AuthorsStudentsResearchersPublishersGovernment & NonprofitsBusinessesMusiciansArtists & DesignersTeachers+ all categories Most FollowedPopular <iframe height="0" src="//www.googletagmanager.com/ns.html?

id=GTM-ZWF6" style="display:none;visibility:hidden" width="0"></iframe> < div style="display:none;">< img src="//pixel.quantserve.com/pixel/p-13DPpbyg8ofc.gif" border="0" height="1" width="1" alt="Quantcast">< /div> Language: English Download 2 Go BackComment Link Embed Saved for later of 217 Readcast Not Readcasted Note: You can always click on the Readcast button to share with your Scribd followers. Auto-Readcasting: OffView Past Readcasts Undo
b73b86888d50f72a44b013da63d043f288321223

Add a comment

Submit

Auto-Readcasting: OffView Past Readcasts logyand Therapeutics: Questions for Self Assessment THIRD EDIT ION TIMOTHY GK MANT BS c FFPM FRCP SeniorMedicalAdvisor,Quintiles,Guy sDrugResearchUnit,andVisitingProfessor,KingsCollegeL ondonSchoolofMedicineatGuy s,Kingsand StThomasHospitals,London,UK LIONEL D LEWIS MA MB BC h MD FRCP Professor of Medicine, Pharmacology and Toxicology at DartmouthMedical School and the Dartmouth-Hitchcock Medical Center,Lebanon, New Hampshire, USA JAMES M RITTER

MA DPH il FRCP FM ed S ci FBPHARMACOLS Professor of Clinical Pharmacology, Kings College London School ofMedicine at Guys, Kings and St Thomas Hospitals, London, UK ALBERT FERRO P h D FRCP FBPHARMACOLS Reader in Clinical Pharmacology and Honorary ConsultantPhysician, Kings College London School of Medicine at Guys,Kings and St Thomas Hospitals, London, UK PART OF HACHETTE LIVRE UK First published in Great Britain in 1995 as Multiple Choice Questions in Clinical Pharmacology Second edition published in 2000This third edition published in Great Britain in 2008 byHodder Arnold, an imprint of Hodder Education,an Hachette Livre UK Company, 338 Euston Road, London NW1 3BHhttp://www.hoddereducation.com 2008 Timothy GK Mant, Lionel D Lewis, James M Ritter and Albert FerroAll rights reserved. Apart from any use permitted under UK copyright law, this publication mayonly be reproduced, stored or transmitted, in any form, or by any means with prior permission inwriting of the publishers or in the case of reprographic production in accordance with the terms oflicences issued by the Copyright Licensing Agency. In the United Kingdom such licences areissued by the Copyright licensing Agency: Saffron House, 610 Kirby Street, London EC1N 8TS.Hodder Educations policy is to use papers that are natural, renewable and recyclable productsand made from wood grown in sustainable forests. The logging and manufacturing processes areexpected to conform to the environmental regulations of the country of origin.Whilst the advice and information in this book are believed to be true and accurate at the date ofgoing to press, neither the authors nor the publisher can accept any legal responsibility or liabilityfor any errors or omissions that may be made. In particular, (but without limiting the generality ofthe preceding disclaimer) every effort has been made to check drug dosages; however it is stillpossible that errors have been missed. Furthermore, dosage schedules are constantly beingrevised and new side-effects recognized. For these reasons the reader is strongly urged to consultthe drug companies printed instructions before administering any of the drugs recommended inthis book.British Library Cataloguing in Publication DataAcatalogue record for this book is available from the British LibraryLibrary of Congress Cataloging-in-Publication DataAcatalog record for this book is available from the Library of CongressI S B N 9 7 8 0 3 4 0 9 4 7 4 3 2 1 2 3 4 5 6 7 8 9 10Commissioning Editor: Sara PurdyP r o j e c t E d i t o r : J a n e T o d P r o d u c t i o n C o n t r o l l e r : A n d r e S i m C o v e r D e s i g n : L a u r a d e G r a s s e Typeset in 9/11.5 Palatino by Charon Tec Ltd (AMacmillan Company),Chennai, IndiaPrinted and bound in MaltaWhat do you think

about this book? Or any other Hodder Arnold title?Please visit our website:www.hoddereducation.com CONTENTS I N T R O D U C T I O N V 1 G E N E R A L P R I N C I P L E S 1 M u l t i p l e C h o i c e Q u e s t i o n s 1 E x t e n d e d M a t c h i n g Q u e s t i o n s 1 5 A n s w e r s 1 9 2 N E R V O U S S Y S T E M 3 9 M u l t i p l e C h o i c e Q u e s t i o n s 3 9 E x t e n d e d M a t c h i n g Q u e s t i o n s 5 3 A n s w e r s 5 5 3MUSCULOSKELETALS Y S T E M 6 9 M u l t i p l e C h o i c e Q u e s t i o n s 6 9 E x t e n d e d M a t c h i n g Q u e s t i o n s 7 1 A n s w e r s 7 2 4CARDIOVASCULAR S Y S T E M 7 5 M u l t i p l e C h o i c e Q u e s t i o n s 7 5 E x t e n d e d M a t c h i n g Q u e s t i o n s 8 6 A n s w e r s 8 9 5 R E S P I R A T O R Y S Y S T E M 1 0 1 M u l t i p l e C h o i c e Q u e s t i o n s 1 0 1 Extended Matching Questions104A n s w e r s 1 0 5 6 A L I M E N T A R Y S Y S T E M 1 0 9

M u l t i p l e C h o i c e Q u e s t i o n s 1 0 9 Extended Mat Questions115A n w e r s 1 1 6 7 E N D O C R I N E S Y S T E M 1 2 2 M u l t i p l e C h o i c e Q u e s t i o n s 1 2 2 Extended Mat Questions127A n w e r s 1 2 9 8 S E L E C T I V E T O X I C I T Y 1 3 5 M u l t i p l e C h o i c e Q u e s t i o n s 1 3 5 Extended Mat Questions144A n w e r s 1 4 7 9 CLINICALIMMUNOPHARMACOLOGY159 M u l t i p l e C h o i c e Q u e s t i o n s 1 5 9 Extended Mat Questions162A n w e r s 1 6 3 1 0 T H E S K I N A N D T H E E Y E 1 6 7 M u l t i p l e C h o i c e Q u e s t i o n s 1 6 7 Extended Mat Questions170A n w e r s 1 7 1 11CLINICAL TOXICOLOGY174 M u l t i p l e C h o i c e Q u e s t i o n s 1 7 4 Extended Mat Questions178A n w e r s 1 7 9 12PRACTICE EXAMINATION184 B e s t o F i v e s 1 4 Problem so l v i n g q u e s t i o n s 1 9 7 A n s w e r s 2 0 2 This page intentionally left blank

ching s

ching s

ching s

ching s

ching s

ching s

f 8

Multiple choice, extended matching, best of five and problem solving ques-tions are now ubiquitous in medical graduate and postgraduate examina-tions. They provide a rapid method for testing a wide range of knowledgeand marking is objective. The authors of this book, who are all practisingphysicians who have taught clinical pharmacology and therapeutics for manyyears, have based it on the fifth edition of Textbook of Clinical Pharmacology andTherapeutics not only to prepare students for their exams but also to empha-size the principles and facts that are the key to safe and effective prescribing.The answers are related to the relevant section in Textbook of ClinicalPharmacologyandTherapeutics, FifthEdition.Inadditiontherearebriefexplana-toryannotations in the answer to each question.Althoughthisbookcanstandalone,werecommendthatstudentswillreadasectionofthemaintextbook andthenreinforceandrevisetheirknowledgebyselftestingusingtheselfassessmentbook.Attheendofthebookisa practiceexaminationof50Bestonecorrectansweroffivequestions,thetypecurrentlymostfavouredinmedical examinations,followedbyfiveproblemsolvingquestions.Thisexaminationcoversthespectrumoftopicsthatmaybe encoun-teredin a final MB (medical degree) examination or even in some postgraduateexaminations(e.g. AmericanBoardofClinicalPharmacology,Inc.).Wesuggestthatstudentsusethisasapracticerunafterfinishingtheir revisionofthesub- ject as a whole. It is best to do it blind at one sitting lasting not more than 60minutes.We thank the generations of students who have provided critical feedbackand Val Brockwell for her word processing skills and patience.Timothy MantLionel Lewis James RitterAlbert Ferro INTRODUCTION This page intentionally left blank CHAPTER ONE GENERAL PRINCIPLES MULTIPLE CHOICE QUESTIONS MULTIPLE CHOICE QUESTIONS 1 The following drugs exert their effects by binding to receptors andmimicking the effects of the endogenous ligand (i.e. are agonists): a) Tamoxifen b) Salbutamol c) Morphine d) Cetirizine e) Lisinopril 2 The following drugs exert their principal effects by enzyme inhibition: a) Pyridostigmine b) Atropine c) Amlodipine d) Digoxin

