancytopenia
• Liver enlargement in 50% cases • Hairy cells present on blood
• Middle aged men smear and bone marrow biopsy
• Recurrent infection

Treatment of Hairy Cell Leukaemia

Older treatment
Efficacy
• Alpha interferon In 20-30% cases response rate 70-80% with 5 year
disease free survival. Rarely used now.
• Splenectomy Rarely done now.
New agents
Drugs Advantages Dose Side-effects
Cladribine • Benefits 90% patients Administered • Leukopenia
(2-chlorodoxy- • Relatively non-toxic fortnightly • Neutropenia
adenosine-CDA) • Complete remission for 5-7 months • Infection
in above 80% cases

Lymphomas (Cancer of lymphocytes)

Diagnostic clues Clinical Lab. investigations
Hodgkin’s disease • Age: 2 peaks 20-yr, over 50-yr • Lymph node biopsy
• Painless lymphadenopathy: Isolated • Tissue biopsy
or widespread, commonly in neck. Pain • Chest X-ray for mediastinal
in lymph node following alcohol ingestion lymphadenopathy
• Constitutional symptoms: Fever, • CT scan of abdomen and pelvis
drenching night sweat, weight loss, for lymph gland enlargement.
generalised pruritus
Non-Hodgkin’s • Lymphadenopathy – Do –
Leukaemias | 555

lymphomas • Fever, night sweat, weight loss

• In Burkit’s lymphoma pain in abdomen
and abdominal fulness.

TREATMENT OF HODGKIN’S DISEASE

Depends upon the staging of the disease
Staging Treatment
Stage I and II
(Stage I: One lymph node region Radiation therapy
involved; Stage II: Two lymph node
areas on one side of diaphragm
involved)
Stage III and IV: Best treated with combination therapy:
(Stage III: Lymph node Regimen Comments
regions involved on both a. Doxorubicin (adria- More effective and less
sides of diaphragm: mycin) + Bleomycin toxic that MOPP
Stage IV: Disseminated + Vincristine + Daca- regimen
disease with bone marrow rbazine (ABVD)
and liver involvement). Or
b. Mechlorethamine +
Vincristine + Pro-
carbazine + Predni-
solone (MOPP)

Treatment of Non-Hodgkin’s Lymphomas

I. Drugs. Depends upon the stage of the disease.
Chemotherapy
Staging and severity Treatment
A. Low grade lymphomas:
i. With limited disease with Because this disease is not curable with
only one abnormal lymph node standard chemotherapy, treatment can be delayed
until the patient is symptomatic (“watch and
wait”). Localised radiation is preferred.
B. With disseminated disease:
i. Asymptomatic and dis- No initial therapy is required. Some patients
ease not bulky: have spontaneous remission and treatment may be
deferred for 1-3 years.
ii. Symptomatic patients: Chlorambucil, 0.6-1 mg/kg every 3 weeks
or
Cyclophosphamide + Vincristine + Prednisolone (CVP)
or
Fludarabine
556 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

or
Chlorambucil + Monoclonal antibody (Rituximab)
directed against the B cell surface antigen.
This combination is very effective in relapsed cases.
C. Intermediate grade:
(diffuse large cell lymphomas)
i. With localised disease: Treated with short course chemotherapy:
Three courses of cyclophosphamide, adriamycin
vincristine and prednisolone (CHOP)
+
Localised radiation
ii. With more advanced disease: Treated with 6-8 cycles of CHOP
D. High grade lymphomas Combination chemotherapy with CNS prophylaxis
(Burkitt’s lymphoma): if CSF is free of tumour cells.
With CNS and bone involvement
II. Allogenic transplantation:
Indications:
i. Occasionally young patients with clinically aggressive low grade lymphomas.
ii. Some patients with high-risk lymphomas are treated early in their course.
 Blood
90
Haemorrhagic Disorders

Aetiological Classification
I. Platelet Disorders:
1. Thrombocytopenia:
a. Decreased platelet production:
• Marrow infiltration by malignant cells, myelofibrosis
• Marrow hypoplasia by radiation, drugs, viruses, alcohol
b. Increased destruction:
• Idiopathic thrombocytopenic purpura (ITP)
• Drug induced thrombocytopenic purpura (DTP)
• Post-transfusion purpura
• HIV infection
c. Increased consumption:
• Thrombotic thrombocytopenic purpura (TTP)
• Disseminated intravascular coagulation (DIC)
• Haemolytic-uremic syndrome
• Cardiopulmonary bypass
2. Thrombocytosis:
a. Essential thrombocythaemia
3. Qualitative platelet disorders:
a. Drugs: Aspirin, ethanol, NSAIDs, ticlopedine,
b. Uraemia
II. Coagulation disorders:
a. Inherited: Haemophilia
von-Willebrand’s disease
b. Acquired:
• Vitamin K deficiency
• Liver disease
• DIC

Thrombocytopenia
Diagnostic Clues: Clinical approach for finding aetiology:
Thrombocytopenia (below 100,000/microlitre, in severe case below 20,000/microlitre) with or without
558 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

bleeding (epistaxis, oral bleeding, menorrhagia, renal bleeding, purpura, petechiae, echymoses) +
prolonged bleeding and poor to absent clot retraction + anaemia

With spleen enlarged Spleen not enlarged

Bone marrow aspiration and Bone marrow aspirates and
biopsy biopsy

Normal marrow Abnormal Abnormal marrow Normal marrow

Causing marrow With decreased mega- With accelerated destruction of
sequestration • Leukaemia karyocytes due to platelets
of platelets: • Lymphoma defective production With microangiopathic haemolytic
Causes: of platelets: anaemia (reticulocytosis, fragmented
• Congestive • Aplasia RBC, bilirubin +,Coombs’ test
splenomegaly • Myelofibrosis negative
• Portal hyper- • Malignant cell
tension infiltration With coagulation Without coagulation
• Splenic tumour • Storage disease disorders disorders
(Macrophase infil- Disseminated • Haemolytic
tration) intravascular uremic synd.
• Drugs (myelo- coagulation (renal failure)
suppressive drugs, (DIC) • TTP (acutely
ethanol, oestrogen) (Hypofibrino- ill with fever,
• Virus infection- genemia, pro- renal failure,
HIV longed proth- confusion,
• Radiotherapy rombin time, aphasia coma,
fibrin degrada- elevated LDH)
tion products). • ITP: Acute in
DIC: (Under- child and chro-
lying serious nic in adult; in
illness especially pregnancy and
sepsis, severe neonates; anti-
tissue injury, platelet anti-
head injury, body in 75%
burn, obstetric cases but not
complication, done routinely
cancer and • Virus infection
major haemo- • Drugs:
lytic transfusion Novobiocin,
reaction; blee- PAS, quinine,
ding; throm- anticonvulsant
bosis-digital methyldopa,
ischaemia and heparin.
gangrene). • Prosthetic
cardiac valve
Treatment of Idiopathic Thrombocytopenic Purpura (ITP)
Haemorrhagic Disorders | 559

I. Chronic ITP of Adult: Flow Chart:

Initial treatment with prednisolone:
Dose Response Monitoring
High dose 1-2 mg/kg/d continued Bleeding stops on day 1, platelet By platelet count
until platelet count normal—then count rises within a week. 80%
tapered and keep on maintenance respond.
dose to avoid splenectomy.
⇓
If prednisolone fails:
Splenectomy (most definitive treatment) is advised:
Other indications Preoperative Postoperative Response
• Risk of intra- Pneumococcal, Soon after surgery 80% responds
cranial bleeding meningococcal platelet count Relapse
as indicated by and H. influenzae shoot up causing Restart predni-
haemorrhagic vaccine given 2 thrombotic episode solone
bleb in mucosa, weeks before needing antipla-
retinal haemor- splenectomy. telet drugs and
rhage and very heparin. In some
low platelet count cases small dosa-
• Side effects of ges of steroid may
steroid be required.
• High dose of
steroid needed for
maintenance
• Pregnancy with
ITP where steroid
and immunosup-
pressive treat-
ment unsuccess-
ful. ⇓
Patients who do not respond to steroid and splenectomy:
Danazol is prescribed:

Dose Response
100-300 mg/d. After control Improves 50% cases
of acute episode, danazol may be
given as a maintenance dose for
2-3 months. May be combined
with steroid.
Refractory Cases
1. Anti-Rh-D immunoglobulin 25 microgram/kg IV on 2 consecutive days effective especially in
Rh-D positive individuals.
560 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

2. Immunosuppressive drugs: Vincristine, vinblastine infusion, azathioprine, cyclosporin and

cyclophosphamide. May be combined with steroid. They are contraindicated in pregnancy.
II. Life-threatening haemorrhage or severe thrombocytopenia (below 10000/microlitre)
Hospitalisation is essential.
Emergency measures:
• Methylprednisolone IV 1-2 gm q.d. for 3 days
• High dose IV immunoglobulin:
Dose Indication Advantages Disadvantages
400 mg/kg/d for • Bleeding emergencies • Benefits 90% cases • Expensive
3-5 days • Preparing a severely • Platelet count rises • Benefit lasts only
thrombocytopenic within 1-5 days 1-2 weeks
patient for surgery
• Platelet transfusion reserved only for life-threatening bleeding since exogenous platelets
will survive no better than the patients’ own and will survive less than a few hours.
III. Treatment of ITP under special circumstances
Pregnancy Neonatal Drug induced
thrombocytopenia thrombocytopenia
• IV immunoglobulin given Has benign course in 90% • Withdrawal of offending drug
during last trimester to prevent cases and spontaneous • Platelet transfusion in severe
neonatal thrombocytopenia recovery is the rule. cases
• IV methylprednisolone 1 gm/day • Corticosteroid arrests platelet
given for 3 days effective in destruction
many cases • IV immunoglobulin given if
⇓ thrombocytopenia is life-
If medical therapy fails: Emergency threatening.
splenectomy may have to be carried
out and caesarean section may also
have to be taken simultaneously.

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

I. A medical emergency and admitted in ICU for: Emergency plasmapheresis:
Dose Duration Additional treatment Response
60-80 ml/kg of Continued for at least i. Methyl prednisolone • 90% recover completely.
plasma removed 5 days or for 2 days 200 mg IV Neurologic abnormalities
and replaced after normalisation of ii. Antiplatelet agents: completely reversed.
with fresh platelet count and LDH Aspirin 325 mg/day • 20% cases relapse and
frozen plasma. and resolution of neuro- and dipyridamole become chronic.
logical signs and improve- 100 mg hourly but bene-
ment in microangiopathy. fit is not conclusive.

II. Patients not responding to plasmapheresis and have rapid recurrence.

• Splenectomy, or
• Combined splenectomy + Glucocorticoid + Dextran
Treatment of other Causes of Thrombocytopenia
Haemorrhagic Disorders | 561

Haemolytic-Uremic Syndrome
Children Adult
• Self limited Treatment of choice is large volume
• Conservative management of acute renal failure plasmapheresis with fresh frozen
replacement (exchange of upto 80 ml/kg),
repeated daily until remission is achieved
Prognosis:
Without effective therapy:
• Death occurs in 40% cases
• 80% develop chronic renal insufficiency.

Hypersplenism
a. Treat underlying conditions
b. Indications for splenectomy:
• If cause of splenomegaly is not remediable
• If splenomegaly is symptomatic
• For diagnosis in idiopathic splenomegaly

Thrombocytosis
Platelet count rises above 500,000/microlitre.
Causes:
Essential thrombocythaemia Reactive thrombocytosis
Diagnosed by Due to:
• Excluding causes of reactive thrombocytosis • Splenectomy
• Absence of Philadelphia chromosomes in bone marrow • Iron deficiency
Slightly predisposes to bleeding and thrombosis • Chronic infection
• Chronic inflammation
• Malignancy
Management: No risk of bleeding and thrombosis
Clinical situations Treatment
• Usual cases: a. Daily aspirin (81-325 mg/dl)
b. Anagrilide or hydroxyurea reduces platelet count
Management of cause
• Pregnancy or child bearing years: Interferon-alpha
• Age above 60 year + prior thrombotic Cytoreduction by anagrilide or hydroxyurea
episode:
• Age less than 60 year + no prior Kept under observation
thrombosis + no cardiovascular risk
factors + platelet count less than
1.5 million per microlitre
562 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

• Asymptomatic patients + platelet Kept under observation

count above 1.5 million/microlitre +
no cardiovascular risk factors
• Acute thrombosis: Plateletpheresis + Aspirin
Platelet transfusion in life-threatening haemorrhage

Coagulation Disorders
Classification
Inherited disorders
• Haemophilia A (Classical Haemophilia)
• Haemophilia B (Christmas disease)
• von Willebrand’s disease
Acquired disorders:
• Vitamin K deficiency
• Liver disease
• DIC

Diagnostic Clues for Inherited Coagulation Disorders

Inheritence and sex Bleeding pattern Laboratory investiga-
tions
Haemophilia A X-linked recessive • Spontaneous haemar- • Prolonged partial
(Classic haemophilia): pattern with only males throsis is diagnostic, thromboplastin time
affected. Affected boy bleeding in knee, ankle (PTT)
acquires it from carrier elbow, into muscles and • Normal bleeding time
mother. Female children from G.I. tract, trau- and prothrombin time
of haemophilic father and matic and postoperative • Low coagulation factor
normal mother will bleeding VIII and normal factor
always be carriers though VIII antigen
sons are unaffected.

Haemophilia B: X-linked recessive – Do – • Low level of coagula-

inheritence with males tion factor IX
affected • Other investigations
same as haemophilia A

von Willebrand’s Family history with auto- Most bleeding mucosal • Reduced level of von
disease: somal dominant pattern (epistaxis, gingival Willebrand’s factor
of inheritence. bleeding, menorrhagia. (VWF)
Bleeding exacerbated • Prolonged PTT
Both men and women by aspirin and decreases • Prolonged bleeding
affected. during pregnancy or time.
oestrogen use.
Treatment of Haemophilia A
Haemorrhagic Disorders | 563

I. Infusion of factor VIII concentrate (Standard treatment)

Dose Advantages Disadvantages
Depending on severity of bleeding: • Heat treated Expensive
Severity of bleeding: Raising of factor Units of reduces likely-
VIII (%) factor VIII hood of trans-
Minor bleeding: To 25% 1000 units-one mission of HIV
infusion • Safe
Moderate bleeding: To 50% and maintain 2000 U followed • Effective
at 25% with repeated by repeated infu-
infusion for 2-days sion of 1000 U
for 2-3 days
Severe bleeding: To 100% and then 4000 U initially
maintain the factor followed by 2000
at above 50% conti- U every 12 hours
nuously for 10-14 days
II. Desmopressin:
Acetate: Mechanism Indication Dose
Releases factor VIII: C and • Mild haemophilics 0.3 microgram/kg
raise its level two to three-fold • Useful in preparing for every 24 hours.
for several hours. minor surgical procedure.
III. Ancillary Measures
Mechanism Indication Dose Contraindication
A. Epsilon-amino- Transiently raises Minor haemor- 4 gm PO every • Aspirin
caproic acid factor VIII level rhage in mild 4 hours for • Genitourinary
haemophilics several days bleeding because of
B. DDAVP: – Do – – Do – 12 hourly the risk of ureteral
occlusion
IV. Management of Inhibitors
IgG antibodies to factor VIII develop in haemophilic patients treated with factor VIII concentrate.
They inhibit (called inhibitors) the efficacy of therapy by accelerating the clearance of infused
factors:
Depletion of factor VIII due to inhibitors is measured by Bethesda unit (BU). Treatment depends
on severity of bleeding:

Life-threatening severe bleeding Less severe bleeding Minor bleeding

100 units/kg of porcine factor VIII, 100 U, IV bolus of human If Bethesda Unit (BU) is less
IV bolus followed by 4U per kg VIII followed by infusion than 5, then DDAVP 0.3
per hour IV of 10 U per kg per hour microgram/kg IV given
↓
If do not improve, 100-200U bolus
of porcine factor VIII given followed
by infusion of 10U/kg per hour
564 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

↓
If still no response, prothrombin
complex concentrates (PCC) at 100
units/kg IV 12 hourly
↓
If still fails, plasmapheresis is done
followed by repeated infusion of
human or porcine factor VIII.

Treatment of Haemophilia B
I. Infusion of factor IX concentrate: Standard therapy:
Dose Comments
100 units/kg IV followed by 50 U/kg • Desmopressin acetate is not useful
IV 24 hourly • Inhibitors develop less frequently in
haemophilia B and are managed with
prothrombin complex concentrate
• Aspirin should be avoided.

Treatment of von Willebrand’s Disease

AIM: To raise vWF: RCO and factor VIII to normal
I. Treatment according to clinical types:

Types Clinical and Management

Laboratory features
Type 1 vWD: • Minor bleeding. • DDAVP: Releases stored vWF from
Quantitative decrease • vWF: Ag and vWF: endothelial cell
in vWD. 70-80% cases RCO proportionately low Dose: 0.3 microgram/kg 24 hourly
• Patient undergoing minor surgical procedure
can receive DDAVP 1 hour before surgery
and 12-24 hourly for 2-3 days postoperatively
Type 2 vWD • Moderate bleeding Some patients benefit with DDAVP
Qualitative deficiency • VIII: C normal
in vWD • vWF: RCO decreased out
of proportion to vWF: Ag
Type 3 vWD • Major bleeding • DDAVP not useful
Severe quantitative • Level of vWF: Ag absent • For extensive surgery: Plasma products
deficiency of vWD infusion 8-12 hourly to raise vWF: RCO
level to 100% initially and then above 50%
for 5-10 days
II. Factor VIII concentrate:
Indicated in patients who require factor VIII. Factor VIII concentration also contains functional
vWF and do not transmit HIV or hepatitis.
Dose:20-50 U/kg depending upon the disease severity.
 Kidney
91
Glomerular Diseases

GLOMERULONEPHRITIS
Clinical Types
1. Acute glomerulonephritis 2. Chronic glomerulonephritis

Acute Glomerulonephritis (Acute GN)

Aetiological consideration
A. Primary glomerular disease:
i. Membranoproliferative GN ii. Mesangial proliferative nephritis
B. Secondary:
1. Infectious diseases:
a. Poststreptococcal b. SBE
c. Hepatitis B d. Sepsis
2. Multisystem diseases:
a. Systemic lupus erythmatosus b. Polyarteritis nodosa
c. Wegener’s granulomatosus d. Henoch-Schönlein purpura
3. Anti-GBM nephritis
Goodpasture’s syndrome
4. Rapidly proliferative GN (RPGN)
a. Most of the causes of acute b. IgA nephropathy (Burger’s disease)
glomerulonephritis

Clinical Consideration
Age and onset
• Acute GN Children. Abrupt onset preceded
by acute respiratory infection
• RPGN Onset like acute GN
Urinary features Extra-renal features
Haematuria (smoky urine); Oedema; hypertension common
Oliguria
Severe oliguria; haematuria Arthralgia; abdominal pain;
nausea; vomiting. Pulmonary
symptoms in SLE

• IgA nephropathy Below age 35 year; onset with upper Haematuria rare Hypertension; gastrointestinal
respiratory tract infection disturbance, oedema

• Anti GBM Like RPGN Cough, haemoptysis

566 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Laboratory Consideration
A. Urinary investigations:
RBC WBC Albumin Casts
• Acute GN + + RBC casts
• RPGN + RBC cast
• IgA Rare +
B. Haematological and biochemical:
Blood urea and creatinine Hb WBC
• Acute GN Temporarily raised
• RPGN Raised Anaemia Leukocytosis

Side-effects of Therapy
Steroid Cyclophosphamide Azathioprine Dipyridamole Plasmapheresis
a. Prednisolone; Bone marrow depres- Drug fever, GI Headache, dizzi- Thrombocytopenia,
Cushingoid sion, alopecia, GI upset; bone ness, upset, rash. coagulation abnor-
facies, cataract, upset, myocarditis, marrow suppres- mality, hypogamma-
osteoporosis, gonadal dysfunction, sion, cholestasis. globunaemia.
hirsutism, cancer bladder.
oedema, hyper-
tension, skin
lesion, venous
thromboem-
bolism.
Prognosis
Poststreptococcal AGN RPGN Anti-GBM GN
95% resolve 75% stabilise if treated early 75% stabilise or improve if
treated early
IgA nephritis
25-50% slowly progress
C. Immunological:
• Acute GN : ASO titre elevated in poststreptococcal GN
• RPGN : ASO titre normal
• IgA : Elevated serum IgA. Normal ASO titre
• Anti-GBM : Anti-GBM antibody present
D. Renal biopsy:
• Acute GN : Endocapillary endoproliferative GN with neutrophil infiltration
• RPGN : Crescentic glomerulonephritis
• Anti-GBM : Focal diffuse proliferation with crescents
Good pas. syndrome
• IgA GN : Focal proliferation. Diffuse mesenchymal IgA

TREATMENT
Early treatment prevents complications and improve prognosis.
 Acute GN RPGN Ig A GN
Glomerular Diseases

Anti-GBM GN
| 567

1. Supportive: a. Rest Rest

Treatment b. Diet with adequ-
ate protein.
c. For decreasing
proteinuria: Rest;
ACE inhibitor,
NSAID and treat-
ment of hyper-
tension.
d. Immunoglobulin
given if hypoglo-
binaemia (which
leads to frequent
infection).

2. Treatment of • Sodium restriction is Rigorous treatment of Rigorous treatment of

sodium retention the key. hypertension hypertension
manifested by • Diuretics: Loop diu-
oedema, hyper- retic. If no response
tension and CCF thiazide added to loop
diuretic.
• Antihypertensive
drugs: Vasodilator,
calcium blocker, ACE
inhibitor.
• Fluid restriction.

3. Specific: Treat- None None None None

ment
4. Antibiotic: Antibiotics (penicillin, Antibiotic given infec-
erythromycin) given tion suspected
only if culture is posi-
tive for group A strep-
tococci.

5. Steroid Indicated only in pro- Indicated prednisolone Indicated

longed oliguria and 1 mg/kg Pulmonary haemor-
crescentic glomerular rhage responds to high
lesion present. dose prednisolone or
pulse methylpredni-
solone.

6. Pulse: Methylpre- Methyl prednisolone Indicated

dnisolone therapy 30 mg per kg to a maxi-
mum of 3 gm IV over
20 minutes on a daily or
alternate basis three
times, followed by oral
contd...
568 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

prednisolone 2 mg/kg,
which is tapered over
several months.

7. Plasma exchange: Indicated Indicated

Not indicated
8. Combination Plasma exchange upto Steroid + cyclophos-
therapy: 4 litres/day or on alter- phamide is also effec-
nate days tive or plasma exchange
+ given until anti-GBM
Expensive Prednisolone 1 mg/kg/ antibody not detected in
day circulation plus steroid
+ plus cyclophospha-
Cyclophosphamide 2- mide.
3 mg/kg/day.

