Viva Voce •
zn
Medical Pharmacology
K
Mukhopadhyay
Private General Practitioner Dhanbad
Former Senior Resident, Department of Pharmacology Institute of Medical Sciences, BHU Medical Officer, Damodar Valley Corporation Additional Professor, Department of Pharmacology College of Medical Sciences Bharat Pur, Nepal
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Viva Voce in Medical Pharmacology © 2004, K Mukhopadhyay 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 pE>rmission of the author and the publisher. This book has been published in good faith that the material provided by author is original. Every effort is made to ensure accuracy of material, but the publisher, printer and author will not be held responsible for any inadvertent error(s). In case of any dlspute,.all legal mattersJo be settled under Delhi jurisdiction only.
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to my father Late Tulsi Das Mukherjee who gave me courage for my education
Preface Medical science has rapidly grown and developed in the last couple
of
decades,
and
so
has
emerged
its
branch
Pharmacology. The real beauty of the subject Pharmacology is that the clinicians of all specialities and superspecialities use its knowledge to prevent, diagnose and cure diseases. This tends to confuse undergraduate students during their viva-voce exams. Viva-voce examination environment has been simulated and model questions and their answers have been provided in this book. Through this book I have attempted to help students get through their viva-voce exams. Many people have helped me put together this book. Birds of the same feather flock together. I am grateful to Dr (Mrs) Barnali Mukherjee, Dr Jhulan Mukherjee, Dr (Mrs) Shrabani Mukhopadhyay and Dr Angshuman Mukhopadhyay who were professional critics outside and loving family near home. I am also thankful to Smt Bina Mukherjee, Shri Basudeb
Mukherjee, Smt Kajoli Mukherjee, Shri Baladeb Mukherjee, Shri Abhijit Banerjee, Smt Jayanti Sinha and Shri GCP Sinha for their blessings and encouragement. I would like to thank Dr TR Roy and Shri Binod Modi and Dr MM Bandopadhyay for encouraging me to go ahead with writing this book. How can I forget to mention my lecturers during my undergraduate and postgraduate studies. I am indebted to Prof MS Dey, Prof Robin Chatterjee, Prof BN Das, Prof S Banerjee, Late Prof AK Sanyal, Prof PK Das, Prof SS Gambhir, Prof SB Acharya, Prof SK Bhattacharya, Prof RK Goel, Dr BL Pandey whose lectures were of immense help in preparing this book. Special thanks go to my department colleagues, Prof AK Chakraborty, Prof SK Tripathy, Dr Anil Jaiswal for suggestions and encouragement. Prof JN Neogi and Prof KK Agarwal of CMS, Nepal also encouraged me to go about writing this book. My heartfelt thanks to them.
Viva Voce in Medical Pharmacology
viii
I must thank Mr Tarun Duneja, GM (Publishing), Mr Sanjay Chakraborty, Asstt. Sales Manager of Jaypee Brothers Medical Publishers to help compile this book. I would like to mention my cousins Aditi Banerjee, Lakshmi Chatterjee, Arundhati Banerjee, Nandini Pandit, Anuradha, Mrinal for their unending enthusiasm. Finally, kisses and love to my son, Sanak, my niece Esha and Idrija for their giggles and laughter which always seemed to tell me: Arise, Awake and Stop not till the goal is achieved.. I must acknowledge my mother, Smt Bedbani Mukherjee who went through with infinite patience and always stood by me. Thanks!
K Mukhopadhyay
•
'!>.
Contents
1. General Pharmacology .............. .. . .. .. ............. ........ .. 1 .
2. Autonomic Nervous System .
...
.
.
.
...
..
.
. ..... .. . ... .......... .............. 8 .
.
.
.
3. Central Nervous System ................................................. 19 a.
Drugs used in Gout
... ......... ... ......... ..... ...........................
b. Analeptics, Psychostimulant, Nootropic c.
Psychopharmacology
d. Alcohol
.............................................. .........
............................................ ................................ .
e. Antiparkinsonian Drugs
f.
Narcotic Analgesic
h. Anti Epileptics NSAID
......... . ............................... .......
................................................ .........
g. Sedative Hypnotics i.
..................................... ....................
.................................................... . ..........
......... .. ........ ..........................................................
g. Rheumatoid Arthritis .
.
.
Local Anaesthetics
.
.
.
.
...
.
..
.....
...
Plasma Kinins, Angiotension
28 30 32 36 39
..
.................... ................. ............... ...
5. Autocoids ........... ... ....
22 27
.... . ..................... 44
........
......... ............................... ................. .
b. General Anaesthetics .
.
19 20
42
......................................................
4. Anaesthetics .... . ...... . .. . ... ... . a.
.......................
44 45
......... ...... . ....................... 48
...
.
.
.
.
..............................................
51
6. Prostaglandins . .. .. .. .. .. ...... .... .. .. . ............ ............ 55 .
.
.
...
.
..
..
..
.
.
.
7. Respiratory System ....... ... .............. ........... . ..... ....... 58 .
..
.
.
.
.
.
..
8. Cadiovascular System ........ ........... ......... . . . . ... ... .. . 61 .
a.
Drugs in Heart Failure
b. Antiarrhythmic Drugs c.
Antianginal Drugs
d. Antihypertensive
.
.
..
..
.
.
.
.
.
............................................... . ...
. ...... ............................................
.
............................................
.....................................
e.
Hypolipoproteinemic Drugs
f.
Plasma Expanders
.
............
...................... .
...........................................
............ ..... . ......................... ... . ............
61 63 65 69 71 72
9. Water, Electrolytes and Drugs Affecting Renal Function . ..... ..... ...... .......... ...... ............. . .. .. .. 74 ..
..
.
..
.
.
.
.
.
x
Viva Voce in Medical Pharmacology
10. Drugs used in Gastrointestinal Tract .......................... 80 11. Haemopoietic System ......................................,............,. 88 12. Endocrine System ........................................................... 98 .
Diabetes mellitus, Insulin, OHG Corticosteroid
....
.
....
.
............................
......................................................................
Drugs Acting on Calcium Metabolims
..
.
....... . . . . . . .............
Anabolic Steroids ..... . . ..
Androgen Oestrogen
..
.....................................................
..........................................
........
Contraceptives
109 112 114
; ................................. 116
............................................................................
Progesterone
104
.
......... . ........... ..........................................
.......... .................................................. ........
117 119 120
13. Antimalarial Drugs ........................................................ 124 14. Antiamoebic Drugs .... ..... ............................ ................ 128 .
.
.
15. Antihelmintic Drugs ................ .
16. Anticancer Drugs
.
............................... 131
... .
. ...................................................... 133
... .
.
17. Drugs Acting on Skin and Mucous Membrane
.....
137
18. Sexually Transmitted Diseases .......................... ........ 140 .
19. Antiseptic and Disinfectant ........................................ 142 20. Radioisotopes .............................. .................................. 144 .
21. Therapeutic Gases ....... .................................................. 145 .
22. Immunosuppresant and Gene Therapy .................... 147 23. Vitamins ........................................................................... 149 24. Enzymes in Therapy .......................•...... ....................... 151 ,
25. Chelating Agents 26. Vaccines and Sera
........................
.
............. ........ ............ 152 .
.
. ............................................ 154
...... ..... .
27. Antibiotics ..................................
.
.....
............................... 156
28. Sulfonamides ................................................. ................. 160 29. Quinolones ....................................................... . ............ 162 .
.
30. Tetracyclines ................................................. . ................. 168 .
31. Chloramphenicol ..................................;........................ 172 32. Macrolide Antibiotics ................................................... 173
Contents 33. Urinary Tract Infection .
...........................
34. Anti Tubercular Drugs 35. ·Anti Leprotic Drugs . .
...
36. Antifungal Antibiotic 37. Antiviral Drugs .
Index
...............
. . .. . .
.
...............
........
.
...............
.
.
.
.
.. ..
.....
. . . .... . .
.
..
..........
.
.
....
. . 175 .
..................
.....
...
.
...
......
.
..
....
.............
.
.........
......
.. .. .
....
.
..........
.
.......
xi
176
.. . 179
....
.
.
.......
.........
.
..
...................................................................................
181 184
187
General Pharmacology Q.l. Define pharmacology, drugs, toxicology, therapeutics, pharmacopeia.
Pharmacology: It is that branch of medical science which deals with history, source, physical and chemical properties, compounding, biochemical and physiological effects, mec hanism of action, absorption, distribution, biotransformation, excretion, therapeutic uses and side effects of a drug.
Drug: i. A chemical substance used for the purpose of diagnosis prevention, relieve or cure of a disease in man or animals. ii. WHO has defined drug as "any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient."
Toxicology: Science of poison. It is the study of measurement, detection and treatment of poisons.
Therapeutics: It is branch of medicine concerned with cure of a disease or relief of symptoms.
Pharmacopeia: A book published by recognised authority of any country containing a list of accepted drugs and formulae for medical preparations with average dose and description of their characteristics test for their identity, purity and potency like IP, BP, USP. Q.2. What is prescription?
It is written order for one or medical agents along with direction to the pharmacist for the preparation and to the
2
Viva Voce in Medical Pharmacology
patient for the use of the medicine at a particular time. It has following parts: 1. Name of patient 2. Superscription
(Rx) Take thou or sign for Jove or Jupiter,
God of healing. 3. Inscription
Body of prescription
��·. t
Basis Adjuvent
c.
Corrective
d.
Vehicle
4. Subscription: Direction of pharmacist for compounding
ingredient. 5. Signa: (Signature) Direction to patient including method
of administration, dose, time of administration. 6. Physicians signature, date, address, registration number.
Q.3. What are the different sources of a drug? It could be i. Minerals: Iron ii. Animals: Thyroid, Insulin iii. Synthetic: Aspirin iv. Microbial: Antibiotic v. Plant: Oils, glycoside, alkaloids, etc.
Q.4. Define bioavailability? Bioavailability of a drug (Biological active drug) is defined as percentage of drug absorbed from a given doses form and reaches systemic circulation following nonvascular adminis tration. In case of intravascular administration it is 100%.
Q.S. What is Apparent volume distribution? Considering body as a single compartment (V) in which drug (M) is distributed and (C) is the plasma concentration of the drug in plasma then apparent volume distribution (Vd)
=
M/
C. The apparent volume distribution is governed by i. Lipid water co-efficient ii. pka of drug iii. Protein binding and affinity for other tissues for the drug. 1v. Diseases like CCF, uraemia, cirrhosis and age.
General Pharmacology
3
Q.6. What are the different routes of drug administration? It may be Systemic
Local
I Topical
Deeper tissues
i. Mouth and Pharynx ii.
supply
Eye, ear, nose, throat
iii. G.I.T. iv. Bronchi lungs v. vi.
Parenteral
Arterial
Urethra
-Oral
-Subcutaneous
""\ Dermojet 1- Pellet
-Sublingual -Intramedullary
L
-Rectal
- Intra arterial
-Cutaneous
-Intravenous
-Nasal
-Intradermal
Biodegradable and
-Intraperitoneal
non-biodegradable
-Intrathecal
implant
Anal canal
Implantation Sialistic
Q.7. What are the factors which influence absorption of drugs? Absorption of a drug is influenced by the following factors:
Factors in drugs i. Particle size (smaller particle better absorbed) ii. pH of drug: Acidic drugs are absorbed in acidic medium iii. Adjuvents used in drug iv. Disintegration and dissolution time of drug.
Factors in patient 1.
pH of G.I.T.
ii. Ionization-Non-ionized particle better absorbed. iii. Gastric hurry decreases absorption. iv. Prevalence of other substance viz. Vit C enhances absorption of iron. v. Area of absorbing surface. vi. Enterohepatic circulation. vii. Disease states viii. Pharmacogenetic.
Q.8. What are different methods of termination of drug action? The drug activities are terminated either by biotrans formation, excretion or redistribution. By biotransformation non-polar lipid soluble drugs are transformed into polar lipid insoluble product. The different methods of biotransformation are phase !-non-synthetic (oxidation, reduction, hydrolysis,
4
Viva Voce in Medical Pharmacology
cyclization etc.) and phase 11-synthetic (Acetylation, methy lation, glucuronide conjugation, etc.) The Atracurium is inactivated by spontaneous molecular rearrangements called Hofmann elimination. Q.9. What is first pass metabolism?
Drug metabolized before reaching systemic absorption either in gastro-intestinal tract or liver. Q. 10. Name some drugs that induce enzyme with their
consequence.
Phenobarbitone, Rifampicin et�. they result in: a. Decrease intensity and duration of action b. Tolerance; c. Interfere with dose adjustment; d. Toxicity. Q.ll. What are the different routes of drug excretion?
The drug may be excreted through urine, faeces, lungs, saliva, milk, etc. Q.12. What are first order and zero order kinetics?
1st order kinetics: Constant fraction of drug eliminated per unit
time. Zero order kinetics: Constant amount of drug is eliminated per
unit time, e.g. ethyl alcohol is eliminated by zero order kinetics. Q.13. What are the factors which modify drug action?
1. Body size 2. Age 3. Sex 4. Species race and genetics 5. Routes of administration 6. Environment 7. Pathological states 8. Simultaneous use of other drug 9. Cummulation 10. Tolerance (tachyphylaxis, resistance, �tc.)
General Pharmacology
5
Q.14. What is Young and Dilling formulae? These are formulae to determine dose in a child: Young Formula
Dilling Formula _
Age =
Age
+
12
Age =
20
Adult dose
x
x
Adult dose
Q. 15. What is structure action relationship? Why it is important? -
Activity of a drug is dependent upon its chemical structure. It is important for: a.· Synthesis of newer compounds b. To know mechanism of action of drug and c.
Synthesis of competitive antagonist.
Q.16. What is a receptor? What are its functions? What is against antagonist and partial agonist? A receptor is a macromolecule on effector cells to produce effect. It propagates regulatory signals from outside to inside of the effector cells to integrate various extracellular to intracellular signals to adopt long and short-term ·changes. Drug capable of combining receptor to produce effect is agonist. Affinity is tendency to occupy receptor and efficacy is ability to produce effect. Antagonist has affinity but without efficacy. Partial agonist has intermediate efficacy and agonist has full efficacy.
Q.17. What is dose response curve? As we increase the dose we get increased drug action till we achieve the plateau. It is rectangular hyperbola type of graph. The logarithm of dose produces-sigmoid curve which has four characteristics: i. Potency ii. Slope iii. Maximal effect and iv. Variability.
Viva Voce in Medical Pharmacology
6
Q.18. Define Median lethal dose, median effective dose, therapeutic index.
Median lethal dose: Dose (mg/kg. body wt.) which is expected
to kill half of unlimited population of same species and strain. Median effective dose: Dose (mg/kg body wt.) which produces
desired response in 50% of population. Therapeutic index: Ratio of median lethal dose to median effective dose. It gives indications of margin of safety. Q. 19. What is ADR? What are the different types of non dose dependent ADR?
Undesirable clinical manifestation arising as a consequence of drug administration. It may be dose dependent or dose independent. The dose independent ADR may be: i. Side effect u.
Secondary effect
iii. Toxic effects iv. Intolerance v. Idiosyncracy vi. Allergy viii. Photosensitivity ix. Teratogenicity x. Iatrogenic xi. Carcinogenic. Q. 20. What is dosage? and what are its strategies?
Appropriate amount of drug required to produce certain degree of response. The strategies are: a. Standard do s e
Same dose appropriate for most of the
-
·patient b. Regulated dose
-
Dose
adjusted with physiological
parameters. c. Target level dose
-
Response demonstrated with drug
concentration in plasma d. Titrated dose
Dose is adjusted by titration by step up or
-
step down.
General Pharmacology
7
Q.21. What are the advantages and disadvantages of fixed drug combination? Advantages: i. Better patient compliance ii. Some drugs are synergetic iii. Side effects are concentrated by other. Disadvantages: i. Patient may not require all ingredients ii. Dose of each drug has to be adjusted iii. Time course of different drugs may vary iv. Adverse effect cannot be explained by individual drug v. Altered renal and liver functions affect pharmacokinetics of individual drug vi. Contraindication of one component contraindicates whole combination. vii. Confusion of therapeutic aim.
Q.22. What are essential and orphan drugs? The drugs which satisfy health• care of majority of population are essential drugs. Drugs which are used to treat prevention, diagnosis and treatment of a rare disease are orphan drugs.
Autonomic Nervous System Q.l. How do autonomic and somatic nervous systems differ? The autonomic and somatic nervous systems differ in the following way:
i. Humoral transmitter li. Organ supply
iii. Distal most
synaptic junction iv. Peripheral plexus formation v. Myelin sheath vi. Results of nerve damage
Autonomic Nr. Sys.
Somatic Nr. Sys.
Acetylcholine, Nor-adrenaline
Acetyl Choline
& Adrenaline
All structures except skeletal muscle Outside cerebro-spinal axis i.e.· at ganglia
Skeletal Muscles Inside cerebro-spinal axis
Present
absent
Preganglionic myelinated, post ganglionic non-myelinated
Myelinated
Smooth muscles and glands maintain autonomic activity
Skeletal muscles are paralysed and atrophied.
Q.2. What are the divisions of A.N.S.? How do they differ? The ANS has two divisions i. Sympathetic and ii. Parasympathetic Differences between parasympathetic and sympathetic nervous systems are following: Parasympathetic
l. Origin 2. Distribution
3. Ganglion
4. Postganglion ganglion 5. Pre to post
Cranial sacral (Ill, VIII, IX, X) Cr. nerves and sacral nerves Limited On or close to organ short 1:1 except enteric pl�xus
ganglion fibre ratio 6. Transmitter 7. Stability of transmitter 8. Important function
Acetyl choline Rapidly destroyed Assimilation of food and conserve energy
Sympathetic
Thoraco-lumber Wide away from organs long 1:20 to 1:100
Noradrenaline Diffuses for wider action Fight and flight emergency function
Autonomic Nervous System
9
Q.3. What is neurotransmitter?
A neurotransmitter should satisfy the following criteria:
i. The transmitter and the enzyme capable for its synthesis must be present at the nerve.
ii. The transmitter should be released on nerve stimulation. m.
Extrinsically applied transmitter should mimic the effect of nerve stimulation.
·
iv. The enzyme or enzyme system capable of inactivating the proposed transmitter must be present in the tissues.
v. The drugs altering response to nerve stimulation should alter the response of proposed transmitter in similar way.
Example Acetylcholine, Noradrenaline, Dopamine. Q.4 What is neuromodulator?
A nerve on stimulation releases more than one active
substance. For example, apart for acetyl choline and
noradrenaline, autonomic nerve releases ATP, vasoactive peptides, neuropeptides; prostaglandins, etc. as co-transmitter
acting as neuromodulator. Many abnormal findings of
cholinergic and adrenergic blockade are due to co-tramission of neuromodulators.
Q.S. What are the different types of cholinoceptors?
The cholinoceptors are of two types:
i. Muscarinic (G-protein coupled receptor) blocked by
atropine present in heart, blood vessels, eye, smooth muscles, glands, gastrointestinal, urinary, respiratory, sweat glands, CNS. Their subtypes are Ml, M2, M3, M4,
MS.
ii. Nicotinic (Ligand gated cation channel) blocked by d
tubocurarine or Hexamethonium. Their subtypes are Nm
and Nn.
Nm-Present in skeletal muscle _end plate stimulated by phenyltrimethylamonium (PTMA) �and blocked by d
tubocurarine.
Nn-Present in ganglion, adrenal medulla, spinal cord
stimulated by Dimethyl phenyl piperazinium (DMPP) and blocked by Hemamethonium.
10
Viva Voce in Medical Pharmacology
Q.6. What are the uses of parasympathomimetic drug?
Therapeutic uses of parasympathomimetic drug are limited i. Methacholine used to treat PSVT; ii. Bethanecol to treat postoperative retention of urine iii. Pilocarpine 0.5-4% drops to treat open angle glaucoma. Q.7. What are the therapeutic uses of choline-esterase inhibitors?
i. Eye-glaucoma to counter effect of mydriatic, to prevent adhesion of iris and lens ii. Myasthenia gravis iii. Postoperative paralytic ileus and retention of urine iv. Postoperative decurarization v. Snake bite cobra
·
vi. Belladona or Atropine poisoning vii. To treat overdose of antihistaminics tricyclic antidepres sants, phenothiazine viii. Alzheimer's disease. Q.S. Name some drugs used in Glaucoma.
A. �-Blockers: a. Timolol (�1, and �2 0.25 - 0.5%) b. Betaxolol ((�1) 0.5%e) Levobunolol (used once daily) c. Cartiolol prevent optic nerve damage d. Metipranolol (has corneal anaesthetic property) B. Mitotics: a. Physostigmine; b. Pilocarpine c.
a-Adren!frgic
agonist:
1. Adrenaline 2. Phenylephrine 3. Dipivefrine (Pro-drug for Adrenaline),
4. Aprachlonidine 0.5 - 1%. They are used as adjuvants to miotics or·� blockers. d. Carbonic Anhydrase inhibitors: 1. Acetazolamide use systematically 2. Dorzolamide used tropically e. Prostaglandins PGF2a·
Autonomic Nervous System
11
Q. 9. Describe the clinical features of organophosphorus poisoning and principle of its treatment. Organophosphorus compounds are irreversable cholinesterase inhibitors leading to accumulation of acetylcholine at cholinergic nerve terminals which in turn stimulates muscarinic and nicotinic receptors. The action produced by: A. Muscarinic receptor stimulations are: a. Miosis; b. Bradycardia; c.
Hypotension;
d. Bronchospasm e. Sweating and salivation f.
Diarrhoea;
g. Urinary bladder contraction h. Convulsion B. The nicotinic receptor stimulation produces skeletal muscle fasciculation.
Principle of treatment i. Termination of further exposure by removing cloths and washing with soap water ii. Washing of stomach with Ryle's tube iii. Supportive measure to maintain BP, hydration, control of convulsion with diazepam iv. Specific antidote atropine v. Cholinesterase reactivator PAM; DAM.
Q.lO. Name the drugs used for myasthenia gravis? i. Neostigmine ii. Corticosteroid and immunosuppressants iii. Thymectomy iv. Ephedrine and potassium chloride as adjuvents.
Q.ll. What are the therapeutic uses of anticholinergic group of drugs? 1.
Antisecretory a. Preanaesthetic medication, b. Peptic ulcer,
12
Viva Voce in Medical Pharmacology
c. Pulmonary embolism d. Salivation in parkinsonism ii. Antispasmodic-Renal, abdominal cramps, dysmenorrhoea, pylorospasm, aneuresis iii. Bronchial asthma and COPD iv. Mydriatic cycloplegic. v. Partial heart block vi. Parkinsonism vii. Motion sickness viii. Muscarinic poisoning.
Q.12. Mention the principle of dhatura and belladona poisoning. a. Gastric lavage with tanic acid (Potassium permanganate
not eff�ctive); b. Cold sponging c. General measures like artificial respiration, blood volume maintenance, treatment of convulsion with diazepam d. Physostigmine 1-3 mg SIC or IV
Q.13. Name some skeletal muscle relaxants and their therapeutic uses.
Skeletal muscle relaxants can be classified as: a. Directly acting (Dantrolene, Quinine) b. Centrally acting mephenasine group (Carisoprodol, Mephenesin, Chlomerzanone), Diazepam and GABA derivative-Beclofen. c. Pheripheral acting i. Depolarizing blockers (Succinylcholine, Decamethonium) ii: Nori.-depolarising blockers- d(d tubocurarine, Gallamine, Pancuronium, Doxacurium, Vecuronium, Atracurium,_ etc.) The skeletal muscle relaxation requires in the following. conditions: i. Adjuvant to anaesthesia in orthopaedic manipulation and abdominal surgery ii. In spastic disorders like tetanus athetosis, status epilepticus m.
In electroconvulsive therapy
iv. Centrally acting skeletal muscle relaxants used for torto colis, anxiety, ECT, tetanus, orthopaedic manipulation.
Autonomic Nervous System
13
Q.14. What is malignant hyperthemia? What is its treatment? Sudden rise of temperature may occur in some genetically susceptable individuals with fluorinated anaesthesic due to release of calcium from sarcoplasmic reticulum of skeletal muscles. Treatment: i. Discontinuation of anaesthesia ii. Oxygen inhalation iii. Maintenance of acid-base balance iv. Dantrolene
25,50, 100 mg caps or IV (1 mg/kg)
Name some mast cell degranulators. Why d•tubo
Q.15.
curarine can precipitate bronchial asthma?
Tubocurarine is mast cell degranulators may release histamine from mast cells producing bronchospasm and asthma. Other mast cell degranulators are histamine itself, heparin.
Q.16. What
happens if d-tubocurarine and aminoglycosides
or tetracycline given together?
Aminoglycosides reduce acetylcholine release and tetracycline chelates calcium and potentiate competitive blocking.
Q.17.
What is Hoffman elimination, which skeletal muscle
relexant eliminated by this process?
It is non-enzymatic degradation. Atracuraium eliminated by this process so can be used in hepatic and renal insufficiency.
Q.18.
What is Dales Vasomotor Reversal?
Adrenaline acts on both
a.
receptor. By stimulating
and � receptors but more on � a.
receptor it ra ises BP and by
stimulating � receptor it decreases BP; which is more prolonged, i.e. produces biphasic response. Dale noticed that prior administration of ergot (an
a.
receptor blocker) it
produces only depressor response.
Q.19. Tachy
What is tachyphylaxis? =
Quick; phylaxis
=
protection
It has been observed that after repeated administration of indirectly acting sympathomimetic their effect gradually decreases; the phenomenon is known as tachyphylaxis.
14
Viva Voce in Medical Pharmacology The mechanism proposed for tachyphylaxis are
i. Gradual depletion of presynaptic stores ii. Prior occupation of receptors.
Q.20. What are the types of adrenergic receptors? The adrenergic receptors are G protein coupled receptors act by production of second messenger c AMP. Ahlquist classified it as stimulatory a and inhibitory p receptors which are further classified as al, a2, pl, p2, depending upon agonistic activity. al are further cloned into ala; alb; and a2 into three subtypes a2A, a2B, a2C.
Q.21. What are the therapeutic uses of the sympathomimetic group of drugs? They are used for the following clinical conditions: A. As pressor agent-Noradrenaline, Ephedrine, Dopamine, Phenylephrine, Methoxamine, Metaraminol, Mephen teramine. B. Cardiac stimulant-Adrenaline, Isoprenaline, Dobutamine C. Bronchodilator: Orciprenaline, Salbutamol, Terbutaline, Salmeterol. D. Anorectics-Ampehtamine, Fenflurarnine E. CNS stimulants-Amphetamine in Narcolepsy, Parkin sonism, Hyperkinetic children. F. Uterine relaxants-Isoxsuprine, Ritodrine. G. Nasal decongestants-Oxymetazoline, Xylometazoline, Naphazoline.
Q.22. What are therapeutic uses of
a
Adrenergic blocking
-
agents? They are used in following clinical conditions: i. Pheochromocytoma: Phentolamine, Phenoxybenzamine n.
Hypertension: Prazosin
·
iii. Secondary shock iv. Peripheral vascular diseases-Tolazine, Prazosin v. Congestive cardiac failure-Prazosin vi. Benign hypertrophy of prostrate-Prazosin, Terazosin, Doxazosin vii. Migraine-Ergotamine
Autonomic Nervous System
15
viii. To induce penile erection-Papavarine and Phentolamine induce penile erection.
Q.22. How the action of catecholamine are terminated? The catecholamine after being released are reuptaken by presynaptic nerve terminals called uptake I and metabolized by mono-amine oxidase. It is also uptaken by extraneuronal other cells called uptake II. The portion diffuses in circulation is acted upon by enzyme catechol-ortho methyl trasferase producing metanephrine and nor-metanephrine which are excreted by glucuronide or sulfate conjugation. The uptake I mechanism can be blocked by tricyclic anti deprassants (imipramine) or cocaine producing potentiation of action of catecholamine.
Q.24. How the a and � receptors are distributed? Discuss broadly. The a receptors are excitatory except in G.l. tract and � receptors are inhibitory except in heart. The al receptors are present in vascular smooth muscle. a2 receptors are responsible for inhibition of renin release from kidney. �1 receptors are responsible for myocardial stimulation lipolysis. �2 receptors are responsible for smooth muscle relaxation, vasodilatation and uterine relaxation.
Q.25. How does True (Acetylcholinesterasd and pseudo (Butyryl cholinesterase) differ? The true and pseudocholinesterase differ in th� following ways: True cholinesterase
Distribution
Pseudocholinesterase
All cholinergic sites, RBC,
Plasma, liver, intestine, white
gray matter
matter
Hydrolysis
Very fast
Slow
Methacholine
Slower than Acetylcholine
Not hydrolysed
Benzoylcholine
Not hydrolysed
Hydrolysed
Butyrylcholine
Not hydrolysed
Hydrolysed
Inhibited by
Physostigmine
by organophosphorous
Function
Terminate action of
compounds acety!choline
Terminate ingested esters
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Viva Voce in Medical Pharmacology
Q.26. What do you mean by direct, indirect and mixed acting sympathomimetic drugs?
Directly acting sympathomimetic drugs act directly on a
and 13 receptors like Phenylephrine, Salbutamol. The indirectly
acting sympathomimetics are generally non-catecholamine act on presynaptic adrenergic nerve terminals to release
catecholamine. NAd which then acts on target receptors viz.
Tyramine. They produce tachyphylaxis. Mixed acting sympathomimetics are Ephedrine, Amphe tamine act both directly and indirectly.
Q.27. How al and a2 receptors differ? The a1 and a2 receptors differ in following ways: al
Location
Post-junctional
a2
Prejunctional mainly also in post junctional pancreatic, platelet and certain blood vessels..
Function
Smooth muscle
Autoregulatioin and inhibition.
contraction, secretion
Noradrenaline release,
from glands,
platelet, aggregation, decrease
GI relaxation
insulin release, vasoconstriction
heart stimulation Agonist
Phenylephrine
Clonidine
Methoxamine Antagonist
Prazosin
Acts through
IP3/increases DAG
Yohimbine ·decreases cAMP, close Ca channel and opens K channel
Q.28. What is Sildenafil? What is its popular trade name? It is FDA approved drug for treatment of erectile dysfunction
popularly known as VIAGRA available as 25,50, 100 mg capsules. It acts by selectively inhibiting phosphodiesterase 5
Nitric oxide causes vascular smooth muscle relaxation through
cGMP. Selective inhibition of phosphodiesterase-S by Sildenafil enhances Nitric oxide action, Generally given 1 hour
before intercourse in the dose of 50-100 mg (below 65 years
of age). The common side effects are headache, dizziness,
visual disturbances, loose motion and nasal congestion.
Autonomic Nervous System
17
It potentiates vasodilator action of nitrates may precipitate myocardial infarction and fall in blood pressure. It is also used by people as aphrodisiac. Q.29. What are the differences between antiadrenergic and adrenergic neuron blocking drugs?
The differences are as following: Antiadrenergic drug
Adrenergic neurone blocking drugs
Site of action
Adrenergic
Effect of adrenergic nerves stimulation
Blocked (less completely)
Blocked
Effect of adrenaline
Blocked
Not blocked
Type of effects blocked by a single drug
Either
Example
a
a
and � receptor Adrenergic neuronal membrane or contents
or�
(labetalol blocks both a and �)
a Phentolamine � Propranolol
Sympathetic function decreased irrespective of receptor type Reserpine Guanethidine Bretylium
Q.30. Name some �-blockers? What are their therapeutic uses?
�-blockers can be classified as follows: a. Nonselective (Blocks both �1 and �2) i. Without intrinsic sympathomimetic activity: Propranolol, Solatol, Nadolol, Timolol ii. With intrinsiC sympathomimetic activity: Pindolol, Oxprenolol, Alprenolol iii. With additional a blocking property: Labetalol, Dilevalol, Carvedalol b. Cardioselective (�)-Metoprolol, Atenolol, Acebutolol, Bisoprolol, Esmolol, Betaxalol, Celiprolol �2
selective: Butoxamine.
�-blockers are therapeutically effective in following clinical conditions: i. Hypertension
18
Viva Voce in Medical Pharmacology
ii. Angina pectons iii. Cardiac arrhythmia iv. Mycardial infarction v. Anxiety vi. Dissecting aneurism vii. Pheochromocytoma viii. Thyrotoxicosis ix. Migraine x. Essential termors xi. Glaucoma xii. Hypertrophic cardiomyopathy
Q.31. What are the contraindications of �-blockers? It should not be used in the following clinical conditions: i. Congestive cardiac failure
·
ii. Heart block iii. Bronchial asthma iv. Prinzmetal's angina v. Carbohydra
� lerance and diabetes
vi. It may modify lipid profile.
Q.32. Why neuromuscular blocking agents are not effective orally? All neuromuscular blocking agents are quarternary com pounds, not absorbed orally, so generally given IV, though intramuscular administration is possible.
Central Nervous System DRUGS USED IN GOUT Q.l. What is gout?
'--
Three types of crystals
ate deposited in joints:
a. Mono-sodium urate deposition affecting big toes-acute gout b. Calcium pyrophosphate often effects knee called pseudo gout. c. Hydroxyapatite deposition causing calcific periarthritis effecting shoulder. Gout is a metabolic disorder characterised by hyper uricemia. Uric acid is the product of purine metabolism. It is deposited in joints, kidney and subcutaneous tissue. It may occur due to excess uric acid production or less uric acid excretion. It may be: 1.
primary or idiopathic or
ii. secondary due to leukemia, lymphoma, polycythemia, with chemo or radiation therapy; drug induced with Thiazide, Frusemide, Ethacrynic acid, Pyrazinamide, Levodopa, Ethambutol, Clofibrate (reduces uric acid excretion.)