e) Selegiline 3 The following drugs are reversible competitive antagonists: a) Suxamethonium b) Loratidine c) Ranitidine d) Phenoxybenzamine e) Naloxone 4 The following drugs are partial agonists: a) Isoprenaline b) Morphine c) Flumazenil d) Buprenorphine e) Oxprenolol CHAPTER 1 GENERAL PRINCIPLES 2 5 The following drugs cause their primary pharmacodynamic effectvia non-receptor mediated mechanisms: a) Magnesium trisilicate b) Mannitol c) Methotrexate d) Dimercaprol e) Sumatriptan 6 The pharmacokinetic elimination half-life of the followingdrugs mirrors their pharmacodynamic duration and intensityof action: a) Salbutamol b) Phenelzine

c) Dobutamine d) Omeprazole e) Cyclophosphamide 7 The plasma clearance of a drug: a) Is the volume of plasma from which the drug is totally eliminatedper unit time b) Is equal to the administration rate divided by the steady stateplasma concentration c) Is a better measure of the efficiency of drug elimination from the body than elimination half-life d) Does not include elimination by hepatic enzyme metabolism e) May be affected by renal function (i.e. GFR) 8 For a drug that obeys first-order (linear) kinetics and fits aone-compartment model for elimination: a) Its rate of elimination (in mass units of drug/unit time) isproportional to its plasma concentration b) Following cessation of an intravenous infusion the plasmaconcentration declines exponentially c) The half-life is proportional to the dose d) The half-life is unaffected by renal function (i.e. GFR) e) The composition of drug products excreted is independent ofthe dose 9 The apparent volume of distribution: a) Can be greater than the total body volume b) Is approximately 3Lfor most drugs in adults c) Is influenced by a drugs lipid solubility d) Alarge value indicates that a drug will be efficiently eliminated byhaemodialysis e) Determines the peak plasma concentration after a single bolusintravenous dose 3 M ULTIPLE CHOICE QUESTIONS 10

The following drugs have an elimination half-life of less than 4 hours ina healthy adult: a) Dopamine b) Heparin c) Amiodarone d) Gentamicin e) Diazepam 11 In repeated (chronic or multiple) dosing: a) If the dosing interval is much greater than the elimination half-life,little if any drug accumulation occurs b) It takes approximately five half-lives to reach 50 per cent of thesteady state concentration c) If a drug is administered once every half-life once steady state isreached, the peak plasma concentration will be double the troughconcentration d) The use of a bolus loading dose reduces the time taken to reachsteady state e) In patients with renal impairment the dosing interval should beincreased when prescribing gentamicin 12 The following drugs obey non-linear (dose-dependent) eliminationpharmacokinetics: a) Acetylsalicylic acid (aspirin) overdose b) Heparin c) Phenytoin d) Ethanol e) Ceftazidime in therapeutic doses 13 The following drugs undergo significant enterohepatic circulation: a) Oestrogens b) Atenolol c) Rifampicin d) Gentamicin

e) Levofloxacin 14 The oral bioavailability of a drug: a) Is a measure of the extent to which it enters the systemic circulation b) May be influenced by changing the excipient after oraladministration c) Is defined as the ratio of the area under the plasma concentrationtime curve (AUC) following oral administration divided by thatfollowing intravenous administration d) May be reduced by hepatic CYP450 induction e) Two preparations of the same drug may have similar bioavailability but different peak concentrations ( C max ) CHAPTER 1 GENERAL PRINCIPLES 4 15 The following are examples of prodrugs: a) Levodopa b) Azathioprine c) Penciclovir d) Sulfasalazine e) Enalapril 16 The following oral drugs do not require absorption from the gut toexert a therapeutic effect: a) Acarbose b) Methionine c) Orlistat d) Olsalazine e) Vancomycin

17 Drug absorption following oral administration: a) Is most commonly through passive diffusion b) Occurs predominantly in the colon c) Is usually complete within 90 minutes d) Non-polar lipid-soluble drugs are absorbed more readily than polarwater-soluble drugs e) Peptides are well absorbed following oral administration 18 The following drugs are absorbed predominantly through activetransport systems: a) Paracetamol (acetaminophen) b) Phenytoin c) Levodopa d) Methyldopa e) Lithium 19 The systemic bioavailability of the following oral drugs is increased iftaken in the fasting state: a) Oxytetracycline b) Amoxicillin c) Levodopa d) Acetylsalicylic acid/salicylates e) Fluconazole 20 The following drugs are effectively administered via the sublingualroute: a) Simvastatin b) Carbamazepine c) Ramipril d) Buprenorphine e) Glyceryl trinitrate

5 M ULTIPLE CHOICE QUESTIONS 21 The following drugs are effectively administered by the rectal route toproduce their systemic effect: a) Indometacin b) Sulfasalazine c) Metronidazole d) Glycerin e) Diazepam 22 The following drugs may be administered transcutaneously to producetheir systemic therapeutic effect: a) Glyceryl trinitrate (GTN) b) Estradiol c) Lidocaine (lignocaine) d) Fentanyl e) Nicotine 23 In the case of an intramuscular injection of a drug: a) Rate of drug absorption is enhanced by exercise b) Rate of drug absorption is greater from the deltoid injection sitethan the gluteus maximus site c) If administered to the buttock should be in the upper outer quadrant d) Should usually be no greater than a volume of 0.5mL e) Is an appropriate route of administration for the decanoate ester offluphenazine 24 The following are commonly associated with phlebitis when given viathe intravenous route: a) Potassium chloride b) Hydrocortisone c) Diazepam

d) 50 per cent glucose e) 5 per cent glucose 25 The following are metabolized by enzymes in the hepatic smoothendoplasmic reticulum: a) Levodopa b) Tyramine c) Metoprolol d) Suxamethonium e) 6-Mercaptopurine 26 The following are substrates for CYP3A: a) Ciclosporin b) Clarithromycin c) Phenytoin d) Adrenaline (epinephrine) e) Warfarin CHAPTER 1 GENERAL PRINCIPLES 6 27 The following drugs undergo phase II metabolism by hepaticacetylation enzymes ( N -acetyltransferases): a) Dapsone b) Ciclosporin c) Gentamicin d) Isoniazid e) Hydralazine 28 The following agents induce hepatic CYP450:

a) Rifampicin b) Carbamazepine c) St Johns wort d) Phenobarbital e) Penicillin 29 The following inhibit at least one of the hepatic CYP450isoenzymes: a) Fluvoxamine b) Grapefruit juice c) Digoxin d) Itraconazole e) Ciprofloxacin 30 The following are subject to extensive presystemic (first-pass)metabolism: a) Metoprolol b) Phenytoin c) Ciprofloxacin d) Morphine e) Verapamil 31 The following decrease the rate of gastric emptying: a) Aspirin overdose b) Migraine c) Fluoxetine d) Amitriptyline e) Metoclopramide 32 Cardiac failure: a) Increases the bioavailability of oral thiazide diuretics

b) Increases the volume of distribution of lidocaine c) Has little effect on the volume of distribution offurosemide d) Decreases the elimination half-life of lidocaine e) Decreases the elimination half-life ofgentamicin 7 M ULTIPLE CHOICE QUESTIONS 33 In severe renal failure: a) Gastric pH decreases b) The therapeutic range for phenytoin decreases c) Drug distribution of famotidine to the brain is increased d) Smaller maintenance doses of digoxin are required e) Omeprazole should be avoided 34 The following statements concerning renal drug handling are correct: a) The kidneys receive approximately 20 per cent of the cardiac output b) In healthy young adults approximately 130mL/min of protein-freefiltrate is formed at the glomeruli c) Non-protein-bound drug of molecular weight 66000 passes intothe filtrate d) Potentially saturable mechanisms for active secretion of both acidsand bases exist in the proximal tubule e) Low lipid solubility favours tubular reabsorption 35 The following drugs must be avoided in severe renal failure(glomerular filtration rate (GFR) 10mL/min): a) Prednisolone b) Amoxicillin c)