9. Cyclophospha- Indicated Indicated

mide

10. Dialysis: Indicated in progressive Renal failure Renal failure

Indicated only in severe renal failure
oliguria, fluid overload,
hyperkalaemia and
renal failure
11. Renal transplant: Indicated in severe Indicated if no reco-
cases very. Prior to trans-
plantation be sure that
anti-GBM antibody
should be absent from
circulation otherwise
transplanted kidney
develops RPGN. If
anti-GBM antibody is
present, keep the
patient on dialysis till
antibody disappears or
removed by plasma
12. Anticoagulants: Occasionally helpful exchange.
Aspirin 325 mg, but hazardous in
dipyridamole uraemic patients
(Pers antin) 75
mg t.i.d.
TREATMENT OF OTHER FORMS OF ACUTE GN
• Steroids : Membranous proliferative GN
• Cytotoxic drugs : Membranous proliferative GN
• Combination of steroid + cytotoxic drug : Severe crescentic form of nephritis; Henoch-Schönlein
purpura; acute SLE; Wegner’s granulomatosus;
polyarteritis.
 Kidney
92
Nephrotic Syndrome

AETIOLOGICAL AND PATHOLOGICAL CONSIDERATION

Aetiological
In two-thirds of adults and most children: In one-third of adults and 10% of child:
Idiopathic nephrotic syndrome (Primary Renal Disease) As manifestation of systemic disease:
a. Minimal change nephrotic syndrome (MCNS) a. Systemic lupus erythematosus
b. Membranous nephropathy b. Amyloidosis
c. Membranoproliferative nephritis (MPGN)
d. Focal glomerular sclerosis (FGS)

Pathological
1. Marked increase in permeability of glomerular capillary resulting in.
a. Proteinuria—Resulting in:
i. Hypoalbuminaemia
ii. Oedema
b. Loss of immunoglobulins and complement leading to defective immunity with increased
susceptibility to infection.
c. Loss of coagulation factors resulting in increased coagulability.
2. Hyperlipidaemia due to increased synthesis of lipids in liver and its increased catabolism.
3. Sodium retention produces hypertension and oedema.

Clinical Consideration
Nephrosis is characterised by triad of proteinuria, oedema and hypertension. Gross haematuria and
RBC casts are infrequent and renal function is preserved in early stage.
Characteristic features of primary renal diseases producing idiopathic nephrotic syndrome are as
follows:
Minimal change Focal glomerular Membranous Membranoproliferative
nephrotic syndrome sclerosis (FGS) nephrosis glomerular nephritis
(MCNS) (MPGN)
A. Clinical:
Age: Children 75% Adult 15% Adult 50% Adult 10%
Asymptomatic No Children 10% 20% Children 10%
contd...
570 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

proteinuria: ++ 10% ++ 40%

++ ++
Haematuria: Less frequent 60-80% 60% 80%
Hypertension 10% 10-20% Infrequent 35%
Associated conditions: Hodgkin’s disease None Renal vein thrombosis, None
(occult lymphoma) cancer GBM nephritis
Allergy
B. Laboratory investi-
gations:
a. Urinary Albuminuria Proteinuria sterile Microscopic haema-
pyuria RBC turia but no RBC
b. Others Marked reduction in Normal C3 Low C1, C4, C3-C9
ASO titre normal C3
c. Renal function Preserved Deteriorates Preserved in 50-70% Deteriorates

C. Renal biopsy
a. Light micro- Normal Focal sclerosis Thickened glomerular Thickened glomerular
scopy: basement membrane basement membrane;
proliferation
b. Immunofluores- Negative Immunoglobulin M, C3 IgG, C3 in lesion IgG, C3 in lesion
cence: in lesion
c. Electron micro- Foot process fusion Foot process fusion Subepithelial deposits Mesangial and sub-
scopy: endothelial deposits

D. Response to a. Steroid ++ a. Steroid a. Steroid + No established

therapy: b. If refractory to + b. Cytotoxic drug + treatment steroid
steroid: Cytotoxic b. Cytotoxic drug Steroid ++ +
drugs + Cytotoxic drugs
c. Frequent relapses Steroid + +
Antiplatelet + Anticoagulant
+
Antiplatelet drug +
E. Prognosis: Good Poor Poor Poor

Treatment of Nephrosis
A. General Management:
1. Fluid and salt intake: In nephrosis excessive amount of salt and water is retained in interstitial
space. Hence salt is restricted mainly. In ill patients water is also restricted. Water intake need
not be restricted in the stable patients.
2. Oedema:
a. Rest; b. Restriction of salt and water; c. Diuretics:

In stable patient with moderate oedema In severely ill patient with massive oedema
Frusemide 40-80 mg b.d. alone or combined i. Hospitalise the patient
with amiloride 5 mg/day for preventing ii. Up to 500 mg of frusemide b.d.
potassium loss. iii. Spironolactone: Starting with 100 mg/day,
 Nephrotic Syndrome

gradually increased to 400 mg/day to combat

| 571

intense secondary hyperaldosteronism

↓
If no response: Oedema can be removed rapidly
and safely by IV frusemide 250-500 mg. But it
reduces circulating volume, hence the need for
IV protein or albumin as a short cut.

3. High protein diet rich in animal protein (100-120 gm/day) is given

4. Reduction of proteinuria:
i. Rest
ii. ACE inhibitor
iii. Indomethacin 150 mg/day. Indomethacin interferes with the production of prostaglandins,
this in turn produces fall in renal blood flow, which in turn reduces glomerular filtration rate
and thus reduces proteinuria. This treatment is controversial, but occasional serious patient
can be helped by indomethacin.
5. Infection: Nephrotic patients are very prone to infection due to immunological abnormality.
Seriously ill patients should be put on prophylactic penicillin. Ascitic fluid may be stained with
gram stain to find out organisms responsible. Occasionally blood culture helps. For established
infection appropriate antibiotics should be prescribed.
6. Management of associated hypertension: Preferred drugs; Vasodilators, ACE inhibitor.
B. Specific Treatment
Minimum change neph- Focal glomerular scle- Membranous nephro- Membranoproliferative
rotic syndrome rosis pathy glomerular nephrosis
Steroids: Dramatic response. Majority do not respond Mainstay of treatment
Monitored by albumin- Prednisolone 2 mg/kg/ to steroid and progres- is prednisolone 100-
uria day for 4 weeks, follo- ses to renal failure. 150 mg every other
wed by alternate day Only 15-20% respond day for two years. This
therapy for 4 more to steroid which has slows rate of progres-
weeks and then tapering better prognosis. sion to renal failure.
over 4-6 weeks.
In case of relapse:
a. A full course of
steroid repeated.
b. Cyclophospha-
mide 2 mg/kg per
day or chloram-
bucil (leukeran)
0.15 mg/kg/day
added to predni-
solone therapy.

Cytotoxic drugs: Indication: Increases duration of Concomitant adminis-

Monitered by haemato- a. Patient serious steroid induced remis- tration with steroid imp-
crit, leukocyte and b. Side-effects of sion. roves result.
platelet count. steroid excessive
contd...
572 |
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Bedside Approach to Medical Therapeutics with Diagnostic Clues

c. Refractory to steroid
cyclophosphamide 2-
3 mg/kg per day given
for 4-8 weeks. This
increases steroid
induced remission

Combination therapy: Steroid + cytotoxic a. Steroid + cyto- Steroid + cytotoxic Two year course of
drugs in severe cases toxic drugs drugs further improve alternate day steroid or
b. Antiplatelet the result a “cocktail” of drugs
agents preserve including steroid, cyto-
renal function toxic drug, anticoagu-
lant and antiplatelet
agents (dipyridamole
225 mg/day, aspirin
325 mg/day). The
above cocktail may help
but it is not a estab-
lished treatment.

Dialysis Indicated in unremitant Same as FGS Same as FGS

proteinuria, persistent
hypertension and pro-
gressive deterioration in
GFR

Renal transplant Ultimately required Same as FGS Recurrence common

after transplant
 Kidney
93
Acute Renal Failure (ARF)

DEFINITION
ARF is defined as an acute failure of the kidney function to excrete waste products of metabolism
resulting in raised blood urea and serum creatinine.

AETIOLOGICAL CONSIDERATION
There are three types of acute renal failure:
i. Prerenal ii. Renal iii. Postrenal
They are commonly due to medical causes (66%), obstetric causes (15-25%) and less frequently
surgical causes.
Prerenal
Prerenal: Medical causes Obstetric causes Surgical causes
i. Fluid and electrolyte loss: Due to i. Septic abortion i. Extensive trauma
diarrhoea, vomiting, burn, diuretic, ii. Placenta previa ii. Crush injury
glycosuria iii. Pre-eclampsia iii. Postoperative disorders
ii. Haemorrhage: Massive haemorrhage iv. Postpartum haemor-
iii. Nephrotoxic drugs/poisons: rhage
a. Drugs: Antimalarials (primaquine,
quinine), analgesics (acetyl salicylic
acid, phenacetin, sulpha, chlo-
ramphenicol)
b. Heavy metals: Copper, Hg.
c. Snakebite
iv. Organ failure: Cardiac and liver failure
v. Infection: Sepsis, malaria, bronchopneu-
monia and meningitis in children
vi. Systemic disease: SLE, Henoch-Schö-
nlein purpura
vii. Anaphylaxis, transfusion reaction Renal parenchyma:
Renal: i. Glomerular: Post-
infectious glomer-
ulonephritis, RPGN,
Good pasture’s synd-
rome, Wegner’s gran-
ulomatosus
contd...
574 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

ii. Tubular: Acute tubular

nephritis, acute inter-
stitial nephritis
iii. Vascular: Thrombo-
embolism of solitary
kidney, renal vein
thrombosis, malignant Surgical:
Postrenal: hypertension Obstructive uropathy due to
stone, enlarged prostate and
bladder, pelvic and retro-
peritoneal tumour

Pathological Consideration
Prerenal ARF Renal ARF Postrenal ARF
Fluid loss Structural lesions of renal paren- Obstruction leads to rise in intra
↓ chyma tubular pressure and ureteral
Hypoprofusion ↓ pressure
↓ ↓
Vasoconstrictors (catecholamine, Increase in renal vascular resis-
angiotensin and vasopressin) ↓ tance
released Renal failure ↓
↓ Fall of GFR
GFR reduced ↓
↓ Renal failure
Renal failure

Clinical Consideration
I. Common clinical features:
History of initiating events Reduction in urine volume Extra-renal features
(See “Aetiological considera- Usually lasting for 10-14 days. If a. Cardiovascular
tion”) lasts for longer than 4 weeks Hypertension, arrhythmia,
suggests acute tubular necrosis, uraemic pericarditis.
RPGN and renal artery occlusion. b. Neurological: Lethargy, som-
Non-oliguric ARF: Urine less than nolence, confusion, agi-
400 ml/day tation, twitching.
c. Gastrointestinal: Nausea,
vomiting, abdominal dis-
comfort, ileus.

II. Features suggestive of different types of ARF

Prerenal Renal Postrenal
a. Hypovolaemic patients: Fever, hypertension, haematuria, a. Upper urinary tract obstruc-
History of fluid loss and proteinuria, pyuria tion. Flank pain, lower
 bleeding. Orthostatic hypo-
Acute Renal Failure (ARF) |
abdominal pain, fluctuating
575

tension, thready pulse, cool urinary output.

extremities, signs of dehyd- b. Lower urinary tract obstruc-
ration (thirst, dry mucosa). tion. Frequency, dribbling,
b. Hypervolaemic patient: lower abdominal fulness in
Signs of cardiac failure. urethritis.
c. Eurolaemic patients: Liver c. Other features: Abdominal
failure, heatstroke, drugs scar, palpable bladder, flank
intake, snakebite. tenderness, prostatic enlarge-
d. Features of systemic disea- ment and pelvic mass.
ses: Especially shown by skin
examination: Scleroderma,
purpura (Henoch-Schönlein
purpura), butterfly rash
(SLE), spider angioma
(cirrhosis).

Investigational Consideration
I. Urinary Abnormalities:
Prerenal Renal Postrenal
A. Specific gravity Above 1020 (High-concen- ---------- ----------
trated urine)
B. Osmolality Above 350 (Concentrated ---------- ----------
urine)
C. Urine/plasma Above 1.1 Less than 1.1 Less than 1.1
osmolality
D. Urine sodium Less than 20 (due to increased Above 40 (due to diminished Less than 30 (due to increased
acidity for sodium) renal sodium reabsorption) acidity for sodium)
E. Urine/plasma Above 40 Less than 20 Less than 20
creatinine
F. Urinary protein Minimum Moderate to severe Minimal
G. Urinary sediment Scanty Epithelial cells/casts Scanty
H. Crystalluria Seen in oxalate and urate
disorders
I. Microscopy
RBC cast ------ Glomerulo-
nephritis
WBC cast ----- Interstitial
nephritis
Eosinophils --- Allergic
interstitial
nephritis
Pigmented
granular cast -- Acute tubular
necrosis

contd...
576 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

J. Fractional excre- Less than 1% Greater than 1%

tion of sodium
II. Biochemical abnormalities: Metabolic acidosis, hyperkalaemia, hyperphosphataemia, hypocalcaemia
III. Radiological: Imaging: Renal Postrenal
A. Plane X-ray abdo- Detects kidney size and Detects radiopaque stone
men: shape.
B. Ultrasound: Reveals number of kidney, size Safe and reliable technique to
and shape of kidney. exclude specially upper
urinary tract obstruction.
Ultrasound in combination
with high dose urography
confirms obstruction without
resort to retrograde exami-
nation.
C. CT scan: Ultra- Detects kidney size, hydro- Provides anatomical confir-
sound is a better nephrosis. mation of obstruction.
alternative and so
CT scan is unneces-
sary.
D. Arteriography and Useful in renal artery throm-
venography bosis and embolism.

IV. Urography retrograde They are not without risk and Retrograde pyelography is
pyelography: similar information as ultra- particularly useful in suspec-
sound in ARF. Its use in ARF ted obstructive uropathy.
is quite limited.

V. Renal biopsy: Only indicated in selected

patients in whom the cause of
ARF not clear and renal
failure is associated with
systemic diseases.

VI. Radionucleonuclide Shows renal blood flow,

studies: cortical function as well as
obstruction. It carries little
risk. It may be helpful when
ultrasound cannot determine
renal blood flow.

VII. Other tests:

In Hypovolaemic patient In Hypervolaemic patient
A fluid challenge of 500 to Diuresis; May improve car- When urethral and bladder
1000 ml of isotonic saline may diac function obstruction is suspected:
stimulate urine formation in
the average adult and oliguria Bladder catheterisation may
is reversed. See further in be diagnostic.
treatment paragraph.
MANAGEMENT
Acute Renal Failure (ARF) | 577

Prophylaxis
ARF can be prevented:
A. Fluid and blood replacement:
a. During and after surgery
b. Burn cases
c. Severe diarrhoea and vomiting
d. Massive haemorrhage due to trauma
B. Precautions during radiography, surgery and chemotherapy:
Biliary and cardiovascular Radiography Chemotherapy
surgery
Mannitol may prevent ARF in Elderly patients with renal insuffi- Should be given prophylactic
situations with high-risk of ciency or with multiple myeloma allopurinol along with alkalisation
developing ARF, i.e. cardiovas- do not tolerate contrast material of urine.
cular and biliary surgery. well.
Management of ARF includes:
i. During oliguric phase:
a. Early phase
b. Continuation phase
ii. During diuretic phase
I. Measures taking during oliguric phase: A. Early Phase:
AIM:
In Prerenal ARF In Renal ARF In Postrenal ARF
i. Circulating blood volume i. Correction of reversible Early diagnosis and relief of
should be corrected. causes. obstruction are essential.
ii. Avoidance of nephrotoxic ii. Prevention of additional
drugs. injury by radiocontrast
iii. Conversion of oliguric to agents.
non-oliguric ARF.
iv. Correction of reversible
causes, e.g. infection, fluid
loss, etc.

Measures for Initiating Diuresis

It converts oliguric ARF to non-oliguric ARF which has better prognosis. It helps in maintaining tubular
patency by removing intratubular debris and casts.
First try 200-500 ml 0.9% sodium chloride over 30 minutes and continued if urine flow occurs
without rise of central venous pressure.
↓
If oliguria not reversed:
Use combined mannitol and frusemide provided hydration is ensured.
578 |
Mannitol:
Bedside Approach to Medical Therapeutics with Diagnostic Clues

Frusemide:
3 dosages of 100 ml of 20% mannitol IV 160 mg IV

Combined given over 20-30 minutes at 2 hours

intervals until urine flow is at least 50 ml per hours
↓
If no diuresis:
Dopamine 1-10 microgram/kg/minute IV Dopamine dilates renal and mesenteric circulation and increases
cardiac output.
↓
If fails:
Suggests establish organic renal disease (Acute tubular necrosis).

Continuation Phase
I. Fluid Intake and Output:
Daily weight taken Fluid
Weight loss of 0.2-0.4 kg/daya. Fluid restricted to match total intake to urine output +
should be ensured GI loss + insensible loss (usually 400 ml/day in temperate
climate and 500 ml in tropics).
b. Serum sodium concentration: It provides guideline for water intake:
i. If serum sodium low, points to excess water is present
ii. If serum sodium is high indicates deficiency of water
II. Management of Biochemical Abnormalities
1. Abnormalities Reasons Remedy
Hypernatraemia: i. Excess salt intake i. Restrict salt intake
Causes volume expansion and ii. Excess sodium bicarbonate ii. Avoid excess sodium bicar-
overhydration, pulmonary oedema administration for acidosis. bonate administration.
and hypertension in glomerulo-
nephritis.
2. Hyponatraemia: Excessive fluid administration Avoid excess fluid administration
3. Hyperkalaemia: i. Hypercatabolic state due to
Assessed by serum potassium and uraemia produces excess
ECG changes (Peaked and tent potassium as a result of tissue Treatment
shaped T, disappearance of P and destruction.
broadened QRS) ii. Acidosis and uraemia enhan-
ces accumulation of potas-
sium in extracellular fluid.

Mild to moderate cases Severe cases with serum potassium

above 7 mEq/litre
Dialysis acts within few minutes
and removes potassium promptly.
Onset of action within few minutes Action in 15-30 minutes
Acute Renal Failure (ARF)

Action in 60 minutes
| 579

i. Calcium gluconate (10%) i. Glucose (50%) 50 gm + Cation exchange resin (K-exylate)

10-30 ml IV regular insulin 10 units IV 30-60 gm rectally as retention
↓ ↓ enema in 70% sorbitol with 100-
Its mechanism: Antagonises Its mechanism: Shifts potas- 200 ml tap water
effect of potassium. sium intracellularly. ↓
ii. Sodium bicarbonate 50-150 ii. Frusemide 0.5 gm to 2 gm Its mechanism: Removes potas-
mEq IV orally or 100-400 mg sium from body by increasing
↓ parenterally faecal excretion of potassium.
Its mechanism: Shifts potas- ↓
sium intracellularly. Its mechanism: Increases
potassium excretion.
4. Acidosis i. Mild cases: Treatment not
required.
ii. Severe cases: 100 ml of 7.5%
sodium bicarbonate every 8-
12 hour.
iii. Severe acidosis + severe
hyperkalaemia + fluid over-
load: Dialysis required.

5. Hyperphosphataemia Due to: Aluminium hydroxide 30-60 ml or

i. Decrease in GFR calcium carbonate.
ii. Enhanced release of phos-
phate from tissue break-
down.

III. Diet
Ideal Diet
Calories Protein
Adequate caloric intake should be ensured to Protein restricted to 0.5 gm/kg/day.
minimise catabolism. For a 70 kg adult patient In mild cases about 30 gm protein per day
2000 calories per day is required. can be given. Essential amino acids have
all been advocated.
Modes of feeding
Oral feeding Enteral feeding by Parenteral feeding
gastrointestinal tube
Indicated in mild cases Moderate cases who are unable to Patients who cannot tolerate enternal
eat needs enternal feeding. feeding parenteral feeding is required.
Then attempts should be made for a
gradual transition from parenteral to
enteral to oral feeding.
580 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

IV. Infection
Pulmonary, urinary and wound infection may occur. Blood culture should be done. Antibiotics
against gram-negative organisms and S. aureus should be started soon:
a. Gentamicin/Amikacin + Cephalosporin
b. If anaerobic organism is suspected give metronidazole/chloramphenicol
V. Gastrointestinal bleeding:
Cemetidine, proton pump inhibitor or lansoprazole
Serious case require dialysis
VII. Drugs in ARF:
Drugs excreted by glomerular filtration or tubular secretion must be given:
a. In reduced dosages, or
b. At longer intervals
Avoid tetracycline (increases protein catabolism) and combination of frusemide and cephaloridine
or gentamicin with cephaloridine (nephrotoxic). In spite of nephrotoxicity gentamicin is frequently
used in ARF with gram-negative sepsis but dosages must be widely spaced.
VIII. Measures to reduce catabolism:
a. Ensure daily intake of at least 100 gm of carbohydrate and fat.
b. Parenteral aminoacids is preferred.
c. Anabolic androgen given to reduce protein catabolism preventing rise in BUN.
d. Control pyrexia
e. Early appropriate antibiotic should be instituted.
IX. Hypertension
a. Volume overload should be avoided
b. Choice of antihypertensive drugs: Drugs not decreasing renal blood flow should be chosen:
Clonidine, prazosin, calcium channel blocker
c. Drugs for hypertensive crisis: IV labetalol or IV sodium nitroprusside. Monitor thiocyanate
level during nitroprusside use.
X. Anaemia
Stop gastric bleeding by desmopressing acetate
Blood transfusion

Treatment of Causes of ARF:

Disorders Preventive and curative treatment
Radiocontrast nephropathy Occurs more in diabetes mellitus, volume depletion, multiple myeloma,
heart failure and elderly above 65 years.
Patients at risk should be hydrated beginning 12-24 hours before
the contrast study and ending 12 hours after the study, by 75-150 ml/
hour of 0.45% saline.
Acetylcystine (600 mg orally b.d.; 4 dosages total) starting 1 day
before the procedure, may reduce the incidence of contrast
nephropathy.

Aminoglycoside nephrotoxicity The risk is less if given at longer intervals.

Pigment induced renal injury
Acute uric acid nephropathy
Acute interstitial nephritis
Acute Renal Failure (ARF)
Occurs during haemolysis or rhabdomyolysis.
| 581
Fluid volume should be expanded aggressively to
establish high urine flow. Raise the urine pH greater
than 6.5 by IV infusion of 2-3 ampules of NaHCO3
in 1 litre of 5% dextrose in water.
Occurs during cytotoxic drugs due to cell lysis
Decreasing uric acid Prevention of uric acid
production precipitation
By allopurinol 600 mg By forced alkaline
orally before cytotoxic diuresis by acetazola-
therapy, followed by mide (250 mg orally
100-300 mg/day. q.i.d. or by 2-3 ampules
of NaHCO3 in 1 litre
5% dextrose in water.
Due to drugs (penicillin, sulfonamide, quinolones
and NSAID. Stop offending agents.
A 1-week course of prednisolone, 60 mg orally q.d.
 Kidney
94
Chronic Renal Failure

Chronic renal failure is defined as chronic irreversible failure of renal function due to permanent reduction
in GFR.