Q.2. Name the drugs used in gout. Following drugs are effective for gout a. In acute conditions: NSAID; Colchicine, Corticosteroids b. For chronic gout i. Uricosuric (l:'robenecid; Sulfipyrazone) n.
Uric acid synthesis inhibitors-Allopurinol.
20
Viva Voce in Medical Pharmacology
Q.3.
What is the mechanism of action of colchicine. How it
is administered? i. Colchicine inhibits
release
of
glycoprotein
as
a
consequence of uric acid deposition in joints. ii. Binds microtubule of mitotic spindle. It is available as 0.25 mg tablet for acute 1 mg orally followed by 0.25 mg every 1-3 hours till control occurs or diarrhoea starts.
Q.4. What
is the mechanism of action of probenecid?
Probenecid competitively blocks active transport of organic acids at all sites. Uric acid is largely reabsorbed by active transport. Probenecid by blocking the absorption of uric acid enhances its excretion. It does not have analgesic anti inflammatory properties.
Q.5.
What is the mechanism of action of Allopurinol?
Xanthine oxidase is the enzyme responsible for uric acid synthesis. Allopurinol is short acting competitive inhibitors or xanthine oxidase, but its metabolite alloxanthine is long acting non-competitive inhibitors of xanthine oxidase Allopurinol thus decreases uric acid production.
Q.6.
How does Probenecid increase the action of penicillin
or Cephalosporin? Penicillin or Cephalosporin is secreted by proximal tubule, but its resorption is minimal. Its secretions are inhibited by Probenecid, therefore it potentiates the action of Penicillin or Cephalosporin and should be used with caution in kidney diseases.
ANALEPTICS, PSYCHOSTIMULANT, NOOTROPIC Q.7. What are analeptics? Where they are used?
Name some
analeptics. These drugs stimulate respiration and have value in coma or fainting.
me resuscitative
Central Nervous System
21
Analeptic's therapeutic values are limited and dubious and given in following therapeutic conditions. a. In hypnotic drug poisoning until mechanical ventilation is started b. Drowning c.
Apnoea in premature babies
d. Respiratory failure e. In general anaesthesia who fails to ventilate spontaneously. Some commonly used analeptics are: i. Doxapram ii. Ethyl and Propyl butamide iii. Nikethamide iv. Smelling strong ammonia or alcohol Q.S. Name some drugs which have psychostimulant action. The drugs are: i. Amphetamine ii. Methylphenidate iii. Pemoline iv. Cocaine v.
Methylxanthine like caffeine
The psychic effects of these drugs are more important than medullary vital centres. Q.9. Mention the pharmacological indications of cere broactive drugs or cognition enhancers. The cerebroactive enhancers are used for i. Senile dementia of Alzheimer's type ahd multi-infarct dementia ii. Common elderly symptoms like dizziness, memory dis turbances m.
Mental retardation, learning defects, learning disorder of· children.
·
iv. TIA, CV A-stroke v. Organic psychosyndrome and sequela of ECT, brain surgery, head injury. The following mechanisms of action for cognitive enhancer have been suggested: i. They increase regional or global blood flow of brain
22
Viva Voce in Medical Pharmacology
ii. To support cerebral metabolism m.
Increase all aspects of memory.
a. Cognitive enhancer (Nootropic agent)-Piracetam
b. Metabolic enhancer: Codergocrine (Semisynthetic ergot) with
a-
blocking properties increases blood flow and
releases Ach from cortical area. Nicergoline is synthetic ergot. Piribedil (Dopamine agonist improve memory,
vigilance, concentration, tinnitus, giddiness.) Tacrine (reversible anticholinesterase used in Alzheimer's disease)
Pyritinol (enhances cerebral metabolism by increasing
glucose transport, enhance cholinergic transmission and improves regional blood flow.) Ginkgo biloba (PAF
antagonist improve microcirculation).
PSYCHOPHARMACOLOGY Q.lO.
Classify Psychiatric disorders br<_>adly.
Psychiatric disorders have traditionallY been classified into two main groups:
i. Organic (physical etiology known)
ii. Functional (without physical factors).
The functional psychiatric disorders are further classified
into neurotic (anxiety, depression) and psychosis (schizo phrenia, mania) etc.
Pathophysiology
of
mental
illness
is
not
clear.
Dopaminergic activity is involved, i.e. schizophrenia and mania where as deficiency of serotonin, noradrenaline are implicated for depression.
Q.ll.
Classify antipsychotic drug.
The antipsychotic drug can be classified as follows:
i. Phenothiazine-Chlorpromazine, Triflupromazine, Thio- . ridazine, Trifluoperazine, Fluphenazine, Thioproperazine.
ii. Butyrophenones: Haloperidol, Trifluperidol, Droperidol, Penfluridol iii. Thioxanthenes: Chlorprothixene, Thiothixene, Flupen thixol.
iv. Others: Pimozide, Molindone, Sulpride, Loxapine, Reserpine v. A typical neuroleptics: Clozapine, Risperidone.
Central N�rvous System
23
Q.12. Classify antianxiety drugs. The antianxiety drugs can be classified as follows: i. Benzodiazepines-Diazepam, Chlordiazepoxide, Oxazepam, Lorazepam, Alprazolam. ii. Azapirone-Buspirone, Gepirone, Ispapirone iii. Other sedative-Meprobamate, Hydroxyzine iv. �-blocker-Propranolol.
Q.13. What are the adverse effects of antipsychotic drug? These are as follows: i. CNS-Drowsiness, Lethargy, tolerance, increased apetite, seizures may be precipitated. ii. a-adrenergic blockade-Palpitation, difficulties with ejaculation, postural hypotension iii. Endocrinal-Gynaecomastia, Amenorrhoea, Infertility iv. Anticholinergic-Dry mouth, Blurred vision, constipation, urinary hesitancy v. Extrapyramidal disturbances-Parkinsonism, muscular dystonia, Akathisia, Malignant neuroleptic syndrome, Tardive dykinesia. vi. Blue colouration of exposed skin, corneal and lenticular opacities, retinal degneration. vii. Hypersensitivity reactions like cholestatic jaundice, skin rash, photosensitivity, agranulocytosis.
Q.14. What are the therapeutic uses of neuroleptics? They are indicated in i. Psychosis (mania, organic brain syndrome) ii. Anxiety iii. Antiemetic iv. Pre-anaesthetic medication to potentiate hypnotics, v vi. vii. viii.
analgesic anaesthetics Intractable hiccough Tetanus Alcohol hallucinations Huntingtons disease.
Q.lS. What is the trade name of chlorpromazine? Why it is so called?
It is marketed in the name of Largectil because of large pharmacological action and wide variety of therapeutic use.
24
Viva Voce in Medical Pharmacology
Q.16.
What is the mechanism ofaction of Buspirone?
It is azapirone group of antianxiety drug acts as partial agonist on SHTl. An autoreceptors and reduces activity of dorsal raphae of serotonergic neurones. It has weak D2 blocking action without much antipsychotic effect.
Q.17.
Name the drugs used for affective disorders?
Two groups of drugs are used for affective disorders: a. Antidepressants
1
b. Antimaniac (mood stabilizers) (Lithium Carbonate)
I Tricyclic and other anti-depressants
Isoenzyme
Non-selective
I
selective
I
Hydrazine
Non-hydrazine
Phenelzine
Tranylcypromine Clorgiline
Isocarboxazid
MAO -A
I
MAO-B Selegiline
Meclobemide
i. Nor Ad and SHT uptake inhibitors-Imipramine Amitriptyline, Trimipramine, Doxepin, Clomipramine ii. NAd uptake inhibitors Nortriptyline, Desipramine, Protriptyline, Amoxapine iii. Selective 5 HT uptake inhibitor-Fluoxein, Fluvoxamine, Paroxetine iv. Atypical anti-depressant: Trazodone, Buproprion, Mianserin, Tianeptine v. Newer compounds, Venlafaxine, Mirtapazine, Citalo pram, Sertraline.
Q.18.
What is the mechanism of action of Lithium?
i. Lithium replaces body Na +and distributed extracellularly affecting ionic fluxes of brain cell membranes. ii. Decrease release of DA and NAd, without affecting SHT release and correcting turnover of brain monoamines.
Central Nervous System
25
Other actions of lithium: i. Inhibits action of ADH on distal tubule producing diabetes insipidus like state. ii. Insulin like efffect on glucose metabolism. iii. Increases Leukocytosis iv. Reduces thyroxine synthesis interfering iodinationof tyrosine.
Q.19. Name the substrate and inhibitors of MAO A and MAO B and their distribution? MAO-A deaminates 5HT and Nad and inhibited by clorgiline MAO-B deaminates phenylethylamine and inhibites by Selegiline. Dopamine is subtrate for both MAO-A & MAO B. MAO-A is distributed in adrenergic nerve ending, intestinal mucosa, human placenta, MAO-B predominates in some areas of brain and platelets.
Q.20. What is Hallucinogens/Psychomimetics/Psycho dysleptics/Psychotogens? Name them The drugs which alter mood, behavior thought and perception like psychosis is called hallucinogens. These are: i. Lysergic acid of diethylamide (LSD) n.
Lysergic acid amide
iii. Psilocybin iv. Harmine v. Bufotenin vi. Mescaline vii. Phencyclidine viii. Tetrahydrocannabinol
Q.21. What are the various forms of cannabis indica (Marijuana) Bhang-dried leaves taken orally Ganja-dried female inflorescence, smoked Charas-dried resinous extract from flowering tops and leaves called hashish.
Q.22. What are the different indications of antidepressants? They are used for: i. Endogenous depression
26 n.
Viva Voce in Medical Pharmacology
Enuresis in children above 5 years (imipramine)
iii. Peptic ulcer because of their anticholinergic action (doxepintremipramine) 1v. Migraine (Amitriptyline) v. Topical doxepin used for pruritis.
Q.23. What is cheese reaction? A patient getting MAO-I if taken food rich in tyramine or dopa etc. (like cheese beer, wines, fish pickled meat) i.e. indirectly acting sympathomimetic may lead to hypertensive crisis or cerebrovascular accidents called cheese reaction.
Q.24. What is drug abuse? It refers by self-administration of any drug which deviates from approved medical and social pattern within a given culture. Non-medical drug use may be due to: i. Experimental curiosity ii. Recreational or casual source-Permissive; Prescriptive; Proscriptive
Q.25. What is drug tolerance? When increased amount of drug is required for a desired action after repeated drug administration, is called tolerance.
Q.26. What is drug addiction? It is a state of periodic and chronic intoxication produced by repeated consumption of a drug (natural and synthetic) characterized by: i. Overpowering desire or need (compulsion) to continue taking the drug to obtain it by any means ii. Tendency to increase dose. iii. Psychic and physical dependence iv. Detrimental effect on individual and society.
Q.27. What is drug habituation? Condition arises on repeated consumption of drug charac terized by: i. Desire but not compulsion to continue the drug for the cause of improved well being. ii. Little tendency to increase the dose.
Central Nervous System
27
iii. Some degree or psychic dependence but no physical dependence iv. Detrimental effect on individual and not on society.
ALCOHOL Q.l. Name some drugs producing dependence. T�se are-opioids, CNS depressants, cannabinoids, CNS sympathomimetics, psychedelic.
Q.2. Why alcohol is not a food? i. 1 gm of ethyl alcohol gives 7.1 calories in the form of acetate sparing carbohydrate and proteins. It cannot maintain basal metabolism from its hourly oxidation ii. They suffer dietary deficiencies. iii. It has addiction liability.
Q.3. What are the therapeutic uses of alcohol? Alcohol is therapeutically used for: i. Symptomatic treatment of fever because of its cooling effect on skin ii. Prevention of bed sores as it hardens skin. iii.. As antiseptic 70% iv. To wash out phenol v. To destroy trigeminal nerve in neuralgia vi. As appetizer 70%
Q.4. What is the mechanism of action of Disulfiram? Disulfiram (Tetraethyl thiuram disulphide) is faintly yellow, slightly water soluble compound, interferes with oxidation of acetaldehyde formed during metabolism of alcohol. The raised acetaldehyde directly stimulate C.V.S. and indirectly increases dopamine level· by inhibiting dopamine P-oxidase all these lead to toxic reactions like flushing, perspiration, palpitation, nausea, vomiting, fall in blood pressure and col lapse and patient realises that on this drug he cannot tolerate even small amount of alcohol and abstain from drinking. This drug is contraindicated in: i. Hepatic and circulatory disease ii. Uncontrolled diabetes mellitus iii. With general anesthetics or paraldehyde.
28
Viva Voce in Medical Pharmacology
The other drugs which can produce similar effects are Chlorpropamide, Nitrofurantoin, Metronidazole, Griseo fulvin, Tolbutamide, Phenylbutazone, Carbimide. Q.S.How you will treat methyl alcohol poisoning? The methyl alcohol poisoning usually occur due to accidental intake of methylated spirit or adulterated wines. The symptoms are CNS depression, acidosis and formaldehyde selectively producing retinal cell damage. The treatment aims at: i. Correcting acidosis as quickly as possible. ii. Correcting of hypokalemia, maintenance of nutrition, water and electrolyte balance. iii. Protect patient eye from strong light. iv. Ingestion of ethyl alcohol slows metabolism of methyl alcohol by competing for same metabolic pathway. Q.6. What is Delirium Tremans? Sudden withdrawal of alcohol for some day produce this symptoms consisting of restlessness, insomnia, tremors, hallucinations, fear, delirium and convulsions. There is no specific treatment. Treatments given are: i. Correction of dehydration ii. Sedative like Benzodiazepine iii. Maintenance of nutrition and with vitamin thiamine.
ANTIPARKINSONIAN DRUGS Q.l. What is Parkinsonism? It is a syndrome first described by James Parkinsonism 1817. Important features of which are akinesia, rigidity and tremor; excessive salivation, seborrhoea mood changes (depression). It may be idiopathic or secondary or drug induced (reserpine, halloperidol, triperidol, chlorpromazine.) Q.2. What is pathophysiology and pharmacological basis of Parkinsonism? Idioathic Parkinsonism occurs due to depigmentation and loss of pigmented neurones in substantia nigra. Since nigrostrial
Central Nervous System
29
neurons are dopaminergic, there is deprivation of adequate dopamine (DA) input; which allows cholinergic transmission to predominate in basal ganglion.
Q.3. What are the aims of the treatment of Parkinsonism? Aims of treatment are: i. Relief of symptoms of rigidity, tremor, akinesia, seborrhoea ii. Correction of mood changes 111.
Treatment of cause if possible.
The modes of treatment are: i. Drug ii. Physiotherapy iii. Surgical treatment
Q.4. Name the drugs used for Parkinsonism? The drugs are: i. Levodopa ii. Amantadine iii. Selegiline iv. Miscellaneous a. Anticholinergics-Atropine, Benzhexol, Cycrimine, Procyclidine, Biperiden, Benztropine b. Antihistaminics: Diphenhydramine, Promethazine, Orpheradrine, Chlorphenoxan c.
Phenothiazines-Ethopropazine
d. Bromergocryptine, Lisuride, Pergolide, Peribedil, Aprophines e. Peripheral decarboxylase inhibitors: Carbidopa, Benserazide
Q.S. Why Dopamine is not effective for Parkinsonism? Dopamine cannot cross blood-brain barrier but its precursor can cross it. The peripheral decarboxylase inhibitors (Carbi dopa and Benserazide) inhibits peripheral conversion of levodopa into dopamine so CNS concentration of Dopamine increases. Levodopa is not effective in drug induced Parkinsonism which responds to withdraw! of the drug and anticholinergic.
Pyridoxine a ccelerates its peripheral
decarboxylation so decreases its potency.
30
Viva Voce in Medical Pharmacology
Q.6.
What is 'on-off' effect?
After 2-5 years of therapy, the control of symptoms with Parkinsonism fluctuates, probably due to progressiveness of disease. Dose fractionation and more freq1.11i�nt administration tends to decrease this effect temporarily.
Q.7.
What is Tardive dyskinesia?
·
On prolong phenothiazine therapy, patients develop involuntary movements like repetative sucking, smacking of lips, grimacing and movements of the tongue and extremities, the syndrome is called " Tardive dyskinesia".
NARCOTIC ANALGESICS Q.l.
What is an analgesic?
These are drugs which relieve pain without loss of consciousness. They are of two types mainly: i. Opioid analgesic ii. Non-opioid analgesics: Opioid analgesics relief pain with simultaneous depression of CNS.
Q.2.
What are the different alkaloids of opium?
Opium is milky exudate obtained by incising unripe seed capsule of poppy plant Papaver somniferum. The pharma cological active alkaloids of opium can be divided into: i. Phenanthrene group-Morphine, Codeine, Thebaine ii. Benzyl isoquinolone group-Papaverine, N arcine, Noscapine group
Q.3.
Mention the therapeutic uses of morphine.
The morphine is used for: i. Relief of pain ii. Sedation and sleep iii. Pre-anaesthetic medication iv. Acute left ventricular failure v. To produce constipation (Tine opium 0.5-1 ml) vi. To suppress cough.
Q.4.
What is Straub's test?
In mice morphine produces severe spasm of anal sphincter resulting in erection of the tail used to detect morphine in biological fluids. Methadone also produce similar results.
Central Nervous System
31
Q.S. What are the different types of opioid receptors? Opioid group of drugs exerts its action by interaction with specific types of opioid receptors.Which are of three types 1-l (mu); K (kappa); 8 (delta) The actions of different opioid receptors are as follows: �
(mu)
K
o (delta)
(kappa)
Analgesia (Supra spinal)
Analgesia (Spinal)
Analgesia
Respiratory depression
Respiratory depression
Respiratory depression
Euphoria
Dysphoria Hi!llucination
Affective behavior
Miosis
Miosis
Reduced GI motility
Reduced GI mobility
Physical dependance (Morphine type)
Physical dependance (Nalorphine type)
Q.6. How does morphine effective for cardiac asthma (acute left ventricular failure)? Morphine: i. Reduces preload of heart by vasodilatation and peri pher'al pooling of blood. ii. Shifts blood from pulmonary to systemic circulation relieves pulmonary congestion and oedema. iii. Depresses respiratory centre and allays air hunger. 1v. Cuts down sympathetic stimulation by calming the patient and reducing work load.
Q.7. What are the precautions and contraindications of morphine? i. Infants and elderly ii. In respiratory insufficiency (Emphysema; cor pulmonale) iii. Bronchial asthma iv. Head injury (because of respiratory depression, vomi ting.) v. Hypotensive condition vi. Undiagnosed acute abdomen vii. Elderly male (may cause urinary retention) viii. Hypothyroid ix. Liver and Kidney damage x. Unstable personalities
·
Viva Voce in Medical Pharmacology
32
Q.8. Name s ome agonist-antagonist/p artial agonist/ antagonist of opioid receptors. I. Agonist-Antagonist a. Not used as analgesic-Nalorphine, Levallorphine b. Used as analgesic-Pentazocine, Nalbuphine II. Partial/weak agonist-Buprenorphine; Butorphanol III. Pure antagonist-Naloxone, Nathrexone
Q.9.
Classify opioids? I. Natural opioids: Morphine, Codeine II. Semisynthetic opioids: Diacetylmorphine (Heroin) Pholcodeine; [Hydromorphone, Oxymorphone, Hydrocodone, Oxycodone- Not used in India]
III. Synthetic opioids: Pethidine, Fentanyl, Methadone, Dextropropoxyphene, Tramadol, Ethoheptazine [Alpha prodine, Anileridine, Levorphanol, Dextromoramide, Dipipanone, Alfentanil, Sufentanil-not used in India]
Q.lO.
What are endogenous opioid peptides?
In 1970's a number of peptides with morphine like action were isolated from mammalian brain, pituitary, spinal cord and GIT. These are active in very small quantites and their actions are blocked by Naloxone. Three distinct types of opioid peptides are derived from distinct la-rge precursor poly peptide. 1. Endorphins: 31 amino acids P-endorphin derive from pro opio-melanocortin(POMC), which also produces y MSH, ACTH. It is primarily 1-1 agonist with d action. 2. Enkephalins: Methionin enkephalin (MetEnk) and Leucine Er,kephalin (Leu Enk) are most important pentapeptides obtained from pro enkaphalin. Met- enkephalin has affinity for 1-1 (mu) and 8 (delta) where as Leu-enk d agonist. 3. Dynorphins: Precursor prodynorphin produces Dynorphin A and B potent for k-receptor, but also activate 1-1 (mu) and 8 (delta) receptors.
SEDATIVE AND HYPNOTICS Q.l.
What are sedatives and hypnotics?
Sedatives are drugs which reduce excitement and hypnotics are drugs which produce sleep resembling natural sleep both of them depress CNS, the differences are qualitative.
Central Nervous System
33
Q.2. Classify sedative and hypnotics. 1. Barbiturates: a. Ultrashort acting-Thiopentone, Hexobarbitone, Methohexitone b. Short acting-Pentobarbitone, Secobarbitone, Butobar bitone c. Long acting-Phenobarbitone, Mephobarbitone 2.
Benzodiazepines: a. Hypnotics: Diazepam, Flurazepam, N itrazepam, Flunitrazepam, Temazepam, Triazolam, Midazolam b. Antianxiety: Diazepam, Chlordiazepoxide, Oxazepam, Lorazepam, Alprazolam c. Anticonvulsant: Diazepam, Clonazepam, Clobazam
3. Newer Non-Benzodiazepam: Zopiclone, Zolpidem 4. Miscellaneous: Chloral hydrate, Paraldehyde, Triclophos,
Bromida, Meprobamate, Methaqualone, Antihistaminics, Scopolamine.
Q.3. What is anodyne hypnotics? Durgs like morphine, pethidine besides analgesic properties produces hypnotic properties-called anodyne hypnotics.
Q.4. Describe sleep pattern. After extensive studies, it has been noted that sleep pattern varies considerably among individual, age in quantity and depth. The sleep has a definite architectural cycle as follows: i. Stage 0 (awake)-From lying down to start of sleep. EEG show
a
activity and p activity when eyes are closed and
open respectively. ii. Stage I (dozing):
a
activity interspersed with e wave.
There are brust of eye rolling. Neck muscle relaxes. iii. Stage II (Unequivocal sleep): e wave interspersed with spindles K complexes can be evoked on sensory stimulation, little eye movement. iv. Stage III (Deep sleep transition)-EEG shows e, delta and spindle K complexes with strong stimulation, eye movements are few, not easily arousable. v. Stage IV (Cerebral sleep): 8 activity predominates K comp lex cannot be evoked. Difficult to arouse, eyes are fixed.
Viva Voce in Medical Pharmacology
34
v1. REM (Paradoxical sleep): Stage 0-4 and REM in sleep alternates at 80-100 min. In REM sleep EEG have waves of all frequency K-complexes with darting eye movements, nightmares and dreams.
Q.5.
What are the therapeutic uses of barbiturates?
The barbiturates· are used in the following conditions: i. As sedative-hypnotic
·
ii. As anticonvulsant iii. In pre-anaesthetic medications iv. As general anaesthetics v. In psychiatry and for narcoanalysis vi. Miscellaneous-neonatal jaundice, to diagnose psychomotor epilepsy in children with EEG abnormalities.
Q.
6.How you will treat barbiturate poisoning?
Barbiturate poisoning occurs either accidentally or excess intake for suicidal intent.
Clinical features Depression of CNS particularly respiration and peripheral circulatory collapse with weak rapid pulse, cold clammy skin, shallow or cheyne stroke respiration, pupil constricted with paralytic dilatation, fatal complications like atelectasis, pulmonary oedema, renal shut down.
Treatment consists of: i. Gastric lavage-forced vomiting with ipecac there should not be any aspiration in respiratory passage. ii. Endotracheal intubation iii. forced diuresis with mannitol or frusemide if there is no shock cardiac failure or renal impairment. Potassium deficiency should be corrected. tv. Alkalinization: prevents absorption and tubular resorp tion 35 mg/50 ml. NaHC03 added per every litre of intravenous fluid administered. v. Prophylactic antibiotic vi. LV. Fluid vii. Dialysis vii. Role of analeptics doubtful.
Central Nervous System
35
Q.7. What is drug automation? The person frequently taking hypnotic fails to fall sleep, gets mentally confused and amnesia takes pills after pills and develops poisoning.
Q.8. ·What are the contraindications of barbiturates? Barbiturates should not be used in the following conditions: 1.
Acute intermittent porphyria
ii. Liver and kidney diseases iii. Pulmonary insufficiency (emphysema) iv. Obstructive sleep apnoea.
Q.9. What is the si te and me chanism of ac tion of Benzodiazepines? Benzodiazepines act on midbrain ascending reticular formation, limbic system and medullary and cerebellum. It acts on pre and post synaptic BZD receptor which is an integral part of GABA receptor CC channel complex. The binding site of GABA is located on �-subunits and BZD on
a
subunits of
transmembrane anion channels. The BZD receptor increases frequency of CC channel opening induced by submaximal concentrations of GABA. BZD have only GABA facilitatory action but no GABA mimetic action.
Q.lO. Name
Be nzodiazepine therapeutic uses.
antagonist
and
thei r
Flumazenil reverses the hypnogenic psychomotor cognitive and EEG effects of BZD. It is absorbed orally has high first pass metabolism in liver and is used for:i. To reverse benzodiazepine anaesthesia ii. To treat benzodiazepine overdose m.
Hepatic coma
iv. Alcohol intoxication
Q.ll. What is melatonin? Melatonin is N-acetyl 5 methoxy tryptamin the principal hormone of pineal gland, secreted at night is important for synchronizing the sleep wakeful cycle. Low dose increases the propensity of falling sleep (2-lOmg). It decreases symp toms of jet-lag disease. Beneficial to shift workers and also
36
Viva Voce in Medical Pharmacology
used for cluster headache. It might decline ageing process. It is used as health food in some countries.
Q.12. What are the requirements of an ideal hypnotic? These are: i. Should be effective orally, quickly with predictable and sufficiently long hypnotic action which should resemble natural sleep. ii. It should be non-irritating, non-toxic and should not produce hangover. iii. It should not produce tolerance, habituation and addiction. iv. It should be cheap v. Its suicidal potential should be low if overdose is taken.
ANTI-EPILEPTICS Q.l. What is an epilepsy? These are group of CNS disorders characterized by chronic, recurrent, paroxysmal cerebral dysrhythmia manifest as brief episodes of seizures or loss of consciousness with or without characteristics body movements (convulsion), sensory or psychiatric phenomenon.
Q.2. What are the different types of seizures? I. Generalized seizures: a. Generalized tonic-clonic seizure b. Absence seizure (EEG shows characteristic 3 cycles per second spike and wave pattern) c.
Atonic seizures
d. Myoclonic seizures e. Infantile spasm
·
II. Partial seizur�s: a. Simple partial seizures b. Complex partial seizures.
Q.3. Name some drugs used for epilepsy. The drugs used for epilepsy can be classified as follows: i. Barbiturates-Phenobarbitone, Mephobarbitone ii. Deoxybabiturates-Primidone
Central Nervous System
37
iii. Hydantoins-Phenytoin (other hydantoins are ethotc;>in, methoin) iv. Iminostilbenes-Carbamazepine v. Succimide-Ethosuximide vi.. Aliphatic Carboxylic acid-Valproic acid vii. Benzodiazepines-Clonazepam, Clobazam, Diazepam viii. Miscellaneous-Trimethadione, Phenacemide, Acetazo lamide ix. Newer drugs-Lamotrigine, Gabapentin,, Vigabatrin
Q. 4. What is the mechanism of action of Phenytoin? i. It prevents repetitive detonation of normal brain cells by prolonging the inactivated state of the voltage sensitive neuronal Na+ channel which governs the refractory period of neurons. ii. Reduces Ca 2+ influx during depolarization. iii. Facilitates GABA response and inhibits glutamate response. iv. Prevents intracellular accumulation of Na+ that occurs during repetitive firing.
Q.5. What are the common adverse effect of Phenytoin? Phenytoin may produce following toxicities: i. At therapeutic level-Gum hypertrophy, Hirsutism, hypersensitivity reactions like-rashes, DLE, lymphade nopathy,
megaloblastic
anaemia,
osteomalacia,
hyperglycaemia due to inhibition of insulin release. ii. The dose related toxicities are-ataxia, vertigo, nystag mus, drowsiness, behavioural changes, hallucination ·
epigastric pain, nausea, hypotension, cardias, arrhythmic.
Q.6. What are the therapeutic uses of phenytoin? Phenytoin is used for Grandma!, Psychomotor, focal cortical status epilepticus, Trigeminal neuralgia, Cardiac arrhythmia.
Q.7. What are the therapeutic uses of carbamazepine? It is used for complex partial seizures may be used for generalized tonic clonic, simple partial seizures, trigeminal and other related neuralgia, mania depressive illness as alternative to lithium, cranial diabetes insipidus.
38
Viva Voce in Medical Pharmacology
Q.8. How acetazolamide acts as an antiepileptics?
The proposed mechanism of action of acetazolamide a carbonic anhydrase inhibitor that it raises level C02 level in brain and thus lowers pH and thereby raising the threshold of seizure and sedation. Q.9. In what other clinical conditions ap,art from epilepsy
acetazolamide can be used? Apart from epilepsy, it can be used as: i. Diuretics n.
Glaucoma
iii. To alkalinise urine iv. Acute mountain sickness v. Periodic paralysis. Q.lO. What adverse effect may arise with acetazolamide
therapy? The adverse effect which may arise due to Acidosis, hypokalemia, drowsiness, paraesthesia, fatigue, fever; rash, bone marrow depression. It should not be used in liver diseases as it may precipitate hepatic coma. It should be used with caution in patient of COPD because it may precipitate acidosis. Q.ll. }Vhat are criteria of an ideal anti-epileptic drug?
An ideal epileptic drug should have following features: i. Effective in all varieties of epilepsies.
ii. It should have direct action on epileptogenic focus iii. Quick acting with long duration action. iv. Should have minimal side effect with non-toxicity and non-addictive. v. It should be orally effective and cheap. Q.12. What is the mechanism of action of: a) Lomotrigine b)
Gabapentin c) Vigabatrin. Lomotrigine: Appears to act by blocking voltage sensitive Na+ channel, stabilizing presynaptic membrane, preventing release of excitatory neurotransmitter mainly glutamate. Gabapentin: Crosses brain and enhance GABA release. Vigabatrin: Inhibits GABA transaminase which degrades GABA, increases synaptic GABA concentration.
·
Central Nervous System
39
Q.13. What is the mechanism of action of sodium valproate?
It appears to have multiple mechanism of action: i. Prolong Na+ channel activation
ii. Attenuation of Cci.2+ mediated T current. Augments
111.
synaptic
concentration
of
inhibitory
transmitters by increasing synthesis and decreasing
degradation.
Q.14.
What drug is effective in infantile spasm?
Infantile spasm is best treated with corticosteroids or ACTH,
Valproate and clonazepam has adjunctive value. Other
antiepileptics are useless.
Q.15.
How you will treat status epileptics?
It is a clinical condition used to indicate repeated grand mal epilepsy without recovery of consciousness. It is medical emergency condition. Treatment aims at:
Quick recovery of fits to prevent brain death and
permanent damage of brain by
a. 10 mg of IV Diazepam (2 mg/min) 1st drug. Clonazepam 1-2 mg IV alternative, Phenobarbitone 100-200 mg, LV.
bolus or Phenytoin-25 mg/min LV. Paraldehyde 5-10 ml b c
deep LM. or 16 ml per rectally.
General anaesthetic with curarization with positive
pressure respiration if above treatment is not effective.
Oxygenation, fluid and electrolyte balance, patent airway,
maintenance of BP, normal heart rate glucose level, care
of bowel, bladder and eyes are to be taken as in other
unconscious patient.
NSAID Q.l.
What is NSAID?
In contrast to narcotic analgesics, these groups of drugs are weaker analgesic with anti-inflammatory, antipyretic mainly
act on peripheral pain mechanism, they also raise pain
threshold called
Non-steroidal Anti-inflammatory Drugs
(NSAID). They are of diverse nature chemically.
·
40
Viva Voce in Medical Pharmacology
Q.2. Classify NSAIDs. They can be classified as follows: a. Analgesic and Anti-inflammatory 1.
Salicylate-Aspirin, Diflunisal
ii. Pyrazolone derivative-Phenylbutazone, Oxyphenbu tazone iii. Indole derivatives-Indomethacin, Sulindac iv. Propionic
acid
derivative-Ibuprofen, Naproxen,
Ketoprofen, Fenoprofen, Flubiprofen v. Anthranilic acid derivative- Mephanamic acid vi. Aryl acetic acid derivative-Diclofenac, Tolmetin vii. Oxicam derivative-Piroxicam, Tenoxicam, Meloxicam viii. Pyrrolo pyrole derivative-Ketorolac ix. Sulfanilamide derivative-Nimesulide x. Alkanones-Nabumetone b. Analgesic but poor antiinflammatory i. Para-aminophenol derivative-Paracetamol ii. Pyrazolone derivative-Metamizol; Propiphenazone iii. Benzoxazocine derivative-Nefopam
Q.3. How does NSAID .produce their action. They block prostaglandin synthesis.
Q.4. What are the beneficial effects of PG synthesis inhibition?
These are: i. Analgesic ii. Antipyresis ii. Antiinflammatory iv. Antithrombotic v. They close ductus arteriosus.
Q.5. What is mechanism of action of gener ation of acid peptic disease by aspirin?