Bumetanide d) Metformin e) Oxytetracycline 36 The following can reduce GFR: a) Naproxen b) Ranitidine c) Iodine-containing contrast media d) Lisinopril e) Amphotericin B 37 Monitoring plasma/serum drug concentrations of the following drugsis recognized as a valuable supplement to clinical monitoring: a) Carbimazole b) Warfarin c) Gentamicin d) Lithium e) Ciclosporin 38 In pregnancy: a) Most drugs cross the placenta by active transport b) Ionized drugs cross the placenta more easily than un-ionized drugs c) Drugs that reduce placental blood flow can reduce birth weight d) The fetal bloodbrain barrier is not developed until the second halfof pregnancy e) The human placenta metabolizes endogenous steroids CHAPTER 1 GENERAL PRINCIPLES 8 39 The following drugs are confirmed teratogens in humans:

a) Ethanol (alcohol) b) Warfarin c) Isotretinoin d) Paracetamol (acetaminophen) e) Amoxicillin 40 During pregnancy: a) Gastric emptying and small intestinal motility arereduced b) Blood volume increases c) Plasma volume increases d) Predominantly water-soluble drugs will have a largerapparent volume of distribution e) Phenytoin metabolism is inhibited 41 During pregnancy: a) Renal plasma flow increases b) GFR increases c) Atenolol excretion increases d) Lithium excretion increases e) Gentamicin excretion increases 42 The following are considered safe during pregnancy: a) Salbutamol b) Erythromycin c) Levofloxacin d) Tobramycin e) Ribavirin 43 The following are appropriate in the management of benigndyspepsia in the second and third trimester of pregnancy: a)

Low roughage diet b) Avoidance of fresh fruit and vegetables c) Small, frequent meals d) Misoprostol e) Omeprazole 44 The following drugs do not cross the placenta in significantamounts: a) Heparin b) Warfarin c) Corticosteroids d) Sodium valproate e) Pethidine 9 M ULTIPLE CHOICE QUESTIONS 45 The use of phenytoin in pregnancy: a) Is absolutely contraindicated b) Is associated with cleft lip and palate c) The therapeutic blood concentration of total drug is lowerthan in the non-pregnant state d) Is associated with ataxia if an excessive dose is used e) Requires oral vitamin D supplements 46 The following drugs are appropriate for managing severehypertension diagnosed in early pregnancy in an asthmaticwoman: a) Bendromethiazide b) Atenolol c) Labetalol d) Lisinopril e) Methyldopa 47

The following are absolutely contraindicated inpregnancy: a) Salbutamol b) Corticosteroids c) General anaesthesia d) Quinine for malaria e) Sucralfate 48 In neonates relative to adults: a) Gastric acid production is reduced b) Fat content (as a percentage of body weight) is low c) Plasma albumin concentration is low d) The bloodbrain barrier is more permeable e) The GFR is reduced 49 The following drugs should be avoided during breastfeeding: a) Amiodarone b) Carbamazepine c) Ciprofloxacin d) Cyclophosphamide e) Ranitidine 50 The following drugs suppress lactation: a) Anthraquinones (e.g. senna) b) Bromocriptine c) Furosemide d) Salbutamol e) Metronidazole CHAPTER 1 GENERAL PRINCIPLES

10 51 The following properties of a drug facilitate its entry into breast milk: a) High lipid solubility b) Un-ionized state at physiological pH c) Low molecular weight d) Weakbase e) Short half-life 52 The following are appropriate in the first-line management of acutesevere asthma in a 5-year-old child: a) Nebulized beta 2 agonists b) Systemic corticosteroids c) Rectal diazepam d) Systemic ipratropium e) Systemic midazolam 53 Anormal man of 75 in comparison with a normal man of 35: a) Is more likely to be on regular drug therapy b) Is more prone to sedation with benzodiazepines c) Has a higher endogenous production of creatinine d) Has an increased liability to allergic drug reactions e) Usually requires a lower dose of warfarin to achieveanticoagulation 54 The following drugs may precipitate acute retention of urine in theelderly: a) Gliclazide b) Furosemide c) Morphine d) Amitriptyline

e) Trimethoprim 55 The half-life of the following is increased in the elderly: a) Gentamicin b) Glibenclamide c) Lithium d) Morphine glucuronide e) Diazepam 56 The following drugs should not be used in patients over75 years old: a) Trandolapril b) Finasteride c) Streptokinase d) Doxycycline e) Fluoxetine 11 M ULTIPLE CHOICE QUESTIONS 57 Awoman of 75 is more likely to have the following adverse effects thana woman of 25: a) Confusion during treatment with cimetidine b) Cholestatic jaundice following treatment with flucloxacillin c) Gastrointestinal haemorrhage during treatment with ketorolac d) Increased incidence of postural hypotension during doxazosintherapy e) Increased risk of agranulocytosis during clozapine therapy 58 The following are type A adverse reactions (i.e. a consequence of thedrugs normal pharmacological effect): a) Propranolol and fatigue b) Atorvastatin and hepatotoxicity c) Naproxen and gastrointestinal haemorrhage

d) Cyclophosphamide and neutropenia e) Diazepam and sedation 59 Stopping treatment with the following drugs may lead to adverseeffects due to drug withdrawal: a) Prednisolone b) Clonidine c) Lorazepam d) Metoprolol e) Ergotamine 60 The following adverse reactions are associated with the drugsnamed: a) Oral contraception gastrointestinal haemorrhage b) Co-amoxiclav acute liver failure c) Cocaine stroke d) Thiazide diuretics impotence e) Prednisolone osteomalacia 61 The following are examples of a type I hypersensitivity reaction: a) Penicillin-induced anaphylactic shock b) Methyldopa-induced Coombs positive haemolytic anaemia c) Hydralazine-induced systemic lupus erythematosus (SLE) d) Amiodarone-induced photosensitivity skin rashes e) Sotalol-induced torsade de pointes 62 The following drugs are associated with erythema multiforme: a) Phenytoin b) Cyclophosphamide c) Salbutamol d) Sevoflurane

e) Co-trimoxazole CHAPTER 1 GENERAL PRINCIPLES 12 63 The following drugs are recognized as causing thrombocytopenia: a) Aurothiomalate b) Thiazides c) Heparin d) Mesalazine e) Atenolol 64 The following combinations outside the body (e.g. in infusion bag)cause drug inactivation: a) Penicillin and hydrocortisone b) Phenytoin and 5 per cent dextrose c) Sodium bicarbonate and calcium chloride d) Erythromycin and 0.9 per cent sodium chloride e) Heparin and 5 per cent dextrose 65 Individuals who are slow acetylators (i.e. have relatively lowactivities of hepatic N -acetyltransferase): a) Have prevalence of 510 per cent amongst the white populationin the UK b) Are more likely to develop agranulocytosis whilst being treatedwith clozapine c) Are more likely to develop hepatotoxicity after a paracetamoloverdose d) Are more likely to develop a lupus-like syndrome duringhydralazine therapy e) Are more likely to develop peripheral neuropathy during isoniazidtherapy 66 The following drugs can produce haemolysis in patients with glucose6-phosphate dehydrogenase (G6PD) deficiency: a) Dapsone

b) Probenecid c) Primaquine d) Co-trimoxazole e) Ciprofloxacin 67 Drug-induced exacerbations of acute porphyria: a) Are usually precipitated by enzyme inhibitors(e.g. selegiline) b) Are often precipitated by a single dose of drug c) Are accompanied by increased urinary excretion of5-aminolevulinic acid (ALA) and porphobilinogen d) May be precipitated by ethanol e) May be precipitated by rifampicin 13 M ULTIPLE CHOICE QUESTIONS 68 Abnormal pseudocholinesterase: a) Is typically inherited as a Mendelian dominant condition b) Results in malignant hyperthermia following exposure tosuxamethonium c) Causes warfarin resistance d) Leads to prolonged paralysis following suxamethonium e) Is associated with treatment failure with donepezil for Alzheimersdisease 69 Phase 1 studies (i.e. initial studies of drugs in humans involving anInvestigational Medicinal Product) in the UK: a) Require authorization by the Medicines and Healthcare ProductsRegulatory Agency (MHRA) b) The control group is usually the current drug of choice for theproposed indication c) Always use the oral route of administration d) Only commence after all animal studies have beencompleted e) Are usually performed in patients who are asymptomaticwith a terminal disease 70