AETIOLOGICAL CONSIDERATION
I. 50% cases due to:
a. Developed countries: Diabetes mellitus hypertension
b. Developing countries: Primary glomerulonephritis: Proliferative, membranous,
membranoproliferative.
Renal stone is very high in certain parts of India.
II. 20-25% cases due to :
a. Chronic pyelonephritis. Tuberculous pyelonephritis
b. Obstructive renal disease:
Lower urinary tract Upper urinary tract
Prostate enlargement Hydronephrosis
Urethral stricture Retroperitoneal fibrosis
Neurogenic bladder Neoplasm
Neoplasm of bladder
c. Hereditary and congenital:
Adult polycystic disease (common)
Hereditary nephritis
Cystinosis
Renal tubular acidosis
d. Systemic diseases:
Collagen diseases Vascular Others
SLE Sickel cell disease Gout
Polyarteritis Thrombotic thrombocytopenic Amyloidosis
purpura Myeloma
e. Nephrotoxins:
Heavy metals Drugs
Lead, gold, cadmium Analgesic
f. Vascular: Renal artery stenosis
III. 10-15% cases:
Idiopathic
Diagnostic Approach
Chronic Renal Failure | 583

Flow Chart
History and physical examination
Symptoms Signs
General: Fatigue Shallow appearance
ENT and Eye: Metallic taste in mouth, epistaxis Pale conjunctiva, urinary breath, retinopathy

Skin: Pruritus, easy bruisability Echymosis, oedema, xerosis, yellow discoloura-

tion, uraemic frost
Neurologic and Restless leg, paresthesia, cramp leg, convulsion Stupor, myoclonus, peripheral neuropathy
Neuromuscular:
Pulmonary: Dyspnoea Rales, pleural effusion
Cardiovascular: Dyspnoea, retrosternal pain Hypertension, cardiomegaly, CCF, pericardial rub
Stomatitis, ulcer
G.I. Tract: Anorexia, nausea, vomiting, hiccup, bleeding
Genito-urinary: Nocturia, haematuria, dysuria, polyuria Enlarged prostate, kidney enlargement, pelvic
mass.
Bone: Bone pain, arthritis Fracture, osteoporosis, osteomalasia
Nephrotoxins History of intake of nephrotoxic drugs, heavy
metals
Also look for features of systemic diseases (see Aetiological consideration) and enquire about family
history of renal disease
⇓

Arrange for Laboratory Investigations

A. Urine Analysis:
Protein RBC and RBC cast Granular and Other findings
Hylaine Cast i. Glycosuria in dia-
Proteinuria above i. RBC: In proliferative glomerulo- Granuloneph- betes
3 gm per day in nephritis, systemic disease, ritis, amyloido- ii. Infection found in
glomerulopathy, malignant hypertension and sis calculi, obstruction
diabetes, malig- polycystic disease. and following ins-
nant hypertension, ii. RBC cast: Rapidly progressive trumentation.
collagen disease, glomerulonephritis, SLE, malig-
amyloidosis nant hypertension.
B. Radiology (Plane X-ray Abdomen, Tomogram and IVP):
Large kidney Small kidney Normal size kidney
In polycystic dis- Some cases of:
ease and hydro- Symmetrical Asymmetrical (irregularly Proliferative GN,
nephrosis Kidney with normal scarred kidney with Membranous GN,
calyces deformed calyces): Diabetes
• GN Chronic pyelonephritis
• Hypertension Interstitial nephritis
584 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

C. Micturating Cystography
Confirms uretero-vesical reflux in adult patients with scar red kidney due to pyelonephritis
D. Renal Angiography
Demonstrates arterial disease associated with severe hypertension, SLE, and aneurysm
E. Ultrasound:
Shows size of kidney: Small, large or normal size kidney. See Radiology.
F. Radiological Evidence of Osteodystrophy
G. Other Findings:
Anaemia, metabolic acidosis, hyperkalaemia, hyperphosphataemia, hypocalcaemia
⇓
Next, differentiate whether renal failure is acute or chronic:

Acute failure Chronic failure

Usually symptomatic i. Chronic slowly progressive renal failure is often asymptomatic
ii. X-ray determination of kidney size suggest the chronicity. See radiology.
Then, differentiate between renal versus extrarenal causes of CRF
First exclude extra-renal causes: ⇓
Extra-renal causes:

Prerenal causes Postrenal causes

As seen in depletion of extracel-
lular fluid due to vomiting, diar- Lower urinary tract obstruction: Upper urinary tract obstruction
rhoea, blood loss. a. Diagnosed by having the Diagnosed by:
patient void completely and a. Absence of residual urine in
then measuring the residual bladder.
urine in the bladder by b. Demonstrating dilated renal
catheterisation. Presence of calyces, pelvis and ureter
residual urine points to lower above obstruction which is
urinary tract obstruction. confirmed by IVP and
b. Enlarged prostate is diag- retrograde pyelography or
nosed by PR examination. by sonogram.
⇓
Once extrarenal causes (Prerenal and Postrenal) of CRF are excluded, we are left with
Renal Causes of CRF.
Determine the treatable causes of renal parenchymal diseases:
Treatable causes: Acute hypertensive nephropathy
Analgesic nephropathy
Lupus nephritis
Pyelonephritis
Haemolytic-uremic syndrome
Hypercalcaemic nephropathy
Multiple myeloma
Oxalate nephropathy
Renal vein thrombosis
Wegner’s granulomatosus
The following additional tests are helpful:
Chronic Renal Failure| 585

Renal arteriography Renal biopsy

Helpful in polyarteritis nodosa, tumour, and severe a. Helpful if kidney disease has not progressed
hypertension much
b. Often useful in patients with normal sized
kidney and progressive renal disease such as
nephrosis, collagen vascular disease, tubular
interstitial disease, rapidly progressive GN.
Management of CRF
AIM:
1. To maintain patient in a state of well-being.
2. To slow the rate of progression by treating complications and aggravating factors.
Management of aggravating factors:
Aggravating factors: Cause Disadvantage Remedy
Hypoperfusion: Due to fluid loss and Reduces GFR and inc- i. Discontinue diure-
overuse of diuretic in reases BUN, creatinine tics
heart failure ii. Severe cases: Lib-
eralise salt or care-
ful IV infusion of
half normal saline.
iii. Treat CCF
Urinary tract obstruction: Urethral stricture, enlar- Further wosens CRF Prompt surgical treat-
ged prostate ment is essential
Nephrotoxins Worsens renal function i. Reversible if treated
(NSAID, aminoglyco- early
side and contrast mate- ii. If contrast material
rial) is used, use in mini-
mal dosages and
ensure volume
expansion by man-
nitol (12.5 g to 25 g)
before and after the
Infection: procedure
Complicated UTI may Treat according to urine
cause severe renal culure and sensitivity.
damage specially if
associated with urinary
tract obstruction.
Hypercalcaemia (above Worsens renal function
12 mg/dl)
Renal vein thrombosis: Occurs in nephrosis due Anticoagulant
to hypercoagulability.
586 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
Treatment of Complications
Complications Cause
Hypertension Sodium and fluid overload
Hyperkalaemia: i. Volume depletion
ii. Tissue breakdown
iii. K-sparing drugs: Spiro-
nolactone. Trimetho-
prine
iv. High intake of K
v. Fever
Hyperphosphataemia: Due to low GFR phosphorous Disturbs phosphorus and
retention occurs and serum calcium metabolism. See
phosphorus rises
Disadvantages Remedy
Accelerates progression of i. Restrict salt
ARF ii. Diuretics:
Frusemide + thiazide
↓
If fails
a. Vasodilators: Hydra-
lazine, calcium channel
blocker.
b. ACE inhibitor and
angiotensin II receptor
blocker. They reduce
intraglomerular pres-
sure and reduces prog-
ression of glomer-
ulosclerosis and are
renoprotective.
c. Other antihypertensive
drugs clonidine, mino-
xidil, methyldopa.
Worsens CRF Moderate hyperkalaemia:
Treat causative factors.
Sever hyperkalaemia: See
ARF.
i. Restrict dietary phos-
osteodystrophy phorus 800-1000 mg/
day.
ii. Use of phosphorus
binder which prevents
gastro-intestinal phos-
phate absorption:
Calcium carbonate 500 mg to
2 gm orally with meals
↓
If fails:
Disadvantages of long-term Aluminium hydroxide 15-
use of aluminium hydroxide: 30 ml or 1-3 cap/day with
Produces osteomalacia, ence- meals.
phalopathy, myopathy and or
anaemia. Hence this should be Sevelamer (phosphate binder)
replaced by other phosphate can be used alternatively.
binder such as calcium carbo-
nate or acetate.
contd...
contd...
Hypocalcaemia: Due to impaired absorption of Worsens CRF.
calcium in CRF.
Metabolic acidosis: Kidney has diminished capa- Disadvantage of sod. bicarbo-
city to excrete acids produced. nate: Fluid overload if long-
Anaemia: i. Decreased erythro-
poietin production
ii. Low grade blood loss
iii. Low grade haemolysis
Hyperlipidaemia: Due to nephrosis
Pericarditis
CCF Fluid overload, anaemia,
hypertension and athero-
sclerosis.
Coagulopathy: Due to platelet dysfunction
Chronic Renal Failure
Disadvantage of D3: May lead
to hypercalcaemia. Start D3
with low dose of 0.25 mg
every other day monitored by
serum phosphorus level.
term administration of sod.
bicarbonate. Treated by
sodium restriction and diure-
tics.
Disadvantage of calcium
carbonate: Hypercalcaemia
occurs, hence close monito-
ring of ser. phosphorus and
calcium is mandatory.
Disadvantage of erythro-
poietin: Hypertension in 10-
20% cases. Well-established
in dialysis. But less recog-
nised on conservative line of
treatment.
Increases risk of athero-
sclerosis.
Absolute indication for
dialysis.
| 587
iii. Restrict dietary protein
because phosphorus is
important constituent of
protein.
i. Calcium carbonate can
be used which is also a
phosphate binder.
ii. There is also deficiency
of D 3 in CRF and
should be given. D 3
corrects hypocalcaemia
and osteodystrophy.
i. Acidosis well-tolerated
unless plasma HCO3
falls below 15-
18 mmol/L.
ii. Sodium bicarbonate
1.5-4 gm/day.
iii. Calcium carbonate can
be used. It is also a
phosphate binder, and
corrects hypocalcaemia
i. Recombinant human
erythropoietin 50-100
units per SC 2-3 times
a week.
ii. Oral ferrous fumerate.
iii. Packed cell transfusion.
i. Dietary restriction of
cholesterol and satu-
rated fat.
ii. 3-hydroxy-3-methyl-
glutaryl (HMG) coen-
zyme (a reductase inhi-
bitor) improves lipid
profile.
i. Water and salt intake
controlled
ii. Loop diuretic
iii. ACE inhibitor moni-
tored by ser. creatinine
level. Dont use if ser.
creatinine above 3 mg/
dl.
contd...
588 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

i. Blood transfusion
ii. Desmopressin (25 microgram IV every 8-12 hours for
2 dosages)
iii. Conjugated oestrogen 2.5-5 mg orally for 5-7 days.
Osteodystrophy
1. Components: Osteodystrophy consists of:
a. Mainly:
i. Osteitis fibrosa (Secondary hyperparathyroidism)
ii. Osteomalacia
b. Less frequently:
i. Osteoporosis
ii. Osteosclerosis
2. Clinical manifestation: Bone pain and proximal muscle weakness
3. Mechanism:
Chronic Renal Failure

Anorexia Loss of renal parenchyma

↓
Low food Phosphate Decreased 1,25 Metabolic Retention of
calcium retention (OH)-D3 synthesis acidosis toxic metabolite

Hyperphos- Less calcium a. Osteomalacia Decrease in respon-

phataemia absorption from gut b. Osteoporosis due to siveness of bone to
dissolution of bone 1,25 (OH) 2-D3
buffers
Hypocalcaemia

Secondary hypoparathyroidism

1. Osteitis fibrosa, 2. Osteosclerosis

4. Management of Osteodystrophy
Control of serum phosphate Adequate calcium intake Vitamin D
(3.5-0.5 mg per dl): Oral calcium 1-2 gm/day after i. Vit. D2 or D3 50000 to
a. Restrict phosphorus serum phosphate is con- 250000 IU (1.25-6.25
intake in diet to 600-
trolled. mg per day).
800 mg/day. ii. Dihydrotachysterol
0.25-2 mg/day.
b. Phosphate binders: iii. 1,25 dihydroxy vitamin
Calcium carbonate and D3 (calcitrol) 0.5-1.0
alm. hydroxide. microgram/day.
iv. Paricalcitrol (synthetic
vitamin D analog) three
times weekly. More
effective than calcitrol
Parathyroidectomy
Indications: Severe secondary
hyperparathyroidism with
bone erosion.
+
Persistent hypercalcaemia
(Ser. calcium above 11.5-
12 mg/dl).
or
Extraskeletal calcification.
or
Refractory pruritus.
or
Ischaemic ulcer and necrosis.
Diet
Chronic Renal Failure| 589

Protein Calories Sodium and fluid

a. Low protein diet: Protein
reduced to 0.6-0.8 gm/kg per
day.
b. Protein of high biological
value (egg, fish, meat and milk
products) recommended.
c. Supplements of essential
aminoacids (EAA) or keto-
acids (KA). EAA 10-20 gm/
day. Disadvantage of EAA:
Costly and poor acceptibility.
d. Low protein diet often have
deficiency of water soluble
vitamins specially pyridoxin
and folic acid. Pyridoxin
50 mg and folic acid 1-5 mg
daily should be given.
Adequate caloric a. When GFR decreases below 10 ml/
intake (35-50 kcal per minute kidney cannot handle sodium,
kg per day) needed to resulting in excessive sodium and
prevent endogenous water retention, oedema, hypertension
catabolism. and CCF.
Less caloric is needed Treatment:
in obese and more in i. Sodium and water restriction.
underweight patient. ii. Diuretics: Frusemide or metalozone
augments diuretic effect of frusemide.
Potassium sparing diuretics (spiro-
nolactone) should be avoided to
prevent hyperkalemia.
b. Failing kidney also cannot conserve
sodium, if sodium intake is not
adequate resulting in hyponatraemia.
Treatment: Salt liberalised
c. Fluid intake equal to daily urine output
+ 500 ml of insensible loss.

Treatment of Endstage Renal Failure Refractory to Conservative Management

I. Dialysis:
Indications:
A. ARF with hypercatabolic states (burn, septicaemia, crush injury) and multiple organ failure:
1. Clinical:
Symptoms Complications
a. Neurologic: a. Cardiovascular:
• Encephalopathy • Pericarditis
• Seizure • Hypertensive encephalopathy
• Resistant heart failure
• Pulmonary oedema
b. Urinary: b. Bleeding disorders:
Urinary oliguria less than 300 mg/day • Coagulopathy
• Bleeding diathesis
c. Fluid overload unresponsive to diuretics
2. Biochemical criteria:
• Blood urea above 200 mg/dl
• Serum creatinine above 10 mg/dl
• Serum potassium above 6 mEq/L
• HCO3 above 10 mEq/L
• pH less than 7.2
• GFR 10 ml/min (15 ml/min in diabetics)
590 |
B. CRF:
Bedside Approach to Medical Therapeutics with Diagnostic Clues

1. Clinical
Major uremic complications:
a. Neurologic:
• Encephalopathy
• Seizure
• Neuropathy
b. Cardiovascular:
• Pericarditis
2. Biochemical:
• Creatinine clearance less than 8 ml/min (Less than 10 ml/min in diabetic)
• pH less than 7.2
• Serum potassium above 6 mEq/L
• GFR: 10 ml/min (15 ml/min in diabetic)
• Serum creatinine 8 mg/dl (6 mg/dl in diabetic)

Types of Dialysis
1. Haemodialysis:
a. Procedure: Needs constant flow of blood along one side of a semipermeable membrane with a
cleansing solution or dialysate, on the other.
Diffusion and convection allow the dialysate to remove unwanted substances.
Vascular access:

By arteriovenous fistula: Prosthetic shunt: Infection,

Lasts longer than prosthetic thrombosis and aneurysm
shunt formation more than fistula
b. Duration: Usually required 3 times a week. Session lasts for 3-5 hours.
2. Peritoneal Dialysis:
a. Procedure: Peritoneal membrane (visceral and parietal layers) is the dialyser, fluids and solute
move across the capillaries that lie between the membrane layers into the dialysate. Dialysate
enters the peritoneal cavity through a catheter. Patient exchanges with dialysate 4-6 times a day.
There are two methods:
i. Continuous ambulatory peritoneal dialysis (CAPD).
ii. Continuous cyclic peritoneal dialysis (CCPD).
Utilises a cycler machine to automatically perform exchange at night.
b. Complications:
i. Peritonitis usually due to S. aureus
ii. Abdominal pain, diarrhoea, constipation, fever.

Survival Rate of Dialysis

i. 5-years survival rate:
a. 8% for diabetic
b. 40% for glomerulonephritis
ii. Average life expectancy of patient undergoing dialysis: 3-4 years
II. Kidney Transplantation
Chronic Renal Failure| 591

A. Types:
Cadaveric donor Living related or unrelated donor
• Immunosuppressive drugs:
• Corticosteroids, azathioprine,
• Mycophenolate mofetil, cyclosporin.
• Cadaveric transplant requires
stronger immunosuppression
than living transplant.
B. Absolute contraindications to kidney transplantation:
• Active infection
• HIV infection
• Disseminated malignancy
• Uncontrolled psychosis, drug abuse
• Advanced cardiovascular, respiratory and liver diseases
• Severe congenital urinary tract abnormalities
C. Survival rate
1-5 years in 83 to 93% for living donor and 74 to 85% for cadaveric donor. Transplanted patients’
life becomes normal.
 Kidney
95
Urinary Tract Infection

Classification
I. Acute:
a. Lower urinary tract infection:
Urethritis, cystitis, prostatitis
b. Upper urinary tract infection:
Acute pyelonephritis
II. Chronic: Chronic pyelonephritis

Aetiological and Pathological Consideration

I. Organisms associated with upper urinary tract: 1. Gram-negative:
a. Non-catheter associated:
K. coli 85%
Proteus, Klebsiella, Enterobacter and Pseudomonas
b. Catheter associated:
Proteus, Klebsiella
2. Gram-positive: Staphylococcus
3. Fungal infection: Due to long-
standing catheterisation, prolonged
antibiotic therapy and immuno-
compromised patients.
II. Organisms associated with lower urinary tract (Cystitis and urethritis) C. trachomatis, Gonorrhoea,
Trichomonas, Candida, herpes, E. coli, staphylococci, chlamydial infection.

Route of Infection
i. Ascention of pathogens from bladder and prostate
ii. Haematogenous spread (only 3%).

Aggravating Factors
Age
Sexual activity
Obstruction by tumour, stricture, stone, prostatic enlargement
Neurogenic bladder:
|
Urinary Tract Infection 593

Due to spinal cord injury, tabes dorsalis, multiple sclerosis, diabetes.

Vesico-urethral reflux in children.

Clinical Consideration

Acute Cystitis Acute Urethritis Acute Prostitis Acute Pyelonephritis

Symptoms: Dysuria, fre- Symptoms: Dysuria fre- Symptoms: Fever, chill, Symptoms: Fever 103° F,
quency, urgency, supra- quency dysuria shaking chill, nausea,
pubic pain, strangury, Signs: Pyuria Signs: Tender prostate vomiting, diarrhoea
low back pain. Signs: Marked tender-
Signs: Urine cloudy, ness on deep pressure in
malodorous and bloody costovertebral area and
in 30% cases, tender abdominal palpation.
urethra and suprapubic Complications: Persis-
region. tent flank pain, fever and
leukocytosis unrecessive
to adequate chemo-
therapy suggests papil-
lary necrosis, perinephric
abscess or renal car-
buncle
Diagnostic Evaluation
Enumeration of the number of bacteria in the urine is extremely important investigation in UTI.
A. Urine examination (freshly voided: Sympto- Number of bacteria diagnostic of UTI (excludes
matic infection: contaminants)
a. Males 105 or more bacteria per millilitre
b. Females 102 - 104
B. Asymptomatic patients: 2-3 consecutive urine 105 or more per millilitre of urine
should be examined bacteriologically
C. Direct microscopic examination of a gram If bacteria found it is assumed that the number
stained film of uncentrifused freshly voided present about 100,000 per millilitre
urine
D. Suprapubic aspirate or urine obtained by 102 or more per millilitre
catheterisation

Investigations of Different Entities of Acute UTI

Urethritis Cystitis Prostatitis Acute pyelonephritis

i. Negative urine cul- i. Pyuria with bacteri- i. Urine culture posi- i. Urine: Pus cell casts
ture in presence of uria. Pyuria without tive ii. Urine culture posi-
dysuria and fre- bacteriuria suggests ii. Culture of urethral tive
quency and pyuria. tuberculosis. discharge after pro- iii. Blood culture may
static massage. be positive.
contd...
594 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

ii. Sterile pyuria sug- ii. Organisms revealed by iv. WBC: Leukocytosis.
gests tuberculosis. urine culture and v. Excretion urography
microscopy of stained reveals stone and con-
film. genital malformation.
iii. Excretion urography is vi. Blood urea and serum
indicated in children creatinine for renal
and women to detect function.
treatable abnormalities. vii. Ultrasound of kidney,
iv. Micturiting urography ureter, and bladder for
indicated in children. anatomical and physio-
v. Ultrasound. logical anomalies.

TREATMENT OF ACUTE URINARY TRACT INFECTION

Therapeutic Principles
i. Treatment is based on urine culture and sensitivity and positive gram stain.
ii. Management of predisposing factors: Obstruction by stone, tumour and stricture, neurogenic bladder
should be corrected if possible.
iii. Lower urinary tract infection has special consideration:
a. Response to lower dosages of antibiotics and short course may be needed. Seven days course is
enough.
b. Even single dose antibiotic may eradicate infection.
iv. Upper urinary tract infection:
a. Requires long course of treatment—2-6 weeks course may be required.
b. Single dose or even 7-days course therapy fail.

TREATMENT OF LOWER URINARY TRACT INFECTION (ACUTE)

Urethritis
In sexuality active females: In males:
a. Attendance to vaginal and/or cervical infection Best drugs:
b. Attendance to perineal hygiene a. Amoxicillin 500 mg q.d.s. for 7 days
c. Stop rubber, vaginal spray or spermicidal jellies b. Trimethoprim 200 mg b.d. for 7 days
d. If symptom is related to sexual intercourse, a
trial of postintercourse antibiotics (cotrimoxa-
zole 1 tab, trimethoprim 50 mg, nitrofurantoin
50 mg or norfloxacin 400 mg) may be given after
intercourse.
e. Sometimes diazepam 5 mg t.d.s. daily bring
relief.
f. Chlamydia trichomates: Oral doxycycline
(100 mg b.d.) or tetracycline (500 mg q.d.s.) for
7 days.
Prostatis:
|
Urinary Tract Infection 595

Treatment is difficult because few antibiotics penetrate the prostatic fluid.

Drugs penetrating prostatic fluid
Drugs Course in Acute Course in Chronic Recurrent Infection
Infection Infection
a. Trimethoprim 200 mg b.d. 4-6 weeks Prolonged low dose
or 7 days suppressive therapy
b. Erythromycin 500 mg q.d.s. (trimethoprim
or 100 mg or erythro-
c. Doxycycline 500 mg q.d.s. mycin 2 caps)
or
d. Norfloxacin 400 mg b.d.
or
e. Ciprofloxacin 500 mg b.d.

Surgical Treatment
If acute prostatis is due to staphylococcal infection surgical drainage of prostatic abscess is necessary.
Cystitis
A. First choice of drugs:
Cotrimoxazole 200 mg b.d. for 7 days
or
Trimethoprim 200 mg b.d. for 7 days
or
Nitrofurantoin 500 mg t.d.s. for 7 days
or
Nalidixic acid 100 mg t.d.s. for 7 days
B. Single dose therapy: Amoxicillin 3 gm
C. Recurrences: There are two types of recurrences:
Relapses Reinfection
Occurs soon after cessation of treatment due to treatment Usually occurs 6 weeks after
failure. It is commonly associated with renal infection. High cessation of treatment due to
fluid intake is always helpful. failure of host defence mechanism:
Treatment based on cause of relapse: a. Provide the patient with one
week course of treatment to
1. Causes of relapse Remedies
be taken at the first evidence
• Wrong choice of Treat according to culture
of recurrence
drug and sensitivity
b. In elderly if prostate is
enlarged, it should be
• Inadequate duration Ensure 7-10 days course
operated upon
of treatment
• Low-dose of drug High-dose treatment
• Stone Removal
596 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

2. Suppressive therapy: Low-dose antibiotics: Nitrofurantoin 50 mg, trimethoprim 100 mg, co-
trimethoxazole 1 tab or cephalexin 125 mg nightly for long duration (one-year).
3. Infection related to sexual intercourse: A single dose of NFT 50 mg, trimethoprim 100 mg, co-
trimethoxazole 1 tab or cephalexin 125 mg after intercourse.