Aspirin inhibits PG synthesis which is responsible for reduction of acid in stomach production of mucus secretion this may produce peptic ulcer.
Central Nervous System
41
Q.6. Name some therapeutic uses of aspirin.
Aspirin is used for following therapeutic conditions: i. As analgesic ii. Antipyretic iii. Acute rheumatic fever iv. Rheumatoid arthritis v. Osteoarthritis vi. Postmyocardial infarction and poststroke patient. vii. Aspirin can close PDA and surgery can be avoided viii. To delay labour. Q.7. What are the precautions and contraindications of aspirin therapy?
Aspirin therapy is contraindicated in: i. Peptic ulcer ii. Children below 12 years suffering viral disease induced fever may cause Reye's syndrome iii. Chronic liver disease iv. It should be avoided in diabetics, low cardiac reserve v. It should be stopped before surgery vi. During pregnancy it is responsible for low birth weight, delaying of labour, greater post partum blood loss, premature closure of PDA. vii. It should be avoided in lactating mother and G-6 PD patients. Q.S. What is the mechanism of action of paracetamol poisoning? How it can be treated?
N-acetyl-benzoquinone-imine is highly reactive arylating minor metabolite of paracetamol, which is detoxified by conjugation with glutathione with high dose of paracetamol glucuronidation capacity is saturated and hepatic glutathione is depleted the metabolite binds co-valently to proteins of liver and renal tubule producing necrosis. In chronic alcoholics even 5-6 gm may produce toxicity. The clinical features are nausea, vomiting, abdominal pain, liver tenderness, renal tubular necrosis, hypoglycaemia and may end with coma, jaundice, fulminant hepatic failure may occur.
Viva Voce in Medical Pharmacology
42
Treatment aims at gastric lavage, activated charcoal given orally to prevent further absorption. N-Acetylcyteine 150mg/kg should be infused I.V. for 15 minutes followed by same dose I.V. over next 20 hours. It replenishes glutathione store of liver and prevent binding of toxic metabolite. Earlier treatment is started, better prognosis is expected.
RHEUMATOID ARTHRITIS Q.l.
Name the drugs used in Rheumatoid arthritis.
The drugs used for Rheumatoid arthritis are of three types: ·
i. NSAID groups to relief pain
ii. Disease modifying agents a. Gold b. d-Penicillamine c. Chloroquine d: Sulfasalazine e. Immunosuppressants (Methotrexate Azathioprine, cyclosporine, cyclophosphamide, chlorambucil) iii. Corticosteroids with NSAID or disease modifying agent as adjuvents.
Q.2.
What is the mechanism of action of gold? What are
their toxicities and contraindications?
It is effective for arresting rheumatoid process and preventing involvement of newer joints. Gold salt lower RA factor, ESR, prevents destruction of synovial membrane, reduces chemotaxis, phagocytosis, macrophage, monocyte diffe rentiation, inhibits CMT. The toxicities of gold salt are vasodilatation, dermatitis, exfoliation of skin, stomatitis, membranous glomerulonephritis with albuminuria, Hepatitis, Peripheral neuritis, encephalo pathy, pulmonary fibrosis, bone marrow depression, eosinophilia. It should not be used in kidney, liver, skin disease, pregnancy, lactation, colitis.
Central Nervous System
43
Q.3. What are the toxicities of d-penicillamine?
The d-penicillamine, the copper chelating agent is used for RA may produce toxicities like rash, proteinuria, anorexia, bone marrow depression, antinuClear antibodies may develop, SLE-or myasthenia gravis may be precipitated. .
·,
'
_,,,
Q.4. What is the mechanism of action of chloroquine as anti RA drug?
Chloroquine is antimalarial drug, effective mechanism of action as anti RA is not known. Reduce interleukin I leading to inhibition of B-lymphocyte also interferes antigen antibody reaction. Prolong use of chloroquine may produce retinal damage,
corneal opacities (less common with hydroxychloroquine) rash, graying of hair, IBS, myopathy, neuropathy may occur.
Q.S. What is the mechanism of action of sulfasalazine in RA?
Exact mechanism not known. It suppresses the generation of superoxide and cytokines by inflammatory cells. It is better tolerated to gold and penicillamine. Q.6. Discuss the mechanism of action of following anti RA drug.
·.
i. Methotrexate ii. Azathioprine cycloserine, corticosteroids. a. Methotrexate: Probably inhibits cytokine production chemotaxis, cell mediated immune reaction. b. Azathioprine: affects differentiation and function of T cells, natural killer cells, supresses inflammation.
c.
Cyclosporine: T cell specific immunosuppressants.
d. Corticosteroids: Anti-inflammatory, immunosuppres sants..
Anaesthetics LOCAL ANAESTHETICS Q.l. Define local anaesthetics. Where they are used? These are drugs which on local injection or topical application causes surmountable loss of sensation specially pain. They are used as: i. Surface anaesthesia ii. Infiltration anaesthesia iii. Conduction block anaesthesia iv. Spinal anaesthesia v. Epidural anaesthesia vi. Intravascular regional anaesthesia
Q.2. What are the complications of spinal anaesthesia? The complications which may arise out of spinal anaesthesia are: i. Respiratory paralysis ii. Hypotension treated by Ephedrine, Mephenteramine. iii. Headache can be minimized by small bone needle and head raising iv. Cauda Equina Syndrome v. Meningitis vi. Nausea and vomiting can be prevented by premedication with opioid analgesic inhibits reflex initiated by traction on abdominal viscera.
Q.3. When are spinal anaesthetics not suggested? Spinal anaesthestics are generally not used in the following conditions: i. Hypotension and hypovolemia
Anaesthetics
45
ii. In non-co-operative, mentally ill patient iii. In infants and children control level is difficult iv. If there is kyphosis, scoliosis or lordosis like spinal defects and sepsis at injection site.
Q.4. How local anaesthesia differs from general anaesthesia? They differ in the following ways: General anaesthesia
Local anaesthesia
1.
Site of action
Central nervous system
Peripheral nerves
2.
Involvement
Whole body
Localised area
3. 4.
Consciousness Lost For vital functions and not Precaution
5.
Preferred for
Remains Usually not required
suitable for poor health patient
Q.S.
Major surgery
Not used for major surgery
Name some local anaesthetics?
These are: Procaine, Choropocaine, Cocaine, Lignocaine, Prilocaine, Tetracaine, Bupivacaine, Benzocaine, Dibucaine, Oxethazine.
GENERAL ANAESTHETICS Q.
1. What are general anaesthetics?
They are group of drugs which cause loss of all sensations with consciousness which all are surmountable. The cardinal features of GA are: i. Loss of all sensations ii. Loss of consciousness iii. Muscle relaxation iv. Abolition of reflexes.
Q.2.
What are the different stages of anaesthesias?
They produce descending depression of CNS. The Ether produces G.A. in following 3 stages and 4 planes: i. Stage of Analgesia: ii. Stage of Delirium
· ·
iii. Surgical anaesthesia stage with 4 plane Plane 1 Roving eyeballs Plane 2 Loss of corneal and laryngeal reflexes
46
Viva Voce in Medical Pharmacology Plane 3 Pupils start dilating Plane 4 Intercostal paralysis
iv. Stage of medullar paralysis Q.3. What are the properties of ideal anaesthesia? An ideal GA agent should have following properties: For the patient: It should be pleasant, non irritating non nauseating and vomiting. For the anaesthetist: Its margin of safety should be wide, it should not lower blood pressure and should not have adverse effect on heart, liver and other organs should be potent enough and it should not hamper oxygenation of patient. It should be cheap and easily storable and stable and non interfering with rubber tubing· and soda lime. For the surgeons: Adequate analgesia, muscle relaxations should be provided by it. Q.4. What is preanaesthetic medication? These are drugs use before anaesthesia to make it safe and aims at: i. To allay anxiety, apprehension ii. Amnesia for pre- and postoperative events iii. To supplement analgesic action of anaesthetics iv. To decrease vagal stimulation v. Antiemesis v1. To decrease acidity and volume of gastric juice. The different drugs used are: i. Opioids ii. Antianxiety drug like Diazepam, Lorezepam iii. Sedative hypnotics like Phenobarbitone, Secobarbitone, Promethazine iv. Anticholinergic atropine v. Neuroleptics Chlorpromazine, Haloperidol vi. H2 blockers, Ranitidine, etc. vii. Antiemetics-metoclopramide, Domperidone, setron.
Ondan
Anaesthetics
47
Q.S. What is dissociative anaesthesia?
Ketamine is chemically related to hallucinogen phencyclidine
produces anaesthesia called "dissociative anaesthesia". It produces profound analgesia, immobility, amnesia, light sleep and feeling of dissociation of body and surrounding. Q.6. What is Neuroleptanalgesia?
When Fentenyl a potent short acting opioid analgesic is given with Droperidol or neuroleptic like Haloparidol are given
together it is called neuroleptanalgesia. This can be used for
endoscopies, angiographies, dressing of burns. A fixed ratio combination of fentanyl 0.05 mg
+
droperidol2.5 mg/ml, 4-6
ml diluted with glucose is infused LV. over 10 minutes. Q.7. Name some anaesthetic agents.
Inhalations
Gas-Nitrous oxide
Liquids�Ether, Halothane, Enflurane, Isoflurane, Desflurane,
Sevoflurane
Intravenous
for induction i.
Thiopentone
Methohexitone Propofol
Etomidate
Dissociative Short (Ketamine)
�
Diazepam
. Lorazepam Midazolam
Neuiolepto
analgesic
Fentanyl
+
Droperidol
Auto.coids Q.l. What are autocoids? Greek autos= self
akos =remedy
These are various substances produced by variety of cells in the body with extensive biological activities. They are also called local hormones. Autocoids may be classified as: a. Amine autocoids-Histamine, 5-hydroxytryptamine b. Peptide autocoids-Plasma Kinine, Angiotensin c.
Lipid derived autocoids-Prostaglandins, Leukotriene, platelet activating factors.
Q.2. What is histamine? How are they produced? Mention some of its therapeutic uses. It is an alkaloid (Hista = tissue) present mostly in storage granules of mast cells. Tissue rich in histamine are skin, gastric and intestinal mucosa, lung, placenta. It is produced from amino acids. Histidine by decarboxylation, is used for: i. To test acid secreting capacity of gastric cells, now pentagastrines are preferred ii. To diagnose pheochromocytoma by provocative test iii. To test asthmatics iv. To test leprosy by triple reaction test v. Betahistine a Hl selective histamine analogues are used to control vertigo in Meniere's disease which probably acts by vasodilation of internal ear.
Q.3. Name some Histamine releasers. It is released from mast cells by: i. Tissue damage, trauma, stings, venom, proteolytic enzymes,
Autocoids
49
antigen antibody reactions, dextran, polyvinyl pyrrolidone, d-tubocurarine, morphine, stilbamidine, vancomycin, poly myxin B, antihistaminics, surface acting agents like (Tween
80, 48/80) Q.4. What are the different types of Histamine receptors? What are the therapeutic role of classical Hl and H2 receptor blockers? Histamine receptors are of two types Hl and H2 as per Asch and Schild. A third receptor H3 is involved in autoregulation of histamine release as proposed by Schwartz. Hl Receptor blockers are used for: i. Allergic conditions ii. Condition involving histamine like insect bite, ivy poisoning iii. Pruritis iv. Common cold v. Motion sickness vi. Vertigo vii. Preanaesthetic medications viii. Parkinsonism ix. Cough x. Sedative, hypnotic, anxiolytes H2 Blockers: Ranitidine, Famotidine, Roxatidine, Nizatidine, Loxatidine, etc. are all used for peptic ulcers and other gastric hypersecretory state.
Q. 5. What are the different types of serotonergic receptors? Gaddum classified serotonergic receptors into musculotropic D and neurotropic M type. At present four families of SHT receptors are identified. SHTl: Are autoreceptors which inhibit serotonergic neural activity. 5HT2: Gaddum D type mediate action. Vascular and visceral smooth muscle, platelet aggregation, neuronal activation in brain, ketanserin is its blockers. 5HT3: Gaddum M type produces emesis, gut paristalsis, bradycardia, apnoea, hypotension, pain, itch, onolansetron blocks this receptors.
50
Viva Voce in Medical Pharmacology
5HT4: Augments peristalsis and mediates intestinal secretion.
Cisapride and Renzapride are its agonists.
Q.6. What is migraine? Mention different drugs used for it. Migraine is a disorder characterized by pulsating headache usually unilateral which comes and lasts for 4-48 hours. It may be associated with nausea, vomiting. Photosensitivity vertigo, loose motion and other symptoms. Migraines are of two types: i. Classical i.e. migraine with aura ii. Common The drugs commonly employed for migraine are: a. -For mild migraine: Simple analgesics, NSAID and antiemetics b. For
moderate
sumatriptan c.
+
migraine:
NSAID/Ergot
alkaloids/
antiemetics
For severe migraine: Ergot alkaloids/Sumatriptan
+
antiemetic d. For prophylactic of migraine: �-blockers; and other tricyclic antidepressants, flunarizine and Ca2+ channel blockers, Cyproheptadine and Methiserzide
Q.7. Explain the mechanism of action of Ergotamine and DHE/Sumatr iptan, Flunar izine and Cypr oheptadines/ Methysergide, Pizotifen as an.timigraine. A. Ergotamine and DHE: i. Constricts dilated cranial vessels ii. Reduces shunting of blood flow from carotid artery by specific constriction of the A.V. Shunt channel 111.
Reduces neurogenic inflammation.
B. Sumatriptan -SHTlD agonist mediated inhibition of SHT
and inflammatory neuropeptide release around affected blood vessels. C. Flunarizine: It is weak Ca2+ channel blocker and also inhibits Na+ channel.
D. Cyproheptadine acts as antimigraine by virtue of combined SHT, histamine and cholinergic antagonists. E. Pizotifen is 5H2A antagonist with antihistaminic and anticholinergic properties used in migraine prophylaxy.
Autocoids
Q.8.
51
Name some antihistaminics.
Highly sedative
Moderately sedative
Mild sedative
Diphenhydramine
Pheniramine
Cetrizine
Dimenhydrinate .
Antazoline
Mepyramine
Promethazine
Trimeprazine
Terfenadine
Meclizine
Astemazole
Chlorphenaram1JAe
Clemastine
Cyclizine
Newer antihistamines: Terfenadine, Astemizole, Cetrizine,
Loratadine, Fexofenadine, Cinarazine.
Q.9.
Name the drug used in vertigo.
a. Labyrinthine suppressants: i. Antihistamines-Cinnarizine, Cyclizine, Dimenhydrinate, Diphenhydramine, Promethazine ii. Anticholinergics-Hyoscine, Atropine Antiemetics-Prochlorperazine
m.
b. Vasodilator: Betahistine, Codergocrine, Nicotinic acid, Naftidrofuryl c.
Diuretics: Acetazolamide, Thiazide
d. Anxiolytes: Diazepam e. Corticosteroids: To suppress intralabyrinthine oedema.
PLASMA KININS AND ANGIOTENSIN Q.l.
What are plasma kinins? How are they formed?
Plasma kinins are polypeptides from plasma globulins by the action of specific enzymes kallikreins viz. kallidin (decapep tide) and bradykinin -a nonpeptide.
Q.2.
•
What are the actions of Bradykinin and Kallidins?
CVS-Vasodilatations through nitric oxide, larger arteria constricts, release histamine from mast cells. I.V. injection causes throbbing headache, flushing, hypotension, increases tissue permeability. Smooth muscle: Contraction, bronchospasm in asthplatic patient. Nerves: Produces pain release catecholamine from adrenal
medulla, increases permeability of blood brain barrier.
52
Viva Voce in Medical Pharmacology
Kidney: Increases renal blood flow and salt and water excretion.
Q.3. What are the pathological role of kinins? Kinins are involved in the following pathological condition: 1. Mediation of inflammation-rubor,dolor,leukocyte mobi lization, production of IL-l, TNFu and other inflammatory mediators. 2. Produces pain: Produces pain by PG-b2 antagonist blocks pain produced by kinins. 3. Regulates microcirculation 4. Kinins are related to clothing,fibrinoly�is and complement system.
5. It closes PDA, dilates foetal pulmonary artery, constricts umbilical vessels.
·
6. Involved in shock, angioedema, rhinitis, asthma, ACE induced cough, Dumping syndrome, carcinoids secreting diarrhoea, immune reaction, pancreatitis.
Q.4. What are different types of kinin receptors? They are mainly two types B1 and B2 Bl: Present in smooth muscle of large arteries and veins to constrict them. Inflammation induces synthesis of Bl. Most kinin actions in noninflamed tissues are mediated by B2 receptor i. Smooth muscle contraction (in intestine,respiratory tract, uterus).
·
ii. Vascular endothellium (EDRF release, vasodilation, permeability) m.
Sensory nerves to produce pain.
•Bradykinin has higher affinity for B2 while des-Arg bradykinin for B1 receptor.
Q.5. What is Angiotensin II? How Angiotensins II are produced? They are the most potent vasoconstrictor, octapeptide generated from precursor plasma u2-globulin involved in electrolyte, blood volume and pressure maintenance. Heart blood vessels, brain, kidney, adrenals all have components to generate angiotension II locally A1 is 1/100 times less potent to All and Alii 2-10 times less potent to All.
Autocoids
53
Q.6. What are the different actions of All? It has following actions: a. On CVS-Vasoconstrictor by direct action and enhancing action of Adr and NAdr release. Increases myocardial 2 contraction by promoting Ca + influx, hypertrophy of myocardium occurs b. Smooth muscles contracts c.
Adrenal cortex-enhanced Na absorption potassium and Hydrogen excretion by All and Alii
d . Kidney-All enhances Na+, CC, HC03 resorption e. CNS-ADH release and increases central sympathetic out flow f.
All enhances peripheral sympathetic activity, stimulates adrenal medulla and autonomic ganglion.
Q.7. What are the different types of Angiotensin receptors? They are of two types: •
AT1-y-protein coupled receptor most of the actions are
•
AT2 receptor are present in adrenal medulla and CNS PD
mediated vja AT1 receptor. Losartan is AT1 antagonist. 123177 is antagonist function of AT2 is not known.
Q.S. Is there any therapeutic use of All? Yes; in anaesthetics hypotension as because it does not produce secondary hypotension, tissue necrosis. It may precipitate myocardial infarction. Q.9. How renin-Angiotensin system can be inhibited? i. Sympathetic blockers W-blockers) decreases renin release. ii. Renin inhibitory peptides and renin specific antibodies interferes with AI generation. iii. ACE -1 inhibits AI to All conversion iv. AT receptor blockers v. Aldosterone
antagonist
block
mineralocorticoid
receptors. Q.lO.What are the therapeutic uses of ACE-I? This is used for the following conditions: i. Hypertension ii. CCF
0
54
Viva Voce in Medical Pharmacology
iF. Myocardial infarction iv. Diabetic nephropathy v.
Scleroderma crisis
vi. In diagnosis of reno-vascular hypertension
Q.ll. Name some angiotensin converting enzyme inhibitors. Nowadays number of ACE are in market like Captopril, Enalapril, Lisinopril, Benazepril, Ramipril, Perindopril, Quinapril, Cilazapril, Zofenopril, Fosinopril.
Q.12. What adverse effects may be encountered with ACE inhibitors? i. Hypotension ii. Hyperkalemia iii. Cough iv. Rash, angioedema, urticaria v. Dysgeusia vi. Foetal damage vii. Headache, dizziness, nausea viii. Granulocytopenia, proteinuria ix. Acute renal failure.
Prostaglandins and Leukotrienes Q.l. What are Prostaglandins and Leukotrienes? These are biologically active derivatives of 20 carbon atom polyunsaturated essential fatty acids released from cell membrane phospholipids.
Q.2. How the synthesis of prostaglandins can be inhibited? Their synthesis can be inhibited by non-steroidal anti inflammatory drugs. Aspirin acetylates Cox at a serine residue, causes irreversible inhibition, while other NSAID are competitive and reversible inhibitors. There are two types of Cox enzyme. The newer drugs like nimesulide, nabumetone, meloxicams are Cox-2 inhibitors relatively. Glucocorticoids inhibit release of arachidonic acid from membrane lipids so reduce production of PGs, TXs and LTs.
Q.3. What do you mean by Cox-1 and Cox-2? The enzyme cycle-oxygenase Cox releases PGs, PGI2, TXA2 from arachidonic acid which exists in two iso form. Cox-1 (constitutive) and Cox-2 (inducible). The Cox-1 is responsible for physiological house keeping while Cox-2 induced by cytokinesis in minute quantities at the site of inflammation.
Q.4. What are the functions and pathophysiological role of prostaglandins, Thromboxanes and Prostacyetines?
The actions of eicosanoids vary widely depending upon PG, TX, PGI species hormonal milieu, etc. Some of their actions are mentioned below:
·
56 1.
Viva Voce in Medical Pharmacology
CVS: PGI 2 vasodilatation TXA2-vasoconstriction PGE2 and F2a stimulate heart directly and reflexly by fall of BP. PGE2 and PGI2 are responsible for patency of PDA.
ii. Platelet: TXA2 induces platelet aggregation PGI2 is potent inhibitor of platelet aggregation. iii. Uterus: PGE2 and PGF2a contract human uterus pregnant and nonpregnant. Foetal tissues produce PG at term to initiate labour. Semen contains PGs and it help transport
of
sperm
to
facilitate
fertilization.
Dysmenorrhoea is due to PG in endometrium. iv. Bronchial muscle: PGF2a, PGD2, TXA2 and LTs produce bronchoconstriction,
while
PGE2,
PGI2
produce
bronchodilation. v. G.I.T.: In stomach they produce increased blood flow to mucus and mucus production, reduce acid secretion. In intestine, the y contract smooth muscle and water y diarrhea. vi. Kidney: Increases water Na+ and K+ excretion. In Batter's
syndrome due to increase PG production there is decrease sensitivity to Ail. vii. CNS: Act as neuromodulator and produces febrile condition viii. Peripheral nerves: Produces pain ix. Endocrine s y stem: PGE2 releases anterior pituitar y hormones like GH, PRL, ACTH, FSH, LH and other hormones like adrenal steroids, insulin.
x. Metabolism: Mobilizes Ca2+ from bone and antilipolytic. Q.5. Mention some of the therapeutic uses of PGs?
These are rarely used for availability cost and side effects but indicated for: i. Abortion ii. Induction of labour iii. Cervical priming iv. PPH v. Peptic ulcer vi. To maintain PDA vii. PGI2 to prevent platelet aggregation during hemodialysis and cardiopulmonary bypass and harvest platelets.
Prostaglandins and Leukotrienes
57
viii. Peripheral vascular diseases ix. To reduce infarct size x. Impotence xi. Contraceptive xii. PGE2 for bronchial asthma. The viii to xii are at investigational level.
Q.6. Mention some of the pathological role of p latelet activating factors?
They are implicated in i. Inflammation ii. Bronchial asthma iii. Anaphylactic shock iv. Haemostasis v. Rupture of graafian follicles and implantation vi. Ischaemic state of brain, heart, GIT vii. Progression of labour by PAF produced by foetus.
Q.7. What is ginkgolide? It is obtained from Chinese plant. P AF antagonist h as therapeutic potential in stroke, intermittent claudication, Meniere's disease, myocardial infarction, shock, GI ulcer, asthma and contraceptive role.
Respiratory System Q.l. What is cough? Cough is a protective reflex, which helps to expel, irritant matter from respiratory tracts.
Q.2. What are expectorants or Mucokinetics? These group of drugs increase the production of bronchial secretion or reduce its viscosity facilitating its removal by coughing. The Latin word expectorant means "drive from the chest". The expectorants may be i. Direct stimulants (volatile oil of eucalyptus, alcohol or cedar wool oil when added to steam for inhalation) ii. Reflex expectorants stimulate gastric reflexes to help increase respiratory secretions as for example emetic drug given in subemetic doses,
or saline expectorant
(Ammonium salts, potassium salts Ipecacuanha etc.)
Q.3. What are mucolytics? What is mechanism of action of Bromhexine? Mucolytic makes tenacious sputum less viscid. Bromhexine a derivative of the alkaloid vasicine obtained from Adhatoda vasica (Vasaka) is capable of inqucing thin copious bronchial secretion. It depolymerizes mucopolysaccharides directly as well as by liberating lysosomal enzymes which breaks tenacious fibres of sputum.
Q.4. Name some antitussives? Drugs which raise cough threshold and peripherally suppressing tussive impulse called antitussive viz Codeine, Pholcodeine, Ethyl morphine, Morphine, Noscapine, Dextro methorphan, Carbatapentane, Chlophedianol, Pipazethate, Antihistamines, Bronchodilators, etc.
Respiratory System
59
Q.5. What is bronchial asthma? It is clinical condition characterized by hyper responsiveness of tracheo bronchial smooth muscle to a variety of stimuli resulting in narrowing of air tubes due to bronchospasm, increased secretion, mucosal edema, mucus plugging.
Q.6. What are the different approaches to the treatment of asthma? Different approaches to treatment are i. direct bronchodilator-Xantine ii. Sympathomimetics iii. Block brancho constrictor-Anticholinergics, neurotrans mitter iv. Mast cell stabilizers v. Prevention of Ag, Ab reaction vi. Nonspecific reduction of bronchial hyperactivity and anti inflammatory-Corticosteroid vii. Antagonism of released mediator-Antihistamines, PAF-antagonist
Q.7. Name the drugs used in bronchial asthma. I.
Bronchodilators: A. Sympathomimetics: Adrenaline, Ephedrine, Isoprena line, Orciprenaline, Salbutamol, Terbutaline, Salmeterol B. Xanthine-Theophyline, Aminophylline C. Anticholinergics-Atropine, Ipratropium, Tiotropium
II. Mast cell stabilizer: Na-cromoglycate, Nedocromil, ketotifen III.Corticosteroids: Hydrocortisone, Prednisolone, Flunisolide, Triamcinolone acetonide, Fluticasone proprionate.
Q.8. What precaution should be taken to administer aminophylline? It should be given slowly, intravenously.
Q.9. Why do Na-cromoglycate not effective in acute asthma? It inhibits release of bronchoconstriction mediator by stabilizing mast cells. It does not have any action or released mediator, so it is given prophylactically.
60
Viva Voce in Medical Pharmacology
Q.lO. How you will treat refractory asthma/status asthmatic?
i. Patient should be hospitalized ii. 02-inhalatioin intermittently iii. Hydrocortisone hemisuccinate-100 mg LV. stat then every 8 hrs. iv. Nebulized salbutamol + Ipratropium bromide v. Salbutamol/terbutaline 0.4 mg IM or SC vi. Chest infection with antibiotics vii. Correct dehydration and acidosis with saline sodium bicarbonate and lactate infusion. viii. Aminophylline 250 mg diluted in 20-50 ml in 5% glucose injected over 20-30 minutes. Q.ll. What is the m e chanism of action of Xanthine
derivative?
They are phosphodiaesterase enzyme inhibitors leadng to accumulation of cAMP in bronchial smooth muscles which sequester Ca2+ and makes bronchial smooth muscle to dilate.
Cardiovascular System
DRUGS IN HEART FAILURE Q.l.
What is congestive heart failure? Name the drug used
in CHF.
CHF occurs when cardiac output is insufficient to meet the demands of tissue perfusion in spite of adequate venous return. The drugs used in this condition are: i. Diuretics ii. Digitalis iii. Vasodilators iv. Phosphodiesterase III inhibitors v. Cardiac stimulants
Q.2.
What is the source of "source digitalis"? Why digitalis
purpura is so called? What is its chemical structure?
Digitalis is obtained from digitalis purpura. It is so called because of it's finger shape and purple color. Other sources are strophantus and squill. A cardiac glycosides consists of aglycone (a cyclopenta noperhydrophenanthrene-steroid ring) to which attached 5-6 membered. Lactone ring. A sugar is attached to it which
is responsible for solubility, cell permeability of the glycosides.
Q.3. What is mechanism of action of digitalis in heart failure? i. It inhibits Na/K ATP ase pump, increases intracellular Ca level of myocardial cells and increases force of contraction of heart muscle. ii. Resets receptors to control heart rate iii. Stimulates heart and acts as indirectly acting diuretics.
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Viva Voce in Medical Pharmacology
Q.4. What are the indications of digitalis?
It is indicated for: i. CCF n.
Left ventricular failure
iii. Atrial flutter and fibrillation iv. Paroxysmal supraventricular tachycardia. Q.S. What are the symptoms and signs of improvement after
digitalis therapy.
The improvement signs and symptoms are: i. Increased urinary output ii. Relief from insomnia, orthopnoea and basal crepitation iii. Jugular venous pressure is decreased 1v. Disappearance of tachycardia and ventricular gallop v. The skin changes to normal elastic from dry paper like skin Q.6. What are the adverse reactions of digitalis?
Digitalis is a drug with low therapeutic index may lead to severe toxicities like i. Cardiac toxicities: Disturbances in impulse formation and conduction like multifocal extrasystole, bigemini, paroxysmal atrial tachycardia with block (PATB) ii. G.I.T. toxicity, anorexia, vomiting, diarrhea iii. Neurotoxicity-Vertigo, visual disturbance delirium iv. Miscellaneous-skin rash, eosinophilia, gynecomastia may cross placental barriers. Q.7. How will you treat digitalis toxicity?
Stop digitalis and diuretics. KCl orally. Supraventricular tachyrhythmia with �-adrenergic blocking drug. Ventricular tachycardia with Lignocaine 'or Phenytoin. Antibodies to digitalis may be given if available. Q.S. How does digitalis act as antiatrial flutter drug?
i. Digitalis corrects associated failure with atrial flutter ii. Converts flutter to fibrillation and slows down ventricular rate. Withdrawal of digitalis at this stage may restore sinus rhythm.
Cardiovascular System
Q.9.
63
What are the contraindications of digitalis therapy?
Absolute contraindications of digitalis is digitalis toxicity. May prove harmful to myocardial infarction, heart block. Diphtheric myocarditis, Stokes-Adam syndrome, constrictive pericarditis, WPW syndrome, tachycardia due to fever, anemia, thyrotoxicosis.
Q.lO.
How does vasodilator act in heart failure?
They cause preload reduction (nitrates); After load reduction (hydralazine); Pre and after load reduction (ACE inhibitors, All antagonist losartan, al blocker prazosin, Phentolamine, Nitroprusside).
Q.ll.
How does Dopamine or Dobutamine act in heart
failure?
They are used for their positive inotropic effect and vasodilator properties in acute heart failure with myocardial infarction. Dopamine in the dose of 3-10 �/g/kg/min IV used in cardiogenic shock also improves renal perfusion. Dobutamine 2-8 p.g/kg/min infused for acute heart failure with myo�ardial infarction.
Q.l2. What is the mechanism of action of Phosphodiesterase III inhibitors?
Amrinone and Milrinone (more potent) are inotropic drugs belong to phosphodiesterase III inhibitors. The enzyme is specific for intracellular degradation of cAMP thereby increases myocardial cAMP and transmembrane influx of Ca2+.
ANTIARRHYTHMIC DRUGS Q.l. What are different mechanisms of production of cardiac arrhythmia?
The ischaemia, electrolyte imbalance, pH imbalance, mecha nical injury, dr.ug, stretching, neurogenic ir.npulse may produce cardiac arrhythmia by: i. Enhanced ectopic pacemaker activity ii. After depolarization (early and delayed)
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Viva Voce in Medical Pharmacology
iii. Re-entry (circus or microentry circuits) iv. Fractionation of impulse v. Conduction block
Q.2. What are the different methods of treating arrhythmia? Different methods of treatment of treating arrhythmia are: i. Drugs ii. Pacemakers iii. DC shock iv. Operations depending upon type of arrhythmia.
Q.3. Classify antiarrhythmic drug. Vaughan and Williams have classified the antiarrhythmic drug into 4 classes.
Class I (Membrane stabilizing effect Na channel blockers) Moderately decrease dv I dt of 0 phase of action:
A.
Quinidine, Procainamide, Disopyrarnide, Moricizine B. Little decrease in dv I dt of phase 0-Lidocaine, Mexiletine, Tocainide, Phenytoin C. Markedly decreasing dv I dt of 0 phase Flecainide, Encainide, Propafenone.
Class II Class III
Antiadrenergic agents
Propranolol
13 blockers
Esmolol
Agents widening action potential Amiodarone and prolong effective refractory
Bretylium
period
Class IV
Calcium channel blocker
Veraparnil Diltiazem
Miscellaneous: for Paroxsymal supraventricular tachycardia., (Adenosine, digitalis) for A.V. Block-Isoprenaline, Atropine, Digitalis is used for AF, AFI, PSVT.
Q.4. What is the mechanism of action of Quinidine? Quinidine blocks Na+ enamel of myocardium, reduces automaticity, increases APD due to K+ channel. It decreases availability of Na channel as well as delay their reactivation.
Cardiovascular System
Q.5.
65
What is the mechanism of action of lignocaine?
It suppresses automaticity of ectopic foci, enhances phase 4 depolarization and antagonizes after depolarization. It is a blocker of inactivated Na2+ channel more tha:n open state. It is used for ventricular tachyrhythmia and digitalis toxicity because it does not worsen AV block.
Q.6.
What is Tocainide?
It is orally effective lidocaine analogue used for ventricular arrhythmia but potential risk of agranulocytosis, pulmonary
fibrosis or thrombocy�openia is there.
Q.7. What is the mechanism
of action of amiodarone where
they are indicated?