The MHRA: a) Is an independent group of clinicians, clinical pharmacologists,toxicologists, pathologists and others who advise the drug licensingauthority b) Is financed directly by the pharmaceutical industry c) Considers the quality, safety and efficacy of medicinalproducts d) Considers the investigation, monitoring and response to adversereactions once a drug has been licensed e) Appoints the committees on ethical practice, which assess drug trials 71 The following adverse reactions should be reported to the MHRAusing the yellow card system: a) Atransient mild skin rash in a patient taking a new non-steroidalanti-inflammatory drug (NSAID) marked with a black triangle inthe British National Formulary (BNF) b) Aggravation of asthma in a known asthmatic with the druginvolved in question a above c) Aconvulsion following pertussis vaccination d) Acute anaphylactic shock leading to death following intravenous benzylpenicillin e) Fatal agranulocytosis associated with clozapine CHAPTER 1 GENERAL PRINCIPLES 14 72 The following licensed drugs are produced by insertion of humangenes into bacterial, yeast or mammalian cell lines: a) Human insulin b) Growth hormone c) Factor VII d) Erythropoietin e) Interferon Answers: see pages 1933 15 E XTENDED MATCHING QUESTIONS

73 PHARMACODYNAMICS EXTENDED MATCHING QUESTIONS A Omeprazole B Clopidogrel C Morphine D Glucagon E Fluoxetine F Atenolol G Dobutamine H Warfarin I Magnesium trisilicate J Insulin Select the drug that causes the pharmacodynamic effect described below: 1 Prolongation of prothrombin time 2 Reduction in blood glucose 3 Reduction in exercise-induced increase in heart rate 4 Pupil constriction 5 Inhibition of gastric acid secretion 74 PHARMACOKINETICS A Prednisolone B Amiodarone C Carbamazepine D Lithium E Enalapril F Metoprolol G Simvastatin H Paracetamol

I Gentamicin J Bendroflumethiazide Choose the drug from the list above which is a good example for the pharma-cokinetic characteristics listed below: 1 Absorption into the systemic circulation following oral administrationis minimal 2 The mean elimination half-life is greater than 28 days in someone withnormal hepatic and renal function 3 Is a prodrug which is hydrolysed to its active metabolite 4 Induces its own metabolism such that plasma concentrations mayreduce significantly on repeated dosing 5 Undergoes active tubular reabsorption CHAPTER 1 GENERAL PRINCIPLES 16 75 PHARMACOGENETICS A Warfarin B Digoxin C Omeprazole D Cefuroxime E Fluconazole F Sildenafil G Suxamethonium H Isoniazid I Heparin J Codeine Match the drug from the above list whose metabolism is most affected by theenzyme genetic polymorphism below: 1 CYP2D6 2 CYP2C9 3

N -Acetyltransferase 4 Pseudocholinesterase 5 CYP2CI9 76 ABSORPTION AND ROUTE OF ADMINISTRATION A Digoxin tablets B Intravenous insulin C Glyceryl trinitrate D Aspirin preparations E Simvastatin preparations F Levodopa G Prednisolone H Methotrexate I Diltiazem preparations J Rectal diazepam Link each of 1 to 5 below with the most appropriate item from Ato J: 1 Unsuitable for generic substitution 2 Bioavailability is 100 per cent 3 Prodrug 4 Sublingual administration circumvents extensive presystemicmetabolism 5 Intrathecal injection is used in childhood leukaemia because of poorpenetration of the bloodbrain barrier 77 DRUG METABOLISM A Azathioprine B Irinotecan C Clozapine D Dalteparin E Phenylephrine

F Rimonabant G Midazolam H Amoxicillin I Isoniazid J Warfarin Choose the drug from the list above which is significantly affected by theenzyme below: 1 Monoamine oxidase 2 CYP1A2 3 CYP3A4 4 Uridine diphosphoglucuronyl transferase (UGT1AI) 5 Thiopurine methyltransferase (TPMT) 17 E XTENDED MATCHING QUESTIONS 78 RENALELIMINATION A Clarithromycin B Para-aminohippuric acid C Probenecid D Salicylate E Atorvastatin F Lithium G Gentamicin H Senna I Thyroxine J Orlistat Link each of 1 to 5 below with the most appropriate item from Ato J: 1 Depends mainly on renal elimination 2

Competes for organic anion transport (OAT) 3 Excretion is enhanced by high urinary pH 4 Shares a proximal tubular transporter with Na 5 Is used to measure renal plasma flow 79 RENALTRACT A Sildenafil B Finasteride C Furosemide D Oxybutinin E Spironolactone F Acetazolamide G Bendroflumethiazide H Eplerenone I Desmopressin J Tamsulosin Link each of 1 to 5 below with the most appropriate drug from Ato J: 1 Causes proximal renal tubular acidosis (RTA) 2 Oestrogen-related adverse effects 3 Blocks distal tubular Na /Cl reabsorption 4 Enhances ototoxicity of gentamicin 5 Adverse interaction with glyceryl trinitrate 80 ADVERSE DRUG REACTIONS A Gentamicin B Amoxicillin C

Simvastatin D Prednisolone E Salbutamol F Isoniazid G Spironolactone H Clarithromycin I Fluoxetine J Flupentixol For each adverse drug reaction match a likely causative drug: 1 Gynaecomastia 2 Osteoporosis 3 Myositis 4 SLE-like syndrome 5 Tardive dyskinesia CHAPTER 1 GENERAL PRINCIPLES 18 81 MONOCLONALANTIBODIES A Infliximab B Bevacizumab C Basilixumab D Anti-D (Rh) immunoglobulin E Natalizumab F Abciximab G Omalizumab H Alemtuzumab I Rituximab J

Palivizumab Match the monoclonal antibody with the mode of action described below: 1 Binds to respiratory syncytial virus 2 Anti IgE 3 Anti-tumour necrosis factor alpha (TNF ) 4 Inhibition of vascular endothelial growth factor (VEGF) 5 Inhibition of glycoprotein IIbIIIa ANSWERS: see pages 3338 19 MCQ ANSWERS ANSWERS MCQ ANSWERS 1 a) F a l s e T a m o x i f e n i s a n a n t i - o e s t r o g e n w h i c h b i n d s t o t h e oestrogen receptor in breast tissue and inhibits oestrogenaction and is used in breast cancer b) TrueSalbutamol is a beta agonist. It is relatively s e l e c t i v e f o r beta 2 effects (bronchodilation) but at higher doses beta 1 effects (tachycardia and tremor) also occur c) TrueMorphine mimics the endogenous encephalins d) FalseCetirizine is an antihistamine (H 1 blocker) e) F a l s e L i s i n o p r i l i s a n a n g i o t e n s i n - c o n v e r t i n g e n z ym e ( A C E ) inhibitor 2 a) TruePyridostigmine is an inhibitor of a c e t y l c h o l i n e s t e r a s e a n d is used in myasthenia gravis b) FalseAtropine blocks muscarinic receptors c) FalseAmlodipine is a calcium channel blocker d) T r u e D i g o x i n i n h i b i t s N a