TREATMENT OF ACUTE PYELONEPHRITIS

Dealt under the following heads:
I. Asymptomatic bacteriuria (covert bacteriuria):
II. Symptomatic patients:
(a) Uncomplicated (b) Complicated (c) Recurrent infection
I. Asymptomatic Patients:
a. Better left untreated.
b. But treat the following categories of patients—pregnant, diabetic, polycystic kidney,
neurogenic abnormalities, immunocompromise patients—without symptoms but with
significant bacteriuria because they are at higher risk of developing symptomatic infection:
I. Symptomatic Patients:
A. Uncomplicated patients:
1. Mildly symptomatic cases:

Single oral dose therapy Multidose therapy

Amoxicillin 2-3 gm, trimethoprim- Norfloxacin 400 mg b.d. for 7 days
sulfamethoxazole (bactrim, septran) Ciprofloxacin 500 mg b.d. for 7 days.
2 double strength tabs, trimethoprim
400 mg and doxycycline 400 mg.
2. Severe cases:

With normal renal function With renal insufficiency

Ampicillin 1 gm IV 6 hourly + gentamicin Third generation cephalosporin
1.5 mg/kg loading dose followed by 1 mg/ (taxim) IV for first 48 hours.
kg every 8 hours IV for first 48 hours.

After initial response oral antibiotics should be

continued for 4-6 weeks:
Effective drugs: Tetracycline, amoxicillin or ampicillin, cotrimoxazole,
nitrofurantoin
↓
Follow-up urine culture 1 week after completion of therapy.
B. Complicated patients: It is difficult to eradicate the infection and best left untreated under
certain circumstances. Treat acute episode.
1. Structural evaluation: By IV pyelography, ascending/retrograde pyelogram or micturiting
cystourethrogram which will detect vesicoureteric reflux, posterior urethral valve,
ureterovesical or ureteropelvic obstruction and ureteric and bladder diverticuli. Appropriate
surgical correction should be advised.
 2. Urinary culture and sensitivity:
|
Urinary Tract Infection 597

Organisms isolated Suggested antibiotics

Proteus • Cephalosporin
• Cephalexin 250 mg q.d.s. or 500 mg t.d.s. depen-
ding upon bodyweight whether above or below
Resistant E. coli, Klebsiella, Pseudomonas 50 kg
• Gentamicin
• Netilmicin
• Amikacin
• Tobramycin
They are nephrotoxic. Single daily dose therapy
c. Recurrent infection: should be given to obviate this problem.
1. Treatment of each episode
2. Prophylaxis:
i. Nitrofurantoin
ii. Trimethoprim or cotrimoxazole
iii. Urinary antiseptics: Methenamine mandelate with acidification of urine by vitamin (1000 mg
per day): Used after infection is eradicated by more effective drugs. Prophylaxis should be
given for 3-6 months.
Prophylaxis is ineffective in patients with indwelling catheter and with structural abnormalities
of urinary tract.
3. Advise patients to drink fluid generously and asked him to void frequently.
d. Treatment of UTI in young:
i. Treatment of hidden foci of sepsis in prostate, cervix and Bartholin’s glands of vagina. See
treatment of prostatitis.
ii. Treatment of both sexual partners.
e. Treatment of UTI in pregnancy:
i. First trimester: Ampicillin/amoxicillin or cephalexin given for 10-14 days.
↓
If relapse occurs:
Long-term therapy with suppressive dosages of cephalexin given at bedtime.
ii. Second and third trimester: Obtain organisms from culture: Nitrofurantoin 50 mg q.d.s. or
nalidixic acid 500 mg q.d.s. can be resorted to.

CHRONIC PYELONEPHRITIS
Aetiological and Pathological Consideration
Aetiology
I. Obstructive chronic pyelonephritis: Urethral stricture, stone, enlarged prostate, bladder stone and
tumour, ureter and kidney stone, tuberculosis, ureter obstruction by extension of cervical and
prostatic cancer and external compression by abdominal malignancy.
II. Non-obstructive:
a. Ascending urinary tract infection from bladder and prostate
b. Vesicourethral reflux in children
c. Neurogenic bladder
598 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Pathogenesis
Recurrent bacterial infection ascending from prostate and bladder and less frequently haematogenous
spread to kidney leads to:

Focal scarring of kidney resulting in High blood pressure

smaller and scarred kidney

Renal failure

Clinical Consideration
Symptomatic less common: Asymptomatic more common
Hypertension, few patients present with end
stage renal failure characterised by nocturia,
letharginess, weakness, nausea and vomiting

Diagnostic Evaluation
Urine Examination Urine Culture Renal Function Radiological
• Bacteriuria in some Usually sterile Impair as shown Excretion urography:
• Pyuria and pus cell by raised blood urea Cortical scarring, dilated
cast in some and serum creatinine calyx, irregular outline,
of renal pelvis

Treatment of Chronic Pyelonephritis

I. In children with infection and vesico-ureteric reflux
a. Every effort should be made to eradicate infection by long-term low dose suppressive treatment.
b. Child is advised to practice double or triple micturition (emptying bladder at bed time with two
additional voiding at night).
c. Tend to clear spontaneously as the child grows older.
II. In adult
a. Adequate treatment of hypertension
b. Appropriate antibiotic therapy as detailed in acute pyelonephritis
c. Obstructive lesions should be corrected surgically as much as possible
d. Treatment of chronic renal failure. See separate chapter.
 Kidney
96
Urinary Incontinence

DIAGNOSTIC EVALUATION
Flow Chart
Types of Incontinence Cause Symptoms Signs
I. Total incontinence i. Loss of sphincter effi- Loss of urine all the time and i. Vesicovaginal and
ciency due to previous in all positions. ureterovaginal fistula
surgery, nerve damage can be demonstrated.
and cancerous infiltra- ii. PR examination: Lax.
tion. anal sphincter, loss of
ii. Vesicovaginal and ure- bulbocavernous reflex.
terovaginal fistula.
II. Stress incontinence: i. Laxity of pelvic floor Loss of small volume of urine PR examination: Normal anal
muscle in multiparous during coughing, sneezing, sphincter.
women or after pelvic exercising.
surgery or ageing. No leak in supine position. Neurological abnormalities
ii. Descent of bladder Uncontrolled loss of urine (spasticity, flaccidity, rectal
neck. preceded by strong urge to sphincter tone).
III. Urge incontinence: Results from detrusor hyper- void. Not related with posi- PR examination: Tender
reflexia or sphincter dysfunc- tion, coughing, sneezing and levator ani.
tion due to inflammatory or exercising.
neurological disorder of Dribbling of small amount of Distended bladder.
bladder. urine due to overfilled
bladder.
IV. Overflow incontinence: Due to bladder distention
with overflow.
⇓
LABORATORY FINDINGS
Urine Analysis Renal Function Cystogram Ultrasonography
Urinary tract infection Abnormality of renal i. Demonstrates site Postvoidal residual urine
points to urge inconti- function suggests over- of fistula. volume is assessed by
nence. flow incontinence. ii. Lateral stress cysto- catheterisation and ultra-
gram may show sonography.
descent of bladder
neck greater than
1.5 cm in stress
⇓ incontinence.
600 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

⇓
Special Tests
Indications: i. Moderate to severe incontinence
ii. Neurological disorders
iii. Urge incontinence when infection and neoplasm excluded

To assess bladder disturbances To assess sphincter disturbances

Cystometry is done by filling bladder i. Urethral profilometry
with fluid and simultaneously recording ii. Electromyography
intravesical pressure: iii. Combined video studies

Filling phase of bladder Voiding phase of bladder Response to medication Bethane-

Uninhibited contraction a. Increased urinary capacity points to chol IV
points to urge inconti- incontinence, infection, interstitial i. Lack of response points to
nence, infection, inters- cystitis, UMN lesion, and post- intrinsic muscle damage.
titial cystitis, UMN operative changes. ii. An exaggerated response
lesion and postoperative b. Increased bladder capacity points to point to LMN lesion.
changes. chronic urinary tract obstruction,
LMN lesion and sensory neuropathy.

TREATMENT
Types of Inconti- Surgical treatment Medical Treatment
nence
Total incontinence a. Congenital and acquired causes
needs surgical correction
b. Periurethral collagen injection
c. Placement of artificial sphincter
Stress incontinence Bringing down the bladder neck to appro- Mild cases: Phenylpropanolamine
priate position 50 mg orally. It increases urethral resis-
Urge incontinence Sacral nerve stimulation in refractory tance
cases a. Antispasmodic: Oxybutynin 5 mg
t.d.s. orally
b. Anticholinergic: Propantheline
15 mg t.d.s. orally
c. Tricyclic antidepressant: Imipra-
mine 25-75 mg orally at bedtime
Over flow inconti- a. Benign hypertrophy of prostate: d. Antispasticity drug: Beclofen in
nence Prostatectomy neurogenic bladder
b. Urethral stricture: a. BHP: Pharmacotherapy. See
Urethrotomy chapter on BHP
or b. Neurogenic bladder: Intermittent
Urethroplasty catheter regimens with or without
pharmacotherapy bethanechol
chloride 50-100 mg/day may
improve emptying
 Kidney
97
Nephrolithiasis

Factors Increasing Stone Formation

1. Environment: High humidity and elevated temperature as in tropics and summer
2. Diet and fluid:
a. Increased sodium intake and decreased fluid intake
b. Excess intake of oxalate and purine rich diet—form oxalate and uric acid urine respectively
3. Occupation: Sedentary occupation
4. Genetic factor as in cystinosis and distal tubular acidosis.
Major types of stone Pathogenesis:
I. Hypercalciuric calcium stone Renal stones form by an initial crystal-
a. Absorptive type I ⎫ lization of a nidus (nucleation) from a
b. Absorptive type II ⎬ See further supersaturated urine with subsequently
c. Absorptive type III ⎭ crystal formation and its growth and
d. Reabsorptive hypercalciuric calcium stone aggregation of the nidus into a stone.
e. Renal hypercalciuric calcium stone
II. Hyperuricosuric calcium stone
III. Hyperoxaluric calcium stone
IV. Uric acid stone
V. Cystine stone
VI. Struvite stone.

Clinical Consideration
Only obstructive stones produce symptoms

Colic: Haematuria Sterile pyuria Predisposition Oliguria and

• Onset: Sudden to urinary tract ARF when both
• Site: Flank infection calyceal systems
• Severe are blocked.
• Radiation: Anterior over abdomen
• Progression of stone downward:
Along ureter referred to ipsilateral
testes or labium
602 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Diagnostic Evaluation
Flow Chart
I. Uncomplicated first time stone former: Initial screening:
First step: Secure stone for analysis if at all possible. See further “characteristic of stone”.
↓
Followed by carefully taken history:

Family history Patient with gout: History of chronic High purine Excessive ingestion
If positive suggests: Points to uric acid diarrhoea, ileal intake in diet of vitamin D and C
Commonly primary stone or calcium disease or intesti- Suggests: Hyper- and oxalate rich
idiopathic hyper- oxalate stone. nal surgery: uricosuric and food (spinach and
calciuria or rarely Suggests calcium calcium oxalate brewed tea)
cystinuria, primary oxalate stone or uric stone. Suggests oxalate
hyperoxaluria or acid stone. stone.
type I renal tubular
acidosis. ↓
Followed by Laboratory Investigation:
Urine analysis Urine culture sensitivity Routine blood screening
For recognition of stone by If positive for pseudomonas, a. Primary hyperparathyroi-
biochemical analysis: Urine Klebsiella, or staphylococcus dism is suggested by hyper-
calcium, phosphorus, oxalate with alkaline urine, suggests calcaemia plus hypophos-
and uric acid. struvite stone. phataemia.
b. Gout suggested by hyper-
↓ uricaemia.
Next, Imaging:

Plane X-ray abdomen IVP Ultrasound

i. Radiopaque stones: Calcium Shows stone and anatomy of Shows obstructing stone and
stone, struvite stone, cystine stone. kidney. renal anatomy.
ii. Radiolucent stone: Uric acid
stone.
iii. Staghorn stone points to struvite
stone and cystic stone.
iv. Nephrocalcinosis: Due to deposi-
tion of calcium salts in renal
parenchyma:
a. Finely stippled nephrocalci-
nosis suggests long-standing
hypercalcaemia.
b. Dense coarse nephrocalcinosis
points to primary hyperoxa-
luria or renal tubular acidosis.
 Nephrolithiasis

II. Recurrent stone formation or patient with family history of stone disease (in-depth evaluation).
| 603

Laboratory Investigation
Urine analysis Blood screening
Find out 24 hours urinary: • Serum calcium
• Volume • Serum parathyroid hormone (PTH)
• pH: • Serum calcium load test (consult larger text-
book)
i. Persistent pH below 5 suggests • Serum HCO3
uric acid or cystine stone • Serum sodium
ii. Persistent pH above 7.5 suggests • BUN, creatinine
struvite stone or type I renal tubular acidosis • Phosphorus
• Calcium
• Uric acid Absorption test:
• Oxalate A measure or renal intestinal
• Phosphate absorption of calcium (from
• Sodium urinary calcium level during
• Citrate fasting and excessive ingestion
• RBC of calcium).
↓
Next, proceed for imaging:
First arrange for plane X-ray abdomen and ultrasound:
Plane X-ray abdomen Ultrasound examination Stone located at uretero-
Detects radiopaque stone. See above Renal ultrasound: Detects vesical junction can be
most stones and evaluate detected by:
anatomy of kidney and a. Abdominal ultrasound
calyceal system with the aid of acous-
tic window of a full
bladder.
b. Transvaginal or trans-
↓
rectal ultrasound.
If diagnosis uncertain:
Spiral CT scan: IV urography Isotope renography
Evaluates causes of flank pain with sensitivities for Detects stone and evaluates Informs about renal func-
kidney stone exceeding those of ultrasound and IV anatomy of kidney and tion
urography. collecting system.
If fails to show kidney:
a. Retrograde urography is
done
b. Percutaneous (entering
kidney through renal
pelvis) antegrade uro-
graphy. It reduces the
need for retrograde
urography.
604 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Characteristics of Renal Stone

Types Morphology Incidence Cause Diagnosis

I. Calcium stone Calcium oxalate 75-85% most Serum Urine

stone: Biconcave, common Calcium, Calcium,
oval like RBC, phosphorus, oxalate,
dumble shaped. PTH, uric acid pH
Radiopaque Vitamin D cystine,
uric acid culture
A. Absorptive
type: Secondary
to increased
absorption of
calcium from
small bowel:
i. Type I Calcium, Calcium
phosphorus, normal
PTH, vitamin
D normal
ii. Type II do do
iii. Type III a. Calcium and Calcium high
PTH normal
b. Phosphorus low
c. Vitamin D high
(renal phosphate
leak increases
vitamin D
synthesis)
B.Reabsorptive Calcium, PTH and Calcium high
type: Secondary vit. D high. Phos-
to hyperthyroi- phorus low
dism.

C.Renal hypercal- a. Calcium and Calcium high

ciuria: Renal phosphorus
tubule unable to normal
reabsorb filtered b. PTH and Vit. D
calcium. Spilling high.
urinary calcium
leads to secon-
dary hyperpara-
thyroidism.

D.Hyperuricosuric Uric acid above 750

calcium stone. per 24-hr in women
Due to: and 800 mg per
i. Dietary excess 24-hr in males. pH
of purine above 5.5.
contd...
contd...
|
Nephrolithiasis 605

ii. Uric acid meta-

bolic defect in
hereditary.
E. Hyperoxaluric Urine oxalate inc-
calcium stone: reased
i. Due to primary
intestinal dis-
order frequen-
tly associated
with diarrhoea
and steatorr-
hoea. Increased
bowel fat +
intraluminal
calcium for-
ming soap like
product.
Calcium is
therefore un-
available to
bind to oxalate
which is then
freely and
rapidly absor-
bed leads to
stone forma-
tion.
ii. Hereditary
hyperoxaluria.
iii. Excess oxalate
in diet. Hyperuricaemia Urine pH less than
II. Uric acid stone. Red orange, tear 5-8% Due to: may be present 5.5
drop shape; flat, i. Gout
opaque, squire ii. Idiopathic
plates. iii. More frequen-
Relatively radiolu- tly in patients
cent but most have with high pro-
calcium content and tein diet and
can be visualised on highly acid
plane X-ray abdo- and concen-
men. trated urine.
iv. Other contri-
buting factors:
Myeloproli-
ferative disor-
ders, malig-
nancy, abrupt
and dramatic
contd...
606 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

weight loss and

uricosuric drugs.
Lemon yellow, sparkle, 1-3% Congenital cystinuria Elevated cystine in
III.Cystine stone: flat hexagonal plates. urine

IV. Struvite stone: Rectangular, prism like 10-15% Due to infection with Urine culture +
coffin lid, staghorn proteus, pseudomo-
stone. nas, klebsiella, Staph.
mycoplasma. A mag-
nesium ammonium
phosphate stone.
TREATMENT OF NEPHROCALCINOSIS
Treatment of Individual Stone Episode
Conservative treatment:
I. Renal colic: Pethidine is advised.
II. Patients kept under surveillance:
a. Stone causing colic but without infection and obstruction as shown by imaging between the
attacks of colic may pass spontaneously.
b. Stone measuring less than 5 mm in diameter on plane X-ray of abdomen may also pass
spontaneously or migrate to lower part of urinary tract from where they can be easily removed
by endoscopic procedure.
Spontaneous passage of stone is occasionally aided by high fluid intake, if necessary by IV
fluid and the effect may be augmented by a short course of IV frusemide.
c. Pelvicalyceal stones should not be treated surgically unless they are greater than 5 mm in diameter
or cause obstruction.
The above situations need constant supervision and kept under surveillance by abdominal radiography
or ultrasound every 6-8 weeks to assess the migration of stone.
III. Urinary tract infection with partial ureteric obstruction should be treated vigorously with antibiotics
according to sensitivity.
IV. Treatment of individual stone:
Types of stone Drugs Mechanism of action Dose Comments
Calcium stone:
A. Absorptive type I: Cellulose phosphate Chelating agent. It 10-15 gm in three divi- Long-term use without
binds to calcium and ded dosages with metabolic evaluation
impedes small bowel meals. leads to:
absorption due to inc- • Negative calcium
reased bulk. balance
• Hypomagnesaemia
• Secondary hyperoxa-
luria
• Recurrent stone for-
mation.
Decreases renal cal- Increases bone density
Thiazide cium excretion but no
contd...
contd...
Nephrolithiasis | 607

effect on intestinal
absorption.
Dietary restriction of
B. Absorptive type II: No drug calcium to 50%
C. Absorptive type III: Orthophosphate Inhibits vitamin D 0.5 gm t.d.s.
synthesis Surgical resection of
D. Reabsorptive type: No drug adenoma of parathy-
roid.

Effective long-term
E. Renal hypercalci- Thiazide therapy.
uria calcium stone:

F. Hyperuricosuric See uric acid stone

calcium stone: below
Increased fluid intake.
G. Hyperoxaluric Calcium supplement if Compensates for loss
calcium stone: diarrhoea not control- of calcium
led
Uric acid stone: Potassium citrate Increases urinary pH to Liquid prep. or tab.
(alkali) 6.5, increases solubility (10 mEq) two 3-4 times
and can dissolve stone a day

Allopurinol Decreases uric acid 300 mg/day Indicated if hyperuri-

caemia is present or
alkali fails.
Low animal protein
and purine diet
advised.
Cystine stone: i. Alkalisation of Increased fluid intake
urine above pH 7.5 about 3 titres/day.
ii. Pencillamine
iii. Triopronin They are large and
Struvite stone: hence amenable to per-
cutaneous nephroli-
thotomy.
Special remarks on the treatment of commonest stone, i.e. calcium stones:
General:
i. High fluid intake
ii. Avoid vitamin D and C
iii. Avoid calcium containing antacids
iv. Less intake of dairy products
v. Avoid oxalate rich diet and beverages. Tea contains much oxalate.
Drugs in idiopathic calcium stones:
Thiazide 5-10 mg/day with potassium supplement
↓
If fails:
608 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Cellulose phosphate 5-30 gm/day

↓
If fails:
Combined thiazide + Cellulose phosphate

Surgical Treatment
Usual Indications:
i. Renal colic with infection
ii. Stones causing obstruction between attacks of renal colic
iii. Impaired or deteriorating renal function
iv. Absence or poor function of contralateral kidney
v. Bilateral ureteric stones.

Emergency Surgery
Associated fever due to infection and pain is a medical emergency and require immediate surgery:
Prompt drainage by urethral catheter or by a percutaneous nephrostomy under cover of antibiotics.

Elective Surgery
A. Ureteral stones: Stones less than 6 mm in diameter as seen on plane X-ray abdominal radiograph
will usually pass spontaneously and conservative management with pain medicines is appropriate.
↓
If fails:
⇓
Distal ureteric stone: Proximal and midureteric stone
a. Ureteroscopic stone extraction: a. ESWL tried first
Indications for early intervention: b. Rarely ureteroscopic stone extraction
i. Severe pain unresponsive to medications required
ii. Fever indicating infection
iii. Nausea and vomiting
iv. Requiring early return to work
v. Anticipated travel
b. Extracorporeal shockwave lithotrophy (ESWL):
Done under anaesthesia as an outpatient procedure.
Most stone fragments will pass uneventfully
within two weeks, if have not passed within three
months, needs surgical intervention.
B. Renal stone
Patient with renal stone without pain, UTI or obstruction need not be treated by surgery. They
should be followed with serial abdominal radiographs or ultrasound examination.
Indications for Surgical Intervention
|
Nephrolithiasis 609

a. If stones are growing

b. If stones become symptomatic:

ESWL Percutaneous nephrolithotomy

Indications: Indications:
Stone less than 3 cm in diameter i. Stones larger than 3 cm in diameter
ii. Stones located in inferior calyx.
 Kidney
98
Benign Prostatic Hyperplasia (BPH)

BPH is probably the most common neoplastic growth of prostate in men above the age of 40 year.

Aetiological Consideration
The aetiology of BPH is multifactorial. Two factors are recognised:
Ageing Hormonal control
Animal experiments suggest secretion of Positive correlation exists between free
growth hormone which induces BPH testosterone-oestrogen level and volume of prostate.
Ageing increases oestrogen level inducing androgen
receptors and thus sensitizing the prostate to free
testosterone producing hyperplasia.

Diagnostic Evaluation
Symptoms
Obstructive symptoms Irritative symptoms
Hesitency, decreased force and caliber of Urgency, frequency, and nocturia
stream, sensation of incomplete voiding,
double voiding, postvoidal dribbling

Signs
Physical examination Digital rectal examination
Bladder distension
Exclude bladder stone causing haematuria; i. Smooth, firm, elastic enlargement points to BPH
evidence of urethritis, instrumentation, trauma; ii. Exclude irregular enlargement of prostate due
neurological disease, diabetes and back injury. to cancer
↓
Next, investigate for confirmation
Laboratory findings Imaging (IVP, ultra- Cystography Cystogram and urodyna-
sound) mic profile
i. Urine analysis: Note Indications: Indication: When surgery Indications:
infection by urine i. Concomitant other is contemplated. i. Suspected neurolo-
urinary tract disease gical disorder.
contd...
 culture and haematuria ii. Complications of
Benign Prostatic Hyperplasia (BPH) |
ii. When surgery fails
611

(macroscopic and micro- BPH: Haematuria,

scopic) UTI, renal insuffi-
ii. Serum creatinine for asses- ciency, stone disorder
sing renal function:
a. Prior to surgery
b. If raised warrants upper
urinary tract imaging
iii. Serum PSA:
If raised points to cancer

Treatment
Mild Cases
Mild cases should be managed by watchful waiting on the assumption that some mild cases undergo
spontaneous improvement.