Amiodarone prolongs APD by blocking K+ channel. Pre ferentially blocks inactivated Na+ channel. Inhibits myocardial Ca2+ channels and has noncompetitive� adrenergic blocking property therefore APD and ERP are prolonged, conduction is slowed. It is used in wide range of ventricular and supraventricular arrhythmia, WPW syndrome.
Q.S.
What is the mechanism of action of adenosine?
Rapid LV. infusion adenosine terminates PSVT. It activates Ach sensitive K+ channel and hyperpolarizes the membrane leading to pacemaker depression causing bradycardia, ERP prolongation in AV node slowing conduction. Indirectly reduces Ca2+ current in AV node and blocks re-entrant circuits and coronary dilation. It is used for PSVT,diagnosis of tachycardia dependent on AV block, to produce controlled hypotension in surgery, coronary vasodilatation during diagnostic and interventional procedure.
ANTIANGINAL DRUGS Q.l.
Name the different drugs used in angina.
The different drugs used for angina or ischaemic heart diseases may be classified as follows: I. Nitrates: a. Short acting-Glyceryl trinitrate
66
Viva Voce in Medical Pharmacology b. Long acting-Isosorbide mononitrate, Erythrityl, tetranitrate, Erythrityl tetranitrate.
II. �-blockers-Propranolol, Atenolol, Metoprolol III. Calcium channel
blockers-Verapamil,
Ditiazem,
Nifedipine, Felodipine, Nicardipine, Amlodipine, Nitrendipine, Lacidipine IV. Potassium channel openers: Nicorandil, Pinacidil, Cromakalim V.. Miscellaneous-Dipyridamole, Lidoflazine, Oxyphedrine Q.2. What is the mechanism of action of nitrates as anti
anginal? Organic nitrates are denitrated in smooth to release free radicals nitric oxide which increases cGMP level causing dephosphorylation of myosin light chain kinase. Less phosphorylated interferes with contraction and reduces Ca2+ entry. They reduce preload, after load, redistribute coronary flow. Q.3. What are the therapeutic uses of nitrates?
Nitrates are effective in: i. Angina pectoris u.
CCF and LVF
iii. Myocardial infarction iv� Intervention procedure in heart v. Biliary and oesophageal spasm vi. Cyanide poisoning Q.4. How does nitrates act in cyanide poisoning?
Cyanide damages cytochrome and oxidative enzyme causing cytotoxic anoxia. Nitrates form methaemoglobin which has high affinity for cyanide radicals and form cyanomet haemoglobin which may dissociate again. Sodium thiosulphate given simultaneously forms sodium thiocyanate which is less dissociable and excreted with urine. Q.S. What are the criteria of an ideal antianginal agent?
They should: i. Selectively dilate coronary arteries
Cardiovascular System
67
ii. They should not increase cardiac output, BP, pulse rate and 0 consumption 2 iii. It should protect the
heart from stress induced
adrenergic effect iv. Action should start rapidly and last for long time.
Q.6. What ari the different types of Ca2+ channels? The calcium channels are of three types: "i. Voltage seqsitive channel-Activated when membrane potential drops to -40 mv (are of three types L type, T·
type, N-type) ii. Receptor operates channel (activated by Adr) iii. Leak channels, small amount of Ca2+ leaks into resting cell and are pumped out by Ca2+ ATP ase.
Q.7. WbS.t are the different therapeutic uses of calcium ·
channel, blockers?
Calcium channel blockers are used for: i. Angina pectoris ii. Hypertension iii. Antiarrhythmia iv. Hypertrophic cardiomyopathy v. Migraine vi. Premature labor vii. Nocturnal muscle cramp viii. Raynaud's episode ix. Peptic ulcer disorders
Q.S. Name some Potassium channel opener. What is their mechanism of action? What are their potential chemical applications?
Nicorandil, Pinacidil, Chromakalin are potassium channel activators. Potassium channel opener causes opening of K+ channel and outflow of K+ ions leading hyperpolarization, in smooth muscle viscera and vasculature. The hyperpolarization of smooth muscle produces smooth muscle relaxation. Their potential clinical application can be: i. Angina pectoris ii. Hypertension
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Viva Voce in Medical Pharmacology
iii. CCF iv. MI v. In Insulinoma vi. Alopecia vii. Bronchial asthma viii. Urinary incontinence ix. Raynaud's phenomenon x. Penile erection disorder xi. Premature labor.
Q.9. Name the drug used for peripheral vascular disorder. The principle of treatment of peripheral vascular disorders are: i. To correct underlying cause like diabetes, anaemia and polycythemia ii. To increase local circulation by covering and exercise iii. To prevent from cold iv. Prevent precipitating factors-smoke, ergot v. Local hygiene to prevent trauma, infection vi. Drug The effective drugs are: a. �-stimulants, Nylidrine, Isoxsuprine b. a-blocker-like Phenoxybenzamine, tolazoline c.
Anticoagulants
d. Miscellaneous-Nicotinic acid, Cyclandelate
Q.lO. Mention the principle of treatment of acute myocardial infarction. After establishing diagnosis: i. Relief pain, anxiety apprehension by opioid analgesics, diazepam ii. 02 inhalation iii. Correction of acidosis iv. Prevention of arrhythmia v. Treatment of pump failure by frusemide, vasodilator, inotropic agent vi. Prevention of thrombosis extension with heparin and oral anticoagulants
Cardiovascular System
69
vii. Thrombolysis by streptokinase viii. Prevention of subsequent CCF by ACE inhibitor ix. Prevention of future attack with Clofidogrel, Aspirin, Hypolipidaemic drugs.
ANTIHYPERTENSIVE Q.l. What are the requirements of an ideal antihypertension? i. It s]:lould produce predictable reduction of systolic and diastolic BP
·
ii. It should be rapid in action for sufficient duration. iii. It should not produce tolerance iv. It should not reduce circulation to vital organs like brain, kidney, heart v. It should synergise with other antihypertensive agents vi. It should be cheap.
Q.2.
Name the drugs used in hypertension.
The drugs used in hypertension either reduces cardiac output or peripheral resistance. The antihypertensives may be grouped as follows: I. Drug acting centrally-Clonidine, Methyldopa II. Drug acting on autonomic ganglion-Hexamethonium, Pentolinium, Chlorisondamine, Mecamylamine, Pempi dine, Trimethaphan. They are rarely used as better drugs are available.
·
III. Drug acting on postganglionic sympathetic nerve ending Catecholamine depletor, Reserpine, Adre:hergic neurone blockers-Guanethedine, Bethanidine, Debrisoquine, Bretylium. IV. Drugs acting on adrenergic receptors:
ex
Phentolamine, Phenoxybenzamine; �-blockers,
blockers, ex
and �
blockers: Labetelol. V. Vasodilator: Arteriolar-Hydrallazine, Diazoxide, Minoxidil, Calcium channel blockers, arteria and venodilator, sodium Nitroprusside. VI. Reflexly stimulating baro-receptors: Veratrum VII. Acting on Renin-Angiotension system a. Blocks-Renin release �-blockers b. ACE-inhibitors; captopril and others
Viva Voce in Medical Pharmacology
70
c. Blocks Angiotensive II receptors saralasin
d. Counters action of aldosterone-sipronolactone
VIII. Diuretics
IX. Miscellaneous-MAO I, Pargyline, Metyrosine
Q.3. What are the advantages of calcium channel blockers? Apart of negative inotropic and dromotropic effect of
verapamil and diltiazem which may worsen CCF and heart
block, these are very effective drugs if selected properly. The important advantages of CCB are:
i. Do not compromise with haemodynamics, no sedation or impairment of cerebral or renal circulation, sexual function is not disturbed nor does effect lipid profile,
can be used in pregnancy.
Q.4. What are the advantages of prazosin as antihyper tensive?
The
c:x.
blocker prazosin has following advantages as
antihypertensive:
i. Improves carbohyd_�ate metabolism and counteracts insulin. resistance wit!Navourable effect on lipid profile
ii. Effective in hypertension with BPH and CCF iii. Does not have effect on uric acid level or exercise tolerance.
Q.
5. How does clonidine act as antihypertensive? What are
the uses of clonidine? What are its adverse effects?
It is
c:x.2
agonist decreases sympathetic outflow and fall in BP.
Apart from tise in antihypertensive it is used for: i. Opioid withdrawal and smoking caesation ii. Migraine iii. Analgesic activity
iv. Decreases anaesthetic requirement if used pre-operatively v. Improved vasodilator symptoms of menopausal syndrome
vi. Pheochromocytoma
vii. Used for diabetic neuropathy induced diarrhoea Sedation, impotence, postural hypotension, depression, dry mouth, sudden rise of BP in sudden withdrawal are its important adverse effects.
Cardiovascular System
71
Q.6. Name the antihypertensive which may cause hyper trichosis. How it is effective in alopecia?
Vasodilator Minoxidil may produce pulmonary hypertension, hypertrichosis, pericardia! effusion. Used for male type baldness. The mechanism of hair growth are claimed to be as follows: i. Enhanced microcirculation around hair follicles ii. Stimulation of hair follicles iii. Alteration of androgen effect on genetically programmed hair follicles. Q.7. Name the drugs used for hypertensive emergencies.
i. Na-Nitroprusside.002 mg/min ii. Captopril sublingual iii. Diazoxide 300 mg LV. stat iv. Phantolamine and Phenoxabenzamine in hypertensive crisis of pheochromocytoma. Q.S. Name the antihypertensives which can be used in pregnancy.
Hydralazine, Methyldopa, calcium channel blockers (but should be discontinued before labor); �-blockers Atenelol, Pindolol, Acebutanol, Prazosine and clonidine provided postural hypotensive can be avoided. Q.9. Name the antihypertensive which should be avoided in pregnancy.
Diuretics; ACE inhibitors and Losartan; Reserpine Non selective �-blockers, Nitroprusside should not be used in eclampsia.
HYPOLIPOPROTEINEMIC DRUGS Q.l.What are different types of hyperlipoproteinemia?
The hyperlipoproteinemia may i. Primary due to single gene defect or multiple gene defects. ii. Secondary due to diabetes myxoedema, nephrotic syndrome, alcoholism, OCP, �-blockers.
Viva Voce in Medical Pharmacology
72
Q.2.
What are the different groups of drugs used to treat
hyperlipoproteinemia condition?
The different hyperlipoproteinemia drugs are: i. HMG-CoA reductase-inhibitors-Lovastatin, Simvas tatin, Pravastatine ii. Interfere with intestinal absorption-Cholestyramine, Cholestipol iii. Fibric
acid
derivative-Clofibrate,
Gemfibrozil,
Bezafibrate, Fenofibrate iv. Inhibit VLDL production-Nicotinic acid v. Antioxidants-Probucol vi. Others: Neomycin, Gugulipids.
Q.3.
What are the mechanism of action of
i. HMG -CoA reductase inhibitors. ii. Bile salt sequaters iii. Fibric acid derrivatives iv. Nicotinic acid
i. HMG-CoA reductase inhibitors: Decrease cholesterol synthesis. ii. Bile salt sequesters-Decreases bile acid absorption, increases hepatic conversion of cholesterol to bile acid, Increases LDL receptors. iii. Fibric acid derivatives: Increases activity of lipoprotein lipase, decreases release of fatty acids from adipose tissue. iv. Nocitinic acid: Decreases the production of VLDL and decreases lipolysis in fat cells.
PLASMA EXPANDERS Q.l.
What is plasma expander? Name some of the plasma
expanders. What are the desirable properties of plasma expanders? Where they are used? What are their contra indications?
These are high molecular weight substances, which exert colloidal osmotic pressure when infused LV. retain fluid in the vascular compartment. The substances are: i. Human albumin
Cardiovascular System
73
ii. Dextran iii. Degraded gelatin polymer iv. Hydroxyethyl starch (HES) v. Polyvinyl pyrrolidone The plasma expander desirably should have following properties: i. Should exert osmotic pressure comparable to plasma ii. Should remain in circulation and not leak out in tissues or dispose rapidly iii. It should be pharmacodynamically inert, nonpyrogenic or antigenic, should not be interfering with grouping and cross-matching iv. It should be cheap, sterilizable stable.
Water, Electrolytes and Drugs Affecting Renal Functions Q.l. What are electrolytes? What are their functions? Body fluids contain various substances which are vital for normal functioning of life. Some of these exist as ionized particles, when placed in an electrical field, they migrate to the cathode (cation) or anode (anion) called electrolyte. The functions of electrolytes are as follows: i. Maintenance of osmotic pressure ii. Maintenance of electroneutrality iii. In production of energy iv. In impulse conduction v. Miscellaneous-As for example calcium in clotting and bone formation.
Q.2. How will you treat hyperkalemia? The hyperkalemia can be treated by: i. Avoiding potassium in the diet ii. By preventing tissue breakdown promoting protein anabolism by anabolic steroids iii. Promoting entry of potassium into cells by insulin iv. Promoting potassium excretion by glucocorticoids. v. Using potassium exchanging resins. vi. Carrying peritoneal dialysis . vii. Controlling infection.
Water, Electrolytes and Drugs Affecting Renal Functions
75
What is the principle of therapy for correction of
Q.3.
dehydration in cholera or acute diarrhoea?
The principles are: Correction of water loss, electrolyte loss and correction
1.
of acidosis. Suitable antibiotics for pathogenic organism
n.
iii. Associated treatment of shock, renal failure iv. Maintenance of nutrition with glucose, Antidiarrhoeal compounds are not recommended now-a-days.
Q.4.
What is the WHO recommended Oral Rehydration
Therapy?
The WHO recommended ORT contains 3.5 g NaCl; 1.5 KCl; NaHC03 2.5 g Glucose 20 g per 1000 ml of boiled water. It contains Na 90 mEq/L; K 20 mEq/L, Cl 80 mEq/L and HC03 30 mEq/L which is supplied in ready dissolving sachet. Where such packets are not available, the composition can be modified using domestic measures, like: NaC11 teaspoon 4.20g Pot-citrate 1 teaspoon 5.75g Add boiled water 1 litre Sod-bicarbonate 4.0 g Glucose 20g
Q.5.
What is diuretic?
Drugs which increase rate of urine formation and cause net loss of Na and water are called diuretics.
Q.6.
Describe in brief mechanism of counter current
multiplier system.
The composition and volume of urine formation is governed by� 1.
Glomerular filtration
ii. Tubular resorption iii. Secretion nearly 80% of filtered sodium, K, amino acid are reabsorbed in proximal tubule along with pro portionate quantities of water absorbed with Na called obligatory resorption. The descending and ascending limbs of loop of Henle have different permeability for water and Na. In ascending limb, Na is absorbed without free water delivering hypotonic fluid
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Viva Voce in Medical Pharmacology
to distal convoluted tubule. In descending limb, water diffuses out into hypertonic surrounding and sodium enters tubular lumen, i.e. to the tubular fluid, progressively becomes hypertonic as it approaches the tip of the loop. From tip of the loop osmolality diminishes progressively because of active extrusion of chloride, i.e. the isotonic at the beginning becomes hypertonic at its entry into descending limb of the loop of the Henle and there onwards osmolality diminishes gradually. The circular and repetitive transfer of sodium in ascending limb, interstitium descending limb and ascending limb is called hairpin counter current mechanism. In distal convoluted tubule, sodium along with anions are reabsorbed Na is exchanged forK and largely under influence of aldosterone. Urine entering collecting tubules is isotonic with plasma under influence of ADH absorb water and concentrates urine. The collecting ducts also reabsorbs Na+ and secrete H+ and NH3+ ions.
Q.7. What is the function of enzyme carbonic anhydrase in tubular cells?
The tubular cell contains an enzyme C.A. helps to form carbonic acid H20
+
C02-H2C03. The H+ derived from H2C03 is
exchanged with Na from tubular lumen combines with HC03 in tubular cells and returns to ECF as NaHC03. Thus body conserves base. Addition of H+ in tubular fluid makes urine acidic. . Renal tubular cell also produces NH3 which diffuses �nd reacts with NH3 to form ammonium which is not absorbed.
Q.B. Classify diuretics. Diuretics may be classified as follows: I.
High efficacy diuretics (Inhibitors of Na+, K+ 2CC) a. Sulfamoyl
derivative
(Frusemide
Piretamide b. Phenoxyacetic acid-Ethacrynic acid c. Organomercurals: Mersalyl
Bumetanide,
Water, Electrolytes and Drugs Affecting Renal Functions
77
II. Medium efficacy diuretics (Inhibitors of Na+, CC symport) a. Benzothiadizine (thiazide) Chlorthiazide, Hydrochlor thiazide, Polythiazide, Cyclopenthiazide, Benzthiazide, Hydroflumethiazide, Clopamide, Bendroflumethiazide. b. Thiazide like-Chlorthalidone, Metolazone, Xipamide, Indapamide III. Weak Diuretics: a. Carbonic
anhydrase
inhibitors:
Acetazolamide,
Ethoxzolamide b. Potassium sparing diuretics: Spironolatone, Triamterine, Amiloride c. Osmotic diuretics-Mannitol, Isosorbide, glycerol, acidifying or alkanizing salts-NH4Cl, Potcitrate IV.Indirectly acting by stimulating heart and increasing renal perfusion-Theophyllin, Digoxin
Q. 9. What are indications of High ceiling diuretics? i. Oedemia of cardiac, hepatic or renal origin ii. Acute pulmonary oedema iii. Cerebral oedema iv. Forced diuresis v. Hypertension vi. In blood transfusion to prevent vascular overload vii. Hypercalcaemia and renal stone to increase calcium excretion.
Q.lO. What are the therapeutic uses of thiazide diuretics? They are used for oedema, hypertension, diabetes insipidus, hypercalciuria.
Q.ll. What complications may arise out of high ceiling and thiazide diuretic therapy? The complications may be: i. Hypoklaemia ii.. Acute saline depletion iii. Dilutional hyponatremia iv. Nausea, vomiting headache, giddiness, weakness, paresthesia, impotence, hearing loss, allergic reactions, renal insufficiency by thiazide, hepatic coma may be aggravated, placental insufficiency.
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v. Metabolic-Hyperuricaemia, Hyoperglycaemia, Hyper lipidemia, Hypercalcaemia with thiazide, hypocalcaemia with high ceiling, Hypomagnesemia. Q.12. What are the therapeutic uses of acetazolamide?
i. Diuretic ii. Glaucoma iii. To alkalinize urine iv. Epilepsy
. v. Acute mountain sickness HAPA
vi. Periodic paralysis. Q.13. How does acetazolamide act as diuretics?
The enzyme carbonic anhydrase play important role in tubular resorption of Na+ and HC03- by providing carbonic acid which
makes
H+
available
for
exchange
with
Na.
Acetazolamide non-competitively blocking inhibits carbonic anhydrase so H+ is not available for Na+ exchange leading to excretion of Na and water. Q.14. What is the mechanism of action of Mannitol and what are their therapeutic uses? What are their contra indications?
Mannitol is osmotic diuretic appears to act by: i. Expanding extracellular fluid volume and increasing g.f.r. and inhibiting renin release and ii. passive salt resorption is reduced by mannitol They are used for to maintain: i. g.f.r. in acute renal failure (shock, trauma, diarrhoea, haemolytic reaction, cardiovascular surgery) ii. Forced diuretics in poisoning iii. Decreases intraocular and intracranial tension iv. To counteract low osmolality due to haemodialysis in peritoneal dialysis. They are contraindicated in tubular necrosis, anuria, LVF, cerebral haemorrhage. Headache, nausea, vomiting may occur.
Water, Electrolytes and Drugs Affecting Renal Functions
79
Q.15. Mention the therapeutic use of orally active osmotic diuretic isosorbide and glycerol?
They are used in the dose of 1.5 g/kg oral solution to reduce intraocular and intracranial tension.
Q.16. What are antidiuretics? The drugs which reduce urine volume are called antidiuretics. They are: 1.
Antidiuretic hormone (ADH, vasopressin), Desmopres sin, Iypressin
ii. Thiazide diuretic, amiloride iii. Miscellaneous:
Chlorpropamide,
Carbamazepine,
Clofibrate
Q.17. What are the indications of ADH? They are used for: 1.
Diabetes insipidus
ii. Bed wetting in children iii. Renal concentration test iv. Bleeding oesophageal varices v. To drive out gases before abdominal radiography vi. To check bleeding in haemophilia and von-Willebrand disease.
Q.18. Which drug is effective in lithium induced diabetes insipidus?
Amiloride.
Q.19. What are the different types of ADH-receptors: They are of two types Vl and V2
Vl-All vasopressin receptor except those on CD cells V2-Collecting duct CD Activation of V2 receptor on CD cells increases cAMP intra cellularly. Activation of cAMP prophorylates relevant protein which promotes exocytosis of aquaporin CD water channel containing vesicles. The water permeability of CD cells is increased depending upon aquaporin CD channels in the apical membrane at any given time.
Drugs used in Gastrointestinal Tract Q.l. What is emetics? The drugs which evoke vomiting are called emetics viz. which act on CTZ-apomorphine and act reflexly and on CTZ Ipecacuana. They are indicated in poisoning otherwise it is discouraged.
Q.2. What are the contraindications of emetics? Emetics should not be used in corrosive poisoning, kerosene or petroleum poisoning, CNS stimulant poisoning to avoid convulsion, morphine and phenothiazine poisoning they are ineffective. It should not be used in unconscious patients.
Q.3. What are anti-emetics? Name them. Drugs used to suppress vomiting are .called anti-emetics. These are: 1. Anticholinergic-Hyoscine, Dicyclomine 2. HI-Blocker-Promethazine, Diphenhydramine, Dimen hyrinate, Cyclizine, Medizine, Cinnarazine 3. Neuroleptics:
Chlorpromazine,
Prochlorperazine,
Haloperidol 4. Prokinetics: Metoclopram1de, Domperidone, Cisapride 5. 5HT3-Antagonist: Ondansetron, Granisetron 6. Others: Dexamethasone, Benzodiazepines, Cannabinoids.
Q.4. When Neuroleptics are used as anti-emetics? The neuroleptics which have broad spectrum anti-emetic action used for:
Drugs Used in Gastrointestinal Tract
81
i. Drug induced and postanaesthetic nausea and vomiting
ii. Vomiting associated with gastroenteritis, uraemia, liver disease migraine, malignancies' and chemotherapy induced vomiting, radiation sickness. In hyperemesis gravideru� but not in morning sickness.
Q.5. What are the indications of prokinetic drugs?
They are used as:
i. Antiemetic in postoperative, drug induced radiation sickness, migraine
ii. As gastrokinetic: To accelerate gastric emptying when
emergency general anesthesia has to be given; to relieve vagotomy and diabetes associated gastric stasis.
iii. To facilitate duodenal intubation
iv. Gastroesophageal reflux diseases (GERD)
Q.6. Name the drug j:!ffective for GERD.
The drugs effective in GERD are: i. Antacids
ii. Sodium alginate
iii. Metachloprarnide iv. H+ blockers
v. Proton pump inhibitors
Q.7. What are carminatives? Where they are used?
The drug which propels gases from G.I.T. and gives feeling of warmth and comfort in epigastium.
They are used for flatulent dyspepsia and to prevent
regurgitation of milk in infants.
Q.8. What are digestants?
The substances believed to promote digestion of food.
Q.9. What is the mechanism of action of methyl poly siloxane?
It is silicon polymer pharmacologically inert and reduces
surface tension and collapses the froth, acting as defoaming agent relieves flatulence, coats and protects ulcer surface,
helps dispersion of antacids in gastric content and prevents gastro-oesophageal reflux.
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Viva Voce in Medical Pharmacology
Q.lO. Name the drug used to dissolve gallstone.
Chenodeoxycholic acid (Chenodiol) and ursodeoxycholic acid (Ursodiol) decrease cholesterol content of bile enabling solubilization of cholesterol from gallstone surface. Q.ll. What are the di fferences between chenodiol and ursodiol? Chenodiol
i.
Ursodiol
Act primarily by inhibiting Ch-synthesis
Acts by intestinal absorption of
HMG -CoA reductase inhibition
cholesterol. Has inconsistant effect on
Raises plasma LDL cholesterol
Does not raise plasma LDL cholesterol
HMG-CoA reductase. ii.
by reducing LDL receptor in liver iii. iv.
Reduces cholesterol secretion in bile
Promptly reduces cholesterol secretion in
after prolong use
bile
Generates more litholytic bile acid pool.
Lowers cholesterol saturation index of bile.
v.
Promotes micellar solubilization of
Promotes solubilization by liquid
of cholesterol
crystal formation
The gallstone dissolving agents dissolve small stone slowly in presence of functioning gallbladder. It should not be used in pregnancy. Q.12. Define: Laxative, Purgatives.
The drugs which promote evacuation of bowels are called laxative or aperients are milder in action eliminates soft formed stools whereas purgative or cathartics have a stronger acting with more fluid evacuation. Q.13. Name some laxatives.
The laxatives can be classified as follows: 1.
Bulk purgative-dietary fibres, psyllium, lspaghula, methyl cellulose
ii. Stool softener-Docusates iii. Lubricants-Liquid paraffin iv. Stimulant purgative: a. Diphenylmethanes-Phenolphthalein Bisacodyl b. Anthraquinone--Senna Cascara Fixed oil-castor oil v. Osmotic purgative: Magnesium sulfate, Sodium Potassium Tartarate, Lactulose.
Drugs Used in Gastrointestinal Tract
83
Q.14. What is the mechanism of action of purgatives?
All purgatives increase the water content of the faeces, increase volume of colonic content and make it easily propelled, decrease absorption of water and electrolyte, increase propulsion activity. Purgatives modify fluid dynamics of mucosal cell and accumulate fluid in the gut lumen in one of the following mechanism: Inhibits Na/K ATPase impairing water absorption, stimulate adenylyl cyclase to increase water secretion. They cause structural damage to mucosal cells hindering absorption. Q.15. What are the disadvantages of liquid paraffin and
dietary fibres. Disadvantages of liquid paraffin are: i. Bland, unpleasant to swallow ii. May pass into mucosa, carried into lymph, may produce foreign body granulomas in the intestinal submucosa, mesenteric lymph nodes iii. May tride into lung producing pneumonia 1v. Carries away fat soluble vitamins with stool and vitamin deficiency may occur v. May interfere with healing in anorectal region and leakage of oil at and sphincter may be embarassing. Q.16. What is the mechanism of action of castor oil?
Castor oil is bland vegetable oil seeds of Ricinus communis contains triglyceride of Ricinoleic acid which is hydrolysed in the ileum by lipase to ricinoleic acid and glycerol. Ricinoleic acid being polar poorly absorbed and irritate GI mucosa. Other proposed mechanism producers structural damage to villious tips, decreases intestinal absorption. Q.17. What is the mechanism of action of Lactulose?
The semisynthetic disaccharides of fructose and lactose which is not digested or absorbed retain water, broken down by colonic bacteria to osmotically more active product. It is also used for hepatic encephalopathy. Lactulose causes reduction of blood NH3, the breakdown products of lactulose are acidic and reduce pH of stool. Ammonia produced by bacteria in gut is ionized to NH4 which is not absorbed. +
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Viva Voce in Medical Pharmacology
Q.18. What are the therapeutic uses of purgatives?
They are used for: i. Functional constipation ii. Bed ridden patient iii. To avoid straining at stools iv. Preparation of bowel in surgery, colonoscopy X-rays v. Food poisoning vi. Some antihelminths require purgative to propel them out. Q.19. What are the dangers of purgative abuse?
It may cause flaring of intestinal pathology, fluid an<;l electrolyte imbalance; steatorrhoea and malabsorption, spastic colitis. Q.20. What is absorbants, antidiarrhoeals? Where are they used?
They are the colloidal bulk forming substances which absorb water and swells up. Used for IBS, ilostomy, colostomy diarrhoea. The drugs are ispaghula, psyllium, methyl cellulose. Q.21. Name some antisecretory .antidiarrhoeal agents.
Sulfasalazine, Mesalazine, Bismuth subsalicyate, Altropine Octreotide. Q.22. Name some antimotility antidiarrhoeal and their uses.
These are codeine, Dipheoxylate, Loperamide used for non infective mild travellers diarrhoea, diarrhoea of AIDS, after colostomy and anal surgery. Q.23. What is pseudo-membranous enterocolitis?
It is produced by Clostridium difficile by misuse of antibiotics, vancomycin and metronidazole is useful in this condition. Q.24. What is peptic ulcer? Name the drug useful in this condition.
Peptic ulcer is an ulcer in those parts of g.i. tract which are exposed to acid pepsin digestion viz lower oesophagus, stomach duodenum, anastomosis site of stomach with jejunum, Mickel's diverticulum.
Drugs Used in Gastrointestinal Tract
85
The drugs effective in peptic ulcer can be grouped into: i. Acid Neutralizers: Systemic (Sodium bicarbonate, citrate local-Magnesium trisilicate, Magalarate-Al(OH)3 ii. Anti secretory to gastric acid secretion a. H2 Antihistaminic-Cimetidine, Ranitidine, Famoti dine, Roxatidine, Nizatidine, Loxatidine b. Proton pump inhibitors-Omeprazole, Lansoprazole, Pantoprazole, Rebeprazole. c.
Anti cholinergic: Propantheline, Oxyphenonium, Doxepin, Trimipramine, Pirenzepine
d. PG analogue: Misoprostol, Euprostil, Rioprostil iii. Ulcer insul,ators: Sucralfate, Colloidal bismuth subcitrate iv. Ulcer healing drug: Carbenoxolone sodium, Deglycyr hizinised liquorice. v. Anti H. pylori drugs: Amoxycillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline
Q.25. What is acid neutralizing capacity (ANC)? It is defined as a number of mEq of IN HCl which are brough to pH 3.5 in 15 minutes by a unit dose of antacid preparation.
Q.26. What are the therapeutic use of antacids? They are used in peptic ulcer. Zollinger-Ellison syndrome, Gastro-qesophageal reflux, Prophylaxis to aspiration pneumonia, during endoscopis, comatose patient.
Q.27. What are the the therapeutic uses of H2 receptor blockers? They are used for: i. Peptic ulcer n.
Stress ulcers
iii. Zollinger-Ellison syndrome iv. Castro-oesophageal reflux disease v. Prophylactic to aspiration pneumonia vi. At times with H2 blockers to treat urticaria as adjuvants.
Q.28. How does Cimetidine produce gynaecomastia? Cimetidine has anti-androgenic action (displaces dihydro testosterone from cytoplasmic receptors), increases plasma prolactin, inhibits degradation of oestradiol by liver.
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Viva Voce in Medical Pharmacology
Therefore if high dose given for long time, may produce gynaecomastia, loss of libido and decrease sperm count. Q.29. What is the mechanism of action of proton pump
inhibitors (Omeprazole)? Substituted benzimidazole inhibits the final common steps of gastric acid secretion. Omeprazole reacts covalently with SH group of H+ K+ ATPase enzyme and inactivates it. Acid secretion resumes only when H+K+ATPase molecules are synthesized. Q.30. How does prostaglandin analogue act in peptic ulcer
diseases? What are their limitations? PGE2 and PGI2 produced in gastric mucosa have got protective role in peptic ulcer. They: i. Inhibit acid secretion ii. Promote mucus secretion and HC03· secretion. Some of the PG analogues have been released in some countries are: i. Misoprostol 800 ].lg/ day ii. Enprostil70-140 ].lg/ day and Rioprostil600 ].lg/ day given in 2-4 divided doses. PG analogues have major drawback of diarrhoea, abdominal cramps, uterine bleeding, abortion. They are mainly used for NSAID or Aspirin group of drug, induce peptic ulcer. Q.31. How does sucralfate act as antipeptic ulcer drug?
Sucralfate is basic aluminium salt of sucrose sulfate. It polymerizes at pH less than4 by cross-linking of the molecules assuming gel like consistency and adheres to the ulcer base and remains there for more than6 hours. It precipitates surface proteins at ulcer base acting as physical barrier to act upon by acid, pepsin, bile over ulcer. It interferes with binding of pepsin to eroded mucosa to digest them. The protective action is enhanced by gastric mucosa PG synthesis. It has no acid neutralizing property.
Drugs Used in Gastrointestinal Tract
87
Q.32. What.is the mechanism of action of Colloidal Bismuth
subcitrate? This compound precipitates at pH less than 5. It is not antacid, probably its mechanisms of action are:
·
i. Increases mucus and HC03- secretion by PG ii. Coats ulcer and acts as a diffusion barrier iii. Detaches H. pylori and kill them iv. Absorbs pepsin and reduces its output. Q.33. What is the mechanism of action of carbonexolone
Na? What are their limitations? Carbonexolone Na found in liquorice root heals peptic ulcer without changing volume or acidity of gastric juice and augmenting the mucus production, and interferes with activation of pepsinogen. It prevents back diffusion H+ in gastric mucosa probably mediated through PG. It may lead to Na retention, oedema, spironolactone blunts its action. Q.34. What is the mechanism of action of Pirenzepine?
They are Ml selective anticholinergic without extensive side effect of nonselective anticholinergic drug can be given safely in glaucoma and prostratic hypertrophy. Q.35. Name the drugs effective against H.pylori.
The H. pylori is gram-negative, urease positive bacillus uniquely adapted to survive in hostile environment of stomach. The effective drugs are Amoxycyllin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline. Q.36. What are the criteria of ideal peptic ulcer drug?
i. It should be effective in both duodenal and gastric ulcer ii. Relief pain iii. Heals ulcer iv. Prevents complication and relapse.
Haemopoietic System Q.l. Define anaemia? It is qualitative or quantitative decrease of RBC or haemo globin or both in respect to age, sex and altitude.