/K adenosine triphosphatase(ATPase) e) TrueSelegiline is a monoamine oxidase B (MAO-B) i n h i b i t o r used in Parkinsons disease 3 a) FalseSuxamethonium is an agonist that causes a s e e m i n g l y paradoxical inhibitory effect (neuromuscular blockade) bycausing long-lasting depolarization of the neuromuscular junction b) TrueLoratidine is a histamine (H 1 ) antagonist c) TrueRanitidine is a competitive histamine (H 2 ) antagonist d) F a l s e P h e n o x yb e n z a m i n e i s a n i r r e v e r s i b l e a l p h a - r e c e p t o r antagonist e) T r u e N a l o x o n e i s a c o m p e t i t i v e a n t a g o n i s t a t t h e o p i a t e mureceptor 4 a) FalsePartial agonists combine with receptors but are incapable b) Falseof eliciting a maximal response whatever their c) F a l s e c o n c e n t r a t i o n ( s e e Textbook of Clinical PharmacologyandTherapeutics, Chapter 2) d) TrueBuprenorphine is a partial agonist at the opiate mureceptor e) TrueOxprenolol is a partial agonist at the betaadrenoceptor CHAPTER 1 GENERAL PRINCIPLES 20 5 a) TrueMagnesium trisilicate is an antacid which n e u t r a l i z e s gastric acid b) TrueMannitol is an osmotic diuretic c) TrueMethotrexate is a competitive inhibitor of d i h y d r o f o l a t e reductase and inhibits folate metabolism

d) TrueDimercaprol is a chelating agent used in heavy m e t a l poisoning e) FalseSumatriptan is a 5HT 1D agonist used in migraine 6 a) TrueThe magnitude of pharmacological effect usually depends b) Falsedirectly on the concentration of drug (or active metabolites) c) Truein the vicinity of their receptors. However, some drugs d) Falsebind to their target irreversibly so their effects e) Falseoutlast their presence at these sites (e.g. alkylating a g e n t s at DNA) 7 a) TrueClearance and not half-life should be used as a measure of b) Truethe efficiency of drug elimination c) T r u e d) False e) T r u e 8 a) TrueAlthough the one-compartment model is an b) Trueoversimplification, once absorption and distribution are c) Falsecomplete many drugs do obey first-order elimination d) F a l s e k i n e t i c s . S e e F i g . 1 e) T r u e (a) Time (b) Time DruginplasmaLogdruginplasma Fig. 1

One-compartment model. Plasma concentration-time curve following abolus dose of drug plotted (a) arithmetically, or (b) semi-logarithmically. This drugfits a one-compartment model, i.e. its concentration falls exponentially with time. 9 a) T r u e V o l u m e o f d i s t r i b u t i o n dose/ C 0 , where C 0 is the plasma b) Falseconcentration at time 0 calculated by extrapolation of the c) Truelog concentration versus time relationship back to zero 21 MCQ ANSWERS d) Falsefollowing a bolus intravenous injection. 3Lis the e) Trueapproximate total plasma volume in an adult 1 0 a ) T r u e D o p a m i n e t 1 2 , 2 minutes b) T r u e H e p a r i n t 1 2 , 0.52.5 hours c) F a l s e A m i o d a r o n e t 1 2 , mean 53 (range 26107) days d) T r u e G e n t a m i c i n t 1 2

, 1.52 hours e) F a l s e D i a z e p a m t 1 2 , 2050 hours 1 1 a ) TrueIt takes approximately three half-lives to reach 87.5 per cent b) Falseof steady state. After four half-lives it is 93.75 per cent and c) Trueafter five half-lives 96.9 per cent d) T r u e e) T r u e 1 2 a ) TrueImplications of non-linear elimination kinetics include: the b) Truetime taken to eliminate 50 per cent of a dose increases with c) Trueincreasing dose, i.e. half-life increases with dose; once the d) Truedrug elimination process is saturated, a relatively modest e) Falseincrease in dose dramatically increases the amount of d r u g in the body see Textbook of Clinical Pharmacology andTherapeutics , Chapter 3 1 3 a ) TrueEnterohepatic circulation is when a drug is excreted into b) Falsethe bile, reabsorbed from the intestine and returned via the c) Trueportal system to the liver to be recycled d) False e) False 1 4 a ) T r u e S e e

Textbook of Clinical Pharmacology and Therapeutics, b) TrueChapter 4. Although the bioavailability of two preparations c) Truemay be the same, the kinetics can be very different as seen d) Truein some immediate and slow-release drug formulations e) T r u e 1 5 a ) T r u e L e v o d o p a : dopamine b) T r u e A z a t h i o p r i n e : 6-mercaptopurine c) T r u e P e n c i c l o v i r : aciclovir d) T r u e S u l f a s a l a z i n e : aminosalicylate sulfapyridine e) T r u e E n a l a p r i l : enalaprilat 1 6 a ) TrueAcarbose is a competitive inhibitor of intestinal -glucosidases b) FalseMethionine, an antidote to paracematol poisoning, acts n o t in the gastrointestinal tract but predominantly in the liverwhere it repletes glutathione which inactivates the toxicparacetamol metabolite c) TrueOrlistat is used to reduce weight and is an inhibitor o f gastrointestinal lipases and this impairs fat absorption CHAPTER 1 GENERAL PRINCIPLES 22 d)

TrueOlsalazine delivers 5-aminosalicylate to the colon where i t has a local action in inflammatory bowel disease e) TrueVancomycin kills toxin-producing Clostridium difficile , thecause of pseudomembranous colitis within the bowel 1 7 a ) TrueMost oral drugs are absorbed by passive diffusion in the b) Falsesmall bowel. In general low molecular weight, high lipid c) Falsesolubility and lack of charge encourage absorption. Most d) Truepeptides are broken down enzymatically e) False 1 8 a ) FalseActive transport requires specific carrier-mediated energyb) Falseconsuming mechanisms. Naturally occurring polar c) Truenutrients and aliments including sugars, amino acids and d) Truevitamins are absorbed by active or facilitated transport e) Truemechanisms. Drugs that are analogues of such m o l e c u l e s compete for uptake. Further examples includemethotrexate and 5fluorouracil 1 9 a ) TrueFood and drink dilute the drug and can adsorb or b) Trueotherwise compete with it. Transient increases in hepatic c) Falseblood flow such as those that occur after a meal may result d) Falsein greater availability of drug by reducing presystemic e) F a l s e h e p a t i c m e t a b o l i s m 2 0 a )

FalseSublingual administration can be an effective means of b) Falsecausing systemic effects, and has potential advantages over c) Falseoral administration (i.e. when the drug is swallowed) for d) Truedrugs with pronounced presystemic metabolism, e) Trueproviding direct and rapid access to the s y s t e m i c circulation bypassing intestine and liver 2 1 a ) TrueRectal indometacin administered at night is useful i n reducing early morning stiffness in rheumatoid arthritis b) FalseRectal sulfasalazine is used for its local effect i n inflammatory bowel disease c) TrueRectal metronidazole is well absorbed (and much l e s s expensive than the intravenous preparation) d) F a l s e G l yc e r i n s u p p o s i t o r i e s e x e r t a l o c a l e f f e c t t o s t i m u l a t e defecation e) TrueRectal diazepam is used to control convulsions w h e n venous access is difficult (as may be the case in children) 2 2 a ) TrueTransdermal GTN is used in ischaemic heart disease b) TrueTransdermal estradiol is used for hormone r e p l a c e m e n t therapy in menopausal women c) FalseLocal lidocaine is used for its local anaesthetic action ( e . g . for intravenous cannulation in children) 23 MCQ ANSWERS d) T r u e T r a n s c u t a n e o u s f e n t a n yl m a y b e a d m i n i s t e r e d a s a p a t c h for the treatment of chronic severe pain e) TrueNicotine is used to assist cigarette smokers to abstain 2 3 a ) TrueExercise and local massage increase the rate of absorption b)