Pharmacotherapy
Drugs Action Oral Dose Advantages Disadvantages
Preparations
Phenoxybenzamine: • Alpha-blocker 5-10 mg b.d. • Safe and effective • Higher side-effect
• Short acting • Degree of sympto- than prazosin due to
matic relief same as lack of specificity for
prazosin alpha receptor.
• Side-effects: Ortho-
static hypotension,
dizziness, tiredness,
retrograde ejacula-
tion, rhinitis, head-
ache
Prazosin: • Alpha blocker • 1-5 mg t.d.s. Safe and effective • Same side-effects but
• Short acting Starting 1 mg at less than prazosin
bedtime for 3 nights,
increasing to 1 mg
b.d. and then 2 mg
b.d. if necessary.
• Minipress XL (Pfizer)
2.5, 5 mg tab Prazo-
press (Sun) 1, 2 mg
Terazosin: • Alpha blocker tab. do do
• Long acting • 1-10 mg/day.
Started 1 mg/day for
3 days increased to
2 mg/day for 11 days,
then 5 mg/day if
necessary.
contd...
612 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

• Olyster (Cadila)
Teralfa (Torrent)
Terapress (Intas)
1 mg, 2 mg, 5 mg tab

Doxazosin: do • 1-8 mg/day do do

Started 1 mg/day for
7 days, increased to
2 mg/day for 7 days,
then 4 mg/day, then
8 mg/day if needed.
• Doxacard (Cipla)
Duracard (Sun)
1 mg, 2 mg, 4 mg tab

Tamasulosin: • Selective alpha recep- 0.4-8 mg/day • Most recent

tor blocker resulting • Less side-effect than
in less side-effect other alpha blocker
• Long acting-once • Safe and effective
daily dose

Finasteride: Blocks 5 alpha reduc- • 5 mg/day, 6-12 • Effective and safe May mask the serum
tase enzyme that blocks months of therapy • Serum PAS reduced PAS (marker of pros-
the conversion of testo- needed by 50% tatic cancer)
sterone to dihydro- • Finast (Dr. Reddy)
testosterone reducing Finacar (Cipla) 5 mg
prostatic hyperplasia tab
Combination therapy: Significant decrease of Efficacy and safety not
Terazosin + Finasteride symptoms tested by double blind
Phytotherapy: clinical trials
Plant extract: Palmato
berry, bark of pygerum
africana, rooperi, pollen
extract
Table 98.1: Comparative chart of treatment of BHP
Effect of treatment Surgical Medical

TUIP TURP Open Watchful Alpha- Finasteride

surgery waiting blocker
Improvement +++ ++++ +++++ + ++ ++
Morbidity and ++ ++ ++ + ++ +++
complications
Impotency +++ +++ +++ ++ ++ +
Retrograde ejaculation ++ +++ +++ 0 + 0
Total incontinence + + + ++ ++ ++

Key: TUIP = Transurethral incision of prostate; TURP = Transurethral resection of prostate

Surgical Therapy
|
Benign Prostatic Hyperplasia (BPH) 613

TURP TUIP Open prostatectomy

Procedure Resection of prostate
endoscopically under
spinal anaesthesia.
Hospital stay 3-5 days
Indications Mild to moderate enlar-
gement.
Disadvantage Retrograde ejaculation
(75%), impotency (5-
10%), urinary incompe-
tence (less than 3%),
bleeding, stricture, perfo-
ration of prostate capsule.
Better relief than laser,
Advantage electrovaporisation,
hyperthermia, needle
aspiration and focussed
ultrasound ablation.
Incision of posterior Removal and enucleation
commisure of prostate of prostate under general
under spinal anaesthesia anaesthesia.
1-3 days. 5-10 days
Mild to moderate enlar- a. Large prostate over
gement 100 gm
b.Associated with
bladder diverticula
and bladder stone.
Impotency, retrograde Impotency, retrograde
ejaculation ejaculation.
More rapid and less mor-
bidity than TURP. Less
retrograde ejaculation.

LESS INVASIVE THERAPY

Laser therapy Transurethral elec- High intensity foc- Transurethral
trovaporization of ussed U/S ablation needle aspiration
prostate
Mechanism Coagulation necro- Heat vaporization Thermal tissue Coagulative necro-
sis ablation sis

Advantage Minimum blood

loss, outpatient sur-
gery

Disadvantage No tissue recovered Take longer time Bladder neck and

for histology. More than TURP median lobe enlar-
irritative voiding. gement not well
Expensive treated. Durability
of response not
known.
614 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

CLINICAL APPROACH TO ANTIMICROBIAL THERAPY

First guess clinically based on organ involved and the organisms causing infection empirical treatment
should be started especially in acutely ill patients after sending laboratory specimens for culture and
sensitivity:

Empirical Therapy for Acutely Ill Patients Pending

Identification of Causative Organisms
Suspected diagnosis based Likely organisms
on organs involved
1. Meningitis, bacterial Pneumococci, meningococci
2. Bacterial meningitis in Pneumococci, meningococci,
above age 50 years Listeria monocytogenes, gram-
negative bacilli
3. Brain abscess Mixed aerobes, pneumococci,
streptococci
4. Acute pneumonia, severe, Pneumococcus, M. pneumoniae,
community acquired Legionella, C. pneumoniae
5. Aspiration pneumonia Mixed oropharyngeal Clindamycin, 0.3 gm
flora including orally 4 times daily
anaerobes for 10-14 days
Treatment of choice
i. Cefotaxime 2-3 gm IV
6 hourly (ceftriaxone, cefta-
zidime, ceftizoxime can be
used)
or
ii. Ceftriaxone 2 gm IV
12 hourly + vancomycin
10 mg/kg every 8 hours
i. Ampicillin 2 gm IV every
4 hours, plus cefotaxime or
ceftriaxone and vancomycin
as in 1.
ii. TPM-SMZ can be used to
treat Listeria monocytogenes
in patients allergic to peni-
cillin.
i. Penicillin G, 4 million U IV
every 4 hours.
or
ii. Metronidazole 500 mg IV
every 8 hours plus cefo-
taxime or ceftriaxone as in 1.
i. Erythromycin (other macro-
lides such as azithromycin or
clarithromycin can be used)
0.5 gm orally or IV four
times daily
or
ii. Doxycycline 100 mg IV or
orally 12 hourly
Phenoxymethylpeni-
cillin 0.5 gm orally
4 times daily for 10-
14 days.
6.Pneumonia S. pneumoniae, Myco-
Benign Prostatic Hyperplasia (BPH)

i. Doxycycline 100 mg Fluoroquinolones

| 615

plasma pneumoniae, b.d. (see below) or

Chlamydia pneumoniae ii. Erythromycin 0.5 gm Amoxicillin 0.5gm
4 times/day or 4 times per day
iii. Clarithromycin 0.5 gm
b.d. for 10-14 days or
iv. Azithromycin 0.5 gm on
day 1,0.25 gm on days 2-5
7.Cystitis E.coli, Klebsiella, i. Fluoroquinolones or i. TPM-SMZ (double
Proteus, Staph. sapro- ii. Nitrofurantoin strength) bd for
phyticus 3 days or
ii. Cephalexin 0.5 gm
orally 4 times daily
for 7 days
8.Pyelonephritis E.coli, K. pneumoniae, Fluoroquinolones: TMP@-SMZ (double
Proteus, Staph. sapro- Ciprofloxacin 500 mg strength tab) b.d.
phyticus orally b.d. or
Ofloxacin 400 mg b.d.
orally or
Levofloxacin 500 mg/day
or sparfloxacin 500 mg
loading dose and then
200 mg/day
9.Gastroenteritis Salmonella, Shigella, i. For Salmonella: Do not
Campylobacter, E.histo- needs treatment
lytica ii. Shigella: TPM-SMZ
(double strength) b.d.
for 5 days or
Ampicillin 0.5 gm 4 times
daily for 5 days or
Ciprofloxacin 500 mg b.d.
X 5 days
iii. Campylobacter: Erythromycin
0.5 gm orally 4 times daily
for 5 days or
Ciprofloxacin
iv. E. histolytica: Metronidazole
750 mg orally t.d.s. for 5-
10 days followed by diiodo-
hydroxyquin 600 mg t.d.s. for
3 weeks
10. Urethritis, N. gonorrhoeae, i. Cefixime 400 mg orally Ceftriaxone 250 mg
epididymitis: Chlamydia once or IM once + doxy-
trachomatis Ciprofloxacin 500 mg cycline 100 mg b.d.
orally once for 10 day for
616 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

ii. N. gonorrhoeae: N. gonorrhoeae

Doxycycline 100 mg
b.d. for 10 days
iii. C. trachomatis:
ofloxacin 300 mg
orally b.d. for 10 days
11. Pelvic inflammatory N. gonorrhoeae, i. Ceftriaxone 250 mg Cefoxitin 2 gm IM
disease C. trachomatis, IM once followed by with probenecid, 1 gm
anaerobes, gram- doxycycline 100 mg orally, followed by
negative rods orally b.d. for 14 days doxycycline 100 mg
orally b.d. for 14 days
12. Syphilis: Treponama pallidum Benzathine penicillin Doxycycline 100 mg
a. Early syphilis G 2.4 million units IM b.d. for 2 weeks
(Primary, secondary once
or latent of less
than 1 year duration)
b. Latent syphilis of Do Benzathine penicillin Doxycycline 100 mg
more than 1 year G 2.4 million units IM orally b.d. for 4 weeks
duration or cardio- once a week for 3 weeks
vascular syphilis) (total: 7.2 million units)
c. Neurosyphilis Do Aqueous penicillin Procaine penicillin G,
G 12-24 million units/ 2-4 million units/day
day IV for 10-14 days IM plus probenecid
500 mg orally 4 times
daily both for 10-14
⇓ days
Next, find out the proved microbial pathogens and modify the treatment accordingly:
Specific treatment of proved microbial pathogens:

Proved microbial Drugs of first choice Alternative drugs

A. Gram-positive:
a. Cocci
i. Streptococcus pneumoniae
(Pneumococcus)
ii. Strep. haemolyticus
A,B,C,G
iii. Staphylococcus viridans
iv. Staphylococcus:
• Methacillin resistant
Parenteral penicillin
Paranteral penicillin
Penicillin ± Gentamicin
Vancomycin ± Gentamicin
± Rifampin
Erythromycin, cephalosporin,
vancomycin, TMP-SMZ, clin-
damycin, azithromycin, clari-
thromycin, tetracycline, imi-
penem, fluoroquinolones
Erythromycin, cephalosporin,
vancomycin, clindamycin, azi-
thromycin, clarithromycin
Cephalosporin, vancomycin
TMP-SMZ, minocycline,
fluoroquinolone
 • Non-penicillinase Parenteral penicillin
Benign Prostatic Hyperplasia (BPH)

Cephalosporin, vancomycin,
| 617

producing imipenem, fluoroquinolone,

clindamycin
• Penicillinase Parenteral nafcillin, Vancomycin, cephalosporin,
producing cloxacillin clindamycin, amoxicillin +
clavulanic acid, ampicillin +
sulbactam, imipenem, fluoro-
quinolone, TPM-SMZ
v. Enterococcus Ampicillin Vancomycin
Severe enterococcal Ampicillin + Gentamicin Vancomycin + gentamicin
b. Gram-positive rods:
i. Actinomyces Penicillin • Tetracycline
ii. Anthrax Penicillin • Clindamycin
Erythromycin, tetracycline,
fluoroquinolone
iii. Clostridium (gas Penicillin Metronidazole, chlorampheni-
gangrene, tetanus) col, clindamycin, imipenem,
iv. C. diptheriae Erythromycin Penicillin
v. Listeria Ampicillin ± TPM-SMZ
Aminoglycoside
B. Gram-negative:
a. Cocci:
i. Moraxella catarrhalis TPM-SMZ Cefuroxime, ceftriaxone, ery-
thromycin, tetracycline, azithro-
mycin, amoxicillin + clavulanic
acid, clarithromycin, fluoroqui-
nolones
ii. N. gonorrhoeae Cefixime, ciprofloxacin, Ceftriaxone, spectinomycin
ofloxacin
iii.N. meningitidis Penicillin Cefotaxime, ceftriaxone, ampi-
cillin, chloramphenicol
b. Gram-negative rods:
i. Acinetobacter Imipenem Minocycline, TPM-SMZ, doxy-
cycline aminoglycoside,
fluoroquinolone
ii. Bacteroids (gastro- Metronidazole Chloramphenicol, clindamycin,
intestinal strains) cefmetazole, ampicillin + sul-
bactam
iii.Brucella Tetracycline + TMP-SMZ ± Gentamicin,
gentamicin Chloramphenicol ± Gentami-
cin, doxycycline + Rifampin
iv. Campylobacter jejuni Fluoroquinolone Tetracycline, erythromycin, azi-
thromycin
v. Enterobacter TPM-SMZ, imipenem Aminoglycoside, fluoroquino-
lone
618 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
vi. E. coli (sepsis)
vii. E. coli (uncomplicated
UTI)
viii. Haemophilus (menin-
gitis)
ix. Haemophilus (respira-
tory infection, otitis)
x. H. pylori
xi. Klebsiella
xii. Legionella (Pneumonia)
xiii. Proteus mirabilis
xiv. Proteus vulgaris
xv. Pseudomonas:
• Aeruginosa
• Pseudomallei
(melloidosis)
• Mallei (glanders)
xvi. Salmonella
xvii. Shigella
xviii. Vibrio (cholera)
xix. Yersina pestes (plague,
tularemia)
C. Spirochaetes:
a. Borrelia burgdorferi
lyme disease)
Borrelia recurrentis
(relapsing fever)
b. Leptospira
D. Mycoplasma
Cefotaxime, ceftrizoxime Imipenem, aminoglycoside,
fluoroquinolone
Fluoroquinolone, nitrofuran- TPM-SMZ, oral cephalosporin
toin
Cefotaxime, ceftriaxone Chloramphenicol
TPM-SMZ Ampicillin, amoxicillin, doxy-
cycline, azithromycin, clarithro-
mycin, cefotaxime, ampicillin +
clavulanate
Amoxicillin + clarithromycin + Clarithromycin + omeprazole +
omeprazole metronidazole + tetracycline
Cephalosporin TMP-SMZ, aminoglycoside,
imipenem, fluoroquinolone
Erythromycin or azithromycin TPM-SMZ, doxycycline ±
or clarithromycin, or rifampin
ciprofloxacin
Ampicillin Aminoglycoside, TPM-SMZ,
fluoroquinolone, cephalosporin
Cefotaxime, ceftriaxone Aminoglycoside, imipenem,
TPM-SMZ, fluroquinolone
Aminoglycosic, antipseudo- Ceftazidime, ± aminoglycoside,
monal penicillin (Piperacillin, ciprofloxacin ± piperacillin,
ticarcillin) ciprofloxacin ± ceftazidime
Ceftazidime Chloramphenicol, tetracycline,
TPM-SMZ, amoxycillin +
clavulanic acid, imipenem
Streptocycline + tetracycline Chloramphenicol + strepto-
mycin
Ceftriaxone, fluoroquinolone TPM-SMZ, ampicillin, chlo-
ramphenicol
Fluoroquinolone Ampicillin, TMP-SMZ, ceftria-
xone
Tetracycline TPM-SMZ, fluoroquinolone
Streptomycin ± tetracycline Chloramphenicol, TPM-SMZ
Doxycycline Amoxicillin, ceftriaxone,
penicillin
Tetracycline Penicillin
Penicillin Tetracycline
Erythromycin, or Clarithromycin, azithromycin,
tetracycline fluoroquinolone
E.Chlamydia:
Benign Prostatic Hyperplasia (BPH)| 619

• C. psittaci Tetracycline Chloramphenicol

(psittacosis)
• C. trachomatis Doxycycline, erythromycin Ofloxacin
(urethritis, pelvic
inflammatory disease)
• C. pneumoniae Tetracycline Erythromycin, clarithromycin,
azithromycin, fluoroquinolone
F. Rickettsia ⇓ Tetracycline Chloramphenicol, fluoroquino-
lone
Then find out other characteristics of antimicrobial therapy for devising rational treatment:
Characteristics Examples
a. Bacteriostatic or bactericidal drugs: In infective endocarditis and meningitis
Bactericidal antibiotics such as penicillin, bactericidal drugs are used.
cephalosporins and aminoglycosides kill
bacteria and bacteriostatic drugs, such as
macrolides and tetracycline merely inhibit
growth.
b. Broad spectrum and narrow spectrum Narrow spectrum drug such as benzyl penicil-
therapy: Broad spectrum drugs also encourage lin should be used for pneumococcal pneu-
proliferation of resistant species of gram-nega- monia
tive bacteria in the gut-examples are ampicil-
lin and cephalosporin. Hence narrow spectrum
drugs such as penicillin should be used to
treat specific infection
c. Patient’s condition: In pregnancy certain A. Antimicrobial therapy in pregnancy
antibiotics are avoided. Dosage modification Relatively Avoided in Avoided in
is needed in impaired hepatic and renal safe drug first trimester all stages of
function. pregnancy
• Cephalosporin • Chloramphe- • Amino-
• Erythromycin nicol glycoside
• Ethambutol • Ethinoamide • Ampho-
• Metronidazole • Nalidixic acid teric in B
• Penicillin • Rifampicin • Chloro-
quine
• Griseoful-
vin
• Isoniazid
• NFT
• Primaquine
• Quinine
• Tetracycline
• TMP-SMZ
• Vancomy-
cin
620 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

B. Antimicrobial therapy in impaired renal function

Normal dose Modified dose Drugs
avoided
• Chloramphe- • Aminoglyco- • Cycloserine
nicol side
• Cloxacillin • Ethambutol • Nalidixic acid
• Doxycycline • NFT
• Erythromycin • Tetracycline
• Rifampin • Vancomycin
• Amphotericin B
• Ampicillin
• Amoxicillin
• Penicillin
• Clindamycin
C. Antimicrobial therapy in impaired liver function
Use with caution Avoided
Clindamycin • Chloramphenicol
Fusidic acid • Erythromycin estolate
TMP-SMZ • Rifampin
• Isoniazid if fast acetylators
• Tetracycline
Duration of therapy:
Decided by type of infection, site of a. Type of infection: Bacterial infection can be
infection and immunocompetence of cured rapidly than fungal or microbacterial
patients ones
b. Site of infection: Endocarditis and osteomye-
litis require prolonged therapy
c. Immunocompromised patients need pro-
longed therapy

Suspected diagnosis Likely organism Drug of choice Alternative drug

based on organ involved
1. Erysiplas, impetigo, Group Streptococci Phenoxymethyl peni- i. Erythromycin 0.5 gm
cellulitis cillin, 0.5 gm orally 4 orally 4 times daily
times daily or
ii. Cephalexin 0.5 gm
orally 4 times daily
for 7-10 days or
iii. Azithromycin 500 mg
on day 1, and 250 mg
on days 2-5.

2. Furuncle with surr- Staph. aureus Dicloxacillin 0.5 gm Cephalexin 0.5 gm

ounding cellulitis orally 4 times daily orally 4 times daily
for 7-10 days for 7-10 daily.
 3. Otitis media
Benign Prostatic Hyperplasia (BPH)

Strep. pneumoniae, i. Amoxicillin 0.5 gm

|
i. Augmentin 0.5 gm
621

H. influenzae, More- orally 3 times daily or 3 times day

xella catarrhalis ii. TMP-SMZ (double ii. Cefuroxime 0.5 gm
strength) b.d. for orally b.d. or
10 days iii. Doxycycline
100 mg b.d.
4. Acute sinusitis S. pneumoniae, i. Amoxicillin 0.5 gm
H. influenzae, orally 3 times daily Do
M. catarrhalis or
ii. TPM-SMZ (double
strength) b.d. for 10 days

Antiviral Agents
There are two ways to control viral infection: Drugs and vaccines
Drugs Viruses Dose Clinical uses Adverse effects
inhibited comments
Amantadine Influenzal A Oral 200 mg/day Both prophylaxis Insomnia, ataxia
during influenzal and therapy for
season for 6-8 influenza A
weeks for highly
susceptible patients
Rimantadine Do Do Do Less CNS side-effect
but more expensive
than amantadine
Analogue of
amantadine
Acyclovir Herpes simplex i. Oral 400 mg t.d.s. • Herpes simplex, Non-toxic
varicella zoster for genital her- • Varicella zoster
pes and prevents • Herpes encephalitis
recurrent herpes • Herpetic keratitis
ii. IV 15 mg/kg/day • Herpetic whitlow
in three divided • Herpes proctitis
doses for muco- (400 mg 5 times
cutaneous herpes daily for 10 days
simplex • Erythema multiforms
IV 30 mg/kg/day
in three divided
dosage in varicella
zoster and herpes
encephalitis
iii. Topical 5% ointment
for herpes simplex
622 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Ribavirin aerosol:
Respiratory
syncytial virus
IV. Ribavirin • Lassa fever
• Hantavirus pneumonia
Ganciclovir Broad antiviral
activity including
CMV
Lamivudine HIV Orally once
Hepatitis B daily (100 mg)
for a year
Human Antiviral, • Chronic hepatitis Influenza like fever
Inteferons antitumour B,C, and D arthralgia, myalgia
and immuno- • Hairy cell leukaemia, Bone marrow suppr-
regulatory pro- Kaposi’s sarcoma, ession
perties chronic myelogenous
leukaemia, multiple
myeloma, renal cell
carcinoma
• Relapsing multiple
sclerosis
• Leishmaniasis, toxo-
plasmosis, leprosy
Zidovudine 500-1500 mg/day HIV encephalomyelopathy Nausea, myalgia, anaemia
(AZT) insomnia, headache, neutro-
penia
Better to use in combination
to prevent drug resistance
Zalcitabine 0.75 mg every Advanced HIV infection • Painful peripheral neuro-
(DDC) 8 hours pathy
May be combined • Pancreatitis,
with 200 mg of • Hepatic failure
zidovudine • Lactic acidosis
• Stomatitis
• Skin rash
Didanosine Adult: 200 mg b.d. Advanced HIV patients • Peripheral neuropathy
(DDI) who do not respond or • Pancreatitis
cannot tolerate zidovudine • Retinal depigmentation
• Diarrhoea
Stavudine 40 mg b.d. Advanced HIV • Peripheral neuropathy
• Nausea, vomiting abdominal
pain
• Skin rash
 Infectious Diseases
99
Respiratory Tract Infection