Q.2. What is haematinics? The agents which are required in the formation of blood and used for treatment of anaemia as for example Iron, Folic acid, B12, Cu, Co, B6, Riboflavin, etc.
Q.3. What is the daily requirement of iron? Daily requirement for adult male 0.5-1 mg; adult female 1-2 mg; Infants 60 p.g; children 25 p.g, pregnancy 3-5 mg.
Q.4. How iron is absorbed? What are the factors facilitating iron absorption and what factors impedes iron absorption? Dietary iron present as haeme or inorganic iron is absorbed from upper GI tract, The inorganic iron as fe"rric form is reduced to ferrous form before absorption. The gut has mechanism to prevent entry of excess iron. The iron reaching inside mucosal cell is either transported to plasma or oxidised to ferric form and complexed with apoferitin to form ferritin. Ferritin generally remains stored in mucosal cells and is lost when it is shed called mucosal block. Iron absorption is facilitated by acid, reducing substances (ascorbic acid, amino acids with SH group of meat). Its absorption is impeded by: i. alkalis, phosphates, phytate, tetracycline, presence of other substances in stomach.
Haemopoietic System
89
Q.S. Whar are the therapeutic uses of iron? It is used for: i. Iron deficiency anaemia ii.
As astringent ferric chloride is used as throat pain.
Q.6. How will you treat iron poisoning? Iron toxicity occurs in children manifested with vomiting, abdominal pain, diarrhoea, haematemesis, cyanosis, dehydra tion, acidosis, convulsion, shock and death. Treatment should be prompt aimed at: i. To prevent further absorption by vomiting, gastric lavage, egg yolk or milk orally. Desferoxamine 5-10 mg in 100 ml saline is left in stomach after lavage. n.
To remove already bound iron. Desferoxamine 0.5 mg1'gIM every4-12 hours or withDTPA.Don't useBALas it produces toxic complexes with iron
iii. S upportive measures like fluid, electrolyte, acid base balance should be maintained byLV. infusion.
Q.7. What is the requirement of B12? What are their dietary sources? What are their metabolic functions? What are the causes of its deficiency? B12 or cyanocobalamin and hydroxycobalamin are complex cobalt containing compounds.Its daily requirement is 1-2 pg; in pregnancy and lactation3-5 pg. Its metabolic functions are as follows: i. Converts homocysteine to methionine ii. Purine and pyrimidine synthesis iii.
Malonic acid is converted to succinic acids in its presence responsible for demyelination seen in B12 deficiency.
iv. Responsible for cell growth and maturation v. Methionine is converted toS-adenosyl methionine in its presence. Its deficiency occurs due to: i. Absence of intrinsic factor(Addison's pernicious anaemia) ii. Gastric mucosal damage (gastric carcinoma, chronic gastritis, malabsorption, bowel resection, increased demand-pregnancy and infancy); increased consumption by abnormal flora(blind loop syndrome, fish tape worm).
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Viva Voce in Medical Pharmacology
Q.S. How Vit B12 is utilized?
From food as protein conjugates released by protoeolysis by gastric acid. Intrinsic factor (a glycoprotein of MW 60000) secreted by stomach forms a complex with B12 and attaches to specific receptor on intestinal mucosal cells absorbed by carriet mediated complex. It is transported in blood in combination with specific � globulin transcobalamin II. Congenital absence ofTCII or abnor mal protein TCI or TCIII in liver and bone marrow disease interferes with deliver of B12 in tissues. It is excreted with bile and enteroheppatic circulation occurs.
Q.9. What are major manifestations of Bl2 deficiency?
These are megaloblastic anaemia, glossitis, g.i. disturbances peripheral neuropathy, paraesthesia, mental changes, poor memory hallucinations, subacute combined degeneration of spinal cord
·
·
Q.lO. What are the therapeutic uses of B12?
B12 deficiency; Prophylaxis; Megadose are given in
neuropathy, psychiatric disorders, emperically used to allay fatigue, improve growth, tobacco amblyopia.
Q.ll. What is Folic acid chemically? What is its dietary source and daily requirements? Folic acid is Pteroyl Glutamic acid chemically consisting of pteridine, paraamino benzoic acid and glutamic acid. Its daily requirement is O.lmg; in pregnancy and lactation 0.8 mg/ days is obtained from dietary source of liver, green leafy vegetables, :gg, milk.
Q.12. What are the metabolic functions of folic acid? Folic acid is inactive as such and reduced to Dihydrofolic acid and tetrahydrofolic acid by folate reductase THFA mediates one carbon transfer reaction by carrying methyl group involved in: i. Conversion of homocysteine to methionine, B12 acts as intermediary carrier of methyl group. ii. Generates thymidylate essential constituent of DNA iii. Conversion of serine to glycerine
Haemopoietic System
91
iv. Purine synthesis v. Generation and utilization of formate pool vi. Histidine metabolism. Q.13. What are the causes of folic acid deficiency? How they
are manifestated? Folic acid deficiency occurs due to: i. Inadequate intake ii. Malabsorption (Coeliac disease, tropical sprue, ileitis, Biliary fistula, chronic alcoholism) iii. Increased demand: Pregnancy, lactation, haemolytic anaemia iv. Drug induced (Phenytoin,OCP) They are manifested as anaemia, epithelial damage (glossitis, enteritis, diarrhoea, steatorrhoea), General debility, weigh loss, sterility. Q.14. Mention the therapeutic uses of folic acid.
They are used for: a. Megaloblastic anaemia due to i.
Nutritional folate deficiency
ii. Pregnancy and lactation, infancy, pernicious anaemia
b. As prophylaxis iii. Methotrexate toxicity (folinic acid is reduced) iv. Citrovorum factor rescue (folinic acid is used) Q.l5. What is shot gun preparation for anaemia?
A large number of preparation contains iron, folic acid, B12, protein etc all haematinics in subtherapeutic doses or they are not required at all, which hampers diagnosis of patient are called shot gun preparation. Q.16. What is Erythropoietin? What are its therapeutic uses
and what are their adverse effects? Erythropoietin is sialoglycoprotein hormone produced by peritubular cells of the kidney are essential for normal erythropoiesis, hypoxia is its major stimulation for formation. Erythropoietin i. Stimulates proliferation of colony forming cells of erythroid cells;
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Viva Voce in Medical Pharmacology
ii. Induces haemoglobin synthesis and iii. Erythroblast maturator iv. Releases reticulocyte in circulation. It is used in anaemia of CRF; Anfiemia of AIDS treated with Zidovudine, cancer chemotherapy induced anaemia. Adverse effects are related to sudden increase of haematocrit, rise in blood viscosity and increase in vascular resistance; increased clot formation in
A.V.
shunts,
hypertensive episodes, occasionally seizure and flu like symptoms.
Q.17. What are coagulants? Name some coagulants. Coagulants are agents which promote coagulation of blood indicated in haemorrhagic conditions. They can be classified as follows: A. Systemic acting: i.
Vitamin K (Phytonadione, Menaquinone, Menadione)
ii. Other-Fibrinogen, Antihaemophillic factor, Adreno chrome, monosemicarbazone, Rutin, Ethamsylate. B. Local haemostatic: Thrombin, Fibrin, Gelatin foam, Russel
viper venom, vasoconstrictors, Astringent like tannic acid in 20% glycerine.
Q.18. What is the mechanism of action of Vitamin K? Vit K helps in synthesis of coagulation proteins prothrombin, Factor VII; IX and X causing g carboxylation of glutamate residues of these zymogen proteins and gives them ability to bind Ca2+ to get bound to phospholipid surface; essential for coagulation process.
Q.19. Name some therapeutic uses of Vit K? This is used for: i. Dietary deficiency ii. Prolonged antimicrobial therapy iii. Obstructive jaundice iv. Malabsorption syndrome v. Liver diseases vi. Newborn vii. To reverse the effect of overdose of oral anticoagulant.
Haemopoietic System
93
Q.20. What is sclerosing agents? Name some sclerosing agent. These irritants which cause inflammation,coagulation and fibrosis of haemorrhoids or vericose vein when used locally, such as: i. Phenol 5% in almond oil or peanut oil ii. Ethanolamine oleate 5% in25% glycerine 111. Quinine 12.5%
+
Urethane
iv. Sodium Tetradecyl sulfate 5% with benzyl alcohol2%.
Q.21. What is anti-coagulants? Name them. These are drugs used to reduce coagulabity of blood. They can be classified as drug used in vitro-heparin. Calcium complexing agent. Used in vivo-Heparin, low molecular weight heparin, Heparinoids, heparin sulfate, Dextran sulfate. Orally effective anticoagulants are: i." Coumarine derivatives, Bishydroxycommarin, Warfarin Na, Acenocoumarol, Ethylbiscoumacetate ii. Indandione derivative-Phenindiorte
Q.22. What is the chemical nature of Heparin? What are the actions of heparin? It is mixture o£ straight chain mucopolysaccharides contains polymers of two sulfated disaccharide, is the strongest organic acid in body with strong electronegative charges found in mast cells, loosely bound to granular proteins. It acts as: i. Anticoagulants ii. Higher dose inhibit platelet aggregation iii. Lipemia clearing agent.
Q.23. What are the contraindications of heparin? It should not be used in: i. Bleeding disorders thrombocytopenic ii. Hypertension
,
iii. Threatened abortion, piles, GI bleeding 1v. Subacute bacterial endocarditis, malignancy, tuberculosis, ocular neurosurgery LP, alcoholics, cirrhosis, patient on antiplatelet drug.
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Viva Voce in Medical Pharmacology
Q.24. What adverse effect which may arise out of heparin therapy?
It may produce bleeding, thrombocytopenia, transient and reversible alopecia, osteoporosis, hypersensitivity. Q.25. What are the advantages of LMW Heparin? What are their indications?
The main advantages of LMW Heparin are their pharma cokinetics. i. Better S/C availability ii. Lmi.ger and consistent effect iii. A PTT and clotting times are not prolonged. The LMH are indicated for: i. Prophylactic of deep vein thrombosis and pulmonary embolism in high risk patient n. Treatment of established deep vein thrombosis iii. To maintain potency of cannulae and shunts in dialysis patient.
Q.26. Name some LMW Heparin.
Enoxaparin, Reviparin, Nadoparin, Dalteparin, Heparin sulfate. Q. 27. What is semisynthetic heparinoids?
These are sulfated mucopolysaccharides are potent anti coagulants like dextran sulfate. Q.28. What is protamine sulfate?
It is a strongly basic, low molecular weight protein obtained from sperm of some fish neutralises heparin and act as heparin antagonist. In absence of heparin it act as weak anticoagulant. Q.29. What is the mechanism of action ofwarfarin Na?
They act as anticoagulant in vivo, by interfering synthesis of vit K dependent clotting factors in liver interfering with regeneration of active hydroquinone form of Vit K, which carries out final step of y carboxylating glutamate residues of prothrombin VII, IX, X which is essential for the ability of the clotting factors to bind Ca2+ and get bound to phospholipid. surfaces.
Haemopoietic System
95
Q.30. How will you treat blee ding due to oral anti
coagulants?
Anticoagulant should be withheld, fresh blood transfusion or frozen plasma as a source of clotting .factors. Give Vit K but it acts slowly. The dose of oral anti coagulant must be measured by repeated prothrombin time. Q.31. What are the factors which enhance and decrease effect
of oral anticoagulants?
Factors enhancing anticoagulant effects are: i. Malnutrition, prolong antibiotic therapy reducing vit K ii. Liver disease, alcoholism, hyperthyroidism, new born with low level of vit K and clotting factors. Factors decreasing anticoagulant effects are: i. Pregnancy ii. Nephrotic syndrome iii. Genetically warfarin resistance Q.32. What are the therapeutic uses of anticoagulants?
They are used for: 1. Deep vein thrombosis, pulmonary embolism ii. Myocardial infarction iii. Rheumatic heart disease with atrial fibrillation iv. CVA v. Vascular surgery, prosthetic valve, haemodialysis, retinal vessel thrombosis vi. DIC Q.33. What are the fibrinolytic agents available in India?
They are streptokinase, urokinase, alteplase Q.34. What are the uses of Fibrinolytics?
They are used in following conditions: 1. Acute myocardial infarction ii. Deep vein thrombosis iii. Pulmonary embolism
iv. Peripheral arterial occlusion. Q.35. What are the uses of antifibrinolytics?
Antifibrinolytics [Epsilon Amino Caproic acid (EACA)] are used for:
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Viva Voce in Medical Pharmacology
i. Overdose of streptokinase, urokinase, alteplase n.
To prevent traumatic and surgical bleeding prostetectomy in haemophiliacs
iii. To prevent recurrence of subarachnoid and GI bleeding iv. Bleeding of PPH; Abruptio placenta, menorrhagia
Q.36. Name some antiplatelet, antithrombotic drugs? These are: i. Aspirin ii. Dazoxiben iii. Sulfinpyrazone iv. Dipyridamole v. Ticlopidine vi. Clofidogrel
Q.37. What are the therapeutic uses of antiplatelet drug? i. Coronary artery disease ii. Cerebro-vascular disease iii. Coronary bypass implants iv. Prosthetic heart valve and arteriovenous shunts v. Venous thromboembolism vi. Peripheral vascular disease.
Q.38. Name the drugs which can produce agranulocytosis and haemolytic reactions.
Drugs producing agranulocytosis: i. Chlorpromazine,
Meprobamate,
Phenylb utazone,
Analgesic, Indomethacin, Chloraphenicol sulfonamide, Pot. perchlorate, Thiouracil, Troxidone, Procainamide, Gold salts, Thiacetazone, Imipramine. ii. Drugs causing haemolytic reaction: Sulfonomide, Furazolidine,
Nitrofurantoin,
DDS,
Primaquine,
Pamaquin, Mepacrine, Quinine, Acetanilid, salicylate, Phenacetin, Napthalene, Methyl dopa, vit K.
Q.39. What are the advantages of Clopidogrel over Ticlopidine.
i. Clopidognel does not have neutropenic side effects, so routine complete blood count is not required. ii. Doses required once a day.
Haemopoietic System
97
iii. It is 6 times more potent than ticlopidine in inhibitioin of ADP induced aggregation of human platelets. iv. It has faster onset of action v. Cheap vi. Ticlopidine increases total cholesterol by 9%.
Endocrine System Q.l. What is Hormone? Hormone is derived from Greek word "hormaein" means to stir up. It is a substance produced by specific cells in the body and is transported through circulation to act on target cells.
Q.2. Name the hormones released by pituitary gland? Pituitary gland has two portions i. Anterior and ii. Posterior. The hormones produced by anterior pituitary are: 1.
Growth hormones
ii. Prolactin iii. Adrenocorticotropic hormone iv. Thyroid stimulating hormone v. Gonadotropin follicular stimulating hormone (FSH) and Luteinizing hormone (LH) The hormones from posterior pituitary are: 1. Oxytocin 2. Antidiuretic hormone
Q.3. Name the hormone released from hypothalamus? The hormones released from hypothalamus are: i. Thyrotropin releasing hormone (TRH)-(tripeptide) ii. Corticotropin releasing hormone CRH (with 41 amino acids) m.
Gonadotropin releasing hormone (decapeptide)
iv. Prolactin release inhibitory hormone PRH (Dopamine) v. Prolactin releasing factor (PRF) vi. Somatostatin, Growth hormone releasing inhibitory hormone (peptide with 14 amino acids)
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vii. Growth hormone releasing hormone (peptide with 40; 44 amino acids)
Q.4. Name the hormones released by placenta. These are chorionic gonadotropin, oestrogen, placental lacto gen, prolactin, progesterone, chorionic thyrotropin.
Q.S. Mention the therapeutic use of growth hormone. The only approved indication for growth hormone is pituitary dwarfism now produced by recombinant DNA technology.
Q.6. What are the functions of somatostatin? This is a 14 amino acid peptide inhibits secretion of GH, TSH and prolactin in pituitary, glucagon and insulin in pancreas and almost all gastrointestinal secretions including gastrin and HCl.
Q.7. What is the therapeutic use of somatostatin or octreolide? Somatostatin used for only acromegaly but its limitation is lack of specificity and rebound after discontinuation. so synthetic peptide octreolide is used to treat acromegaly or metastatic carcinoid tumors.
Q.B. How is the prolactin secretion regulated? Prolactin is under inhibitors control of hypothalamus PRIH which is dopamine and acts on lactotrope D2 receptors. Dopamine agonist (DA, Bromocriptine, apomorphine) decreases plasma PRL level where as its level is increased by dopaminergic antagonist (CPZ, Haloperidol, metoclo paramide), DA depletor (methyl dopa and reserpine) causes hyperprolactinemia.
Q.9. What are the therapeutic uses of Bromocriptine? This synthetic ergot derivative with DA agonistic activity is used clinically in i. Hyperprolactinemia ii. Suppression of lactation and breast engorgement iii. Acromegaly iv. Parkinsonism v. Hepatic coma
•
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Viva Voce in Medical Pharmacology
Q.lO. What are the gonadotropin hormones secreted by
anterior pituitary? What are their chemical nature and therapeutic uses? Anterior pituitary secretes two gonadotropins FSH and LH which are amino acids. FSH and LH has mol. wt. of 32000 and 30000 respectively. Their therapeutic uses are: i. Amenorrhoea and infertility Hypogonadotropic hypogonadism in males
u.
iii. Cryptorchism iv. To aid in vitro fertilization. Q.ll. What is TSH? What is its function and therapeutic
uses? These are 210 amino acid, two chainglycoprotein with MW 30000 from anterior pituitary. It stimulates thyroid to synthesize T4 and T3, induces hyperplasia and hypertrophy of thyroid follicles and increase blood supply to the gland, promotes iodide trapping and releases more T3 and T4. It is used only to diagnose myxoedema of pituitary dysfunction and primary thyroid disease. Q.12. What is the chemical nature of adrenocorticotropic
hormone? What is its physiological function? It is 39 amino acid containing single chain polypeptide derived from larger peptide pro-opiomelanocortion. Endorphins lipotropins and MSH are also derived from it. ACTH promotes steroidgenesis in adrenal cortex increasing availability of cholesterol for conversion to pregnenolone, the rate limiting step in production of gluco, minerals, androgenic steroids slowly inducing steroidogenic enzymes. ACTH exerts trophic influence on adrenal cortex through cAMP.It produces metabolic effect like lipolysis, ketosis, hypoglycaemia. Q.13. What are the hormones secreted by thyroid gland?
The thyroid gland secretes thyroxine (T4); tri-iodothyronine (T3)
by follicular cells
interfollicular C cells.
and
calcitonin produced
by
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Q.14. How the thyroid hormones are synthesized? Thyroid hormones are synthesized and stored in the thyroid follicles in thyroglobulin molecules as follows: i. Iodide trapping: Under the influence of TSH thyroid cells concentrate iodine. ii. Oxidation of Iodine: Trapped Iodide is oxidised by peroxidase enzyme with H202 to iodinium I+ and combines with tyrosil residues of thyroglobulin apparently without enzymatic intervention to form moniiodotyrosine, di-iodot yrosine still attaches to thyroglobulin chains. iii. Coupling: Pairs of iodinated tyrosil residues couple to gether to produce T3 and T4, more T4 is formed than T3. iv. Storage and release: Thyroglobulin with iodinated tyrosil is transported to the interior of the follicles and remains stored in thyroid colloid till it is taken back into the cells by endocytosis and broken down by lysosomal proteases. T4 and T3 are secreted into circulation while MIT and DIT residues are deiodinated. v. Conversion ofT4 and T3 in periphery: Liver, Kidney convert T4 to T3. T3 is taken up by target tissues almost equal amounts of 3,5,3, T3 and 335 T3 reverse inactive T3 are produced in the periphery. Propylthiouracil, Propranolol, amiodarone and glucocorticoids inhibit peripheral conversion of T4 to T3. Q.lS. How are the thyroid hormones transported? They are transported in binding three plasma proteins; i. Thyroxine binding globulin ii. Thyroxine binding pre albumin 'iii. Albumin Q.16. What are the therapeutic uses of thyroids? They are used in: i. Cretinism n.
Adult hypothyroidism
iii. Myxoedema coma iv. Nontoxic goitre
I
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v. Papillary carcinoma of thyroid vi. Empirically used for refractory anaemia, menstrual disorder, infertility, chronic nonhealing ulcers, obstinate constipation.
Q.17. What is the relationship between T4 and T3? Thyroid gland secretes more T4 than T3. T4 is major circulating hormone because it is tightly bound to plasma proteins and T3 is faster acting: About 1/3 of T4 is converted to T3 in peripheral tissues.
Q.18. Name some thyroid inhibitors. These are drugs us�d in hyperactive thyroid gland and can be classified as follows: i. Inhibiting iodide trapping (Thiocyanate, Perchlorates, Nitrates) ii. Inhibit hormone synthesis (Propylthiouracil, Methimazole, Carbimazole) iii. Inhibiting hormone release: Iodine, Iodides of Na and K.
.
iv. Destroy thyroid tissue: Radioactive iodine
Q 18.What are the uses of antithyroid drugs? What are their .
advantages and disadvantages?
They are used for remission of Graves' disease, preoperatively to make hyperthyroid patient euthyroid, along with P31• The advantages are: i. No surgical risk ii. Hypothyroid state is reversible iii. Can be used in all ages. The disadvantages are: i. Prolong therapy ii. Drug toxicity iii. Patients co-operation required
Q.19. What are the therapeutic uses of iodine? This is used for i. Preoperative preparation of thyroidectomy patient ii. Thyroid storm
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iii. Prophylactic in endemic goitre iv. Expectorant v. Antiseptic Q.20. Name the drugs which can produce hypothyroidism.
They are: i. Lithium ii. Amiodarone iii. Sulfonamide iv. Phenobarbitone v. Phenytoin vi. Carbamazepine viii. Rifampicin Q. 21. What are the t/2 of J131, p23, J12s?
The t/2 of P31 is 8 days; P23 is 13 hours; P25 is 60 days Q.22. What are therapeutic uses of P31?
This is used for diagnostic and therapeutic purposes (Graves' disease, toxic nodular goitre), metastatic carcinoma of thyroid). Q.23. What are the advantages and disadvantages of radio active iodine?
The advantages are: i. Simple treatment without surgical risk, if hyperthyroidism is controlled cure is permanent can be used in CCF, angina The disadvantages are: i. Hypothyroidism ii. Prolong treatment time iii. Cannot be given in pregnancy iv. Young patients develop hypothyroidism quickly. Q.24. How does P-blocker propranolol help in thyro toxicosis?
i. They overcome the manifestation of sympathetic overactivity n.
For preparation of thyroidectomy with iodine.
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DIABETES MELLITUS, INSULIN, OHG Q.l. What is diabetes mellitus? Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia, glycosuria, negative nitrogen balance hyperlipemia and sometimes ketonemia.
Q.2. What is insulin? Who discovered it? It is a hormone liberated by pancreatic �-islet cells. It was discovered by Banting and Best and its structure was worked out by Sanger in 1956.
Q.3. What is the structure of insulin? (Achain has
Insulin has two polypeptide chain
21amino acid;
B chain has 30 amino acid). They are synthesized as single chain peptide of 110 amino acids in � cells to produce proinsulin. The connecting C peptide is spit off by proteolysis in Golgi apparatus.
Q.4. What do you mean by
I.U.
insulin?
1 I.U. of insulin decreases blood glucose of fasting rabbit to 45 mg%, 1 mg of standard insulin =24 units.
Q.S.How is the secretion of insulin regulated? Insulin secretion is regulated by: i. Chemical: �cells of glucose has glucose sensing mechanism acting as principal regulator, other regulators are amino acids, fatty acids, ketone bodies. ii. Hormonal: Growth hormone,corticosteroid,thyroxine and PG modify·insulin release. iii. Neuronal: Richly supplied by sympathetic and vagal nerves a2 receptor activation inhibits, �2 stimulation increases insulin releases, muscarinic activation increases insulin secretion.
Q.6. What is the mechanism of action of insulin? Insulin acts on insulin receptor present in all the cells,specially in liver and fat cells.The insulin receptor is tetrameric glyco protein with 2a and 2� subunits linked by di -sulfide bonds. The a subunits bind insulin whereas �-subunits activate \ tyrosine •kinase.
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1 05
Q.7. What is the fate of insulin?
Being protein in nature, it is not absorbed orally,. Injected insulin or secreted insulin is metabolized in liver, kidney, muscle. During biotransformation A and B chains are separated, the disulfide bonds are reduced which are further broken down to constituent amino acids. Q.S. What are the therapeutic uses of insulin?
It is indicated in diabetes mellitus type I and type II: In type II diabetes insulin is required in: i. If not controlled by diet or exercise ii. Primary and secondary failure of OHG. iii. Under weight patient Emergencies like infection, trauma, surgery, pregnancy
IV.
v. Complications of diabetes like ketosis, gangrene, etc. vi. Diabetk ketoacidosis vii. Hypermolar nonketotic hyperglycaemic coma Q.9. What-are the adverse reactions of insulin?
These are hypoglycaemia, local reaction like lipodystrophy, allergy, edema Q.lO. How will you treat diabetic ketoacidosis?
i. Insulin 0.1-0.2 U/kg LV. bolus, followed by 0.1 U kg/hr infusion ii. LV. fluid normal saline to correct dehydration after blood sugar reaches 300 mg%, 5% glucose in 1/2 N saline can be used iii. KCl 4-10 mEq/hr Kcl LV. to be guided by serum monitoring and ECG iv. NaHC03 to tackle acidosis v. P04 infusion if values are low vi. Antibiotics. Q.ll. What is Somogyi effect?
The problem of Somogyi effect is common in insulin dependent diabetes with aggressive effort to control hyperglycaemia. Day time episodes of hypoglycaemia are recognised by sweating, nervousness, tremor, hunger. If hypoglycaemia not aborted it worsens diabetic control, with
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the results of counter regulatory hormones results in hyperglycaemia with mild ketosis and this phenomenon is called Somogyi effect. It should be suspected if there is wide moving of plasma glucose or urine sugar in a short period.
Q.12. What is insulin resistance? What are their causes? When requirement of insulin is increased by 200 I.U./ day, physiologically it is said to be insulin resistance. It may be acute due to infection, trauma, corticosteroid therapy or, due to ketoacidosis or chronic where patient takes conventional beef or pork insulin due to antibodies to insulin. Pregnancy or oral contraceptives often produce low grade reversible insulin resistance.
Q.13. What is human insulin? Human insulin is produced by recombinant DNA technology in E. coli (proinsulin recombinant bacterial prb) or precursor yeast recombinant (pyr) or by enzymatic modification of porcine insulin (emp).
Q.14. What are the indications of purer/human insulin? In developing countries purer insulin is used for:
i. Insulin resistance ii. Allergy to conventional preparations iii. Lipodystrophy iv. To tide over surgery, trauma, infection, ketoacidosis, pregnancy
Q.15. What are the nondiabetic uses of insulin? i. To test completenes of vagotomy ii. Hyperemesis gravidarum, anorexia nervosa, cachexia, alcohol intoxication, shock therapy of schizophrenia (outdated)
Q.16. Name the oral hypoglycaemic agents. Oral hypoglycaemic drugs are of following types: i. Sulfonylureas derivative: a. 1st generation-Tolbutamide, Chlorpropamide, Aceto hexamide, Tolazamide b. 2nd generation-Glibenclamide, Glipizide, Gliclazide
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1 07
ii. Biguanide derivatives: Phenformin, Metformin iii. Miscellaneous: Acarbose, Guargum Q.17. What is the mechanism of action of sulfonylurea?
Sulfonylurea acts on sulfonylurea receptor on the pancreas � cells, causes depolarization by reducing coductance of ATP sensitive K+channel, enhancing Ca2+ influx and degranulation. They do not act on type I diabetes and pancreatonised animal They reduce glucagon and increases somatostatin release. But these are minor action. On chronic administration they sensitize the target tissues because of increase in insulin receptors. Q.18. What are the adverse effects of sulfonylurea?
Following adverse effect may arise with sulfonylurea: i. Hypoglycaemia ii. Nonspecific effects (nausea, vomiting, flatulence diarrhoea, constipation, headache, paraesthesia, weight gain) iii. Hypersensitivity rash, photosensitivity, purpura, tran sient leukopenia, agranulocytisis. Chlorpropamide may produce cholestatic jaundice, disulfiram like action with alcohol, dilutional hyponatremia. Tolbutamide reduces iodide uptake and hypothyroidism. Q.19. What is the mechanism of action of biguanides?
They i. Inhibit intestinal absorption of glucose, hexose amino acids, B12 ii. Suppress hepatic gluconeogenesis iii. Enhance binding of insulin to its receptor iv. Interfere with mitochondrial respiratory chain and promote peripheral glucose utilization. Q.20. What are the adverse effects of biguanides?
They may produce i. Lactic acidosis ii. Vit B12 deficiency
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Q.21. Whe1t are the indications of OHG? This is indicated in: i. Patient above 40 years ii. Obesity iii. Duration of disease less than 5 years iv. Fasting blood sugar less than 200 mg% v. Insulin requirement less than 30 U I day vi. Without complications Q.22. What is the mechanism of action of Acarbose? Acarbose is complex oligosaccharides, reversibly inhibits
a
glucosidases, the final enzyme in the digestion of carbo hydrates in the brush border of intestine. It decreases post parandial blood sugar without increasing insulin level. Q.23. What is the mechanism of action of guargum? Administered just before food, it slows down gastric emptying, intestinal transit time. It forms a viscous gel on contact with water. It is used to lower the dose of sulfonylurea. Q.24. Mention some other uses of OHG. i. Tolbutamide produces marked hypoglycaemia in insulinoma ii. Chlorpropamide effective in pituitary diabetes. Q.25. What are the therapeutic uses of glucagon? It is used in: i. Hypoglycaemia ii. Cardiogenic shock iii. Diagnosis of pheochromocytoma Q.26. Name some hyperglycaemic agents? They arei. Glucacon ii. Diazoxide iii. Thiazide and phenytoin iv. Somato$tain v. Streptozocin. Q.27. What is the mechanism of action of thiazolideones? They decrease insulin resistance by increasing number of insulin transporters in liver, adipose tissue and skeletal muscles.
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109
·The drugs are Ciglitazone, Troglitazone, Pioglitazone, Englitazone.
Q. 28.
What is the special feature of Glimepride?
It is new sulfonylurea with weak insulin releasing but stronger extrapancreatic action of peripheral disposal of glucose by enhancing translocation of transporter to the plasma membrane.
Q.29.
What are the full forms of abbreviations NPH, PZI,
UGDH?
NPH =Neutral protamine hagedron PZI =Protamine Zinc insulin] UGDH =University group diabetic programme (of USA)
Q.30.
Name some insulin delivery devices.
i. Insulin syringe ii. Pen devices iii. Jet injector without needle iv. Insulin pumps v. Implantable pumps vi. External artificial pancreas vii. Other routes of insulin delivery: (intraperitoneal; oral (complexing with liposomes), rectal, intranasal application with surfactants).
CORTICOSTEROIDS '
Q.l.
What are hormones secreted by adrenal cortex?
Microscopically adrenal cortex has three zones;i. Zona glomerulosa ii. Zona fasiculata iii. Zona reticularis which secrete Aldosterone, Hydrocor tisone, Dihydroepiandrosterone having mineralocor ticoid, glucocorticoids and weaker androgenic activity respectively.
Q.2.
What is the mechanism of action of corticosteroids?
Corticosteroids after penetrating cells bind to high affinity cytoplasmic receptor protein producing structural change in
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steroid receptor complex which migrates to nucleus and bind to specific sites of chromatin leading to regulation of protein synthesis after transcription of m-RNA. The actions of glucocorticoids are not immediate, take 30-60 min but persists longer. Q.3. What is the chemical nature of corticosteroid group of drugs? Name some corticosteroids.
Chemically they contain cyclopentanoperhydrophenanthrene nucleus. Corticosteroids can be therapeutically classified into: i. Those having mainly glucocorticosteroid activity viz Hydrocortisone, Cortisone, Prednisolone, methylpredni solone, Triamcinolone, paramethasone, Betamethasone, Dexamethasone. ii. Those having mainly mineralocorticoids activity: Desoxy corticosterone
acetate
(DOCA);
Fludrocortisone,
Aldosterone (not used clinically) Q.4. What are the therapeutic uses of glucocorticosteroids?
They are used for: 1. Replacement therapy: Acute adrenal insufficiency 2. Used for non-endocrine diseases:
·
i. Arthritis (Rheumatic, Rheumatoid) ii. Collagen diseases (SLE, polyarteritis nodosa, dermato myositis, nephrotic syndrome) iii. Allergic reactions (anaphylaxis, angioneurotic oedema, serum sickness) iv. Autoimmune diseases (Haemolytic anaemia, thromo cytopenia, chronic active hepatitis) v. Bronchial asthma to accelerate lung maturation in premature babies. vi. Eye diseases (generally used as drops or ointment) conjunctivitis, iritis, iridocyclitis, keratitis. vii. Skin disease (Topical steroids are commonly used for eczema). Systemic steroid used for pemphigus, vulgaris, exfoliative dermatitis, Stevens-Johnson syndrome. viii. Intestinal disease-Ulcerative colitis, Crohn' s disease, Coeliac disease ix. Cerebral oedema
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x. Malignancies-Leukemia, Hodgkin disease xi. Organ transplantation xii. Shock xiii. To test adrenal-pituitary axis.
Q.5. What are the therapeutic uses of Mineralocorticoids? They are indicated in replacement therapy in Addison's disease, congenital adrenal hyperplasia, idiopathic postural hypotension.