TrueTransport from the injection site is governed by m u s c l e blood flow deltoid vastus lateralis gluteusmaximus c) TrueThis avoids the risk of sciatic nerve palsy d) FalseUp to maximum of 5mLis acceptable in the buttock o f a n adult e) TrueThis depot preparation is slowly hydrolysed in m u s c l e t o release active drug and is used to improve compliance inschizophrenic patients 2 4 a ) TruePlus potentially fatal cardiotoxicity if rapid infusion b) False c) TrueAn oily emulsion (Diazemuls) reduces this complication d) TrueUsed in hypoglycaemic coma but 20 per cent d e x t r o s e usually preferable e) False 2 5 a ) F a l s e L e v o d o p a i s d e c a r b o x yl a t e d t o d o p a m i n e i n c e n t r a l n e u r o n s b) F a l s e T yr a m i n e i s m e t a b o l i z e d b y m o n o a m i n e o x i d a s e ( M A O ) i n intestine, liver, kidney and nervous tissue. MAO is amitochondrial enzyme c) TrueMetoprolol is extensively metabolized by the C Y P 4 5 0 (CYP2D6) enzyme family d) FalseSuxamethonium is metabolized by plasma cholinesterase e) F a l s e P u r i n e s ( e . g . 6 - m e r c a p t o p u r i n e ) a r e m e t a b o l i z e d b y thiopurine methyl transferase and xanthine oxidase whichare non-microsomal enzymes 2 6 a ) TrueCiclosporin is metabolized by the CYP3Afamily o f isoenzymes b) TrueClarithromycin as well as being metabolized by C Y P 4 5 0 enzymes inhibits the metabolism of other drugs subject toCYP3Ametabolism (e.g. warfarin, theophylline andterfenadine). Azithromycin does not inhibit CYP3A c) T r u e P h e n y t o i n a l s o i n d u c e s s e v e r a l C Y P 4 5 0 enzymes

d) F a l s e A d r e n a l i n e i s a c a t e c h o l a m i n e a n d i s m e t a b o l i z e d b y catecholO -methyltransferase which is present in thecytosol and MAO in mitochondria e) TrueWarfarin has a narrow therapeutic index CHAPTER 1 GENERAL PRINCIPLES 24 2 7 a ) TrueDapsone is used in leprosy and dermatitis herpetiformis b) FalseCiclosporin, an immunosuppressant, is metabolized b yCYP3A c) FalseGentamicin is eliminated unchanged by the kidney d) TrueIsoniazid is used to treat tuberculosis e) TrueHydralazine is a vasodilator used as an adjunct to o t h e r treatment for hypertension. When used alone it causestachycardia and fluid retention. It can cause an SLE-likesyndrome, which is more common in slow acetylators.An intravenous preparation is available to treathypertensive crises in pregnancy 2 8 a ) TrueRifampicin is a broad-spectrum antibiotic used i n tuberculosis and Legionnaires disease b) TrueCarbamazepine autoinduces its metabolism and is a n anticonvulsant c) T r u e S t J o h n s w o r t , a h e r b a l r e m e d y, m a y b e p u r c h a s e d w i t h o u t a prescription. It is a potent, broad-spectrum CYP450enzyme inducer d) TruePhenobarbital is an anticonvulsant e) FalsePenicillin is predominantly eliminated unchanged in t h e urineDrug interactions secondary to hepatic enzyme induction and inhibition areclinically significant when there is a close correlation between plasma concentration and effect, and a steep dose response curve. Regular use of ethanolinduces CYP450 metabolism but has minimal effect on its own metabolism,which is predominantly via cytoplasmic alcohol dehydrogenase 2 9 a ) TrueFluvoxamine, an antidepressant, is a selective s e r o t o n i n reuptake inhibitor (SSRI) which inhibits the metabolism oftheophylline and warfarin b) TrueGrapefruit-containing products inhibit C Y P 3 A predominantly in the intestine

c) F a l s e D i g o x i n i s p r e d o m i n a n t l y e l i m i n a t e d u n c h a n g e d i n t h e urine d) TrueItraconazole is an azole antifungal agent e) TrueCiprofloxacin is a fluoroquinolone antibacterial drug 3 0 a ) TruePresystemic metabolism occurs in the gastrointestinal b) Falsemucosa and liver; presystemic (first-pass) metabolism c) Falsenecessitates high oral doses in comparison with the d) T r u e i n t r a v e n o u s d o s e e) T r u e 3 1 a ) TrueAspirin overdose decreases the rate of gastric emptying b) T r u e 25 MCQ ANSWERS c) T r u e d) TrueAnticholinergic properties reduce gastroi n t e s t i n a l motility e) FalseMetoclopramide accelerates gastric emptying 3 2 a ) FalseThe absorption of thiazides is reduced b) FalseThe volume of distribution of lidocaine is r e d u c e d probably because of decreased tissue perfusion c) TrueThe distribution volume of furosemide is largely c o n f i n e d to the vascular compartment d) FalseIs prolonged predominantly due to decreased h e p a t i c perfusion e) F a l s e G l o m e r u l a r f i l t r a t i o n i s r e d u c e d i n c a r d i a c f a i l u r e a n d hence the elimination half-life of gentamicin is prolonged(i.e. not decreased) 3 3 a ) FalseGastric pH increases

b) TrueThe ratio of unbound:bound phenytoin rises in r e n a l failure. It is the unbound drug which is active and thelaboratory assay for phenytoin measures total bloodconcentration (bound and unbound) c) TrueThe bloodbrain barrier becomes functionally less of a barrier to drug distribution in severe renal failure.This may be the reason for the increased incidence ofconfusion associated with cimetidine and famotidine inrenal failure d) T r u e e) False 3 4 a ) TrueThe kidney is involved to some degree in the elimination b) Trueof many drugs in the unchanged form and most drug c) Truemetabolites in humans. High lipid solubility and the d) Trueun-ionized state favour tubular reabsorption e) False 3 5 a ) False b) FalseBut reduce dose; rashes more common c) FalseMay need very high doses for any diuretic effect d) TrueIncreased risk of lactic acidosis e) T r u e D i r e c t n e p h r o t o x i c i t y , a n t i - a n a b o l i c , i n c r e a s e s blood urea 3 6 a ) TrueNSAIDs cause salt and water retention and reduce renal b) Falseblood flow by inhibition of prostacyclin and prostaglandinE 2 synthesis in patients with renal compromise. Thisdisrupts autoregulation of renal blood flow and GFR thuspreventing the normal physiological mechanism which CHAPTER 1 GENERAL PRINCIPLES 26

ensures preferential perfusion of the functioning kidney.NSAIDs are less commonly associated with papillarynecrosis or interstitial nephritis c) TrueRadiographic contrast media cause a transient d e c r e a s e i n GFR. The mechanism is not completely understood d) TrueACE inhibitors, although often effective in treating h e a r t failure and hypertension in patients with renal disease, canimpair renal function. They must be avoided in bilateralrenal artery stenosis e) TrueCan cause acute tubular necrosis and renal t u b u l a r acidosis 3 7 a ) F a l s e C a r b i m a z o l e i s a n a n t i t h yr o i d d r u g . T h e e f f e c t i v e d o s e i s determined by monitoring blood thyroid function tests.Carbimazole should be stopped promptly if there is clinicalor laboratory evidence of neutropenia b) FalseWarfarin therapy is monitored by measurement of t h e prothrombin time (INR) c) TrueGentamicin peak concentrations (30 minutes after d o s e ) correlate with efficacy, trough concentrations correlate withtoxicity. Aminoglycosides are associated with ototoxicityand nephrotoxicity. Extended interval dosing foraminoglycosides uses nomograms of drug concentrationrelated to time post dosing to guide further dosing d) TrueInsidious increases in serum lithium concentrations c a n lead to tremor, diarrhoea, gastrointestinal upsets, reducedconscious level and ultimately convulsions. Thyroidfunction should also be monitored e) TrueNot only does ciclosporin show marked i n t e r i n d i v i d u a l variability but also compliance is a particular problem inchildren. Deterioration in renal function post transplantmay reflect either graft rejection possibly associated withlow ciclosporin concentrations or toxicity from excessiveconcentrations 3 8 a ) FalseMost drugs cross the placenta (a cellular membrane) by b) Falsepassive diffusion down a concentration gradient. Lipid c) Truesolubility enhances transport across membranes and drugs d) Truein the un-ionized state are more lipid soluble. The human e) Trueplacenta possesses multiple enzymes, including e n z y m e s that metabolize endogenous compounds and drugs 3 9 a )