UPPER RESPIRATORY TRACT INFECTION

Aetiology Clinical Laboratory investi- Treatment
gations
Pharyngitis a. Infectious: Fever, sorethroat, a. Indications for A. Therapy for GABHS:
Viral and dysphagia throat culture: • Penicillin V 250 mg PO q.d.s. or
bacterial Hist. of rheumatic 500 mg
(responsible fever, sympto- PO b.d. for 10 days
for rheumatic matic patients • Benzathine penicillin G 1.2 million units
fever and (fever, pharyngeal IM as single dose
pyogenic exudate and cer- • Penicillin allergy: Erythromycin 250 mg
complications vical adenopathy) PO q.i.d. for 10 days
due to Group and failure to Or
A beta resolve with sym- Azithromycin 500 mg/day for 3 days
haemolytic ptomatic therapy • Cefuroxime for 5 days
streptococci- b. Antigen detection B. Therapy for non-GABS: Symptomatic
GABHS) test for GABHS measures: Analgesic, NSAID, benzocaine
b. N o n - i n f e c - lozenges, saline gargle
tious: Pem- Prophylaxis against GABHS:
phigus, SLE Indications for prophylaxis:
• Patients at high-risk (children, parents of
young children, school teachers, medical
or military personnel, patients living in
crowded living condition
• Those who have had rheumatic fever within
last 5 years
Prophylactic regimens
Benzathine penicillin G, 1.2 million units IM
every 4 weeks (regimen of choice)
Or
Penicillin V, 125-250 mg PO b.i.d.
Or
Sulfadiazine, 1 gm PO q.d. (for adults with
normal renal function)
Or
Erythromycin 250 mg PO b.i.d. indefinitely
for those at high-risk.
624 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Fever severe sore a. Lateral soft tissue a. Ampicillin sensitive: Ampicillin

throat dysphagia X-ray of neck to b. Ampicillin resistant:
Epiglottitis H. influenzae assess airway Ceftriaxone (1-2 gm IV/day)
obstruction Cefotaxime (1-2 gm 6-8 hourly)
b. Throat and blood Or
culture Cefuroxime (0.75-1 gm IV 8 hourly)
Cough, purulent a. Antimicrobial treatment: Amoxicillin/
postnasal dis- clavulanate for 10 days
Acute • S. pneumo- charge, fever in Or
sinusitis niae 50% cases, pain TMP/SMX one double strength tab b.d.
• H. influenzae over affected sinus Or
• Rhinovirus Cefuroxime axetil
• Aerobes b. Adjunctive measures: Topical decon-
gestants (phenylephrine or oxymetazoline)
only for 3-5 days; nasal irrigation with
saline spray
Nasal congestion, CT of sinus with • Antimicrobial therapy, nasal steroid spray,
obstruction, pain, bone window. Nasal some chronic cases require endoscopic
Chronic S. pneumoniae, pressure, post nasal endoscopy surgery
sinusitis H. influenzae, discharge, fatigue
rhinovirus, S.
aureus, C.
diptheriae,
bacteroids
Flow Chart for Management of Chronic Sinusitis
Medical Management
Antibiotics Adjunctive Measures
• Amoxicillin (500 mg tds) possibly • Analgesic
with clavulanate (125 mg t.d.s.) • Decongestants
Or • Nasal steroid spray
TMP/SMZ b.d. • Saline nasal spray
Or
Cephalexin (250-500 mg PO q.d.s.)
Or
Cefuroxime (250 mg PO b.d.)
Or
Cefaclor (250 mg PO tds)
Or
Cefixime (400 mg PO daily)
Or
Quinolone: Ciprofloxacin (500 mg b.d.), levofloxacin
(500 mg/daily), sparfloxacin (200 mg/day after initial
dose of 400 mg)
Or
Macrolides: Azithromycin (500 mg/day for 3 days)
Or
Clarithromycin (500 mg PO bd for 14 days)
Resolves, but recurs in a few weeks Resolves
Respiratory Tract Infection | 625

Another course of medical therapy:

i. IV antibiotic
Or
ii. Extended antibiotic regimen for 3-4 weeks
Does not resolve or recurs shortly Resolves.
a. CT scan or MRI of sinuses confirming the diagnosis of sinusitis (soft tissue density without bone destruction) or
showing bone destruction (points to neoplasm) or identifying anatomic blockage of osteomeatal complex (may
help guide endoscopic sinus surgery) referred to otorhinolaryngologist.
b. Investigate for suspected underlying allergy and if found, treated by:
i. Environmental control
ii. Drugs
iii. Immunotherapy
c. Investigate for suspected immune deficiency by analysing immunoglobulins and pre and postpneumococcal
titre and if found positive, treated by:
Supplementary IVIG

LOWER RESPIRATORY TRACT INFECTION

Aetiology Clinical Laboratory Investiga- Treatment
tions
Acute bronchitis: • Usual causes: Acute productive • Symptomatic:
Viruses such as cough with or without Cough by dextro-
corona virus, rhino- fever, symptoms of methorphan 15 mg
virus, influenza or upper respiratory tract PO 6 hourly; for per-
parainfluenza infection sistent cough ery-
• Rare causes: Myco- thromycin or doxy-
plasma pneumoniae, cycline used
Chlamydia pneumo- • Antimicrobial is
niae and Bordetella controversial
pertussis • For pertussis: TMP/
SMX, ampicillin,
chloramphenicol
Acute exacerbation of a. H. influenzae, S. Productive cough, • Antimicrobial:
chronic bronchitis: pneumoniae dyspnoea TMP/SMX, doxy-
b. Precipitating factors: cycline, amoxicillin/
Smoking, air pollu- clavulanate, third
tion, viral infection, generation fluoro-
allergy, occupational quinolone
exposure
Pneumonia:
a. Community acqui- — Fever, productive a. Chest X-ray: New See Flow chart
red: cough, dyspnoea, pulmonary infil-
signs of pleurishy, trates, effusion and
consolidation and consolidation
crepts b. Sputum for gram
stain and culture
c. Fibroptic broncho-
scopy
contd...
626 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

d. Examination of
pleural fluid

b. Hospital acquired or • Gram-negative Do Do

nosocomial pneu- • S. aureus Occurs in hospitalised
monia patient more than
48 hours after admis-
sion. Fever with or
without cough

c. Lung abscess: • Follows aspiration Fever, weight loss, foul • Sputum culture a. Antimicrobial:
of oropharyngeal smelling sputum points • Bronchoscopy if Aqueous penicillin
content, extensive to anaerobic infection obstruction or G 1.5-2 million units
and dental diseases foreign body IV 4 hourly
predispose, tuber- suspected Or
culosis, cancer, • X-ray chest: Clindamycin
fungal disease, pne- Cavitation, air b. Surgical: Resection
umonia, lymphoma, filled cavity, or percutaneous
septic emboli, pul- infiltrates pleural drainage of lung
monary embolism effusion, empyema abscess rarely requi-
red.
Indications for sur-
gery:
Bronchopleural fis-
tula, empyema, per-
sistent haemoptysis,
enlarged cavity
c. Penicillin resistant
organisms:
Clindamycin
(600 mg IV every 8
hours until imp-
rovement, then
300 mg orally
a. Antibiotics
d. Empyema: Signs of effusion, fever, • X-ray chest: b. Large tube drainage
weight loss • Pleural fluid: Pus c. Intrapleural throm-
cells, pH less than bolytic therapy:
7.3, glucose less Streptokinase
than 40 mg often 2,50,000 units in
very low 100 ml in 0.9%
• WBC 25,000- saline daily via
100,000 poly. high chest tube may
RBC low accelerate drainage
• LDH above 1000 U/ d. Surgery: Decorti-
L cation thoracoscopy
and open surgical
drainage may be
required.
ENTERIC INFECTION CAUSING DIARRHOEA
Respiratory Tract Infection| 627

Aetiology Treatment
Acute diarrhoea: E. coli, Shigella, Salmonella, a. Most cases are self limiting and
Infective Campylobacter, Yersina species, requires no treatment
viruses b. Empirical antibiotic therapy:
Indicated in moderate to severe
diseases with systemic symptoms.
Fluoroquinolone (ciprofloxacin
500 mg PO b.d. for 3 days), SMP/
SZX b.d. for 5 days
Pseudomembranous Seen in settings of antibiotic therapy a. Metronidazole (250-500 mg PO
colitis: and caused by C. difficile tid-IV if not tolerated)
b. Resistant cases: Intolerant to
metronidazole:
• Vancomycin (125 mg PO q.i.d.,
or IV)
• Cholestyramine (1 gm PO t.i.d.)
and given 2 hours after antibiotic
Amoebiasis: E. histolytica shown in stool Metronidazole 750 mg PO t.i.d. or
500 mg IV 8 hourly for 5-10 days,
followed by paromycin 500 mg PO
t.i.d. for 7 days or iodoquinol 650 mg
Giardiasis: Trophozoites of Giardia lamblia in PO t.i.d. for 20 days to eliminate cysts
stool Metronidazole 250 mg PO tid for
Drug diarrhoea: Laxative, antacids, digitalis, quinidine, 7 days
colchicin and antimicrobial agents Discontinue offending agents

Chronic diarrhoea: See chapter on “Diarrhoea”

General management: Omit lactose-containing products (milk). Give nutritional supplements (vitamin,
minerals)
Treatment of specific causes:
Secretary diarrhoea ...... ...... ...... Diphenylate or loperamide
Contraindicated in infectious diarrhoea
and inflammatory bowel disorders
Neuroendocrine tumours of
pancreas, carcinoid syndrome
HIV diarrhoea ...... ...... ...... Octreotide
Diabetic diarrhoea ...... ...... ...... Clonidine
Zollinger-Ellison syndrome ...... ...... ...... Proton pump inhibitor
Bile salt malabsorption ...... ...... ...... Cholestyramine
628 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Flow Chart for the Management of Pneumonia

Essential diagnostic clues and complications:
Clinical Investigations Complications
Symptoms a. Chest X-ray: • Bacteremia
Fever or hypothermia, consolidation, patchy infiltrations, • Meningitis
cough (dry or productive), pleural effusion, cavitation • Pericarditis
dyspnoea, chest discomfort, b. Gram stain and culture of sputum • Endocarditis
sweats or rigor c. Culture of blood and pleural fluid • Lung abscess
d. Serology: For HIV, legionella,
Mycoplasma pneumoniae, Chlamydia
pneumoniae
Signs:
Bronchial breath-
sound and crepts
(signs of consolidation)
First start antimicrobial therapy as early as possible on empirical basis.
Differentiate whether primary community acquired pneumonia (begins
outside the hospital or is diagnosed within 48 hours after admission to
hospital) or hospital-acquired or nosocomial, pneumonia (occurs more than
48 hours after admission to the hospital especially common in patients
requiring intensive care and mechanical ventilation) exist:

Empirical
Antibiotic therapy of community acquired pneumonia:
a. Patients who do not need hospitalisation and treated as outpatients.
1. Macrolides: Clarithromycin 500 mg PO b.d., or azithromycin 500 mg PO as a first dose and
then 250 mg/day for 4 days
2. Doxycycline 100 mg b.d.
3. Fluoroquinolones: Levofloxacin 500 mg/day, gatifloxacin 400 mg/day or moxifloxacin 400
mg/day
4. Alternatives especially for suspected aspiration pneumonia: Amoxicillin-potassium clavulanate
500 mg PO t.d.s. + second and third generation cephalosporins (cefuroxime axeteil 250-500 mg
PO bd)
Duration of treatment:
i. For S. pneumoniae: Therapy until the patient is afebrile for atleast for 72 hours.
ii. For M. pneumoniae, C. pneumoniae or Legionella pneumoniae: A minimum 2 weeks of
therapy is needed. A 5 days of therapy is usually sufficient if azithromycin is used.
b. Patients who can be treated in general medical ward: Ceftriaxone or cefotaxime with or without
clarithromycin or azithromycin
or
Levofloxacin or gatifloxacin
c. Patients who need intensive care: Erythromycin, azithromycin or levofloxacin with ceftriaxone or
cefotaxime
 d. Other subsets of patients:
|
Respiratory Tract Infection 629

• Penicillin allergy: Levofloxacin or gatifloxacin with or without clindamycin

• Suspected aspiration pneumonia: Levofloxacin or gatifloxacin plus clindamycin
• Patients with prexisting structural disease of lung such bronchiectasis or cystic fibrosis:
Antipseudomonal penicillin, carbapenem, or cefepime plus a macrolide
or
Fluoroquinolone plus aminoglycoside.

Empirical Therapy of Hospital-acquired Pneumonia

Differentiate two categories of patients:
Mild to moderate cases without unusual Severe, late cases needing mechanical
risk factors and early onset: ventilation and ICU
Second generation cephalosporin Antibiotics against most virulent organisms,
or particularly P. aeruginosa, Acinetobacter species
Nonantipseudomonal third generation and Enterobacter species:
cephalosporin a. Aminoglycoside or fluoroquinolone + Anti-
or pseudomonal penicillin or an antipseudomonal
Combination of a beta-lactam and cephalosporin or imipenem. Vancomycin is
beta-lactamase inhibitor added if infection and methicillin resistant
S. aureus is present.
b. For anaerobic infection clindamycin or beta
lactam/beta-lactamase inhibitor combination
c. For legionella infection: A macrolide is added
to the above regimen.
When culture and sensitivity is known, treat accordingly:
Organisms Clinical settings Antimicrobial therapy
Streptococcus Chronic cardiovascular Preferred penicillin G or V, amoxicillin
pneumoniae: disease, follows upper or
respiratory infection Macrolides, cephalosporins, doxycycline,
fluoroquinolones, vancomycin
H. influenzae: Do Preferred: Cefotaxime, ceftriaxone or cefuroxime,
doxycycline
or
Azithromycin, TMP: SMZ, fluoroquinolones
Staphylococcus Hospital-acquired, a. For methicillin sensitive strains:
aureus: influenza epidemics, Preferred: Pencillinase resistant penicillin
cystic fibrosis, vancomycin or
bronchiectasis, injec- Cephalosporins, clindamycin, fluoroquinolone,
tion drug uses TMP/SMZ, vancomycin
Vancomycin with or without gentamicin
with or without rifampin
Klebsiella Diabetes, alcohol Preferred: Third generation cephalosporin,
pneumoniae: abuse, nosocomial For severe infection add an aminoglycoside
630 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

E. coli Nosocomial
Pseudomonas Nosocomial,
aeruginosa: cystic fibrosis,
bronchiectasis
Anaerobes: Aspiration pneumonia,
poor dental hygiene
Mycoplasma Young adult, summer
pneumoniae: skin rashes, bullous
myringitis, haemolytic
anemia, PMNs and no
bacteria on gram stain,
extensive patchy infiltrates
in chest X-ray, complement
fixation titre four-fold rise
Legionella Summer, exposure to water
species: source, air conditioner,
both community acquired or
nosocomial. Few PMNs and
no bacteria on gram stain.
Direct immunofluorescent
examination of sputum or
tissue and four-fold rise in
immunofluorescent titre
Chlamydia Similar to mycoplasma pne-
pseudomoniae umonia. Heart failure
Pneumocystis AIDS, cancer, cytotoxic
carinii: drug therapy, pneumoth-
orax, respiratory failure
or
Imipenem or beta-lactam/beta-lactamase
inhibitor or fluoroquinolone
Same as for Klebsiella pneumoniae
Preferred: Antipseudomonal beta-lactam +
aminoglycoside
or
Ciprofloxacin + aminoglycoside
Preferred: Clindamycin, penicillin + metronida-
zole, beta-lactam/betalactamase inhibitor
Preferred erythromycin
or
Doxycycline, clarithromycin, azithromycin,
fluoroquinolones
Preferred: Macrolide with or
without rifampin, fluoroquinolone
or
TMP/SMZ or doxycycline with or
without rifampin
Preferred: Doxycycline
or
Erythromycin, clarithromycin, azithromycin or
fluoroquinolone
Preferred: TMP/SMZ or pentamidine
isothionate + prednisolone
or
Dapsone + trimethoprim or clindamycin +
primaquine

Supportive Therapy
a. Patient frequently dehydrated and needs dehydration therapy 5% dextrose with half normal saline
b. Some patients require mechanical ventilation, intensive care and oxygen
c. If patient is confused, do a LP to exclude meningitis
d. Pleural effusion should be aspirated to exclude empyema needing chest tube drainage
e. Adequate analgesia: Codeine, parenteral meperidine 50-100 mg every 3-6 hours, intercostal nerve
block to relieve pleuritic pain
f. Cough suppressant
Preventive Therapy
Polyvalent pneumococcal vaccine:
Advantage:
It has the potential to prevent or lessen
the severeity of pneumococcal infections in
immunocompetent patients.
Indications:
• Age above or equal to 65 yrs
• Any chronic illness that increases the
risk of community-acquired pneumonia
Regimen:
a. Immunocompromised patients: Should
receive a single revaccination 5 or
more years after the first vaccination
b. Immunocompetent persons:
Aged 65 years or older should receive
a second dose of vaccine if the patient
received the vaccine 5 or more years
previously and was under 65 years old
at the time of vaccination
|
Respiratory Tract Infection 631
Influenzal vaccine:
Advantage:
Effective in preventing severe disease due to
influenza virus responsible for both primary
influenzal pneumonia and secondary bacterial
pneumonia
Indications:
• Administered annually to persons at risk for
complications of influenzal infection (age 65 yr
older, patient with pulmonary and cardiovascular
disorders, patients recently hospitalised with
chronic metabolic disorders, residents of
chronic care facilities
 Infectious Diseases
100
Treatment of Tuberculosis

Principles and Scientific Basis of Chemotherapy

a. Frequency and number of drugs: Atleast three drugs should be used to reduce bacterial resistance.
Drugs can be given daily or intermittently (twice or thrice a week). All drugs except PAS and
thiocetazone inhibit M. tuberculosis growth for 3-4 days after a single dose. This is the principle
behind using anti-TB drugs intermittently. Most popular short-course treatment programmes consist
of two phases. An initial 2 months intensive phase of daily therapy includes isoniazid, rifampicin,
pyrazinamide and either streptomycin or ethambutol. After that a consolidation phase with isoniazid
+ rifampicin (or any other effective drug) should be given at least for 4 months, and preferably
6 months. But many clinicians recommend four drugs for 6 months in India due to high level of
primary resistance and where sputum culture is rarely performed.
b. Bactericidal versus bacterostatic drugs: Tubercle bacilli occur in the patient in three pools:
Metabolically active Relatively inactive Necrotic caseous
extracellular pool intracellular pool pool
Rifampicin: Bactericidal Bactericidal Bactericidal
(killer drug)
Isoniazid and Bactericidal
streptomycin:
Isoniazid and Bactericidal
pyrazinamide:
Ethambutol is only bacterostatic.
c. Patient default in taking drugs is the major problem. Default causes treatment failure and also
produces drug resistance. Since most patients default occurs within the first 6 months, short course
therapy has been recommended. Directly observed therapy (DOT) is highly successful for non-
compliant (alcoholic) patients and prevent multi-drug resistant tuberculosis.
d. Follow-up for improvement:
Period of drug therapy
• Symptomatic improvement Occurs within 2-3 weeks of drug therapy
• Clearing of lung infiltrates on X-ray Between 2nd and 4th months
• Sputum conversion Within 2 months
e. Drug toxicity: If drug is discontinued promptly with the onset of jaundice, drug hepatitis can be
resolved without untoward incident. Pyridoxin prevents isoniazid neuropathy.
f. Drugs of pregnancy: Isonazid and ethambutol are safe in pregnancy. Rifampicin should be used in
disseminated tuberculosis. Streptomycin should not be used because of foetal ototoxicity.
 Treatment of Tuberculosis

g. Drug resistance: In one-third of patients who relapse after adequate drug therapy, the relapse is
| 633

caused by drug resistant organisms. Therapy of drug resistant tuberculosis should be instituted with
two drugs which the patient has not taken previously. When resistance studies become available,
the regimen should be modified appropriately. It is beneficial to continue isoniazid even when
laboratory studies indicate drug resistance.

ANTI-TUBERCULOUS DRUGS
First line oral drugs:
Dose Common Tests for Drug Remarks
side-effects side-effects interactions
Isoniazid Adult: 300 mg Hepatitis with rif- AST and ALT, Increases Bactericidal,
doubled in ampicin; nausea, neurological effect and Pyridoxin 10 mg
meningitis. vomiting, epigastric examination toxicity of per day as pro-
Children: 6- pain, peripheral phenytoin phylaxis for
10 mg/kg/day neuritis and carba- neuritis: 50-
Prophylaxis: mazepine. 100 mg/day as
Adult: 300 mg/day Steroid treatment.
for 6-12 months decreases
for 6 months INH level
Child: 10-15 mg kg
Rifampicin: 450-600 mg/day Hepatitis, fever, AST and Inhibits the Bactericidal
Children: 10-20 mg GI disturbance, ALT effect off
per kg per day influenza like oral contra-
symptoms, head- ceptive, quini-
ache, urine and dine, steroid,
tears reddish digoxin, oral
coloured hypoglycemic
agents
Pyrazina- Adult 20-35 mg/kg/ Hyperuricaemia, Uric acid, Affects control
mide: day daily max. 3 gm hepatotoxicity, AST, ALT of diabetes Bactericidal
Children: 15-30 mg anorexia, nausea,
per kg per day
Intervomiting,
arthramittent fever
therapy:
a. Under 50 kg 2 gm C/I pregnancy
thrice weekly or
3 gm twice weekly
b. Over 50 kg: 2.5 gm
thrice weekly or
3.5 gm twice weekly
Ethambutol: 15-25 mg/kg/day • Optic neuritis: Red-green Bactericidal
Intermittent therapy: reversed with dis- colour
contd...
634 |
contd...
Bedside Approach to Medical Therapeutics with Diagnostic Clues

50 mg/kg 2-3 times continuence of discrimin-

a week drug; rare at ation and
15 mg/kg visual acuity
• Rash

First Line Injectable Drugs

Streptomy- 15 mg/kg 8th nerve Vestibular Neuromus- Bactericidal
cin: damage, function- cular blo- Use with
nephroto- (audiogram), cking agent caution in
xicity BUN, creatinine and may elderly and
cause those with
paralysis renal disease.