Q.6. What are the contraindications of corticosteroids? Corticosteroids should not be used in: i. Peptic ulcer ii. Diabetes mellitus iii. Hypertension iv. Pregnancy v. Tuberculosis and other infection vi. Osteoporosis vii. Herpes simplex viii. Psychosis ix. Epilepsy X.
CCF
xi. Kidney failure
Q.7. What adverse effect may arise out of corticosteroid administration?
Because of mineralocorticoid activity it may produce Na and water retention, rise of BP, hypokalemia alkalosis. Because of glucocorticoid activity, it may produce: i. Cushing ii. Fragile skin easy bruising, telangiectasis iii. Muscular weakness iv. Infection proneness v. Delayed healing of surgical wounds vi. Peptic ulcer vii. Osteoporosis viii. Cataract, glaucoma ix. Growth retardation x. Psychiatric disturbances xi. Suppression of hypothalamo-pituitary adrenal axis.
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Q.8.
Name a glucocorticoid antagonist and its therapeutic
uses.
Mifepristone is antiprogestion, has glucoreceptor antagonist is tried for Cushing syndrome.
DRUGS ACTING ON CALCIUM METABOLISM Q.l.
What are the physiological role of calcium?
Calcium is engaged in the following important physiological functions: 1.
Controls excitibility of nerves and muscles, adhesion of cells and integrity of cell membrane, regulates release of exocrine glands and release of transmitters
ii. It acts as intracellular messenger for hormones, autakoids and transmitters iii. Generates impulse in heart iv. Coagulation of blood.
Q.2.
What hormones involved in plasma calcium main
tenance?
Three hormones: i. Parathormone ii. Calcitonin and
iii. Calcitriols (Vit D) are engaged to regulate plasma calcium level.
Q.3.
What are the factors influencing bone turnover?
Factors increasing the resorption of bones are: i. Corticosteroid, ii. Parathormone iii. Thyroxine iv. Hyper·vit
D
v. PGE2, vi. Alcoholism vii. Loop diuretic viii. Interleukin 1 and 6.
·
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113
Factors decreasing the resorption of bones are: i. Androgen and oestrogen, ii. Calcitonin iii. Growth hormone iv. Fluoride v. Bisphosphonate vi. Gallium nitrate vi. Mithramycin vii. Thiazide diuretics.
Q.4. What are the therapeutic uses of calcium? Calcium is used in: ·i. Tetanus ii. Dietary supplement iii. Antacids iv. Empirically in paraesthesia weakness, vague complains.
Q.5. Why parathormone is not used in tetanus? It is not used in tetanus because it quickly produces antibodies to it making it ineffective and the same function can be done by vit D. It is only used therapeutically to differentiate true from pseudohypoparathyroidism.
Q.6. What are the therapeutic uses of calcitonin? Produced by parathyroid, parafollicular C cells of thyroid used therapeutically for: i. Hypercalcemic slate (Hyperparathyroidism, Hyper Vit D; osteolytic bone metastasis. ii. Postmenopausal osteoporosis iii. Paget's disease
Q. 7. What are the therapeutic uses of Vit. D? They are used for: 1.
Prophylaxis
ii. Metabolic rickets (Vit D-resistant; vit D dependant, Renal rickets) iii. Senile postmenopausal osteoporosis iv. Hypoparathyroidism v. Fanconi syndrome
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vi. Nonhypercalcaemic analogue of vit
D
like calcipotriol
tried locally psoriasis and systematically for skin cancer and immunological disorders.
Q.8.
Can vit D be considered as hormone?
Yes, it can be considered as hormone because: i. It is synthesized by specific tissues, skin ii. Transported by blood and acts through specific receptors iii. Feedback regulation of Vit
D
activation occurs through
plasma Ca2+ level.
Q.
9. How Vit D is activated?
In man Vit D2 and form of
D3)
D3
are equally active. Calcitriol (active
is important physiologically 25-0H
D3
is
released in blood from liver and binds loosely to specific D binding globulins. Finally it is hydroxylated in kidney induced by calcium, Vit
D
deficiency and PTH. Oestrogen prolactin
and inhibited by calcitriol.
Q.lO.
What are the therapeutic uses of Bisphosphonates?
Biophosphonates
(Etidronate
Na;
Pamidronate
Na,
Alendronate) are bisphosphonates used in: i. Paget's disease ii. Osteolytic bone metastasis m.
Hypercalcemia of malignancy
iv. Osteoporosis
ANABOLIC STEROIDS Q.l.
What are anabolic steroids?
These are synthetic androgens with higher anabolic and lower androgenic activities.
Q.2.
Name some anabolic steroids?
These are Methandienone, Nandrolone phenyl propionate, Nandrolone decanoate, Oxymetholone, Oxandrolone, Ethylestrenol, Stanozol
Q.3.
What are the therapeutic uses of anabolic steroids?
They are used for: i. Osteoporosis
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115
Catabolic states llike illness, trauma, surgery
iii. Renal insufficiency iv. To counteract glucocorticoids v. Suboptimal growth in children vi. Aplastic haemolytic, renal failure or malignancy associated anaemia vii. To enhance physical ability in athletes (included in dope test).
Q.4. What are the therapeutic uses of antiandrogens? Danazol is orally active ethisterone with mild androgenic, anabolic and progatational activity used for: i. Endometriosis ii. Menorrhagia iii. Fibrocystic breast disease iv. Hereditary angioneurotic oedema· v. Gynaecomastia vi. Infertility vii. Precocious puberty in boy. Danazol suppresses Gonadotropin secretion from pituitary in both men and women leading to inhibition of testicular and ovarian function.
Q.5. What are the therapeutic conditions where cyproterone acetate may be tried? It is a potent antiandrogen which competes with dihyro sterone for intracellular androgen receptor and inhibits its binding. It has mild progesterone activity. They are tried for: i. Precocious puberty in boy ii. Inappropriate sexual behavour iii. Male type baldness iv. Hirsutism and virilization iv. Acne v. Carcinoma of prostate.
Q.6. Name the therapeutic condition where flutamide is indicated? Flutamide is a nonsteroidal drug with antiandrogenic effect used as pallative in advanced prostatic carcinoma.
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Q.7.
Viva Voce iri Medical Pharmacology What is the mechanism of action1of fenastride?
It is competitive inhibitor of S-a-reductase which converts testosterone to active dihyrotestosterone selectively present in male urogenital tract decreases prostratic size.
ANDROGENS Q.l.
What is androgens?
Androgen produces secondary sex characters in castrated male. The natural androgens are testosterone and dihyro testosterone.
Q.2.
What is mechanism of action of testosterone?
Testosterone is prohormone converted to dihydrotesto sterone which combines with cytoplasmic receptor. After combining with receptors DNA transcription is enhanced and expressed as modification of protein synthesis.
Q.3.
What are functions of androgens?
Actions of androgens are mediated by Testosterone-LH inhibition, spermatogenesis, development of epididymis,vas deferens, seminal vesicle, skeletal and muscular growth. Dihydrotestosterones are engaged in scrotum formation, penis, male urethra, sexual maturity, male behaviour, skeletal and muscular growth.
Q.4.
What are the adverse effects of Androgens?
These are virilization, menstrual irregularities in female. Acne in male and female, frequent sustained painful erection, oligozoospermia, precocious puberty and early closure of epiphysis, oedema, cholestatic jaundice, hepatic carcinoma, gynaecomastia.
Q.S.
What are the therapeutic uses of Androgens?
They are used for: 1.
Testicular failure
ii. Hypopituitarism iii. Carcinoma of breast iv. Menopausal syndrome v. Hereditary angioneurotic oedema.
Endocrine System
Q.6.
117
What are the contraindications of Androgens?
They are contra-indicated in carcinoma of breast in male and carcinoma prostate. In liver and kidney diseases and during pregnancy. They sould be used with caution in patient with CCF, Epilepsy, migraine.
Q.
7. Why testosterone is inactive orally?
They are inactive orally because of high first pass metabolism in liver. Methyl testosterone is given sublingual.
OESTROGENS Q.l.
What are the sources of oestrogens?
The substances which can induce oestrous in animal is called oestrogen. In human being oestradiol is the major oestrogen secreted by ovary.It is synthesized in graafian follicles, corpus luteum, placenta.
Q.2.
Name some synthetic oestrogens.
Natural oestrogens are orally inactive and have shorter duration of action where as synthetic oestrogens are not. Synthetic oestrogens are: i. Steroidal-Ethinylestradiol, Mestranol, Tibolone ii. Nonsteroidal-Diethylstilbestrol, used orally; Hexestrol, Dienestrol used topically.
Q.3.
What is the mechanism of action of oestrogen?
Oestrogen binds to cytoplasmic receptors in target cells and via nucleus regulates protein synthesis.
Q.4.
Mention some actions of oestrogens.
Oestrogen bring the changes of uterus, fallopian tubes and vagina.
Vagina are cornified. It
increases rhythmic
contractions of fallopian tubes, uterus and induce watery secretion from cervix. It helps development of breast, pubic and axillary hair, feminine body contour. It decreases LDl, increases HDL. Blood coagulability is increased, mild salt and water retention.
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Q.5. What adverse effect oestrogen can produce?
They suppress libido, gynecomastia in males when given for Ca prostrate. Fusion of epiphysis and reduction of adult stature if given for test of pregnancy, stilboestrol increases incidence of vaginal and cervical carcinoma. In post menopausal women increases risk of endometrial carcinoma, prolong use increases chances of gallstone, benign hepatoma, migraine and endometriosis is worsened. Q.6. What are therapeutic indications of oestrogen?
The oestrogen are prepared for: i. Hormone replacement therapy ii. Senile vaginitis iii. Delayed puberty in girls iv. Dysmenorrhoea v. Acne vi. Hirsutism vii. DUB viii. Suppression of lactation ix) Carcinoma of prostrate Q.7. What is transdermal oestradiol?
Transdermal patch (oestradiol TTS) is available in sizes 5,10, 20 cm2 delivering 0.02Smg, O.Smg, O.lmg in 24 hours used to treat menopausal syndrome. Q.S. What is Clomiphene citrate?
It induces Gn secretion in women by blocking oestrogenic feedback inhibition of pituitary. The amount of LH/FSH released is increased. It is used to treat sterility concurrent use with HCG increases success rate; also used to aid in vitro fertilization. In male is is used to treat oligospermia. Q.9. What are the uses of tamoxifen?
Tamoxifen is chemically related to clomiphene with oestrogen and antioestrogen activity used for adjunct therapy after mastectomy in breast .cancer patient. It is also used for male infertility.
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PROGESTERONE Q.l. What is the function of progestins in broad sense? Progestins convert oestrogen primed endometrium to secretory phase to maintain pregnancy (Progestin =i.e. which favours gestin i.e. pregnancy).
Q.2. What is the mechanism of action of progesterone? Progesterone acts on specific receptors in target cells (female genital tract, breast, CNS and pituitary) which is translocated to the nucleus causing RNA transcription and regulates protein synthesis.
Q.3. What are the therapeutic uses of progesterone? Progesterone preparations are used for: i. Contraceptive ii. Replacement therapy in postmenopausal women iii. DUB iv. Endometriosis v. Pre-menstrual tension vi. Threatened abortion and habitual abortion vii. Palliative to advanced metastatic endometrial carcinoma.
Q.4. What are the adverse effects may arise out of progesterone therapy? The progesterone may produce following adverse effects: Breast engorgement, headache, rise of body temperature, irregular bleeding or amenorrhoea, Lower LDL blood sugar may arise, may produce masculinisation of female foetus with congenital abnormalities.
Q.S. What is Mifepristone? Mifepristone is potent competitive antiprogestational and antiglucocorticoids given during follicular phase. It causes attenuation of midcycle Gn surge from pituitary slowing follicular development and delay and failure of ovulation. It is partial agonist of progesterone. It is used for: i. Termination of pregnancy ii. Contragestational
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iii. Tq induce labour by antagonising relaxing effect proges terone iv. In inoperable Cushing syndrome because of antigluco corticoid activity.
CONTRACEPTIVES Q.l.
What is a contraceptive?
These are hormonal preparation which produces reversable suppression of fertility.
Q.2. What are the different methods of female contraception? The female contraception can be acheived by the following methods: i. Oral (Cortunonest)-Combined pill, sequential pills, mini pills, poscoital pills, phased regimen. ii. Injectable iii. Implants
Q.3.
What are combined pills?
It contains oestrogen and progesterone.
Q.4.
What are sequential pills?
This OCP contains oestrogen in 1st 15 days then progesterone for next 15 days.
Q.S.
What is phased regimen?
In this OCP the dose of oestrogen is kept constant, amount of progesterone is low in 1st phase and progressively higher in second and third phase, recommended for women over 35 years of age to avoid other risk factors.
Q.6.
What are minipills?
These are low dose progesterone only pills.
Q.7.
What are postcoital pills (Yuzpe's method), where they
are used?
These are used for unprotected pregnancy where levonor gestrol 0.5 mg
+
Ethinyloestradiol 0.1 mg (OVRAL 2 tab) are
taken within 72 hours, preferably within 12 hours.
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121
Q.S. Name some injectable preparations of contraceptive? Two compounds are available in market: i. Depot medroxyprogesterone acetate (DMP A) 150-400 at 3-6 months interval ii. Norethinidrone enanthate (NEE) 200mg at 2-3 months interval.
Q.9. Name some implants. Implants are drug delivery system implanted under skin from which steroids are released gradually. The nonbiodegradable implants have to be removed on expiry. Norplant a set of 6 capsules each containing levonorgestrol (total 216 mg) available for implantation in USA and some countries, works upto 5 years. Progestasert, is impregnated intrauterine insert with less quantities
of
progesterone,
act
primarly
locally
or
endometrium.
Q.lO. How does OCP act? i. They reinforce normal feedback inhibition of gona dotropin release (by progesterone), so ovulation does not occur. ii. Progesterone makes the cervical secretion thick and hostile to sperm penetration. iii. Postcoital pile inhibits implantation. iv. They modify uterine and tubular contraction, which is unfavourable for fertilization.
Q.ll. Mention some adverse effects of OCP. i. Nonserious side effects: Nausea, vomiting, morning sickness, headache migraine, breast discomfort, break through bleeding. ii. Late side effects: Weight gain, chloasma, Pruritis, valve, swinging mood, carbohydrate intolerance. iii. Serious complications: Leg vein and pulmonary thrombosis, cerebral and coronary trombosis, rise in BP, Genital carcinoma, benign hepatoma, gallstone.
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Q.12. How the OCP increases the risk of different thrombotic
manifestations?
The i. ii. iii. iv.
OCP Increases blood clotting factors Decreases antithrombin III Decreases plasminogen activator in endothellium Increases platelet aggregation.
Q.13. What are the contraindications of OCP?
i. ii. iii. iv. v. vi. vii. viii. ix. x.
Diabetes Obesity Smoking Undiagnosed vaginal bleeding Fibroid Age above 35 Mentally ill Migraine Gallstones Hypertension.
Absolute contraindications
i. Thromboembolic coronary CVA ii. iii. iv. v.
Hypertension Hyperlipidemia Liver disease of history of jaundice in past Porphyria
vi. Suspected malignancy in breast and genital tract vii. Before surgery to avoid thromboembolism. Q.14. What are the other benefi t s of OCP apart from
prevention of unwanted pregnancy?
i. Lower chances of endometrial and ovarian carcinoma ii. Reduces menstrual blood loss and prevents anaemia iii. PID and endometriosis is improved iv. Reduces incidence of fibrocystic breast diseases. Q.15. What is centchroman?
It is nonsteroidal oestrogen antagonist developed at CDRI act as anti-implantation has long plasma t/2 dose given 30 mg biweekly for 3 months then weekly marketed as Saheli or Centron.
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123
Q.16. What is gossypol? It is nonsteroidal compound, obtained from cotton seeds suppresses spermatogenesis infertility develops after couple of months and fertility returns after several months.
Q.17. What is Oxytocis; Ecbolics, Abortifacients? Name some oxytocics. The drug which increases uterine motility, at term of pregnancy is called oxytocin, ecbolics, abortifaciants. These are i. Posterior pituitary hormone, oxytocin; ii. Ergot alkaloids, Ergometrine, Methyl ergometrin iii. Prostaglandins PGE2; PGF2a; Misoprostol iv. Ethacridine, Quinine
Q.18. What is Tocolytics? Name som.e tocolytics. The drug which relaxes uterus is called tocolytics: These are: i. Adrenergic agonist (Ritodrine, Salbutamol, Terbutaline, Isosuprine. ii. Magnesium sulfate iii. Calcium Channel blockers iv. PG inhibitors v. LV. Ethyl alcohol vi. Progesterone vii. Nitrate, diazoxide, anticholinergic general anaesthetics, phenothiazines.
Q.19. Mention some t.J.Ses of oxytocin? They are used for: i. Induction of labour ii. Uterine intertia iii. PPH iv. Caesariai\ section v. Abortion vi. Breast engorgement vii. To determine utero-placental adequacy by oxytocin challenge test.
Antimalarial Drugs Q.l. N�me the drugs used in malaria. The drugs effective against malaria are: i. 4 Aminoquinolines: Chloroquine, Amodiaquine ii. Quinoline: Mefloquine iii. Acridine: Mepacrine iv. Cinchona alkaloid-Quinine v. Biguanides-Prognanil (Chloroguanides) vi. Diaminopyrimidines Pyramethamine, Trimethoprim vii. 8 Aminoquinolines-Primaquine viii. Sulfonamides
sulfadoxines,
sulfamethopyrazines,
Dapsones ix. Tetracyclines and Doxycycline x. Quinghaosin derivates: Artamismin, Halofantrine
Q.2. What is the causative parasite of malaria? Malaria is caused by protozoal parasite Plasmodium vivax, P. falciparum, P. Ovale, P. malariae. Q.3. What is the principle of treatment of malaria? The objectives of use of antimalarial drugs are: i. To prevent and treat malaria ii. To prevent recurrence iii. To reduce reservoir to cut down transmission.
Q.4. What is causal prophylaxis? Name the drugs used for causal prophylaxis.
The pre-erythrocytic phase in liver causing malarial infection and clinical attack are the target. Drugs used are i. Primaquine for all species ii. Chloroguanide for P. falciparum
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125
Q.S. What is suppressive prophylaxis? The drug which suppresses erythrocytic phase and the schizontocides are suppressive l:'rophylactic agents. They do not have effect on exo-erythrocytic phase. The drugs are: i. Chloroquine ii. Chloroguamide iii. Pyrimethamine iv. Mefloquine
Q.6. What are the drugs used to treat erythrocytic schizon tocides?
The drugs which cause clinical cure are: i. Chloroquine, Mepacrine, Quinine, Mefloquine, Halo fantrine, Artemisimin (quick acting) ii. Pyrimethamine, sulfonamides, tetracyclines, chloro guanides slow acting. For chloroquine resistance: i. Mefloquine ii. Quinine iii. Pyrimethamine iv. Sulfonamide v. Doxycycline vi. Artesunate oral of I.V.
Q.7. Name the drug for radical cure. Drug effective against clinical phase and exoerythrocytic phase is called radical cure agent for falciparum; For P. vivax and P.
oval these drug are: i. Primaquine since P. Jalciparum does not have exoerythrocytic phase there is no extraradical cure for it.
Q.B. Name the gametocidal drug for malaria. Gametocidal drug reduces transmission of plasmodium. Primequine is classical gametocidal to all species of plasmodium. Chloroquine and quinine are effective for P. vivax but not for P. Jalciparum. Gametes exposed to chloroguanide or pyrimethamine fails to carry life cycle in mosquitoes.
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Q.9.Name the drug used for suppressive cure. Pyrimethamine and chloroquine are used for the purpose of suppressive therapy. Q.lO. What are the uses of chloroquine? It is used for: i. Malaria ii. Extraintestinal amoebiasis iii. Rheumatoid arthritis iv. DLE v. Lepra reaction vi. Photogenic reaction vii. Infectious mononucleosis Q.ll. What is the mechanism of action of chloroquine as anti-malarials? Exact mechanism of action of chloroquine is not known. It is concentrated in sensitive intra-erythrocytic plasmodia raises the vesicular pH and thereby interferes with degradation of haemoglobin by para.:;itic lysosomes. Nontoxic haemozin formation is inhibited from toxic haem. Haem then damages the plasmodial membrane.
·
Q.12. What is the dose of chloroquine for clinical cure? Chloroquine 600 mg stat; 300 mg after 8 hrs; and 300 daily for next 2 days. Q.13. Mention some of the ADR of chloroquine? ADR of chloroquine are
i. Nausea ii. Vomiting, anorexia, epigastric pain, on parenteral administration hypotension, depression, arrhythmia, prolong use may produce retinal damage, corneal deposit, loss of hearing, rashes, photoallergy, mental disturbances, graying of hair, mental disturbances, Q.14. What is the use of mefloquine? What will happen it is given with halofant�ine or quinine? Can it be given in pregnancy? It is used for multidrug resistance malaria and to traveller travelling multidrug resistant multidrug resistant malaria or prophylaxis.
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127
It may produce cardiac arrest in patient receiving quinine or Halofantrine due to QTc prolongation. It should be avoided in 1st trimester of pregnancy.
Q.15.
What are the therapeutic uses of quinine?
Quinine is erythrocytic schizontocide of all species of malaria less effective but more toxic. It is used for: i. Resistant falciparum malaria ii. Cerebral malaria iii. Nocturnal muscle cramp and myotonia congenita iv. Diagnosis of myasthenia gravis v. Spermicidal vaginal cream vi. With urathine it is injected to varicose vein to cause thrombosis and fibrosis.
Q.16.
What is the use of Halofantrine?
It is phenanthrene methanol, comparable to mefloquine acts as schizontocide acts against P.Vivax and P. malaria.
Q.17.
What is the mechanism of action of Artemisimin
derivative?
Obtained from Chinese traditional plant Artemisia annua, 'Quinghaosu'. The endo peroxide bridge interact with haem in parasite. Iron cleavage releases a highly reactive free radicals which binds to membrane proteins causing lipid peroxidation, damage of endoplasmic reticulum inhibits protein synthesis and lysis of parasite.
Antiamoebic Drugs Q.l. What is the causative parasite of amoebiasis? Amoebiasis is caused by protozoa Entamoeba histolytica.
Q.2. Name the drugs used to treat amoebiasis. The drug used to treat amoebiasis can be classified into: i. Tissue amoebiasis used both for intestinal and extra intestinal amoebiasis, Nitroimidazoles; (Metronidazole, Tinidazole, Secnidazole) Alkaloids; Emetine, Dihydro emetine used for extraintestinal amoebiasis, chloroquine ii. Luminal amoebicidal-Diloxanide furuate, Quinidochlor, Di iodohyroxyquin, Tetracycline
Q.3. What is the mechanism of act!on of metronidazole? The exact mechanism is not known. It after entering the micro organism by diffusion, its nitro group is reduced to inter mediate compounds causing cell damage by damaging DNA. It is active against anaerobic organism probably by interfering electron transport chain from NADPH. It causes mutagenesis, radio-sensitization and inhibit cell mediated immunity.
Q.4. What are the differenttherapeutic uses of metronidazole? It is used for i. Amoebiasis ii. Giardiasis iii. Trichomonas vaginitis iv. Anaerobic infection v. Pseudo-membranous enterocolitis vi. Uterative gingivitis vii. Peptic ulcer due to H. pylori viii. Nitridazole is drug of choice for Guinea worm infection.
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129
Q.6. What are toxicities of Emetine?
Emetine is highly toxic drug, it produces nausea, vomiting, abdominal cramp, diarrhoea, weakness, stiffness of muscle, hypotension, tachycardia myocarditis, ECG changes. It shoud not be used in patient of heart, kidney or in pregnancy. Q.7. Why chloroquine is effective in hepatic amoebiasis?
Chloroquine is not effective in intestinal amoebiasis and cyst passers, since it is highly concentrated in liver, so it is effective in hepatic amoebiasis. Q.S. Name the antiamoebic drug used for cyst passers?
Diloxanide furoate kills the trophozoite responsible for cyst formation. It does not have any action on amoebic dysentry. Q.9. Name the therapeutic uses of 8-hydroxyquinolines?
These group
of
drugs
are
effective against fungus
(dermatophytes}, Entamoeba, Giardia, Trichomonas, some bacteria. Q.lO. What is SMON?
Prolonged use of high doses of quiniodochlor causes neuropathy with visual impairment called subacute myelo optic neuropathy (SMON). Q.ll. What is the mechanism of action of Tetracycline?
The antibiotics (Tetracycline Paramomycin) not well absorbed systematically inhibits intestinal bacterial flora, with which entamoeba live symbiotically. They ate not effective for acute dysentery and hepatic amoebiasis. Q.12. Name the drugs used for Giardiasis?
Giardiqsis caused by flagellated protozoa Giardiac lamblia can be treated by: i. Metronidazole ii. Mepacrine iii. Quinodochlor iv. Furazolidine Q.13. Name the drug useds for Trichomoniasis.
Trichomoniasis is caused by Trichomonas vaginalis a flagellate protozoa can be treated by:
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Viva Voce in Medical Pharmacology
i. Drug given orally: Metronidazole group (Metrinidazole, Nimorazole, Tinidazole, Secnidazole ii. Used per vaginally-Quiniodochlor, Diiodohydroxyquina, Clotrimazole, Hamycin, Natamycin, Povidone iodine
Q.14. Name the drugs used for Leishmaniasis? Leishmaniasis caused by Leishmania donovani produces Kala-azar. Drugs effective are: i. Antimonial (Sodium slibogluconate; Meglumine antimonate ii. Pentamidine iii. Amphotericin B iv. Ketoconazole v. Allopurinol
Q.15. Name the drugs used for Dermal Leishmanias. The drugs used are: i. Sodium stibogluconate ii. Mepacrine iii. Ketoconazole
Q.16. Mention the therapeutic uses of Pentamidine. Pentamidine is used for 1.
Kala-azar
ii. Pneumocystis carinii pneumonia in AIDS iii. Trypanosomiasis if CNS is involved.
Antihelmintic Drugs Q.l. What is vermicide and vermifuge? Antih�lmintics which kill the intestinal parasite are called . vermicide and which expel are called vermifuge. Q;2. Mention the therapeutic uses of Mebendazole. Mebendazole is broad spectrum antihelmintics used for round worm, hookworm, Trichuris, Enterobius, Tapeworm, Trichinella, Hydatid cyst. Q.3. What are the uses and adverse effect of piperazine? Piperazine is used for roundworm and enterobiasis. It may produce nausea, vomiting, abdominal discomfort, urticaria Q.4. What are the uses of Levamisole? Levamisole is used to treat ascaris infestation. It restores depressed T-cell function tried for rheumatoid arthritis, adjunct to malignancies, aphthous ulcer. Q.S. What are the uses of Diethyl carbamazine? DEC is effective against i. Filariasis ii. Tropical eosinophilia, Ascariasis, Loa-loa, Onchocerca volvulus. Q.6. What are the therapeutic uses of Invermectin? Invermectin obtained from streptomyces overmitis is drug of choice of O.volvulus. May be used for W. bancrofti, B. Malayi, Ascaris, Enterobius, Trichuris.
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Q.7. What are the therapeutic uses of Niclosamide?
It is highly effective drug for T.
saginata, T. solium, Diphyllobothrium latum, Hymenoepis nana. Q.S. Name the drug of choice of guineaworm.
Nitridazole is drug of choice for guinea worm which has also effect on schiotosomes, entamoeba, anaebiotic bacteria. It possess anti-inflammatory property. Q.9. What are the therapeutic uses of Praziquantel?
It is used for i. Tapeworm (T. saginata, T. solium, D .latum, H.nana) N eurocysticercosis iii. Schistosoma iv. Fasciola hepatica
Anticancer Drugs Q.l. Mention the general toxicities of cytotoxic drugs? The cytotoxic drugs are one of the toxic group of drugs which have adverse effects on rapidly multiplying cells: i. Bone marrow-Depression agranulocytosis, aplastic anaemia, thrombocytopenia ii. Lymphocytopeniaiii. G.I.T.-Shedding of mucosa, stomatitis i v. Skin-alopecia v. Gonadal
inhibition
and
damage
foetal
growth,
tetratogenesis vi. Secondary cancers, leukemia lymphoma vii. H yperuricaemia Q.2. Name some cytotoxic drugs? The cytotoxic drugs may be classified as follows: i. Alkylating agenta.
Nitrogen mustards (Mechorethamine, Cyclophosphamides, Ifosfamide, Chlorambucil, Melphalan)
b.
Ethylenimine (Thio TEPA);
c.
Alkyl sulfonate (Busulfan)
d.
Nitrosourea (Carmustine, Lomustine)
e.
Triazine (Dacarbazine)
ii. Antimetabolite: a.
Folate antagonist (Methotrexate)
b.
Purine antagonist (6MP; 6TG; Azathioprine)
c.
Pyrimidine antagonist-SFU; Florafur, Cytarabin
iii. Vinca Alkaloids-Vincristine, Vinblastin iv. Taxanes-Paclitaxels; Docetaxel v. Epipodophyllotixin-Etopoxide
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vi. Antibiotics-Actinomycin D; Doxorubicin, Daunorubicin; Mitroxantrone, Bleomycin, Mitomycin C;-Mithramycin. vii. Miscellaneous: Hydroxyurea, Procarbazine, L-Asparaginase, Cisplatin, Carboplatin viii. Hormones: a.
Glucocorticoids (Prednisolone)
b.
Oestrogen (Diethylstilbesterol, Ethinylestradiol)
c.
Antioestrogen Tomoxifen
d.
Androgen (Testesterone, Fluoxymesterone)
e.
Progesterone
(Hydroxy progesterone acetate,
Medroxyprogesterone acetate) -
Q.3. Why it is difficult to treat cancer by chemotherapy? i. The malignant cells are infact hQst cells (not like bacterial cells) with very little differences. ii. The bacterial organisms are rejected by body's own defence mechanism whereas cancer cells are body's own cells, not rejected by the body.
Q.4. What are the different phases of cell cycle? A proliferating cells enter cell cycle has different phases. Gl phase (Prenucleic acid synthesis interval synthesis of DNA occurs
�
�
S phase where
G2 phase Postsynthetic interval
M phase where mitosis occurs, which either enter next
�
cycle or pass into nonproliferative GO phase of resting.
Q.5. What do you mean by cell cycle specific and cell cycle nonspecific cytotoxic drug? Name some cell cycle specific and cell cycle nonspecific drug. Cell cycle specific kills only actively dividing cells, for e.g. Gl
=
Vinblastine; S
=
Methotrexate, 6MP, Mitomycine C;
Doxyrubicin G2 M
=
=
Daunorubicin; Bleomycin
Vincristine, Paclitaxel.
Cell cycle nonspecific cytotoxic drug kills resting and dividing cells like nitrogen mustard, cyclophosphamide, chlorambucil, cisplatin, etc.
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135
Q.6. How to reduce the toxicities of anti cancer drugs?
The toxicities of anticancer drug to a some extent are blocked by: a. Methotrexate toxicity can be reduced by folinic acid b. Cystitis caused by cyclophosphamide can be blocked by mesna or bladder irrigation with acetyl cystine c. Vomiting produced by cytotoxic drug is tackled by ondansetron d. Lithium carbonate stimulated bone marrow e. Hyperuricaemia can be treated by allopurinol f.
Reducing toxicities by intra-arterial infusion
g. Bone _marrow transplantation h. Granulocyte or platelet transfusion to prevent bleeding and infection. Q.7. What is the mechanism of action of alkylating agents?
Alkylating agents are radio-mimetic like cytotoxic action. They produce highly reactive carbonium ion intermediate which transfers alkyl groups to cellular macromolecules by forming co-valent bonds. The position 7 of guanine residues are susceptible resulting in cross-linking, base pairing and scission of DNA strand. Q.B. What is the mechanism of action of Dacarbazine?
This alkylating agent inhibits RNA and protein synthesis used to treat malignant melanoma. Q.9. What is the major side effect of Busulfan?
Major side effect is hyperuricaemia and pulmonary fibrosis. Q.lO. What is the mechanism of action of Vinca alkaloids?
The vinca alkaloids binds to microtubular protein, tubulin prevents its polymerization and assembly of microtubules causing disruption of mitotic spindle, chromosome fail to separate and mitosis is arrested in metaphase. Q.ll. Name the chemotherapeutic agents used to treat
meningial leukemia, brain tumour.
Lipid soluble alkylating agent crosses blood-brain barrier effective for meningea1 leukemia, brain tumour e.g. Carmustine, Lomustine.
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Q.12. What is the mechanism of action of Etoposide?
Etoposide is plant glycoside, arrest cells in G2 phase, stimu lates DNA topoisomerase II and breaks it. It is used to treat testicular tumour, Hodgkin's lymphoma, carcinoma bladder. Q.13. Name the anti cancer drug which can produce cardio toxicity?
Daunorubicin and doxorubicin antibiotics anticancer drug activate topoisomerase II, breaks DNA. This group of drug produces cardiotoxicities like arrhythmia, hypotension, failure of heart, etc. Q.14. What is the mechanism of procarbazine?
It is used for Hodgkin and Non-Hodgkin lymphoma. It is pro-drug after activation polymerizes DNA and its damage. Q.lS. What is the mechanism of action of L-asparaginase?
L-asparaginase degrades L-asparagine to L-aspartic acid. L asparagine is essential for metabolite for leukemic cells. Q.16. What is the mechanism of action of cisplastin? Where it is used? Mention its important adverse effects.
i. It cross links DNA ii. Reacts with -SH groups in proteins iii. Radioemmetics Effective in metastatic testicular and ovarian carcinoma. Renal impairment and vomiting, deafness, neuropathy, gout are common adverse effects. Q.17. Name some tumours treated by oestrogen.