TrueThe risk of having an abnormal baby is about 10 per c e n t i n mothers drinking 3060mLethanol per day, rising to40 per cent in chronic alcoholics 27 MCQ ANSWERS b) TrueWarfarin has been associated with nasal hypoplasia a n d chondrodysplasia when given in the first trimester andwith CNS abnormalites and haemorrhagic complications inlater pregnancy. Neonatal haemorrhage is difficult toprevent because of the immature enzymes in fetal liver andlow stores of vitamin K c) TrueAll retinoic acid derivatives are teratogens. E f f e c t i v e contraception must be used for at least one month before,during, and at least one month after oral treatment withany retinoic acid analogue or derivative d) FalseThe minor analgesic of choice in pregnancy e) FalseCommonly used to treat urinary tract infection i n pregnancy 4 0 a ) TrueThis is of little consequence unless rapid d r u g absorption/action is required. Vomiting associated withpregnancy occasionally makes oral administrationimpractical b) TrueBlood volume in pregnancy increases by one-third c) TruePlasma volume increases from 2.5 to 4Lat term a n d i s disproportionate to the expansion in red cell mass so thehaematocrit falls d) TrueOedema, which at least one-third of women e x p e r i e n c e during pregnancy, may add up to 8Lto the volume ofextracellular water. For water-soluble drugs (which usuallyhave a relatively small volume of distribution) thisincreases the volume of distribution e) F a l s e M e t a b o l i s m o f d r u g s b y t h e h e p a t o c yt e d u r i n g p r e g n a n c y is increased 4 1 a ) TrueExcretion of drugs via the kidney increases because renal b) Trueplasma flow almost doubles and the GFR increases by c) Truetwo-thirds during pregnancy, see Textbook of Clinical d) T r u e Pharmacology and Therapeutics, Chapter 9

e) T r u e 4 2 a ) T r u e b) T r u e c) FalseMinimal experience, animal data discouraging d) FalseThe fetal VIIIth nerve is more sensitive to a m i n o g l yc o s i d e toxicity e) FalseRibavirin inhibits a wide range of DNAand R N A v i r u s e s . It is used by inhalation to treat severe respiratory syncytialvirus (RSV) bronchiolitis in children and is used incombination with interferon alfa to treat chronic hepatitis Cinfection. It is a very potent teratogen in animal models. CHAPTER 1 GENERAL PRINCIPLES 28 Effective contraception must be ensured for four monthsafter treatment in women and seven months aftertreatment in men. Condoms must be used if partner ofmale patient (ribavirin excreted in semen) is pregnant 4 3 a ) FalseNon-drug treatment (reassurance, small frequent b) Falsemeals and advice on posture) should be pursued in the c) T r u e f i r s t i n s t a n c e d) FalseMisoprostol, an analogue of prostaglandin E 1 , causesabortion e) T r u e 4 4 a ) TrueThis is also true for the low molecular weight h e p a r i n s (which are often the anticoagulants of choice inpregnancy) b) FalseWarfarin is a teratogen and is associated with a h i g h incidence of haemorrhagic complications in latepregnancy c) False d) False e) FalsePethidine, which is commonly used as an analgesic d u r i n g delivery, can cause apnoea of the newborn which isreversed with naloxone 4 5 a )

FalseEpilepsy in pregnancy can lead to fetal and maternal b) Truemorbidity/mortality through convulsions. Although all c) Trueanticonvulsants are teratogenic, the risk of untreated d) Trueepilepsy is greater to the mother and fetus than druge) Falseinduced teratogenicity. To counteract the risk of n e u r a l tube defects, adequate folate supplements are advised 4 6 a ) FalseIf treatment is initiated during pregnancy it is appropriate b) Falseto use methyldopa which has the longest record of use c) Falseand follow-up in children born to mothers following d) Falsetreatment. Beta blockers are contraindicated in asthma. e) TrueACE inhibitors are teratogens. Although not l i c e n s e d f o r use in pregnancy, nifedipine appears effective andrelatively well tolerated. See Textbook of ClinicalPharmacologyand Therapeutics , Chapter 9 4 7 a ) FalseCommonly used to treat asthma and o c c a s i o n a l l y premature labour b) FalseMinimal problems when given by inhalation or in s h o r t courses (e.g. to help immature fetal lung) and althoughcleft palate and congenital cataract have been attributed tolarge systemic doses of corticosteroids the benefit oftreatment usually outweighs the risk 29 MCQ ANSWERS c) False Although there is an increased risk of spontaneous abortionassociated withgeneralanaesthesiaacausallinkisunprovenandinmostcircumstancesfailuretooperatewouldhavedramatically increasedtherisktomotherandfetus d) FalseFalciparum malaria has a high mortality in pregnancy e)

FalseSucralfate is not absorbed 4 8 a ) TrueNeonates are not miniature adults in terms of drug b) Truehandling because of differences in body constitution, drug c) Trueabsorption, distribution, metabolism, excretion and c) Truesensitivity to adverse reactions, see Textbook of Clinical d) T r u e Pharmacology and Therapeutics , Chapter 10 e) T r u e 4 9 a ) TrueSignificant concentration in breast milk and there is a theoretical risk from iodine release b) FalseMinimal concentration in breast milk c) TrueHigh concentration in breast milk, animal e x p e r i m e n t s suggest damage to growing joints d) T r u e e) False 5 0 a ) FalseBut may cause diarrhoea in infant b) T r u e c) T r u e d) False e) FalseBut gives milk an unpleasant taste 5 1 a ) TrueThe total dose of drug in breast milk ingested by the b) Trueinfant is usually too small to cause problems (with some c) Truenotable exceptions, see Table 1). The infant should be

d) Truemonitored clinically if beta-adrenoceptor antagonists e) Falseare prescribed to the mother. Milk is mildly acid, so w e a k bases accumulate in it 5 2 a ) T r u e b) TrueA5- to 10-day course of systemic corticosteroids is o f t e n sufficient c) F a l s e P o t e n t i a l l y f a t a l d) False e) F a l s e P o t e n t i a l l y f a t a l 5 3 a ) T r u e S e e Textbook of Clinical Pharmacology and Therapeutics ,Chapter 11 b) T r u e c) FalseOne reason why plasma creatinine is a less r e l i a b l e indicator of renal function in the elderly is that endogenouscreatinine production is reduced CHAPTER 1 GENERAL PRINCIPLES 30 d) T r u e e) T r u e 5 4 a ) F a l s e G l i c l a z i d e , a s h o r t - a c t i n g s u l f o n yl u r e a , i s c o m m o n l y prescribed to elderly diabetics whose blood glucose isinadequately controlled by diet alone b) T r u e c) TrueMorphine increases bladder neck sphincter tone d) T r u e A m i t r i p t yl i n e , a s e d a t i v e t r i c yc l i c a n t i d e p r e s s e n t , a l s o h a s anticholinergic effects e) False 5 5 a )

TrueRelated to the decrease in GFR associated with ageing b) TrueRelated to the decrease in GFR associated with ageing c) TrueRelated to the decrease in GFR associated with ageing d) TrueRelated to the decrease in GFR associated with a g e i n g reducing the clearance of the active morphineglucuronide e) TrueDue to the increase in volume of distribution and p r o b a b l y also reduced metabolism 5 6 a ) False b) FalseFinasteride is a specific inhibitor of the enzyme5 -reductase which metabolizes testosterone into themore potent androgen, dihydrotestosterone c) False Table1 Some drugs to be avoided during breastfeeding AmiodaroneAspirinBenzodiazepinesChloramphenicolCiclosporinCiprofloxacinCocaineCombined oral contraceptivesCytotoxicsErgotamineOctreotideStimulant laxatives (senna)SulfonylureasThiazide diureticsVitamin A/retinoid analogues CHAPTER 1 GENERAL PRINCIPLES 32 6 2 a ) TrueAlso associated with acne, coarse facies, hirsutism a n d toxic epidermal necrolysis b) False c) False d) False e) TrueUsually due to the sulphamethoxazole component but m a y also be caused by trimethoprim 6 3 a ) T r u e S e e Textbook of Clinical Pharmacology and Therapeutics ,Chapter 12 b) T r u e

c) T r u e d) T r u e e) False 6 4 a ) TrueInactivation of penicillin b) T r u e P r e c i p i t a t e s c) T r u e P r e c i p i t a t e s d) False e) False 6 5 a ) FalseApproximately 45 per cent of the white population are b) Falseslow acetylators. Examples of drugs acetylated include: c) Falseisoniazid, hydralazine, phenelzine, dapsone and d) Trueprocainamide. The usual marker is the m o n o a c e t y l dapsone metabolite: dapsone ratio in the plasma e) T r u e I s o n i a z i d - i n d u c e d p e r i p h e r a l n e u r o p a t h y c a n b e p r e v e n t e d by prophylactic use of pyridoxine 6 6 a ) TrueThe gene for G6PD is located on the X chromosome. G6PD b) Truedeficiency is more common in people from Mediterranean c) T r u e c o u n t r i e s d) T r u e e) T r u e 6 7 a ) FalseThe acute porphyrias are due to hereditary enzyme defects b) Truein haem biosynthesis and may be precipitated by many c) T r u e d r u g s ( s e e l i s t i n