Second Line Antituberculous Drugs

Daily dose Common Serum levels Remarks
psychological monitoring
Ethionamide: 500-1000 mg GI disturbances, Liver function Consider antiemetics
PO (in divided hepatitis tests or bed time dosing
doses if necessary
for tolerance
Cycloserine: 250-750 mg PO Neurological and Serum levels Give pyridoxin
(individed doses) psychological
Adjust for renal disturbances
impairment
Capreomycin 15 mg/kg IM Hearing loss vestibu- Audiogram, ves-
Amikacin 5 days a week lar damage, renal toxi- tibular examina-
Kanamycin Adjust for city, electrolyte dis- tion, BUN, create-
renal impairment turbance nine
Para-amino- 10-20 gm PO in GI intolerance, hepa- Liver function Prolonged use
salicyclic acid divided dises titis, hypersensitivity tests causes hypothyroi-
(PAS) dism
Consider antacids
or dosing at meal time
Cheap.
Ciprofloxacin 500-1000 mg GI intolerance, Avoid antacids
Ofloxacin: q.d.s. for cipro- headache, restle- iron, zinc, and
floxacin; ssness, hypersens- sucralfate which
Ofloxacin: itivity decrease absorption
400-800 mg
q.d.s. PO
Clofazimine 100-300 mg Abdominal pain, skin Consider dosing
q.d.s. PO discolouration, at meal time,
photosensitivity avoid sunlight
List of Drugs for Multi-drug-resistant (MDR) TB
|
Treatment of Tuberculosis 635

I. First line, if not used previously:

• Streptomycin
• Ethambutol
• Isoniazid
• Rifampicin
• Pyrazinamide
II. Second line drugs:
• Kanamycin • Ethionamide
• Viomycin • Prothionamide
• Capreomycin • Para-amino-salicyclic acid (PAS)
• Amikacin
• Cycloserine
Variation of dosages according to weight of the patient
Weight Dose (daily)
Rifampicin • Less than 50 kg 450 mg
• 50 kg or more 600 mg
Streptomycin • Less than 50 kg 750 mg
• 50 kg or more 1 gm (750 mg if over 40 years of age)
Pyrazinamide • Less than 50 kg 1.5 gm
• 50 kg or more 2.0 mg
Ethionamide • Less than 50 kg 750 mg
Prothionamide • 50 kg or more 1 gm

Therapeutic Regimens for Pulmonary Tuberculosis

Long-term regimens:
Initiation phase for 1-3 months Continuation phase for 12-18 months
Daily isoniazid + ethambutol Isoniazid + ethambutol or rifampicin
or rifampicin or streptomycin in developed countries and PAS or
or PAS or thiocetazone thiocetazone in developing countries
Disadvantages of daily long-term therapy
• Patient terminates treatment prematurely or takes irregularly
• The infection is drug resistant to start with
Not highly successful as revealed by controlled trial to obviate the
disadvantages of long-term regimen two ways have been devised for
improving patient compliance: 1. Intermittent supervised chemotherapy
2. Short course chemotherapy.
Daily:
1. Intermittant supervised chemotherapy:
Advantages: Regular treatment possible due to full supervision
Less chronic drug toxicity than long-term daily regimen
Cheapar than long-term daily regimen
Highly effective regimen as revealed by controlled clinical trial.
636 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Regimen:
Initial daily regimen Continuation intermittent twice
weekly regimen
a. For 3 months: a. For 18 monhts:
Streptomycin (less than 50 kg weight: 750 Isoniazid (1mg/kg twice
mg/day and 50 kg or more 1g/day) + weekly)
+
Isoniazid (300 mg/day) + Streptomycin (1 gm twice
weekly)
+
Ethambutol (25 mg/kg for 2 months and then Isoniazid (300 mg biweekly) +
15 mg per kg for 1 month) Ethambutol (30 mg/kg twice a
or week or 25 mg/kg thrice a week)
Streptomycin + Isoniazid + Thiocetazone
(150 mg/day) b. For 12 months:
or Isoniazid (300 mg biweekly)
Streptomycin + Isoniazid + Rifampin +
(Less than 50 kg: 450 mg/day and 50 kg or Rifampicin (600-900 mg twice
more: 600 mg/day) weekly)
or
Streptomycin + Isoniazid + PAS (10-15 g/day)
b. For 2 weeks: Streptomycin + Isoniazid + Rifampin
2. Short course chemotherapy:
Advantages:
• Rapidly reduced bacillary load and thus prevents relapse.
• Controlled clinical trials have revealed that isoniazid, rifampicin and pyrazinamide combined
has proved to be particularly effective in short course chemotherapy: Isoniazid kills rapidly
multiplying bacilli, rifampicin and pyrazinamide kill those bacilli relatively unaffected by other
drugs, streptomycin kill actively dividing bacilli and bacteriostatic drugs such as ethambutol
and thiocetazone probably help to prevent the emergence of drug resistance.
• Controlled clinical trials have revealed that the short course chemotherapy is highly effective
for patients even extensive disease with strains initially resistant to isoniazid and streptomycin.
• The short course is acceptible to patients without disturbing daily life much.
• Relapse if occurs, usually does so soon after the end of treatment and can be identified rapidly
and early and retreated successfully with the drugs of primary regimen.
Regimen:
Initial intensive phase Duration Continuation phase Duration
A. Daily regimen:
E + H + R daily 2 months H + R daily 9 months
or or
S + H + R daily 2 months H + R daily 9 months
or or
S + H + R + Z daily 2 months H + R daily 9 months
H + R daily 6 months
Initial intensive phase
Treatment of Tuberculosis

Continuation phase
| 637

B. Intermittent regimen: Duration Duration

E+H+R+Z 3 times a week 6 months 6 months
or
S+H+R+Z 3 times a week 6 months 6 months
or
S+H+R+Z 3 times a week 3 months H + R 3 times 6 months
or a week
S+R+Z 3 times a week 4 months S+H+Z 8 months
twice a week

CHOICE OF REGIMENS
a. Choice of regimens in developed countries: Medical services are plentiful, bacillary resistance low
and incidence of disease is low.
Regimens:
Usual regimen In alcoholics where self medication is not reliable
Daily regimen of isoniazid and Fully supervised twice weekly regimen
rifampicin for 9 months with or
ethambutol or streptomycin as well Fully supervised short course intermittent
for first 2 months regimen
b. Choice of regimen in developing countries
Usual regimen Urban areas where medical Rural areas
facilities better than rural areas
i. Daily isoniazid plus Short course fully super- Short course daily
thiocetazone for 12 months vised intermittent regimen regimen
or longer with upto 3 months or
of daily streptomycin or Isoniazid + ethambutol +
ii. Isoniazid + rifampicin + rifampicin + pyrazinamide
pyrazinamide + Ethambutol or 3 times a week for 6 months
streptomycin daily for
2 months followed by
isoniazid + rifampicin
daily for 6 months
c. Choice of drugs in special circumstances
Pregnancy Renal failure
Streptomycin should never be given in • Drugs such as isoniazid, rifampicin,
any stage of pregnancy and should be pyrazinamide, ethionamide and prothionamide
withdrawn immediately if pregnancy occurs are not excreted through kidney and hence
during its administration because of should be given in normal dosage
foetal toxicity. No anti-TB drug is teratogenic • Aminoglycosides and ethambutol are excreted
and not at all if pregnancy has advanced by kidney. Hence ethambutol (25 mg/kg
times beyond 12 weeks 3 week) and streptomycin (0.75 gm at long
interval) should be given in reduced dosage
in renal impairment.
638 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

CHEMOTHERAPY OF MULTI-DRUG-RESISTANT TUBERCULOSIS

Basic Principles and Guidelines
• Drugs
i. First line drugs should be preferred
ii. Previously unused drugs should be preferred
iii. INH should be included in all regimens
iv. Bactericidal drugs (INH, rifampicin, pyrazinamide, streptomycin) should be used.
v. Bacteriostatic drugs (ethambutol, capreomycin, vancomycin) should be avoided
vi. Minimum four drugs and preferably six drugs should be used.
vii. Drugs should be administered in adequate dosages and adequate duration: For 24 months after
sputum negativity.
viii. Cross resistant drugs should be avoided as they are not effective an increases toxicity.
Drug with one-way cross resistance:–
Vancomycin and capreomycin
Vancomycin and kanamycin
Kanamycin and streotomycin
ix. Preferably the drugs should be given along with first line drugs, if second line or newer drugs
are prescribed, then atleast 4-6 drugs should be given.
x. Addition of single drug in falling regimen is contraindicated
xi. Retreatment regimens should be supervised
xii. Intermittent regimens should be avoided
xiii. If result of susceptibility tests are not available for two months or more, it is prudent to add
several new drugs
xiv. Serum level of drugs may become necessary to optimise therapy and ensure bioavailability.
• Hospitalisation: Patients require hospitalisation to monitor adverse drug reactions and drug initiation.
• Surgery: Surgical intervention should be done early, if required, when disease is limited.

List of Drugs for MDR-drugs

First line drugs if not used previously:
• Streptomycin (S)
• Ethambutol (E)
• Isoniazid (H)
• Rifampicin (R)
• Pyrazinamide (Z)
Second line drugs:
• Rifampicin-rifampicin derivatives-Rifabuti, Rifapentin
• Kanamycin (K)
• Viomycin (V)
• Capreomycin (C)
• Amikacin (A)
• Cycloserine (CYCLE)
• Ethionamide (ETH)
• Prothionamide (PTH)
 • Para-amino-salicyclic acid (PAS)
|
Treatment of Tuberculosis 639

• Ciprofloxacin, ofloxacin, pefloxacin, lomefloxacin, sparfloxacin

• Clofazinamine-sulphone derivatives
• Macrolides-Roxithromycin, clarithromycin, azithromycin.

Drugs and Doses for MDR-TB

Drug Dose Daily adult dose Adverse
mg/kg max. dose effects
Ofloxacin: 8-10 400 mg b.i.d. Abdominal distress
Ciprofloxacin 15-20 750 mg b.i.d. Headache, anxiety
Sparfloxacin: 8-10 400 mg b.i.d. Tremulousness
Kanamycin: 15 0.75 g-1 gm Vestibular
Capreomycin 15 0.75-1 gm Vestibular
Amikacin 15 0.75-1 gm Auditory
Cycloserine 15 250 mg b.i.d. or t.i.d. Seizure, psychosis
Ethionamide 15 250 mg b.i.d. or t.i.d. Abdominal distress, diarrhoea
Prothionamide 15 250 mg b.i.d. Anorexia, metalic taste
Azithromycin 9-10 Gastrointestinal
Roxithromycin 9-10
PAS 200 10-12 gm Gastrointestinal
Clarithromycin 15-16 Gastrointestinal
Rifabutin ------ 450 ------
Clofazimine 4-5 100-200 GIT, skin

Suggested Regimens for MDR-TB

Resistance pattern Suggested regimens Duration
H+R Z + E + Quinolone + Aminoglycoside 18-24 months
H+S R + Z + E + Amikacin 6-9 months
H+E R + Z + Quinolone + Aminoglycoside 6-12 months
H+R+Z E + Quinolone + Aminoglycoside plus 2 of 24 months after conversion
Ethionamide, cycloserine and PAS
H+R+Z+E Quinolone + Aminoglycoside DO
+ Ethionamide + cycloserine + PAS

Key: H = Isoniazid; R = Rifampicin; Z = Pyrazinamide; E = Ethambutol ; S = Streptomycin

SUMMARY OF DRUG REGIMENS FOR TUBERCULOSIS

i. Daily long-term regimen:
Isoniazid + Other companion drugs
H Plus or H Plus or H Plus Thiocetazone (T)
R or S daily E for 12-18 months PAS for 12-18 months daily for 12-18 months
for 9-12 months
Usual Least Least expensive useful
regimen toxic in developing countries
640 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

ii. Daily-intermittent (Mixed) regimens:

Isoniazid + S Plus Other companion drugs daily
H + S Plus or H + S Plus or H + S Plus or H + S Plus
E T R P
Daily for 3 months Daily for 3 months Daily for 2 weeks Daily for 3 months
Followed by twice weekly regimen: Isoniazid 15mg/kg biweekly + Companion Drugs
Plus or Plus or Plus
S E R
1 gm twice weekly 30 mg/kg 600-900 mg
for 18 months biweekly biweekly
for 18 months for 12 months
iii. Short course regimen:
a. Daily regimen: Isoniazid + R Plus Other companion drugs
H + R Plus or H + R Plus or H + R Plus
E S Z+
Daily Daily for S or E
for 2 months 2 months Daily for 2 months most popular
Followed by Followed by Followed by
H + R daily H + R daily H+R
for 9 months for 9 months daily for 6 months
b. Intermittent regimen:
Isoniazid + R + Z Plus other companion drugs
Plus or Plus or Plus or Plus
H+R+Z H+R+Z H+R+Z H+R+Z
E S S S
3 times/week 3 times/week 3 times/week 3 times/week
for 6 months for 6 months for 2 months for 4 months
Followed by Followed by
H + R times/wk S + H + Z twice
for 6 months week for 8 months
Ethambutol can be substituted for streptomycin with all combinations
Key: H = Isoniazid; R = Rifampicin; Z = Pyrazinamide; E = Ethambutol; S = Streptomycin
 Infectious Diseases
101
Infective Endocarditis

Clinical Approach to Treatment of Subacute and Acute Bacterial Endocarditis

Diagnostic clues
Clinical
a. Fatigue, weight loss, low grade
fever, nephritis, arthralgia and
emboli (renal, splenic and
cerebral infarct, petechiae,
Osler’s nodes)
b. Presence of damaged heart valve,
new or changing heart murmur
Laboratory findings
a. Blood culture positive in 90% cases
b. Echocardiography: Vegetation, but
normal echocardiogram does not
exclude the diagnosis of IE
c. Chest X-ray shows underlying cardiac abnormalities

Find out the type of infective endocarditis

Subacute bacterial endocarditis
Streptococcus bovis, group
B and G streptococci is
associated with lower GI
disease, including neoplasm
a. For Streptococcus viridans:
• Penicillin sensitive: Penicillin
G IV 4 million units 6 hourly for
4 wks. or
Penicillin G 2 million units IV
4 hourly + Aminoglycoside for
2 weeks only to prevent ototoxi-
city and nephrotoxicity
• Penicillin allergy: Vancomycin
b. Group A beta-haemolytic
streptococci and S. pneumoniae:
• Penicillin sensitive: Penicillin
G 2-4 million units IV 4 hourly
for 4-6 weeks
• Penicillin resistant: Ceftriaxone
daily for 4-6 weeks
Prosthetic valve endocarditis
caused by S. aureus,
S. epidermidis, gram-negative
Regimen of choice:
Vancomycin for 6 weeks
+ culture report are available:
Rifampin 300 mg every
8 hour for 6 weeks
+ Naficillin IV 2 gm 4 hourly
Gentamicin 1mg/kg
every 8 hours for the
first 2 weeks
Acute bacterial endocarditis
a. Most likely pathogens:
S. aureus and gram-negative
bacilli
b. Empiric therapy should be
started pending culture report:
Empiric therapy includes
antistaphylococcal agents till
a. Ampicillin IV 2 gm 4 hourly
+
+
Gentamicin IV 1mg per kg
8 hourly or
b. Vancomycin IV 30 mg/kg/day
in 2 divided doses (for penicillin
allergic patients
+
Gentamicin 1 mg/kg 8 hourly
642 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

c. Enterococcus species: e. HACK organisms: Fastidious slow

• Ampicillin, 2 gm IV 4 hourly
or
Penicillin G, 3-5 million units
IV 4 hourly + gentamicin for
4-6 weeks
• Penicillin allergic or with beta-
lactamase-producing strains:
Vancomycin + Aminoglycoside
d. S. aureus:
• Penicillin sensitive: Naficillin
2 gm IV 4 hourly + Gentamicin for
first 3-5 days
• Penicillin allergy: Cefazolin IV
2 gm 8 hourly + Gentamicin for first
3-5 days
• Penicillin and cephalosporin allergy:
Vancomycin IV 30 mg/kg/day in 2
divided doses
Surgery
Indications for urgent cardiac surgery
Cardiac complications
• Refractory heart failure
• An unstable prosthetic valve
• Prosthetic valve obstruction
• Systemic emboli which is recurrent
• Mycotic aneurysm, persistent conduction
defect, chordae tendinea or papillary
muscle rupture
growing gram-negative bacteria
(Haemophilus, Actinobacillus, Cardio-
bacterium, Eikenella, Kingella species)
• Penicillin sensitive: Ampicillin IV 2 gm
4 hourly + Gentamicin 1 mg/kg 8 hourly
• Penicillin allergy: Cetriaxone 2 gm
o.d. IV/IM
f. Enterobacteriaceae: Cefotaxime IV
8 gm/day in 4 divided doses
g. Pseudomonas aeruginosa: Piper-
cillin IV 18 gm/day in 6 divided doses
or
Ceftazidime IV 6 gm/day in 3 divided doses
h. Fungal infection: Amphotericin B IV
1mg/kg perday
i. When IE suspected but routine culture
are negative: Penicillin G, 2-3 million
units IV 4 hourly or ampicillin 2 gm IV
4 hourly + aminoglycoside
Antimicrobial refractory IE
• Fungal endocarditis refractory to medical therapy
• IE due to refractory gram-negative bacilli
• Uncontrolled infection as manifested by sustained
bacteremia

Prophylaxis
Indications Surgical procedures
that warrant prophylaxis
a. High-risk patients: Patients a. Dental procedures: a.
with prosthetic cardiac valves, Dental extraction, peridental b.
history of IE or complex cynotic or endodental procedures,
heart disease professional teeth cleaning
b. Moderate risk patients: Con- b. GI procedures: Oesophageal c.
genital cardiac malformations, sclerotherapy, oesophageal d.
rheumatic valvular disease, stricture dilatation and endo- e.
hypertrophic cardiac myopathy, scopic retrograde cholangio- f.
mitral valve prolapse with graphy with biliary obstruction
valvular regurgitation or
thickened leaflets
Procedures which do not
warrant prophylaxis
Dental: Filling cavities
Gastrointestinal: Routine
endoscopy, transoesophageal
echocardiography
Endotracheal intubation
Bronchoscopy
Caesarean section
Cardiac catheterisation,
pacemaker transplantation
Prophylactic Drugs
|
Infective Endocarditis 643

Clinical situations Drug and dosage

I. Prophylaxis for dental, oral, respiratory tract or oesophageal procedures:
a. Standard prophylaxis:
b. Unable to take orally:
c. Penicillin allergy:
d. Penicillin allergy and unable to take
orally:
procedure
II. Prophylaxis for GI and genitourinary procedure:
a. High-risk patients:
i. Without penicillin allergy:
ii. Penicillin allergy:
b. Moderate risk patients:
i. Without penicillin allergy:
ii. Penicillin allergy:
Amoxicillin 2 gm PO 1 hour before procedure
Ampicillin 2 gm IM/IV within 30 minutes before
procedure
Clindamycin 600 mg PO 1 hour before procedure
or
Cephalexin or cefadroxil 2 gm PO 1 hour before
procedure
or
Erythromycin PO 1 gm 2 hours prior to procedure
and 0.5 gm 6 hours after first dose
Clindamycin 600 mg IV within 30 minutes before
procedure
or
Cefazolin 1 gm IV within 30 minutes before
Ampicillin 2 gm IM/IV + Gentamicin 1.5 mg/kg
(maximum 120 mg) within 30 minutes before
procedure and 6 hours later, ampicillin 1 gm IM/IV
Vancomycin 1 gm + Gentamicin 1.5 mg/kg
(max. 120 mg) within 30 minutes before procedure
Amoxicillin 2 gm PO 1 hour before procedure
or
Ampicillin 2 gm IM/IV within 30 minute before
procedure
Vancomycin 1 gm IV within 30 minutes before
procedures
Index
A prognosis of acute pancreatitis
Achalasia 339
Acromegaly 430
diagnostic clues 430
laboratory investigation 430
treatment 431
Acute cholecystitis 412
Acute gingivitis 396
Acute infective hepatitis 400
aetiology 400
clinical clues 400
definition 400
investigations 401
management of acute hepatitis
403
management of acute viral
hepatitis 403
management of fulminant hepatic
failure 404
specific management of acute
hepatitis 404
Acute interstitial nephritis 581
Acute left ventricular failure 263
Acute myocardial infarction 249
clinical notes 257
general management 249
bowel 250
diet 250
pain 249
rest and activity 250
sedation 250
management 252
treatment of complications 251
Acute pancreatitis 417
additional measures in severe
pancreatitis 419
adverse prognostic signs in acute
pancreatitis 420
causative factors 417
clinical clues 417
diagnostic investigations 418
management 418
management of complications
419
types of drainage procedures 419
420
Acute pneumonia 614
Acute renal failure 573
aetiological consideration 573
clinical consideration 574
continuation phase 578
definition 573
investigational consideration 575
management 577
measures for initiating diuresis
577
prophylaxis 577
pathological consideration 574
treatment of causes 580
types 573
postrenal 573
prerenal 573
renal 573
Acute respiratory failure 40
diagnosis 40
management 40
administration of oxygen 40
maintenance of airway 40, 41
treatment of infection 40
treatment of underlying
conditions and specific
therapy 40
Acute ulcerative gingivitis 396
Acute uric acid nephropathy 581
Acute viral meningitis 181
Addison’s disease 509
aetiological consideration 509
diagnostic clues 510
prophylaxis 513
treatment of Addison’s disease
512
treatment of adrenal crisis 513
Adjunctive therapy 160
Adult respiratory distress syndrome
44
treatment 44
Advantage of exercises 477
Advantages of yoga 477
Alcohol 195
clinical features 195
diagnostic clues 195
investigatioins 195
treatment 195
Algorithm of management of diabetes
mellitus 485
Algorithm treatment of stable angina
294
Alzheimer’s disease 154
aetiology 154
clinical features 154
diagnostic clues 154
investigations 154
pathophysiology 154
treatment 154
drugs 155
specific treatment 155
symptomatic treatment 154
Aminoglycoside nephrotoxicity 580
Amiodarone 247
Anaemia 50, 538
classification 50, 538
diagnostic clues for anaemia 51
acquired haemolytic anaemia
53
aplastic anaemia 54, 545
congenital haemolytic anaemia
53
haemolytic anaemia 53, 54,
540
macrocytic anaemia 52, 540
microcytic anaemia 51, 539
normocytic anaemia 54
sideroblastic anaemia 54
iron deficiency anaemia 543
treatment of anaemia 541
treatment of individual anaemias
543
Antiasthmatic drugs 5
Antibiotics 44
Antibiotics for infective endocarditis
310
Antibiotics in adult and child 160
646 | Bedside Approach to Medical Therapeutics with Diagnostic Clues