Carcinoma prostrate and carcirioma of male breast are used to treat palliatively with oestrogen. Q.18. Name the cancer palliatively treated by Tamoxifen.
Oestrogen receptor containing breast cancer (Pre- and post menopausal women) responds to tamoxifen the antioestrogen. Q.19. Indications of androgen as anticancer.
Secondary palliative measures in premenopausal carcinoma after using tamoxifen. Q.20. Indication of progestin as anticancer.
Progestin gives temporary remission in metastatic endometrial carcinoma after surgery and radiotherapy.
Drugs Acting on Skin and Mucous Membrane Q.l. What are demulcents? Name some demulcents. These are inert substances which smooth inflamed/ denuded mucosa or skin, prevent their contact with air, irritants.. Generally they are high molecular weight substances applied on viscid colloidal solution viz. Gum acacia, Glycyrrhiza, Methyl cellulose, Glycerine, Propylene glycoL Q.2. What are emollients? These are bland oily substances smooth and soften skin, prevents evaporation, restores elasticity, viz. Olive oil, linseed oil, cocoa butter, arachis oil, wood fat, wax, spermacetic, paraffin, etc.
Q.3. What are astringents? Astringents are substances that precipitate protein without penetrating cells; decreases exudation viz: i. Tannic acid ii. Alcohol iii. Min�ral astringents Al (OH)3, ZnO etc.
Q.4. What are the uses of tannic acids? They denature protein forming protein tannate used for bleeding gum, bleeding piles, alkaloidal poisoning.
Q.S. What is adsorbants? These are finely powdered inert, insoluble solids binds noxious irritant substances to their surface. They are also called protectives act as: i. Dermoprotective-Magnesium stearate, Zn stearate, Calamine, ZnO, Bentonite, Starch, Boric acid ii. Occlusive protective-Collodion, Dimethicone
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Viva Voce in Medical Pharmacology
Q.6. What is irritant?
Irritants stimulate sensory nerve ending inducing inflam mation.
•
Q: 7. What is Rubefacients?
Irritants causing local hyperemia with little sensory changes is called rubefacient. Stronger irritants increase capillary permeability and collection of fluids under skin called vesicants. Certain irritants relieve pain in deeper tissues called counter irritants. Q.S. Name some counter irritants.
These are Terpentine oil, Clove oil, Eucalyptus oil, Camphor, Thymol, Menthol, Mustard seeds, _capsicum, Canthridine, Methyl salicylate, Alcohol. Q.9. What are caustics? Name some caustics.
The chemicals causing local tissue destruction and sloughing are called caustics viz: Podophyllium resin, Silver nitrate, phenol, Trichloroacetic acid, Glacial acetic acid. Caustics which cause corrosion with added precipitation of protein are called escharotic. Q.lO. Define keratolytics.
The drugs which dissolve the intracellular substance in horny layer of skin. The epidermal cells sweel, soften and desquamate used for corn, wart, psoriasis, chronic dermatitis viz.: Salicylic acid, Resorcinol, Benzoic acid Q.11. Name some Antiseborrheics?
These are selenium sulfide, Zinc pyrithion corticosteroids. Imidazole antifungals, sulfur, Resocinol, coal tar, amoniated mercury, salicylic acid. Q.12. What is melanizing agents?
The melanizing agents increase the sensitivity of vitiliginous skin to solar radiation and promote repigmentation viz. Psoralen, methoxalen
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139
Q.13.Name some demelanizing agents.
They l ighten up hyperpigmented patches on skin v iz. Hydroquinone, Monobenzone, Azelaic acid. Q.14. Name some sunscreens.
Sunscreens protect the skin from harmful exposure of sunlights. Some chemical sunscreens are-Paraamino benzoic acid, Benzophenone (Oxybenzone) cinnamates. Physical sunscreens: Petroleum jelly, ZnO, Titanium dioxide.
Chloroquine should be reserved for severe cases only. Q.lS. What are the indications for topical steroids? Name some topical steroids.
Atopic eczema, allergic dermatitis, lichen simplex, seborrheic dermatitis, psoriasis, varicose eczema, cystic acne, DLE, Alopecia areata, lichen planus. Topical steroids: Mild: Hydrocortisone acetate, Dexamethasone, Moderate,
Fluocinolone, Clobetasol, Flucortolone. Potent:
Beclomethasone
dipropionate,
Halcinonide,
Triamcinolone acetonide. Q.16. What are the adverse effects of topical steroids?
Local thinning of epidermis, atrophy, telangiectasia, easy bruising, Hypopigmentation, delayed wound healing fungal and bacterial infection. Systematic ADR of topical steroids: Rarely adrenal suppression, Cushing syndrome.
·
Sexually Transmitted Disease Q.l. Name some STD diseases and their causative ag ents. i. Syphilis: Treponema pallidum
ii. Gonorrhoea-Niesseria gonorrhoe iii. Chancroid-Haemophilus ducreyi iv. Granuloma inguinale-Calymmatobacterium granulomatis v. vi. vii. viii. ix. x. xi.
Lymphogranuloma venereum-Chlamydia trichomatis Herpes genetales-Herpe simplex virus AIDS-Human Immune Deficiency virus Hepatitis B-Hepatitis B virus Trachomoniasis-Trachomonis vaginalis Candidiasis-Candida albicans Scabies-Sarcoptes scarbie
xii. Pediculosis-Pthirus pubis Q. 2. How will you treat syphilis? Benzathine penicillin; Penicillin G or Procaine penicillin alternatively Doxycycline, Ceftriaxone, Erythromycin. Q.3. Drugs for Gonorrhoea. i. Amoxycillin or Ampicillin + Probenecid
ii. Ceftriaxone'or Cefuroxine
Alternatively: Cefixine, Doxycycline, Erythromycin, Ciproflo xacin, Ofloxacin Q.4. Mention treatement of chancroid?
Chancroid caused by H. ducrayi can be treated by Co trimoxazole, Erythromycin Alternatively Tetracycline, Ciprofloxacin,· Ceftriaxone.
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141
Q.S. Mention treatment of trichomates.
1st choice-Tetracycline, Doxycycline. Alternatively sulfamet hoxazole, erythromycin Q.6. Mention treatment of Granuloma inguinale?
1st choi ce-Doxycycline, Tetracycline. Alternatively Co trimoxazole, Erythromycin Q.7. Mention treatment for Trichomoniasis.
Metronidazole or Tinidazole for both partner alternatively co-trimazole 100 mg intravaginally. Q.S. Mention treatment for Herpes.
Acyclovir ointment or tab.
Antiseptic and Disinfe-ctants Q.l. What is antiseptic and disinfectant? Antiseptic inhibits or kills microbes on living surfaces whereas a disinfectant kills or inhibits on inanimate objects.
Q.2. What are the criteria of good antiseptics? Ans.A good antiseptic or disinfectants should be stable cheap, no staining, cidal in action, should be effective against (bacteria, fungus, protozoa, viruses, should be effective in presence of blood, pus, exudate and excreta, non-sensitizing, compatible with soap and other detergents, nonabsorbable. A disinfectant should not rust or corrode the instruments.
Q.3. How the potency of a germicide is expressed? One-of the index of expressing potency of germicide is Phenol co-efficient or Rediol walker co-efficient which is the ratio of the minimum concentration of test drug required to kill a 24 hours culture of B typhosa at 37.5C in 7.5 minute to that of phenol under similar condition.
Q.4. Name some antiseptics. i. Phenol-Phenol, Cresol, Resorcinol, Chloroxylenol ii. Oxidising agents-KMn04, H202 iii. Halogens-Iodine chlorine iv. Biguanide-Chlorexidine v. Quaternary amonium-Cetrimide, Benzalkonium vi. Soaps vii. Alcohol-Ethanol
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143
viii. Aldehyde-Formaldehyde, Glutaraldehyde ix. Metallic salts-Hg, AgN03' Silver sulfadiazine, Calamine, ZnO x. Dye-Acriflavine, Gentian violet xi. Furan derivative-Nitrofurazone Q.5. Name the drugs used for pediculosis. The drugs for pediculosis: i. Sulfur ii. Mesulphen iii. Benzyl benzoate iv. Crotamiton v. Gamma benzene hexachloride v1. Dicophane vii. Tetraethyl thiuram monosulphide.
Radioisotopes Q.l. Mention some therapeutic uses of radioisotopes? The isotopes have widespread role in diagnosis and treatment. In hematological system: They are used to measure blood vol., erythropoiesis B12 absorption studies. Clinical pathology: Studies on Na, K, H20, plasma protein estimation, calcium kinetics. C.V.S.-Cardiac out put, pulmonary and cerebral flow of blood studies by krypton. Thyroid uptake studies, Renal clearance by 1131 Na iodohippurate, radioimmunoassays. For therapy 1131-Thyrotoxicosis and thyroid cancer; P32-Polycythaemia, Yttrium 90-Hypophysectomy; Tantallum 182-Ca bladder.
Q.2. What are the properties of radio-isotopes? i. Penetrating ability ii. iii. iv. v. vi.
Radio active delay Ionization Photographic effect Calorigenic effect Photo electric effect (a-rays and X-rays, falling upon certain chemicals called phosphorus emits light flash used for fluoroscopy).
Q.3. What are the different rays emitted by radioactive elements? They emit a-ray (Helium particle); �-ray negligible mass, y ray electromagnetic waves.
Q.4. What is Curie? Curie is defined as 3.7 x 10 10 disintegrating nuclei per second. One curie
=
1000 millicurie.
Therapeutic Gases Q.l. What are the adverse reactions of oxygen administration? i. Respiratory system: 60% or more oxygen concentration damage pulmonary epithelium and surfactants may lead to atelectasis ii. CNS-Para-anesthesia, mental disturbances, convulsion iii. Carbon dioxide narcosis in patient of COPD weakness of respiratory
muscles
(Polio,
myasthenia,
narcotic
poisoning) iv. Fire hazard v. Retrolental fibroplasia. OXYGEN J.P. IS DISPENSED IN COMPRESSED STATE IN CYLINDERS PAINTED BLACK WITH WHITE SHOULDER.
Q.2. What is hyperbaric oxygen? What are its therapeutic uses? Oxygen administered higher than atmospheric pressure is called hyperbaric oxygen. It is used for: i. Respiratory disease of newborn ii. Carbon mono-oxide poisoning iii. Decompression sickness iv. Anaerobic infection v. Circulatory disturbances vi. Surgery
'
vii. Malignancy to make them radio sensitive.
Q.3. What are the therapeutic uses of C02? Name its different preparations. C02 is used for i. Respiratory depression
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ii. Carbon mono-oxide poisoning: C02 5% with oxygen stimulates respiration to wash out carbon mono-oxide iii. Hiccough 10-25% C02 is used to intractable hiccough iv. Used for anxiety neurosis and personality disorders, empirically v. Local use as snow (-80C) to destroy warts, naevi v1. To enhance speed of induction of anaesthesia vii. Terminate petit mal epilepsy viii. Supersaturated solution of C02 is rubefacient, increases gastric juice secretion. Preparation: i. C02I.P. marketed in steel cylinders painted gray in liquid form at 58-72 atmospheric pressure. ii. Carbogens cylinder mixed with oxygen iii. Solid C02 as dry air or snow.
Q.4. What are the therapeutic uses
of
Helium?
The inert gas helium is used intermittently to treat asthmatics ·
as they minimize breathing effort ii. Oedema and spasm of larynx iii. Caisson's disease.
Immunosuppressants and Gene Therapy Q.l. Name some immunosuppressants. The drugs which suppress himmoral and cellular immunity are called immunosuppressants. The drugs commonly employed as immunosuppressants are: i. T cell inhibitors-(Cyclosporine, Tacrolimus) ii. Cytotoxic drug-(Azathioprine, Cyclophosphamide, Methotrexate etc.) iii. Glucocorticoids: Prednisolone etc iv. Antibodies (Antithymocyte globulin, RhO immunoglobulin).
Q.2.Name some therapeutic uses of cyclosporine. It is second line drug for severe rheumatoid, arthritis, uveitis, bronchial asthma, inflammatory bowel disease, dermato myositis, psoriasis.
Q.3. Wh at is the m ain purpose of use of i m m un o suppressants. They are used mainly to avoid rejection in organ transplan tation.
Q.4. Name some of the applications of gene therapy. Gene therapy refers to introc!uction of functional genetic material into target cells to replace or supplement defective gene either by gene modification or gene trasfer (by physical, chemical or biological methods). Gene therapy may have scope in the following diseases: i. Cystic fibrosis
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ii. Growth hormone deficiency iii. Familial hypercholesteromia iv. Parkinsonism v. Alzheimer's disease ·
vi. Stroke, CVA by transfering nerve growth gene vii. Ducheune muscular dystrophy gene viii. Hypertension ix. Anaemia X.
HIV
xi. Malaria xii. Insulin dependant diabetes mellitus.
Vitamins Q.l. What are vitamins? Name them. Vitamins are exogenous essential substances required in very small amounts for various metabolic functions of the body. Some vitamins are also synthesized by intestinal bacterial flora such as Vit K, pantothenic acid, folic acid, cyanocobalamin. Vitamins are broadly classified into two groups: i. Fat soluble vitamins ii. Water soluble vitamins Fat soluble vitamins are A,D,E,K and Water soluble vitamins are B-complex and Vit. C
Q.2 What are the different water soluble vitamins of B complex group?
Different Vit B complex group includes thiamine, Riboflavin, nicotinic acid,pyridoxine, panthothenic acid, inositol,biotin, methionine, folic acid, cyanocobalamin.
Q.3. What are the therapeutic uses of nicotinic acid? It is used therapeutically for i. Pallegra ii. As vasodilator in Meniere's disease iii. To reduce cholesterol iv. Hartnap's disease.
Q.4. What are the therapeutic uses of pyridoxine? It is used to treat: i. Convulsion in children ii. Vomiting in pregnancy iii. Anaemia 1v. Radiation sickness
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v. Empirically in muscular dystrophies vi. Raynaud's disease vii. Peripheral neuritis of INH viii. Alcoholic neuritis ix. Optic neuritis following penicillamine x. Abnormal G.T. T. with OCP
Q.S. What are the therapeutic uses of calcium pantothenate? It is used in streptomycin toxicity, postoperative paralytic ileus, Rheumatoid arthritis, Topically used for dressing of burns, wounds, ulcers, graying of hairs.
Q.6. What are the therapeutic uses of Vit C? It is used to treat scurvy, methemoglobinemia, common cold, non pecific haemorrhagic states anaemia, dental infection.
Q.7. What are the manifestations of Vit A toxicity? The consumption of heavy doses of Vit A or liver of polar bear produces vitA toxicity. It produces: Anorexia, nausea, vomiting, pain, abdomen, headache, papilloedema, diplopia, convulsion, delirium, coma. Chronic vitA intoxication symptoms are dry skin, loss of weight, irritability, low grade fever, alopecia, oedema, erythema, ecchymosis, bleeding, fissuring, refractory skin ulcer, headache, visual upset, subcutaneous swelling, tenderness of long bones, premature closure of epiphysis.
Q.S. What are the therapeutic uses of Vit E? It is used empirically to treat sterility, myopathy.
Enzymes in Therapy Q. 1. What is enzyme? Enzymes are biological catalysts protein in nature which hasten or retard biological reaction. For systemic use, they have to be given parenterally.
Q.2. Name some enzymes, therapeutically used. The enzymes used therapeutically are: i. Pancreatin, diastase, pepsin, pepain in the treatment of certain gastro-intestinal disturbances. ii. Hyaluronidase: Used to promote rapid absorption of drug and fluids givenS I c or IM, also promote absorption of blood and fluid in traumatic oedema. iii. Trypsin iv. Chymotrypsin available as tablet used as adjunct to treatment of traumatically induced inflammation, oedema of soft tissue. v. Alpha-chymotrypsin: Used in opthalmology for dissolving the suspensory ligaments of the lens in intracapsular extraction of lens. vi. Streptokinase: Obtained from � haemolytic streptococci group C. It is used topically into closed body cavities to liquify clotted blood,
haemothorax,
haematoma,
empyema, slowly intravenously for thrombolytic therapy. vii. Urokinase-Obtained from human urine. Used in those patients, earlier received streptokinase.
Chelating Agents Q.1. What are chelating agents? Name some chelating agents therapeutic importance.
These are drugs which produce complex metallic ring with metallic ions, used for heavy metal poisoning. Therapeutically useful chelating agents are: i. Dimercaprol (BAL) ii. Dimercaptosuccinic acid iii. Disodium edetate iv. Calcium disodium edetate v. Calcium disodium DTPA vi. Penicillamine vii. Desferrioxamine viii. Deferiprone
Q.2. What is BAL? What are its therapeutic uses? BAL stands forBritish Anti Lewisite, used in lind world war byBritishers as antidote of As. It is used in i. As, Hg, Au,Bi, Ni, Sb poisoning ii. With Calcium Disodium edetate in lead poisoning iii. With penicillamine in Cu poisoning.
Q. 3. Name the metals poisoning should not be treated with BAL.
The Fe and Cadmium poisoning should not be treated with BAL because FeB - AL; and Cd-BAL complex itself is toxic.
Q.4. Mention the therapeutic uses of Penicillamine? Penicillamine is dimethyl cysteine, degradation product of penicillin chelates copper mainly used for: i. Wilson's disease
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153
ii. Cu and Hg poisoning iii. Pb poisoning iv. Cystinuria v. Scleroderma vi. Rheumatoid arthritis. Q.S. What are the therapeutic uses of Desferrioxamine?
Ferrioxamine is long chain iron containing complex obtained from actiomycete from which iron is removed chemically to produce Desferrioxamine. Used for: i. Acute iron poisoning ii. In repeated tran�fusion to treat transfusion siderosis.
Vaccines and Sera Q.l. Define vaccines.
These are biologial products reinforcing immunological defence impart active immunity, act as antigens to induce specific antibodies. Q.2. What is antisera?
The antisera and immunoglobins impart passive readymade antibodies (produced in other person or animals produced there actively) and then given to recipients. Q.3. What are the different types of vaccines?
Vaccines are of three types: i. Killed (inactivated); ii. Live attenuated iii. Toxoids Q.4. When not to use live attenuated vaccines?
Live attenuated vaccines should not be used in individuals with impaired host defence like: i. Leukemia or other malignancies, receiving cytotoxic drugs. ii. SLE iii. Immunocompromised AIDS patient iv. Patient on corticosteroid therapy. Q.S. Name some vaccines.
1. Bacterial-Typhoid-paratyphoid, Vi typhoid polysaccha
ride, cholera, whooping cough, meningococcal, plague, bacillus calmette grerin, Typhoid Ty 21a. 2.
Viral: Poliomyelitis inactivated, Polimyelitis oral live, rabies
(brain, chick embryo, human diploid vero cells), mumps, measles, rubella, Influenza, Hepatitis B.
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155
3. Toxoids: Tetanus, Diphtheria, Double antigen triple antigen, Typhoid-paratyphoid, cholera, Measles-Mumps, Rubella. Q.6. Mention the immunization schedule for infants and children.
At birth-BCG+ OPV (1st dose) At 6-10-14 weeks-OPT+ OPV At 12 months-Measles/MMR At 15-18 months-OPT + OPV (booster) At 5 years (school entry)-DT, DA, OPV (booster Typhoid (TAB 2 doses/Vi/Ty 21 a (optional) At 10 years-Tetanus toxoid+ TAB/Vi/Ty 21 a (optional) For pregnant women: Tetanus toxoid at
16-24 weeks 1st dose 24-36 weeks 2nd dose
Q.7. Name some antiseras.
Antiseras are purified, concentrated preparation of serum of horses actively immunised against specific antigen used for passive immunity, viz. Tetanus antitoxin (ATS); Antigas gangrene antitoxin (AGS); Diptheria antitoxin (ADS), Antirabies serum (ARS); Antisnake venom polyvalent. Q.B. What are immunoglobulins? Name some immunoglo bulins.
Immunoglobulins (Ig) impart passive immunity seperated from human gamma globulins carrying antibodies. They may be nonspecific (normal) or specific (hyperimmune) viz. Normal human gamma globulin, Anti-D immunoglobulin, Tetanus immunoglobulin, Rabies immunoglobulin, Hepatitis B immunoglobulin.
Antibiotics Q.l. What are antibiotics? These are substances produced by some microorganisms, which suppress the growth or kill the other microorganisms at very low concentrations, excluding the production of natural substances, which also kills microbes in higher concentration like ethanol, H202 and lactic acids.
Q.2. What are the different sites of a micro-organism where antibiotics/chemotherapeutics works? They may act on the following sites: i. Inhibit cell wall synthesis: Penicillin, Cephalosporin, . Cycloserine, Vancomycin, Bacitracin. ii. Leaking cell membrane: a. Polypeptides-Polymyxin, Colistin, Bacitracin b. Polyenes: Amphotericin B, Nystatin, Hamycin iii. Inhibit protein synthesis: Tetracycline, Chloramphenicol, ·Erythromycin. iv. Misreading in RNA code and affecting cell permeability aminoglycosides v. Inhibiting DNA gyrase-Fluroquinolones vi. Interfere DNA function-Rifampicin, Metronidazole vii. Interfering DNA synthesis-Idoxuridine, Acyclovir, Zidovudine. viii. Interfere
intermediary
metabolism-DDS,
PAS,
Ethambutol.
Q.3. What do you mean by bacteriostatic and bacteriocidal? The antibiotics which inhibit bacterial multiplication are bacteriostatic and which kill the bacteria are bacteriocidal.
Antibiotics
157
Q.4. Name some antibiotics obtained from: i. Bacteria ii. Fungi iii. Actinomycetes The antibiotics obtained from: i. Bacteria-Bacitracin, Polymyxin B, Colistin ii. Obtained from fungi-Penicillin, Cephalosporin, Griseo fulvin iii. Obtained from Actinomycetes-Macrolide, Aminoglycosides, Tetracycline
Q.S. What is resistance? What are the different mechanisms of resistance? Unresponsiveness of a micro-organism to an antimicrobial agent is called resistance. It may be: i. Natural-Some microbes have always resistance to some antimicrobials, e.g. penicillin not effective for gram negative ii. Acquired-Where they acquire resistance after the use of anti microbial agent for some period of time. The acquired resistance may develop because of i. Mutation ii. Gene transfer by conjugation iii. Transduction iv. Transformation by becoming drug resistant the microbes become: a.
Drug tolerant
b.
Drug destroying
c.
Drug impermeable
Q.6. What is cross-resistance? Acquisition of resistance to one antimicrobial producing resistance to another antimicrobials generally seen with anti microbial agents with same mechanism of action.
Q.7. How to prevent development of resistance? i. Do not use inadequate, indiscriminate or unnecessary prolong antibiotics. ii. Prefer selective, rapid acting antibiotics.
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iii: Organisms prove to develop resistance treat adequately. iv. In case of prolong antibiotics use combination. Q.S. What is super infection? The new infection arising out of antibiotic therapy is called super or supra infection are difficult to treat. It generally arises when host defence is compromised: i. Corticosteroid therapy ii. Leukemia, malignancy iii. AIDS iv. Agranulocytois v. Diabetes, SLE Q.9. What are the purposes of combining antimicrobial agents? It is used in combination to achieve: i. Synergism ii. To reduce incidence of adverse effects iii. To prevent resistance iv. To broaden spectrum. Q.lO.What are
the disadvantages of antimicrobials
combination? Combination of antimicrobials increases V'!riety of adverse drug effects: i. Super infection ii. Resistance chance increases ·
iii. Cost of therapy increases iv. Causal outlook in the diagnosis of infection. Q.ll. Give some examples where antibiotics are used prophylactically. Antimicrobial agents are used prophylactically for following conditions: 1.
Prophylaxis against specific organism as for exampl'e
Rheumatic fever; Rifampicin in epidemic of meningo coccal meningitis. ii. Prevention
of
infection
in
Catheterization, dental extraction
risky
situation
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159
iii. Prevention of infection in general-In viral infection of URTI antibiotics to prevent bacterial infection, in neonates after prolong instrumental delivery.
Q.12.
What are the reasons of failure of antibiotics?
Antibiotic might fail to respond in the following conditions: i. Improper selection of drug, dose, route ii. Treatment started late iii. Other measures are inadequate like drainage iv. Poor host defence like leukemia v. If dormant and persister organisms are present.
Sulfonamides Q.l. What is the first sulfonamide?
The first sulfonamide sulfonamide-chrysodine (Prontosil).
Q.2. What is the chemistry of sulfonamides?
They are paraminobenzene sulfonamide (Sulfanilamide) derivatives.
Q.3. Name some sulfonamides. These are short acting (4-8 hr) Sulfadiazine, Sulfsoxazole intermediate acting (8-12 hrs), Sulfamethoxazole, Sulfamoxole, long acting (7 days) Sulfadoxine, Sulfametho-pyrazine, Local acting Silver Sulfadiazine, Sulfacetamide.
Q.4. What is the mechanism of action of sulfonamide or what is woods and Fildes hypothesis? Para-amino benzoic acid is constituent of Folic acid is taken
up from medium by those bacteria synthesize their own folic
acid. Sulfonamide being structural analogues of PABA inhibit
bacterial folate synthetase so folic acid is not formed as evidenced by:
i. ·PABA in small quantities antagonise Sulfonamide action
ii. Only those bacteria synthesize their own folic acid are susceptable to sulfonamide.
iii. Pus rich in PABA antagonise sulfonamide action.
Q.S. How the resistance to sulfonamide occur? The resistant mutant bacteria (Gonococci, Meningococci occur due to):
i. Produce increased PABA
ii. Their folate synthetase has low affinity to sulfonamide.
iii. Develop alternate pathway for folate metabolism.
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161
Q.6. Mention some therapeutic uses of Sulfonamide.
Sulfonamide is used in the following conditions: i. UTI ii. Streptococcal pharyngitis iii. Trachoma iv. Lymphogranuloma venereum v. Malaria vi. Toxoplasmosis vii. Nocardiosis viii. Burns Q.7. What is co-trimoxazole?
It is a fixed dose combination of Sulfamethoxazole and Trimethoprim in the ratio of 5:1 which sequentially block folate synthetase and dihydrofolate reductase produced from PA_BA to Dihydrofolic and to tetrahydrofolic acid. Q. 8. What are the uses of co-trimoxazole?
This is used in the following conditions: i. UTI ii. RTI iii. Typhoid iv. Bacterial diarrhoea and dysentery v. Chancroid vi. Granuloma inguinale vii. Pneumocystis carinii viii. Trimethoprim is concentrated in prostate effective in prostatitis.
Quinolones Q.l. What are quinolones? These are synthetic antimicrobials with quinolone structure mainly effective against gram negative bacteria. Fluroquino lones are quinolones with fluro substitution also having activity against gram positive.
Q.2. What is the mechanism of action of fluro quinolone? They inhibit bacterial DNA gyrase, which nicks double stranded DNA and negative super coils and reseal the nicked ends which is required to prevent excessive positive super coiling of the strands permiting replication or transcription. A submits of DNA gyrase carries out nicking and B submits of DNA gyrase prevent negative super coil and than it is resealed.
Q.3. Why fluoroquinolons are not effective in mammalian cells?
Mammalian cells have enzyme topoisomerase II which remo ves positive supercoils with low affinity to fluroquinolones, so it is ineffective to host cells.
Q.4. How does resistance develops with fluoroquinolones? It occurs due to chromosomal mutation producing DNA gyrase with less affinity to fluoroquinolones. It rarely occurs through plasmid mediated mechanism. Other possible mechanism of resistance is less permeability of bacterial cell to fluoroquinolones.
Q. 5. Name some fluoroquinolones. Norfloxacin, Ciprofloxacin, Ofloxacin, Pefloxacin, Lomefloxa cin, Sparfloxacin, Amifloxacin etc.
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163
Q.6. What are the therapeutic uses of ciprofloxacin?
The cirprofloxacin is generally used for: 1.
UTI
ii. Gonorrhoea iii. Chancroid iv. Typhoid v. Gastroenteritis vi. Gynaecological, bone, skin, soft tissue, wound infection vii. R.T.I. viii. Gram-negative septicaemia ix. Topical
use
in
conjunctivitis
by
gram-negative
conjunctivitis x. Prophylactically in neutropenic and cancer patients. Q.7. What are the adverse effect of sulfanamide?
Sulfonamide may produce nausea, vQmiting, crystallauria, hypersensitivity, hepatitis, haemolysis in glucose 6- Po4 deficient patient kernicterus. Q.S. Name some f3-lactam antibiotics.
Pencillins, Cephalosporins, Monobactam and carbapenem are �-lactam antibiotics. Q.9. What is the structure of penicillin?
It consists of thiozolidine ring fused with �-lactam ring with a side chain attached through amide linkage Penicillin G has benzyl side chain. Q.lO. What i s the mechani sm of action of �-lactam antibiotics?
All beta lactam antibiotics interfere with cell wall synthesis of susceptible bacteria inhibiting traspeptidases so that cross linking of the cell wall knit structure does not take place. Interior of the bacteria which are hyper-osmotic swells up brust and bacterial lysis occurs. It is effective in multiplying bacterium since cross-linked peptidogly�an cell wall is unique to bacteria. It is nontoxic to man. Blood, pus, tissue fluid do not interfere with its antibacterial action.
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Q.ll. Name some therapeutic uses of penicillin?
It is used for streptococcal, pneumococcal, staphylococcal, gonorrhoea, diphtheria, syphilis, tetanus, gangrene, anthrax actinomycosis, trench mouth, prophylactically used for (Rheumatic fever, gonorrhoea, bacterial endocarditis, surgical infection, agranulocytosis). Q.12. What are the adverse effect of penicillin?
Local irritancy, nausea on oral ingestion, confusion, muscle twiching, coma, hypersensitivity, superinfection, Jarisch Herxheimer reaction. Q.13. What is Jarisch-Herxheimer reaction?
Penicillin when injected to a syphilis patient (particularly secondary syphilis) may produce shivering, myalgia, fever, exacerbation of lesion vascular collapse. May be due to sudden release of lytic products lasting 12-72 hours. It does not require interruption of therapy for relief of symptoms. Aspirin and sedation can be given. Q.14. What are the advantages of semisynthetic penicillins?
The semisynthetic penicillins are: i. Orally absorbed ii. Not susceptible to penicillinase iii. More wide spectrum iv. Less likely to produce hypersensitivity. Q.15. Name acid resistant penicillin.
Phenoxymethyl penicillin. Q.16. Name some penicillinase resistant penicillins.
Methicillin, Cloxacillin, Nafcillin. Q.17. Name some Aminopenicillins.
Ampicillin, Becampicillin, Amoxycillin Q.18. Name some carboxypenicillins.
Carbenicillin, Carbenicillin indanyl, carbenicillin phenyl Ticarcillin Q.19. Name some Ureidopenicillins.
Mezlocillin, Piperacillin.,
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165
Q.20. Name some �-lactamase inhibitors. Clavulanic acid, sulbactum.
Q.21. Mention some of the therapeutic utility of Amino penicillin.
The aminopenicillin ampicillin are used for: UTI, RTI, Meningitis, Gonorrhoea, Typhoid fever, bacillary dysentry, cholecystitis, infective endocarditis, septicaemic.
Q-.22. Name some prodrug of ampicillin. Talampicillin, Pivampicillin, Hetacillin are prodrug for ampicillin.
Q.23. Mention the mechanism of action and therapeutic uses of Clavulanic acid.
Clavulanic acid is called suicide inhibitor which binds reversibly"initially and then co-valently later with �-lactamase located periplasmically. It is indicated for skin and soft tissue infection, intra
abdominal, gynaecological, urinary, biliary, RTI, Gonorrhoea (PPNG).
Q.24. What-is cephalosporin? Classify them. These
are
semi
synthetic
antibiotics
derived
from
cephalosporin C obtained from fungus Cephalosporium having �-lactam ring is fused to dihydrothiazine ring. The cephalosporin can be classified in many ways but therapeutic classification based on its spectrum is commonly used: 1st Generations: They are highly active in gram-positive but
weaker in gram-negative. Parenteral (Cephalothin, Cefazolin, Cephaloridine) Oral (Cephalaxin, Cephradine, Cefadroxil) 2nd Generations: Cephalosporins are more active against gram
negative with some members active agp.inst anaerobic. Parenteral (Cefuroxime, Cefoxitin) Oral (Cefaclor, Cefuroxime)
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Viva Voce in Medical Pharmacology
3rd Generation:
Having augmented activity against gram
negative enterobacteriaceae and some pseudomonas. Parenteral (Cefotaxime, Ceftizoxime, Ceftriaxone, Ceftazidime, Cefoperazone)
/
Qral (Cefixime)
4th Generation: Spectrum similar to 3rd generation with added advantage of highly resistant to 13-lactamase. Parenteral: Cefepime, Cefpriome
Q.25.
What are the therapeutic uses of cephalosporins?
They are used as alternative to penicillin, RTI, UTI; skin and soft tissue infection (by Klebsiella, Proteus, Serratia) Penicil linase producing staph, septicaemia, surgical prophylaxis, meningitis by H.
influenzae,
enterobacteriaceae, Gonorrhoea,
Typhoid (Cetriaxone, Cefoperazone). Mixed aerobic anaerobic infection, nosocomial infection, Ceftazidine and other 3rd generation is used for neutropenic patients.
Q.26.
What are the therapeutic uses of Imipenem the
carbapenem antibiotic?