Anticoagulation in AF 242 Aspiration pneumonia 614 C

Antidepressant drugs 189 Auricular fibrillation 241 Calcium channel blockers 292
Antiepileptic drugs 132 Autonomic neuropathy 492 Calcium channel blockers in cardiac
Antihypertensive drugs 271 arrhythmias 295
Antihypertensive drugs in pregnancy B Candidiasis 38, 396
285 Cardiac arrest 330
Anti-TB drugs 9, 15 Bacterial meningitis 614
causes 330
Anti-tuberculous drugs 104, 633 Bacteriostatic drugs 106
cardiac causes 330
Antiviral agents 85, 621 Bell’s palsy 179
non-cardiac causes 330
acyclovir 621 Benign prostatic hyperplasia (BPH) potentially reversible causes
amantadine 621 610 330
analogue of amantadine 621 aetiological consideration 610 diagnosis 330
didanosine 622 diagnostic evaluation 610 management 331
ganciclovir 622 signs 610 advanced cardiac life support
human interferons 622 symptoms 610 331
lamivudine 622 less invasive therapy 613 aftercare 332
ribavirin 622 pharmacotherapy 611 basic cardiac life support 331
ribavirin aerosol 622 surgical therapy 613 termination of CPR 332
rimantadine 621 treatment 611 Cardiomyopathy 314
stavudine 622 Beta-adrenoreceptor blocking drugs treatment 314
zalcitabine 622 Cardiotonic agents 45
212
zidovudine 622 Catecholamines 216, 220
classification 212
Antiviral drugs 37 contraindications 220
Blood sugar 487
Anxiety disorders 193 dosage 220
Brain abscess 162, 614
classification and diagnostic clues drug interactions of important
193 aetiology 162
haemodynamic effects 217
treatment 193 diagnostic clues 162
mechanism of action 216
Apathous ulcer 398 laboratory investigations 162
side effects 220
Approach to treatment of RA 521 treatment 162 uses of catecholamines 219
Arrhythmias 226 Bronchial asthma 1 Causes of hypopituitarism 425
drug therapy 226 essentials of diagnosis 1 Causes of stroke in young 116
mechanism and classification management 1 Cephalosporins 82
226 antiasthmatic drugs 1 antibacterial spectrum 82
supraventricular arrhythmias 228 individual drugs 2 doses and side-effects 83
ventricular arrhythmias 228 pulmonary function test 1 Cerebral amoebiasis 182
Arthritis 514 treatment 2 Characteristics of insulin prepara-
classification 514 Bronchiectasis 16 tions 483
orthopaedic surgery 523 medical management 16 Characteristics of renal stone 604
physiotherapy 523 prevention 16 Chemoprophylaxis 161
domestic activities 523 surgical treatment 17 Chemotherapy of multi-drug-
exercise 523 Bronchodilators 44 resistant tuberculosis 109,
occupational therapy 523 Bronchogenic carcinoma 30 638
rest 523 clinical notes 31 basic principles and guidelines
splints and walking aids 523 109
non-small cell lung cancer 31
rheumatoid arthritis 515 drugs and doses for MDR-TB
small cell lung cancer 31
laboratory investigations 516 110
treatment 30
pharmacotherapy 516 list of drugs for MDR-drugs 110
side effects of treatment 31
treatment of RA 516 suggested regimens for MDR-TB
Bulbar palsy 179 111
Aspergillosis 39
Chest infection 301
Choice of digitalis preparation 210
Choledocholithiasis 415
Cholelithiasis 410
diagnostic clues 410
investigations 410
management 410
Chorea 148
hemibellismus 148
Huntington’s chorea 148
rheumatic chorea 148
Chronic cholecystitis 414
Chronic complications of diabetes
mellitus 489
Chronic myeloid leukaemia 63, 551
Chronic pancreatitis 420
aetiological consideration 421
clinical consideration 421
diagnostic investigations 421
surgical treatment 422
treatment 422
Chronic pyelonephritis 597
aetiology 597
clinical consideration 598
diagnostic evaluation 598
pathogenesis 598
treatment 598
Chronic renal failure 582
aetiological consideration 582
diagnostic approach 583
laboratory investigations 583
management 585
treatment of complications 586
Chronic respiratory failure 43
diagnosis 43
heart failure 44
important causes 43
management 43
management of secretions 44
precipitating factors 43
Classification 472
Classification of DMARDs 523
Classification of insulin 482
Clinical approach to antimicrobial
therapy 87, 614
Clinical manifestations of hypo-
pituitarism 426
Clinical notes on angina 295
Clinical notes on antiarrhythmic
drugs 247
Clinical notes on arrhythmias 246
Clinical types of hepatitis 405
Cluster headache 176
Coagulation disorders 77, 562
Coccidioidomycosis 39
Coma in diabetics 494
Combination therapy in ventricular
arrhythmias 237
Congenital heart disease 301
Congestive cardiac failure 260, 301
cardinal clinical features 260
clinical pearls 262
pathophysiology 260
treatment 260
drugs 260
general measures 260
Connective tissue disorders 533
diagnostic clues 533
specific drugs 537
treatment of 535
general supportive measures
535
physical therapy 535
symptomatic treatment 535
Constipation 384
causes 384
definition 384
diagnostic clues 384
enema 388
fecal impaction 388
investigations 385
laxative abuse 388
management 386
surgery 388
Cor pulmonale 319
causes 319
acute corpulmonale 319
chronic cor pulmonale 319
clinical diagnosis 319
electrocardiographic diagnosis
319
roentgenographic diagnosis 319
treatment of CCF 320
Coronary artery disease 316
surgical procedures 316
CABG 316
PTCA 316
Crohn’s disease 363
definition 363
diagnostic clues 363
Index | 647
management 364
medical treatment 364
specific drugs for active disease
365
surgery 367
treatment during pregnancy 366
treatment of extraintestinal
complications 366
Cryptococcosis (tolurosis) 38
Cushing’s syndrome 504
aetiological consideration 504
anatomical localization of tumour
506
diagnostic clues 504
investigations 505
medical therapy 508
other laboratory investigations
506
surgery and irradiation therapy
507
treatment 06
Cyanosis 301
Cysticercosis 182
Cystitis 615
D
Depression 188
classification 188
depression in elderly 190
other modes of treatment 190
plan of treatment of major
depression 190
prophylaxis 190
treatment 188
Dermopathy 437
Diabetes and hypertension 288
Diabetes insipidus 464
aetiological consideration 464
diagnostic approach 465
diagnostic clues 464
patho-physiology 467
treatment 465
Diabetes mellitus 468
classification 468
complications of 470
diagnostic clues 468
laboratory investigations 470
treatment 471
648 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
Diabetic foot ulcer 493
Diabetic ketoacidosis (DKA) 495
complications occurring during
DKA therapy 499
diagnostic clues 496
investigations for monitoring 496
laboratory investigations 496
management 496
monitoring of potassium 498
prevention 499
Diabetic nephropathy 490
Diabetic retinopathy 489
Diagnosis of gallstone 411
Dialysis 589
Diarrhoea 389
clinical types 389
acute 389
chronic 389
diagnostic clues 390
Diet in diabetes 471
alcohol 475
artificial sweetening agents 475
carbohydrate 472
fat 474, 476
fibres 473
protein 473
vitamins and minerals 475
Digitalis glycosides 207
mechanism of action 207
electrophysiological effects
207
haemodynamic effects 208
mechanical effects 207
pharmacokinetics 208
Digitalis toxicity 209
cardiac toxicity 209
criteria of adequate digitalisation
210
extracardiac toxicity 209
indications 210
treatment 209
Digoxin 257, 261
Diseases of hypothalamus 424
Disopyramide 248
Disorders of oesophagus 339
Diuretics 203
contraindications 204
drug interactions 204
indications 204
mechanism of diuretics 205
side-effects 204
Dosages of inderal 215
Dosages of thyroxine 445
Dosing and side-effects of
antiarrhythmic drugs 231
Drug abuse and dependency 197
Drug regimens for tuberculosis 111,
639
Drugs and doses for MDR-TB 639
Drugs and parasites 380
Drugs for acute mania 192
Drugs for bacterial meningitis 158
Drugs for diarrhoea 366
Drugs for GER 338
Drugs for intestinal helminthes 378
Drugs for multi-drug-resistant TB
105, 635
Drugs for MDR-drugs 638
Drugs for protozoa 376
Drugs in angina 293
Drugs in hypertension 275
Drugs of NSAID group 516
Drugs used in ACLS 253, 333
Dystonia 147
aetiology 147
idiopathic 147
juvenile dystonia 147
paroxysmal dystonia 148
secondary 147
E surgery 344
Effects of drugs on the conduction
pathways 229
Electrical therapy for cardiac
arrhythmias 243
Empiric antibiotic therapy 157
Empyema 8
management 8
antibacterial therapy 8
closed drainage 8
surgical management 8
Endstage renal failure 589
treatment 589
Enteric infection causing diarrhoea
627
Enuresis 180
Epilepsy and seizures 129
aetiology of epilepsy 129
classification of seizures 130
diagnosis 131
precipitating factors of seizures
129
Erythema nodosum 398
Extraintestinal amoebiasis 381
F
Factors increasing stone formation
601
G
G-6-PD deficiency 546
Gastric cancer management 352
chemotherapy 352
nutritional support 352
radiotherapy 352
surgery 352
Gastritis 353
acute gastritis 353
chronic gastritis 353
diagnostic clues 353
Gastroenteritis 615
Gastro-oesophageal bleeding 341
balloon tamponade 343
diagnostic clues 341
endoscopic therapy 344
management of medical therapy
342
Gastro-oesophageal reflux disease
337
diagnostic clues 337
management 337
Glomerular diseases 565
Glomerulonephritis 565
clinical consideration 565
clinical types 565
acute glomerulonephritis 565
chronic glomerulonephritis
565
laboratory consideration 566
prognosis 566
side-effects of therapy 566
treatment 566
Glossitis 397
Glossopharyngeal neuralgia 179
Glucocorticoids 518
Goitrous hypothyroidism 444
Gout 525
Grief reaction 191
medications 191
Guidelines for using digoxin 266
H treatment of 441
Haemolytic anaemia 51
Haemolytic-uremic syndrome 561
Haemorrhage 351
Haemorrhagic disorders 72, 557
aetiological classification 557
Hairy cell leukaemia 67, 554
diagnostic clues 67
Haliostosis 398
Headache 168
classification 168
diagnostic clues 169
diagnostic evaluation 170
idiopathic or primary headache
168
important headaches 169
investigations 170
miscellaneous headaches 168
secondary headache 168
treatment of headaches 171
headache medications 174
Hemotherapeutic regimens for
pulmonary tuberculosis 107
Hepatitis A 408
Hepatitis B 408
Hepatitis C 409
Hepatitis D 409
Hereditary spherocytosis 546
Cold sore 398
Encephalitis 181
Hiatus hernia 340
Histoplasmosis 39
Hospital-acquired pneumonia 629
Hydrocortisone 447
Hyperaldosteronism 502
aetiological consideration 502
diagnostic clues 502
laboratory investigations 502
treatment of hyperaldosteronism
503
Hypercyanotic spell 303
Hyperglycaemia in type 1 diabetes
mellitus 488
Hyperprolactinaemia 440
aetiological consideration 440
diagnostic clues 440
laboratory investigations 440
physiological consideration 440
Hypersplenism 76, 561
Hypertension 269
drug therapy 271
Hypertensive crisis 288
Hypertensive emergencies 281
Hyperthyroidism 432
causes 432
diagnostic clues 432
investigations 433
treatment 438
treatment of complications 436
hyperthyroidism and pregnancy
437
Hypoparathyroidism 453
aetiological consideration 453
diagnostic clues 454
laboratory investigations 454
surgical therapy 455
treatment 454
types of hypoparathyroidism
453
functional hypoparathy-
roidism 453
primary hypoparathyroidism
453
pseudohypoparathyroidism
453
Hypothyroidism 443
aetiological consideration 443
diagnostic clues 443
laboratory findings 444
management 446
primary hypothyroidism 443
secondary hypothyroidism 443
treatment of hypothyroidism 445
I treatment of special conditions
Ideal diet for diabetics 476
Idiopathic parkinsonism 141
Immunomodulators and
Index | 649
immunosuppressive drugs
519
Indications of antiarrhythmic drugs
228
Indications of insulin therapy 484
Individualised drug therapy in
hypertension 284
Industrial and chemical poisons 182
Infectious diseases 80
antimicrobial therapy 80
Infective endocarditis 113, 308, 641
acute bacterial endocarditis 113
clinical approach 113
prophylactic drugs 115
prophylaxis 115, 309, 642
prosthetic valve endocarditis 113
subacute bacterial endocarditis
113
surgery 114
clinical notes 312
general principles of treatment
308
medical therapy 308
antibiotic therapy 308
empiric therapy 308
prophylactic drugs 643
type of infective endocarditis 641
Inherited coagulation disorders 77,
562
Inotropes used in cardiac failure 266
Insulin administration 483
Insulin regimens 487
Insulin therapy 482
Insulins in India 482
Intermittent supervised
chemotherapy 107
Interstitial lung disease 18
causes 18
classification 18
clinical notes 20
treatment 19
medical treatment 19
surgical treatment 19
19
Intestinal amoebiasis 380
650 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
Intestinal parasites 375
diagnostic clues 375
investigations 376
Intracerebral haemorrhage 124
common causes 124
diagnostic clues 124
clinical manifestations 124
laboratory investigations 124
treatment 124
surgical evacuation of blood
clot 125
Intravenous drugs for cardiac failure
264
Irritable bowel syndrome 361
clinical features 361
definition 361
management 361
biofeedback therapy 362
diet 362
drugs for symptoms 362
general management 361
psychoneurosis 362
Ischaemic cerebrovascular diseases
116
causes 116
cerebral haemorrhage 116
cerebral infarction 116
cerebral ischaemia 116
laboratory investigations 119
prophylaxis 122
treatment 119
acute stage 119
prevention of recurrence 119
stage of rehabilitation 119
Isonex 15
K Management of pneumonia 628
Kidney transplantation 591
L 136
Laboratory investigations for
hypopituitarism 426
Legionellosis 36
Leukaemias 550
diagnostic clues 550
prognosis 553
treatment 551
Leukoplakia 397
Lignocaine 248
Lung abscess 7
management 7
antibiotic therapy 7
physiotherapy 7
surgical treatment 8
treatment of causes of lung
abscess 7
prevention 7
Lymphomas 67, 554
M Mechanism of anti-ulcer drugs 347
Macrolides 84
Macrovascular complications 493
Malabsorption syndrome 368
causes and mechanism 368
malabsorption 368
maldigestion 368
definition 368
diagnostic clues 369
investigations 369
specific treatment 373
symptomatic treatment 373
treatment 372
Management of AMI 256
Management of cardiac arrhythmias
235
Management of cardiac failure 264
Management of chronic hepatitis
406
Management of chronic sinusitis 96,
624
Management of heart failure 263
Management of myxoedema coma
446
Management of refractory hyperten-
sion 280
Management of status epilepticus
Management of unstable angina 294
Manic-depressive disorders 192
diagnostic clues 192
treatment 192
antimanic drugs 192
use of lithium 192
Mayoclinic drug regime for chronic
active hepatitis 407
MDR tuberculosis 12
basic principles 12
clinical notes 15
drugs used in MDR-TB 13
patients with renal failure 14
prevention 14
BCG vaccination 15
INH prophylaxis 14
suggested regimens for MDR-TB
13
treatment of children 14
treatment of pregnant women 14
Méniére’s disease 179
Meningitis 156, 614
diagnostic clues 156
clinical manifestations 156
laboratory investigations 157
organisms responsible 156
pathogenesis 156
predisposing factors 156
treatment 157
Metabolic bone diseases 460
Metabolic profiles of anti-
hypertensive drugs 288
Method of digitalisation 211
Mexiletine 248
Migraine 171
dementia 178
dosages and treatment plan of
migraine 173
mild hydrocephalus 178
Remarks on antibiotic therapy 160
Monotherapy 138
Mucormycosis 39
Multinodular goitre 449
Multiple myeloma 69
approach for management 72
clinical features and laboratory
features 69
diagnostic clues 69
laboratory diagnostic criteria 70
treatment 70
chemotherapy 70
transplantation 71
Multiple sclerosis 150
aetiology 150
clinical features 150
clinical notes 153
diagnostic clues 150
 focal signs 150
laboratory investigation 150
physical therapy 153
treatment 151
Myasthenia gravis 163
aetiology 163
diagnostic clues 163
investigations 164
management of precipitating
factors 165
pathogenesis 163
plan of treatment 166
anticholinesterase drugs
therapy 166
corticosteroid therapy 167
edrophonium chloride test
166
treatment 164
Mycoplasma pneumoniae 36
Myoclonus 148
aetiology 148
characteristics 148
treatment 148
Mysthenic and cholinergic crisis 166
N laboratory investigations 461
Narcolepsy/cataplexy 180
Nelson’s syndrome 508
Nephrolithiasis 601
clinical consideration 601
diagnostic evaluation 602
laboratory investigation 603
Nephrotic syndrome 569
aetiological and pathological
consideration 569
clinical consideration 569
treatment of nephrosis 570
Neurocysticercosis 182
Neurosyphilis 181
Newer antiepileptic drugs 135
Non-goitrous hypothyroidism 444
Non-surgical treatment of gallstones
413
NSAIDs 517
O 76
Oesophageal spasm 339
Oral antidiabetic drugs 478
classification based on mechanism
of action 478
disadvantages of anti-diabetic
drugs 480
indications of oral antidiabetic
drugs 480
pharmacology of drugs 478
Oral medicines 396
dental caries 396
Organisms found in infective
endocarditis 309
Osteodystrophy 588
Osteomalacia 456
aetiological consideration 456
diagnostic clues 457
laboratory investigation 457
monitoring 459
pathophysiology 456
prevention 459
surgery 459
treatment 457
Osteoporosis 460
aetiological consideration 460
primary osteoporosis 460
secondary osteoporosis 460
diagnostic clues 461
pathogenesis 460
treatment of osteoporosis 461
Other arthritis 525
diagnostic clues 527
drugs and surgical therapy 530
gonococcal infective arthritis 525
non-gonococcal infective arthritis
525
occupational therapy and
rehabilitation 530
osteoarthritis 526
routine investigations 527
specific investigations 527
spondyloarthropathies 526
treatment of other arthritis 529
general therapy 529
physical therapy 529
Other causes of thrombocytopenia
P organisms 100
Parathyroid gland 453
Parathyroidectomy 452
Index
Parenteral diltiazem 296
| 651
Parenteral drugs in hypertensive
crisis 283
Parkinson’s disease 140
aetiology 140
clinical notes 145
diagnostic clues 141
drugs for parkinsonism 141
pathogenesis 140
surgery 145
treatment 141
Paroxysmal nocturnal
haemoglobinuria 546
Pelvic inflammatory disease 616
Peptic ulcer disease 346
clinical features 346
diagnostic clues 346
investigations 346
treatment 346
Pericarditis 322
aetiology 322
acute pericarditis 322
chronic 322
effusive 322
diagnosis 322
treatment 324
Phaeochromocytoma 500
diagnostic clues 500
laboratory investigations 500
treatment of 501
Pharyngitis 399
Pigment induced renal injury 581
Pituitary adenoma 425
Pituitary gland 424
Pneumonia 32, 99, 615
antibiotic therapy 32
clinical notes 35
drugs and dosages 33
prevention 32
primary pneumonia 33
secondary pneumonia 33
supportive treatment 34
aetiology 100
chemotherapy 106
management 100
precipitating factors 99
preventive therapy 103
652 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
Polytherapy 138
Postcholecystectomy syndrome 412
Postmyocardial infarction 259
Primary Addison’s disease 512
Primary hypothyroidism 444
Primidone 135
Principal antianginal drugs 290
Problems of insulin therapy 484
Procedure for ACLS 255
Proctosigmoidoscopy 370
Prophylactic drug in chronic
headache 175
Prophylaxis of recurrent ventricular
arrhythmias 237
Pseudohypoparathyroidism 453
Pulmonary atelectasis 25
acquired causes 25
congenital causes 25
diagnostic clues 25
investigations 25
management 26
Pulmonary fibrosis 26
diagnostic clues 26
investigations 26
management 26
Pulmonary oedema 303
Pulmonary thromboembolism 21
algorithm of treatment 24
diagnosis 22
diagnostic approach 21
prevention 24
treatment 22
Pulmonary tuberculosis 9
treatment regimens 10
WHO treatment regimens 11
Pyelonephritis 615
Pyrazinamide 15
Q
Quinidine 247
R sexual pain disorders 199
Radiocontrast nephropathy 580
Rapid digitalisation 211
Recently introduced two anti-
hypertensive drugs 279
Recommendation of American
Diabetic Association 485
Rifampicin 15
Regimens of insulin therapy 485
Renovascular hypertension 286
Respiratory stimulant 44
Respiratory tract infection 95, 623
empirical therapy 629
lower respiratory tract infection
97, 625
preventive therapy 631
supportive therapy 630
upper respiratory tract infection
95, 623
aetiology 623
clinical 623
laboratory investigations 623
treatment 623
Restless leg syndrome 180
Rheumatic fever 306
drug treatment 306
prevention 307
S Sporotrichosis 39
Schilling test 542
Schizophrenic disorders 186
aetiology 186
diagnostic clues 186
pathophysiology 186
treatment 186
drug therapy 186
neuroleptics 186
Secondary Addison’s disease 513
Secondary hypothyroidism 444
Secondary parkinsonian disease 141
Serological patterns in infective
hepatitis 402
Severe thrombocytopenia 75
Sexual dysfunction 199
characteristics 199
arousal disorders 199
desire disorders 199
dyspareunia 199
orgasm disorders 199
vaginismus 199
treatment 199
biofeedback using penile
plethysmograph 202
cognitive behaviour therapy
202
drug therapy 199
dual sex therapy 201
relaxation therapy 202
sexual education 202
squeeze technique 202
Shock 325
management 325
types 325
vasopressors used in shock 328
Short course chemotherapy 108
Side-effects of calcium channel
blockers 292
Sleep walking 180
Sleep-apnoea syndrome 179
Slow digitalisation 211
Slow viral disease 181
Small bowel barium series 370
Small bowel mucosal biopsy 371
Specific drugs for stroke 118
Specific yoga practices in diabetics
477
Standards of laboratory control of
diabetes mellitus 483
Step care therapy in hypertension
280
Stroke syndrome 117
Stroke therapy 122
Subarachnoid haemorrhage 126, 180
aetiological facts 126
clinical notes 128
diagnostic clues 126
incidence 126
laboratory investigations 126
treatment 127
prevention 127
surgery 127
Sub-clinical hypothyroidism 445
Subtotal parathyroidectomy 452
Suggested regimens for MDR-TB
639
Suicidal tendencies 191
Surgical management of congenital
heart disease 304
Survival rate of dialysis 590
Syncope 335
causes 335
diagnosis 335
management of syncope 335
Syphilis 616
T treatment of co-existing
Tardive dyskinesia 149
Therapeutic regimens for pulmonary
tuberculosis 635
Therapy of pulmonary embolism 23
Therapy with insulin 484
Thrombocytopenia 73, 557
diagnostic clues 73
Thrombocytosis 76, 561
Thrombolytics 251
Thrombotic treatment of thrombocy-
topenic purpura 75
Thyroid enlargement 448
evaluation of single nodule 448
treatment of nodular enlargement
of thyroid 449
Thyroid function 444
Thyroiditis 439
diagnostic clues 439
TICS 149
Tinnitus 179
Tocainide 248
Tonsillitis 399
Toxicity of digitalis 208
Transmission of hepatitis 408
Travellers’ diarrhoea 394
Treatment for eosinophilic diseases
of lungs 27
dosages and indications 27
corticosteroids 27
cytotoxic drugs 27
diethylcarbamazine (DEC) 27
radiation therapy 27
Treatment of acquired haemolytic
anaemia 60, 547
Treatment of acute asthma 3
prevention 4
Treatment of acute diarrhoea 393
Treatment of acute heart failure 263
Treatment of acute pyelonephritis
596
Treatment of amoebiasis 380
Treatment of angina 289
medical treatment 289
drug therapy 289
goal 289
non-pharmacological therapy
289
precipitating factors 289
risk factors 289
conditions 289
Treatment of autoimmune hepatitis
409
Treatment of cardiac arrhythmias
245
Treatment of chronic diarrhoea 394
Treatment of chronic hepatitis 405
Treatment of chronic lymphocytic
leukaemia 65
Treatment of chronic ventricular
arrhythmias 236
Treatment of congenital haemolytic
anaemia 547
Treatment of duodenal ulcer 349
Treatment of empyema 48
diagnostic clues 48
drainage 49
investigations 48
management 48
organisms responsible 48
Treatment of fungal infection of lungs
38
Treatment of gastric ulcer 349
Treatment of haemolytic anaemia 58
Treatment of haemophilia A 79, 563
Treatment of haemophilia B 79, 564
Treatment of hairy cell leukaemia 67,
554
Treatment of Hodgkin’s disease 67,
555
Treatment of hookworm, roundworm
and trichuriasis 382
Treatment of hypercalcaemia 451
Treatment of hyperparathyroidism
450
aetiological consideration 450
diagnostic clues 450
laboratory investigations 451
physio-pathological consideration
450
surgical therapy 452
Treatment of hypocalcaemia of
hypoparathyroidism 455
Treatment of hypopituitarism 427
Treatment of idiopathic thrombocy-
topenic purpura 74, 559
Treatment of individual anaemias 56
Treatment of leukaemia 63
Index |
Treatment of lower urinary tract
653
infection (acute) 594
Treatment of megaloblastic anaemia
61, 549
Treatment of nephrocalcinosis 606
elective surgery 608
emergency surgery 608
indications for surgical interven-
tion 609
surgical treatment 608
treatment of individual stone
episode 606
Treatment of non-Hodgkin’s
lymphomas 68, 555
Treatment of other aetiologies of
hyperthyroidism 437
Treatment of other causes of
thrombocytopenia 561
Treatment of other forms of acute
GN 568
Treatment of pleural disease 46
diagnosis 46
clinical manifestations 46
investigations 46
diagnostic flow chart 46
management 47
Treatment of pneumothorax 49
diagnostic clues 49
investigations 49
management 49
Treatment of PU complications 351
Treatment of sarcoidosis 28
clinical notes 29
Treatment of secondary
hypertension 285
Treatment of sickel cell disease 59,
546
Treatment of systolic hypertension
281
Treatment of tapeworm infection
381
Treatment of thalassaemia 61, 548
Treatment of thrombotic
thrombocytopenic purpura (TTP)
560
Treatment of trichinesis 382
Treatment of trypanosomiasis 382
Treatment of tuberculosis 104, 632
Treatment of type 2 diabetes mellitus
486
654 | Bedside Approach to Medical Therapeutics with Diagnostic Clues
Treatment of von Willebrand’s
disease 79, 564
Treatment of schistosomiasis
(bilharziasis) 383
Tremor 148
parkinsonian tremor 148
rubral tremor 148
Trigeminal neuralgia 179
Type 1 and 2 diabetes mellitus 488
Types of angina 293
Types of dialysis 590
U diagnostic evaluation 593
Ulcer healing drugs 347, 350
Ulcerative colitis 354, 357
clinical features 354
constitutional symptoms 354
definition 354
diagnostic clues 354
gastrointestinal features 354
investigation 354
treatment 355
Uremic syndrome 76
Urethritis 594
Urethritis epididymitis 615
Urgent digitalisation 211
Uric acid stone 605
Urinary incontinence 599
diagnostic evaluation 599
laboratory findings 599
treatment 600
Urinary tract infection 592
aetiological and pathological
consideration 592
classification 592
clinical consideration 593
investigations of different entities
of acute UTI 593
treatment of acute urinary tract
infection 594
Beta blockers 214
Selective beta blockers 214
V
Valvular heart diseases 297
prophylaxis 300
surgical management of valvular
heart disease 298
Vasodilators 221, 223
classification 221
dosages and side-effects
use of vasodilator in primary
pulmonary hypertension 224
use of vasodilators in heart failure
224
use of vasodilators in valvular
heart disease 223
Verapamil 247
Vincent’s gingivitis 396
Vitamin deficiency syndrome 149
W
Water and electrolyte disturbance
206
X
Xerostomia 398