This 13-lactam antibiotic is effective in gram-positive cocci, enterobacteriaceae, Ps-aeroginosa, Listeria, Cl.
difficile. Is also
effective in hospital acquired infection of neutropenia, cancer, AIDS.
Q.27.
What is the limiting factor of Imipenem?
It is rapidly hydrolysed by the enzyme dihydropeptidase I in bush border of renal tubular cells. Innovative solution to this problem is its combination with cilastatin which reversably inhibits dihydropeptidasel.
Q.28.
Name a monobactam antibiotic.
Aztreonam is a 13-lactam antibiotic with single ring inhibit H.influenzae, enteric bacilli; Pseudomonas. It has no action against gram positive cocci in faecal anaerobes.
Q.29.
What adverse effects may arise out of cephalosporin?
These may be i. Pain if given LV. ii. Diarrhoea
Quinolones
iii. Hypersensitivity iv. Nephrotoxicity v. Bleeding (because of hypoprothrombinemia) vi. Neutropenia vii. Antabuse like reaction with cefoperazone.
167
Tetracyclines Q.l. What is tetracyclines? Name some tetracyclines.
These are class of antibiotics having four cyclic ring, as for e.g. chlortetracycline, oxy tetracycline, tetracycline, demeclo cycline, methacycline, lymecycline, doxycycline, minocycline.
Q.2. What is the mechanism of action of tetracyclines?
These are primarily bacteriostatic, inhibit protein synthesis
by binding with 30s subfractions of ribosome of the
susceptible organism as a result peptide chain fails to grow (tetracyclines enters into susceptible organism by energy
dependent active transport). Lipid soluble tetracyclines like
doxycycline and min<;>cycline enter by passive diffusion.
Q.3. How does the resistance develop with tetracyclines?
It occurs because tetracyclines concentrating power to the cell
in less efficient or it is pumped out or a protective protein is synthesized which protects it to bind with tetracycline.
Q.4. What adverse effects may arise out of tetracycline?
Liver damage, kidney damage, Photosensitivity, deposition
on bone and teeth, catabolic effect, increases intracranial
pressure of infants, domecloclyclines, antagonizes action of ADH leading to diabetes insipidus. Minocycline is vestibular
toxic. Hypersensitivity and supersensitivity.
Q.S. What precaution should be taken while prescribing tetracycline?
Should not be used irr lactation, pregnancy, children, should not be used with diuretics, hepatic and kidney damage
patients.
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169
Q.6. Mention some indications of tetracycline. UTI, Amoebiasis. In malaria as adjuvant to quinine, Acne, COPD, Prophylactic to meningococci Meningitis, Anthrax, Actinomycosis, Listeria, Gonorrhoea, Tularemia, organsim sensitive to blood spectrum antibiotics, Lymphogranuloma venerum, Granuloma inguinale, chlamydia! trachoma, Opthamia neonatorum caused by Ch. oculogenitalis, Cholera, Plague, Brucellosis.
Q.7. What are the common properties of Aminoglycosides? i. Aminoglycosides are not absorbed orally, distributed extracellularly. ii. They are excreted by glomerular filtration. iii. They contain amino sugar. iv. Share common toxicity of oto and nephro. v. They interfere bacterial protein synthesis. vi. Generally used as sulfate salts. vii. Bactericidal. viii. More active against gram-negative in alkaline pH.
Q.S. Who discovered Streptomycin? It was discovered by Waksman in 1944.
Q.9. Name some Aminoglycosides. They are Streptomycin. Gentamicin, Kanamycin, Tobramycin, Amikacin, Sisomicin.
Q.lO. What is the mechanism of action of aminoglycosides? All aminoglycosides transport through the cell wall of bacteria on cytoplasmic membrane binds to ribosome (30 S and 50S) results in inhibition of protein synthesis and is bacteriocidal. The bacteriocidal action is concentration dependent based on secondary changes in integrity of bacterial cell membrane.
Q.ll. How does resistance occurs with aminoglycosides? i. Resistance occurs through inactivating enzyme of antibiotic phosphorylate, adenylate, acetylate acquired in cell membrane. ii. Mutation which decreases affinity of ribosomal proteins. iii. The pores in the outer coat become less permeable to aminoglycosides.
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Q.12. What are the common toxicity of aminoglycosides?
They produce i. Oto (Vestibular and cochlear damage) ii. Neprotoxicity iii. Neuromuscular blockade Q.13. How does aminoglycosides produce neuromuscular
blockade? All aminoglycosides reduce Ach release probably interfering mobilization of centrally located synaptic vesicles to fuse with terminal membrane probably by antagonising Ca2+ and decreases sensitivity of motor end plate to Ach Myasthenic weakness is aggravated by aminoglycosides. Q.14. What are the therapeutic uses of aminoglycosides?
They are used for: 1.
Tuberculosis
ii. Infective endocarditis iii. Plague iv. Tularemia (Tetracyclines are alternatives.) Q.15. What is the source of Gentamicin?
It is obtained from Micromonospora purpurae.. Q.16. What is Gentamicin PMMA?
Gentamicin PMMA (Polymethyl methacrylate) is drug delivery system consisting of small acrylic beads each impregnated with 7.5 mg gentamicin sulfate threaded over surgical grade wire :used for osteomyelitis marketed as septopal. Q.17. How to adjust doses of Gentamicin?
For an average adult with normal renal function creatinine clearance
>
70 ml/min 1-1.5 mg/kg is given I.M. or I.V. 8
hrly. Dose is kept constant and doses interval is increased in renal insufficiency. 30-70 ml/min 12 hrly., 10-30 ml/min 24 hrly.; and <10 ml/ min 48 hrly. Q.18. What are the therapeutic uses of Gentamicin?
Being cheaper among aminoglycosides, it is used for RTI (with corticosteroids, AIDS, neutropenia with dialysate fluid,
Tetracyclines
171
Pseudomonal, Proteus, Klebsiella infection in burn, UTI, pneumonia, meningitis with gram-negative bacilli, infective endocarditis.
Q.19. What are the therapeutic uses of of Neomycin? Neomycin is given: Orally-for bowel preparation in surgery; Hepatic coma, Amonia is produced by colonic bacteria which is converted to urea by liver ammonia cannot be detoxified by liver in hepatic coma. Neomycin inhibits growth of intestinal flora diminishing NH3 production and lowers blood level. Topically used in combination with polymyxin, bacitracin for burus, external ear infection, conjunctivitis.
Chloramphenicol Q.l. What is the mechanism of action of chloramphenicol? Chloramphenicol attaches itself to 50 S ribosimal subunits and inhibits bacterial protein syntheis. It is bacteriostatic.
Q.2. How the resistance to chloramphenicol occurs? It occurs through transfer of R. factor by conjugation. There is decrease permeability of it through resistant bacteria. It
shares some cross resistance to erythromycin/Chidamycin all
which act through 50S ribosomal subunits.
Q.3. Mention some adverse effects of chloramphenicol? Bone marrow depression. Hypersensitivity reaction, Gray
baby syndrome, Superinfection.
Q.4. What is Gray baby syndrome? Chlorampenicol if given to neonates stops feeding, vomits becomes hypotonic, hypothermic, with distented abdomen, respiration becomes irregular, ashengray and cyanosed. Blood lactic acid raised. All these symptoms and signs appear as
because it blocks electron transport chain in liver myocardium,
skeletal muscle as because neonates are not able to metabolise and excrete chloramphenicol.
Q.S. Mention some uses of chloramphenicol? They are used for: i. Enteric fever n.
H. influanzae meningitis
iii. Anaerobic infection (B.
fragilis)
iv. Intraocular infection in endophthalmitis v. UTI
vi. Topically for eye and ear infection. It may be used as for
eye and ear infection. It may be used as second choice drug in whooping cough, meningococcal meningitis, shigella
dysentery.
Macrolide Antibiotics Q.l. What is the mechanism of action of Erythromycins?
They are bacteriostatic but bacterocidal in higher doses. Act
on 50 s ribosomal subunits and interfere with bacterial protein synthesis.
Q.2. What are macrolide antibiotics? Name some macrolide antibiotics.
·
Macrolide antibiotics possess a macrocyclic ring with attached sugars. Erythromycin, Roxithromycin, Clarithromycin,
Azithromycin, etc. belong to this group.
Q.3. What are the therapeutic uses of Erythromycin?
It is used in: Streptococcal (Pharyngitis, tonsilitis, mastoditis,
RTI by pneumococcal and H.
whooping cough,
influenzae), Tetanus, Syphilis, Legionnaire pneumoniae, campylobacteria
enteritis, chancroid, chlamydia trachomatis.
Q.4. What happens if erythromycin is given with either of the following: Terfenadine/Astemizole/Cisapride)?
Erythromycin increases level of terfenadine (Astemazole or
cisapride by inhibiting CYP-3A leading to increase in blood levels of these drugs which prolong Q.T. interval and produces
torsades-de-pointes.
Q.5. Name some glycopeptide antibiotics?
Vancomycin, Spectinomycin, Teicoplanin. Q.6. What is drug of choice of pseudomembranous colitis?
Colitis A: Vancomycin given 350-500 mg 6 hrly.
Q.7. Name an antibiotic with steroidal structure?
Fusidic acid is narrow spectrum antibiotic used topically, has
steroidal structure.
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Q.S. Name some polypeptide antibiotics? These are polymyxin B, Colistin, Bacitracin, Tyrothricin. Most of them are topically used. Bacteriocidal having detergent like action (polymyxin B, Colistin)
·
Urinary Tract Infection Q.l. Name some urinary antiseptics. These are nitrofurantoin, Methenamine.
Q.2. Name the- drugs used in the treatment of UTI? __
The drugs which are used in UTI after culture sensitivity are as follows: i. Sulfonamides iii. Trimethoprim
ii. Co-trimoxazole iv. Fluoroquinolones
v. Ampicillin
vi. Cloxacillin
vii. Piperacillin
viii. Carbenicillin
ix. Cephalosporin xi. Chloramphenicol
x. Gentamicin xii. Tetracycline.
Q.3. Name some antimicrobe agents used in UTI ef fective in acidic and alkaline medium? Antimicrobial agents used in UTI effective in acidic medium: Nitrofurantoin, Methenamine, Tetracycline, Methicillin, Cloxacillin Effective in alkaline medium: Sulfonamide, Co trimoxizole, Aminoglycosides, Cephalosporin, Fluoro quinolones.
Q.4. Mention the conditions where prophylactically antibiotics are used to prevent UTI? The conditions are: i. Catheterization and instrumentation ii. Indwelling catheter iii. Uncorrectable urinary tract abnormalities iv. Unoperable prostate or urinary obstruction.
Antitubercular Drugs Q.l. Name the drugs used for the treatment of tuberculosis? The drugs used for the treatment of tuberculosis are clinically based on following groups: 2nd Line drugs:
1st Line drugs:
i. Streptomycin (S) ii. Rifampicin (R) iii. Isoniazid (H) iv. Ethambutol (E) v. Pyrazinamide (Z)
1.
Thiacetazone (Tzn)
ii. Para-'aminosalicylic acid (PAS) iii. Cycloserine (Cys) iv. Kanamycin (Kmc) v. Amicacin (Am) vi. Ethionamide vii. Capreomycin (Cpr)
Newer Drugs: 1.
Ciprofloxacin
ii. Ofloxacin iii. Clarithromycin iv. Azithromycin v. Rifabutin
Q.2. What is the mechanism of action of INH? Exact mechanism of action of INH is not known. It is proposed to inhibit synthesis of mycolic acid which is component of cell wall of mycobacterium. It has also been implicated to have its effect on nucleic acid glycolysis.
Q.3. What ADR may arise out of INH? These are Hepatitis, Neuritis (Paresthesic numbness, mental disturbances, convulsion may be reversed by pyridoxine).
Q.4. What is the mechanism of action of Rifampicin? Rifampicinis bactericidal inhibit DNA dependent RNA synthesis.
Antitubercular Drugs
177
Q.5. Mention ADR of Rifampicin.
These are hepatitis, purpura haemolysis shock, renal failure,
fluid like syndrome, nausea, vomiting, abdominal cramp, urine
is orange coloured but harmless.
Q.6. What is the mechanism of action of Pyrazinamide? What are its ADR?
It is effective in acidic medium, most effective in first 2 months bacteriocidal.
It may produce hepatitis, hyperuricemia, arthralgia, fever,
rash loss of control of diabetes.
Q.7. What is the mechanism of action of Ethambutol?
Tuberculostatic, probably interferes mycolic acid incorporation in cell wall.
Q.8. Why PAS a sulfonamide derivative is effective in tuberculosis?
PAS being sulfonamide derivative is not effective for other bacteria because of difference of affinity for folate synthetase for TB bacteria.
Q.9. What are the special features of Ethionamide?
It is tuberculostatic effective against a typical and typcial mycobacteria both (Extra and intracellular). Cross resistance
seen with thiacetazone. Anorexia, nausea, vomiting seen with
Indian patients.
Q.lO. What is the mechanism of action of cycloserine (Cys)?
Cycloserine is bacteriostatic by inhibiting cell wall synthesis by inactivating enzyme which recemize L-alanine and link
two alanine residues, resistant develops slowly.It also inhibits
some gram-positive and E.coli and Chlamydia. Q.ll. What are the goals of ATD therapy?
The goals are
i. To kill dividing bacteria
ii. To kill persisting bacteria to prevent relapse
iii. To prevent development of resistance.
Viva Voce in Medical Pharmacology
178
Q.12.
What should be ATD regimen for pregnancy and
lactation?
In pregnancy HRZ and E are safe to foetus. All A TO drugs are compatible to lactation.
Q.13.
When to use corticosteroids in tuberculosis patient?
Corticosteroid is used in tuberculosis patient in the following conditions with full ATD coverage: i. Drug reaction ii. Pleural, pericardia!, peritoneal, meningeal TB iii. Miliary tuberculosis iv. To inhibit fibrosis.
Q.14. What are the
other organisms sensitive to Rifampicin?
Many gram-positive gram-negative bacteria like
Staph aureus, meningititis, H.influenzae, E.coli, Klebsiella, Proteus, Pseudomonas, Legionella, Leprosy can be treated with N.
Rifampicin.
Q.15.
When to give chemoprophylaxis to ATD drug?
These are given in following conditions: i. Recent mantoux conversion ii. Neonates with tuberculosis mother iii. Children with positive mantoux and TB patient in family iv. Patient of leukemia, diabetes, silicosis, HIV or steroid showing mantoux positive. v. Old inactive diseases taken inadequate treatment vi. Life long prophylaxis with Rifabutin in HIV positive cases.
Q. 16.
What is the regimen given for mycobacterium ovium
complex?
Clorithromycin or Azithromycin +Ethambutol, Ciprofloxacin, Clofazamine, Rifabutin, Ethionamide, Cycloserine may be added.
Anti leprotic Drugs \
Q.l. Name the different drugs used in leprosy. The drugs used in leprosy could be: i. Sulfone: Dapsone (DDS)
ii. Phenazine derivative, Clofazimine
iii. Antitubular drug: Rifampicin, Ethionamide
iv. Miscelhmeous: Ofloxacin, Minocycline, Clarithromycin _ Q.2. What is the action of Dapsone? Dapsone being sulfonamide inhibits the incorporation of
PABA into folic acid of M.leprae due to specificity forM. leprae due to difference in the affinity of folate synthetase.
Q.3. What are the other uses of Dapsone? It may be used in Chloroquine resistant cases of malaria, pemphegious.
Q.4. Mention some ADR of DDS. It may produce haemolytic anaemia, particularly in Glucose 6-P04 deficient patient nausea, vomiting, methemoglobine mia,-rash, fixed drug reaction, hypermelanosis, phototoxicity, exfoliative dermatitisn Hepatitis, agranulocytosis.
Q.S. What is the mechanism of action of Clofazimine? It is a dye with leprostatic and anti-inflammatory properties. It probably interferes with template function of DNA.
Q.6. Mention some ADR of clofazamine. Skin discolouration, Acne form eruption, phototoxicity, conjunctival pigmentation, enteritis, intermittent, loose stool, anorexia, weight loss.
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Viva Voce in Medical Pharmacology
Q.7. What are the advantages of multi-drug therapy in
leprosy?
They reduce duration of therapy and quick symptomatic relief and reduce MBL cases non-contagious effective in Dapsone resistance and prevents dapsone resistance. Q.B. Name the different drugs used in leprosy regimen.
For multibacillary leprosy: Rifampicin-600 mg/month Dapsone-100 mg daily Clofazimine-300 mg/month supervised 50 mg daily for 2 years Paucibacillary: Rifampicin 600 mg/month and DDS 100 mg daily Alternative regimen: Clofazamine 50 mg +(a) Ofloxacin 400 mg/
(b) minocycline 100 mg/(c) clarithromycin 500 mg (any two of a, b,c) for 6 months. Q.9. What is lepra reaction?
Lepra reaction occurs with lepromatous leprosy with initiation of chemotherapy. It is Jarish-Herxheimer arthus type reaction due to release of antigen from killed bacilli, consists of fever, malaise, lymph node enlargement, skin desquamation, jaundice and anaemia. Treatment withdraw DDS. Increase clofazamine doses. Analgesic, antipyretic, antibitoc, chloroquinine, thalidomide, corticosteroids. Q.lO. What is reversal reaction?
It occurs with tuberculoid leprosy patient as a part of delayed hypersensitivity to M.leprae antigen manifested with cutaneous ulceration multiple nerve involvement with tenderness treated with clofazamine and steroids.
Antifungal Antibiotic Q.l. Name the drugs used for fungal infection. The antifungal drugs may be classified as follows: i. Antibiotics: a.
Polyenes (Amphotericin B, Nystatin, Hamycin, Natamycin)
b.
Heterocyclic benzofuran-Griseofulvin ,
ii. Antimetabolite: Flucytosine (5FC) iii. Azole: a.
Imidazole (topical Clotrirrtazole, Econazole, Mico
b.
Triazoles-(Systemic) Fluconazole, Itraconazole
nazole) (Systemic: Ketoconazole)'iv. Allylamine: Terbinafine v. Other topical agents: Tolnaflate,undecylenic acid,Benzoic acid,Quinodochlor,Ciclopirox,Olamine,Sod. thiosulfate. Q.2. What is the mechanism of action of Amphotericin B? Amphotericin, the polyenes antibiotics have high affinity for ergosterol of fungal cell membranes to orient themselves to produce micropore through which ions,amino acids and water soluble substances move out. It is not effective against bacteria as it does not contain sterol in their cell membrane. Q.3. Name the therapeutic uses of ampthotericin B. It is effective against Candida albicans, cryptococcus,
Blastomyces,
histoplasma,
coccidiodes, Torulopsis,
Rhodtorula, Aspergillus, Sporothrix. It is also active against Leishmania. Q.4. Mention some newer Amphotericin B formulations. These are: i. Amphotericin B lipid complex (ABCL)
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Viva Voce in Medical Pharmacology
ii. Amphotericin B colloidal dispersion (ABCD) iii. Liposomal Amphotericin B (small unilamellar vesicles SUV) used for kala-azar and immunocompromised patients. Q.5. Mention ADR of Amphotericin B.
These are chills, fever, aches, nausea, vomiting, nephrotoxi city, anaemia, CNS toxicity (headache vomiting, nerve palsy). Q.6. Name an antifungal discovered in India and its uses.
Hamycin is developed by Hindustan Antibiotics Ltd. topically used for thrush, cutaneous candidiasis, trichomones vaginitis, Aspergillus otomycosis. Q.7. Mention some therapeutic uses of Natamycin.
Natamycin applied topically for Fusarium Keratitis. Q.S. Mention the source
and
therapeutic
uses
of
Griseofulvin. What is its mechanism of action?
It is obtained from Penicillium griseofulvin used for dermato phytosis (Epidermophyton, Trichophylon, Microsporum) It interferes mitosis of multinucleated fungal hypae. Q.9. What is Flucytosine (5 FC)?
It is narrow spectrum (active against cryptococcus) orally active drug converted to 5 fluorodeoxyuridylic acid, inhibitor of thymidylate inside fungal cell and act as fungostatic. Q. 10. What is Itraconazole?
It is orally active triazole antifungal fungistatic drug, effective in immunocompromised patient also. Q.11. Why Itraconazole produces ventricular tachycardia when used with terfenadine, astemazole cisapride?
Terfenadine, Cisapride, astemazole are drugs which increase Q.T. intervals. ltraconazole inhibits CYP-3A4 and blood level of these drugs are increased leading to lethal ventricular arrhythmia. Q.12. What is Terbinafine?
It is allylamine class of antifungal orally and topically used fungicidal acts as noncompetitive inhibitor of squalene
Antifungal Antibiotic
183
epoxidase which ultimately produces ergosterol biosynthesis in fungal cell membrane and accumulates squalene within fungal cells.
Q.13. Name some topical Antifungals? These are:
·
i. Tolnatate ii. Cyclopirox olarnine iii. Undecylenic acid iv. Benzoic acid v. Quiniodochlor vii. Sodium thiosulfate.
Antiviral Drugs Q.1. Why is viral chemotherpay difficult?
·
Viruses not only take nutrition from the host, but they also direct its metabolic machinery to ·synthesize new virus particle. Therefore the chances of interferences with cellular metabolism by antiviral drugs are common.
Q.2. Name some antiviral drugs? These are i. Nonselective antiviral (Ribovirin, Interferon) ii. Antiherpes virus: Idoxiridine, Vidarabin, Trifluridine, Acyclovir, Ganciclovir, Foscarnet. m.
Antiretrovirus: a.
Reverse
transcription
inhibitors,
Zidovidine,
Didanosine, Zalcitabine, Stavudine. b.
Protease inhibitors: Saquinavir, Ritonavir, Indinavir, Nelfinavir
iv. Anti-influenza virus: Amantadine, Rimantadine
Q.3. What is the mechanism of action of Idoxuridine? 5-iodo-2-deoxyuridine is antimetabolite of thimidine analogue incorporated within DNA for thymidine and DNA directs wrong viral proteins used against DNA viruses Herpes simplex, Trifluridine is related to idoxuridine.
Q.4. What is the mechanism of action of Acyclovir? Acyclovir selectively inhibits viral DNA synthesis with low toxicity to host cells. It is deoxiginase analogue antiviral drug requires virus specific enzymes for conversion to the active metabolite. It is effective against H. simplex I and II, Varicella zoster, Epstein-Barr and Cytomegalovirus.
Antiviral Drugs
185
Ganciclovir is analogue of acyclovir active against all herpes viruses. Q.5. What are the therapeutic uses of foscarnet?
It is used for CMV retinitis in AIDS patients with CMV infection, Acyclovir resistant H. simplex patient. Q.6. What is the mechanism of action of Zidovudine?
Zidovudine is phosphorylated in the body and selectively inhibits viral reverse transcriptase prevents infection of new cells by HIV irtfection. Q.7. What are Didanosine, Zalcitabine, Stavudine?
These are antiviral agents, nucleoside analogue intracellularly converted to active triphosphate derivative which inhibit viral reverse transcription and terminate proviral DNA of HIV. Q.8. Name some protease inhibitors used for HIV infection.
These are-saquinavir, ritanavir, Indinavir, Nelfinavir which acts late step of viral cycle produce immature noninfectous virus. Q.9. What is the mechanism of action of Amantadine? Mention its therapeutic uses.
It inhibits uncoating in an early stage and assembly of virus particles. Used in prophylaxis treatment of influenza virus and Parkinsonism. Q.lO. What is the mechanism of action of Ribavirin?
Its mono and triphosphate derivatives generated intra cellularly inhibit GTP and viral RNA synthesis effective against Influenza Aand Band respiratory syncytal virus and many DNAand RNAvirus. Q.ll. What are interferons?
They are low molecular weight glycoproteins produced in host c.ells in response to viral infection. They are nonspecific antivirals act on multiple steps viral replication viz; penetration, synthesis of viral mRNA; assembly and release. They are host specific. Their approved indications are: i . Chronic hepatitis Band C
186 n.
Viva Voce in Medical Pharmacology AIDS related Kaposi's sarcoma
iii. Hairy cell leukemia 1v. v.
Condyloma accuminata H. simplex, H. Zoster in immunocompromised host
vi. Rhino viral cold used as prophylactic by nasal spray.-·
Index Anodyne hypnotics 33
A a-Adreneric blocking agents 14 Absorption of drugs 3 Acarbose 108 Acetazolamide 38
Antacids 85 Anti RA drug 43 Antianginal drugs action of nitrates 66 therapeutic uses of nitrates 66
adverse effect 38
cyanide poisoning 66
Acetylcholinesterase 15 Acyclovir 184 Adrenal cortex 109 Adrenergic receptors 14 Adrenocorticotropic hormone 100
ideal antianginal agent 66 Antianxiety drug 23 Antiarrhythmic drug quinidine 64 tocainide lignocaine 65
Alcohol
amiodarone 65
therapeutic uses 27 Alkaloids of opium 30 Alkylating agents 135 Allopurinol 20
adenosine 65 Antibiotics 156 Anticholinergic group 11
Amiloride 79
Antidepressants 25
Aminoglycosides 169
Antidiarrhoeal agent 84
Aminophylline 59 Amoebiasis 128 Amphotericin B 181 Ampicillin 165 Anabolic steroids 114 Anaemia 88 Anaesthetics local 43 spinal 43 general 43 preanaesthetic medication 46 dissociative anaesthesia 47 neuroleptanalgesia 47
Antidiuretics 79 Antiplatelet drug 96 Antipsychotic drug 22 Antithyroid drugs 102 Antiviral drugs 184 Apparent volume distribution 2 Aspirin 41 Astringents 137 ATD therapy 177 Attenuated vaccines 154
B 13-blockers 17
anaesthetic agents 47 Analeptics 20
13-lactam antibiotics 163
Androgens 116
Barbiturates
Angiotensin angiotensin II 52 angiotensin receptors 53 angiotensin converting enzyme 54 ACE inhibitors 54
therapeutic uses 34 poisoning 34 Belladona poisoning 12 Benzodiazepine antagonist 35 Benzodiazepines 35 Biguanide 107
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Viva Voce in Medical Pharmacology
Bioavailability 2 Bisphosphonates 114 Bradykinin 51 Bromhexine 58 Bromocriptine 99 Bronchial asthma 59 Buspirone 24
Colchicine 20 . Congestive heart failure 61 Contraceptive 120 Corticosteroids 111 Cycloserine 177
Cyclosporine 147 Cyproterone acetate 115
Cytotoxic drugs 133
Busulfan 135
Butyryl cholinesterase 15
D D-penicillamine 43
c Ca2+ channels 67 Calcitonin 113
Dacarbazine 135
Dales vasomotor reversal 13 Dapsone 179
Calcium 112 Calcium channel blockers prazosin 70 clonidine 70 Cannabis indica 25 Carbonic anhydrase 76 Cardiac arrhythmia 63 Carminatives 81 Castor oil 83 Catecholamine 15 Cell cycle 134 Centchroman 122
Demulcents 137 Desferrioxamine 153 Dhatura 12 Diabetes mellitus 104 Didanosine 185
Diethyl carbamazine 131 Digestants 81 Digitalis signs of improvement 62 adverse reactions of 62 toxicity 62
Dilirium tremans 28
Cephalosporin 165
Dimercaprol BAL 152
Cerebroactive drugs 21
Disinfectant 142
Cheese reaction 26 Chelating agents 152 Chenodiol 82 Chloramphenicol 172 Chloroquine 43, 126 Choline-esterase inhibitors 10 Cholinoceptors 9 muscarinic 9 nicotinic 9
·
Ciprofloxacin 163 Cisplastin 136 Clavulanic acid 165 Clofazimine 179 Clomiphene citrate 118 Co-trimoxazole 161 Coagulants 92
antiseptics 142 gerp1icide 142 pediculosis 143
Disulfiram 27 Diuretic 75 Dopamine 29 Dosage 6
Dose response curve 5 Drug abuse 26 Drug addiction 26 Drug administration 3 Drug automation 35 Drug combination 7 Drug excretion 4 Drug habituation 26 Drug tolerance 26
Index H2 receptor blockers 85
E
Haematinics 88
Emetics 80
Hallucinogens 25
Emollients 137 Endogenous opioid peptides 32 Enzyme 151
189
.
Epilepsy 36 Erythrocytic schizontocides 125 Erythromycin 173 Erythropoietin 91 Essential and orphan drugs 7 Ethambutol 177 Expectorants 58
F
Halofantrine 127 Helium 146 Heparin 93 Histamine receptors 49 Hofmann elimination 4,13 Huntingtons disease 23 Hyperbaric oxygen 145 Hypertension 69 Hypertrichosis 71 Hypnotics 32 Hypolipoproteinemic drugs HMG-CoA reductase inhibitors 72
Factors modify drug action 4 Fenastride 116 Fibrinolytic agents 95 Flucytosine 182
fibric acid derivative 72 Hypothyroidism 103
Fluroquinolone 162
I
Flutamide 116
Idoxuridine 184
Folic acid 90
Imipenem 166
Foscamet 185
Immunosuppressants 147 Infantile spasm 39
G Gallstone 82 Gentamicin 170 Giardiasis 129 Ginkgolide 57 Glaucoma 10 Glimepride 109 Glucagon 108 Glucocorticosteroids 110 Glycopeptide antibiotic 173 Gold salt 42
Insulin 104 Interferon 185 Invermectin 131 Iodine 102 Iron 88 Iron poisoning 89 ltraconazole 182
J Jarisch-Herxheimer reaction 164
Gossypol 123
K
Gout 19
Kallidins 51
Gray baby syndrome 172
Kinins
Griseofulvin 182
pathological role of 52
Guargum 108
kinin receptors 52
H
L
8-Hydroxyquinolines 129
L-asparaginase 136
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Viva Voce In Medical Pharmacology
Lactulose 83 Laxatives 82 Leishmaniasis 130 Lepra reaction 180 Leprosy 179 Leukotrienes 55 Levamisole 131 Lithium 24
M
0 Octreolide 99 Oestrogens 117 On-off effect 30 Opioid receptors 31, 32 Oral rehydration therapy 75 Organophosphorus poisoning 11 Oxytocics 123
p
Macrolide antibiotics 173 Malaria 124 Malignant hyperthemia 13 Mannitol 78 MAO 25 Mast cell degranulator 13 Mebendazole 131 Median effective dose 6 Median lethal dose 6 Mefloquine 126 Melanizing agents 138 Melatonin 35 Metals poisoning 152 Methyl polysiloxane 81 Metronidazole 128 Mifepristone 119 Migraine 50 Mineralocorticoids 111 Morphine therapeutics uses 31 Myasthenia gravis 11
Paracetamol poisoning 41 Parasympathomimetric drug 10 Parathormone 113 Parkinsonism 28 Pentamidine 130 Peptic ulcer 84 Peripheral vascular disorder 68 Pharmacology 1 Pharmacopeia 1 Phenytoin therapeutic uses 37 Phosphodiesterase III inhibitors 63
Piperazine 131 Pirenzepine 87 Plasma expander 72 Plasma kinins 51 Platelet activating factors 57 Postcoital pills 120 Potassium channel 67 Praziquantel 132 Prescription 1
N
Probencid 20
Narcotic analgesics 30
Procarbazine 136
Natamycin 182
Progesterone 119
Neomycin 171
Progestins 119
Nervous system
Prokinetic drugs 81
sympathetic 8
Prostaglandins 55
parasympathetic 8
Protamine sulfate 94
Neuroleptics 23
Proton pump inhibitors 86
Neuromodulator 9
Pseudo-membranous
Neurotransmitter 9 NSAID 39
enterocolitis 84 Psychiatric disorders 22
Index
191
Psychostimulant action 21
Sulfasalazine 43
Pyrazinamide 177
Sulfonamide 160
Q
Sympathomimetic drugs 14, 16
Sulfonylurea 107 Quinine 127 Quinolones 162
T Tachyphylaxis 13 Tamoxifen 118, 136
R Radioisotopes 144 Receptor al 16 a2 16 Rheumatoid arthritis 42
Tannic acids 137 Tardive dyskinesia 30 Terbinafine 182 Termination of drug action 3 Testosterone 116
Ribavirin 185
Tetracyclines 168
Rifampicin 176
Therapeuti� gases 145
Rubefacients 138
Therapeutic index 6
Therapeutics 1 Thiazide diuretics 77
s Sclerosing agents 93 Sedative 32 Seizures 36 Semisynthetic heparinoids 94 Sequential pills 120 Serotonergic receptors 49 Sildenfil 16
Thiazolideones 108 Thromboxanes 55 Thyroid gland 100 Thyroid hormones 101 Thyroid inhibitors 102 Tocolytics 123 Topical steroids 139
Skeletal muscle relaxants 12
Toxiocology 1
Sleep pattern 33
Trichomoniasis 129
Sodium valproate 39
TSH 100
Somatostatin 99
Tuberculosis 176
Somogyi effect 105 Sources of a drug 2 Stavudine 185 STD diseases syphilis 140 gonorrhoea 140
u Urinary antiseptic 175 Ursodiol 82
chancroid 140
v
granuloma inguinale 141
Vaccines 154
trichomoniasis 141
Vertigo 51
herpes 141
VitB12 90
Straub's test 30 Streptomycin 169
Vit D 113 Vit K 92
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Viva Voce in Medical Pharmacology
Vitamins nicotinic acid 149 pyridoxine 149 calcium pantothenate 150 vit C 150 vitA toxicity 150
w Warfarin 94
X Xanthine derivative 60
y Young and dilling formulae 5
z Zalcitabine 185 Zidovudine 185