BNF ), especially inducers of CYP450 d) T r u e e n z y m e s e) T r u e 6 8 a ) FalseThe usual response to a single intravenous dose of b) Falsesuxamethonium is muscular paralysis which lasts for about c) False6 minutes. The effect is brief due to hydrolysis of d) Truesuxamethonium by plasma pseudocholinesterase. e) FalseApproximately 1 in 2500 patients have a b n o r m a l pseudocholinesterase which may result in prolongedparalysis for 2 hours. Inheritance is Mendelian recessive 33 EMQ ANSWERS 6 9 a ) T r u e b) FalsePlacebo is the usual control c) False d) False e) F a l s e P h a s e 1 s t u d i e s a r e u s u a l l y p e r f o r m e d i n h e a l t h y m a l e adults aged 1835 years 7 0 a ) FalseThe MHRAis the regulatory review board of the UK who b) Falseadvise when certificates to perform clinical trials should be c) Trueissued to pharmaceutical companies and advise, following d) Truereview of all the data from a submission, on the granting of e) Falsea product licence which will allow the company to m a r k e t the drug

7 1 a ) T r u e S e e Textbook of Clinical Pharmacology and Therapeutics , b) T r u e C h a p t e r 1 2 c) T r u e d) T r u e e) T r u e 7 2 a ) TrueThe production of human proteins using recombinant b) TrueDNA/RNAtechnology not only produces large quantities c) Trueof natural human proteins but also minimizes the risk d) Trueof blood-borne viral infection such as hepatitis B and C e) T r u e a n d H I V EMQ ANSWERS 73 PHARMACODYNAMICS Pharmacodynamics is the study of the effects of drugs on biological processes. 1H Warfarin prolongs the prothrombin time and is the most commonlyprescribed oral anticoagulant. It is a vitamin K antagonist. The onset ofaction is at least 4872 hours after initiation of treatment following aloading dose. There is wide variability in drug response related togenetics, hepatic function, drug and alcohol interactions. Monitoringof treatment through measurement of INR (international normalizedratio) calculated from the prothrombin time is essential. Prolongationof INR predisposes to haemorrhage. 2J Insulin controls the metabolic disposition of carbohydrate, fats andamino acids. Insulin is inactivated by gastrointestinal enzymes, henceadministration is by injection or occasionally by inhalation. Excessinsulin causes hypoglycaemia. 3F Atenolol is one of the many beta-adrenoceptor blocking drugsavailable. Indications include hypertension and angina. CHAPTER 1 GENERAL PRINCIPLES 34 Beta-adrenoreceptor blockers are contraindicated in second- andthird-degree heart block and asthma.

4C Morphine, an opioid, narcotic analgesic causes pupillary constriction by stimulating -receptors in the EdingerWestphal nucleus in themid-brain. Whilst this action is not of therapeutic importance itprovides a useful diagnostic sign in narcotic overdose or recentexposure. 5A Omeprazole inhibits gastric acid secretion by blockade of the H /K ATPase enzyme system of the gastric parietal cells. Omeprazole andother proton pump inhibitors are indicated in the management ofpeptic ulcers, dyspepsia and gastro-oesophageal reflux. Incombination with antibacterial drugs proton pump inhibitors are usedin the eradication of Helicobacter pylori . 74 PHARMACOKINETICS Pharmacokinetics is defined as the study of the time-course of drug absorp-tion, distribution, metabolism and excretion. 1I The absorption of gentamicin (and other aminoglycoside antibacterialdrugs) following oral administration is minimal. Hence gentamicin isused by injection (intramuscular and intravenous) and topically. 2B Amiodarone, an effective antidysrhythmic drug, is only slowlyeliminated by the liver, with a mean elimination half-life of 53 days.Hence effects may continue for several months after dosing has ceased. 3E Enalapril is hydrolysed to its active metabolite, enalaprilat, which is anACE inhibitor. 4C Carbamazepine, an antiepileptic, induces its own metabolism suchthat plasma concentrations reduce significantly on repeated dosing. Ithas an elimination half-life of 2560 hours following a single dose, butapproximately 10 hours after repeated dosing. 5D Lithium undergoes active tubular reabsorption. It mimics sodium onthe proximal tubular sodium ion reabsorption mechanism, hence co-administration of thiazides prolongs the half-life of lithium andpredisposes to toxicity. 75 PHARMACOGENETICS Pharmacogenetics is the study of variation in drug responses under hereditarycontrol. 1J Approximately 70 polymorphic variants of CYP2D6 have been definedin humans. CYP2D6 enzyme is deficient in about 710 per cent of theUK white population. Drugs affected include codeine (minimalanalgesia as poor metabolizers convert little to morphine), 35 EMQ ANSWERS dextrometorphan, metoprolol, some SSRIs (e.g. fluoxetine) and someantipsychotics (e.g. haloperidol). 2A

Drugs metabolized by CYP2C9 are eliminated more slowly by poormetabolizers who are more susceptible to dose-related adverse drugreactions (ADRs), e.g. warfarin, losartan and sulphonylureas. 3H Slow and rapid acetylator status are inherited in a simple Mendelianmanner, rapid metabolism is autosomal dominant. Drugs that are N -acetylated include isoniazid, dapsone, procainamide andhydralazine. 4G Pseudocholinesterase hydrolyses suxamethonium, a muscle relaxantused for short procedures such as intubation since muscle paralysislasts only 36 minutes. There is an autosomal recessive enzyme variant(1:2500 of the population) which is associated with prolongedparalysis requiring artificial ventilation for 2 hours or longer after anintravenous dose. Heterozygotes are unaffected. 5C CYP2C19 polymorphism affects metabolism of some proton pumpinhibitors e.g. omeprazole and lansoprazole. Poor metabolizers obtaingreater acid suppression and improved healing rates. Other substratesfor CYP2C19 include certain tricyclic and SSR1 antidepressants andR-warfarin. Warfarin is primarily a CYP2C9 substrate. 76 ABSORPTION AND ROUTE OF ADMINISTRATION Drug absorption, and hence the route by which a particular drug may usefully be administered, is largely determined by the rate and extent of penetration of biological phospholipid membranes. 1I Generic substitution seldom causes clinical problems but slow-releasepreparations of diltiazem, a calcium channel blocker, are anexception. 2B When a drug is administered intravenously its bioavailability is bydefinition 100 per cent. 3F Levodopa (unlike dopamine) can enter nerve terminals in the basalganglia where it undergoes decarboxylation to form dopamine,partially correcting the nigrostriatal dopamine deficiency present inParkinsons disease. 4C Glyceryl trinitrate is used most commonly to relieve and preventanginal pain. 5H Intrathecal injection predisposes to neurotoxicity. This route shouldnever be used without expert training. CHAPTER 1 GENERAL PRINCIPLES 36 77 DRUG METABOLISM Drug metabolism is one of the primary mechanisms by which drugs are inac-tivated. However, drug metabolism in certain cases leads to increased drugactivity, e.g. activation of prodrugs. 1E Phenylephrine, an indirectly acting sympathomimetic, may cause ahypertensive crisis if taken by a patient on an MAO inhibitor. 2C Clozapine is metabolized by CYP1A2, which is inhibited byfluvoxamine (SSRI antidepressant).

3G Midazolam, a short-acting benzodiazepine, is often used as a probe instudies to determine if a drug induces or inhibits CYP3A4 metabolism. 4B Patients with Gilberts disease have unconjugatedhyperbilirubinaemia caused by an inherited deficiency of UGT1AI.Fasting and oestrogens may aggravate jaundice. Gilberts disease isalmost always irrelevant to drug metabolism with the exception of theactive metabolite of irinotecan (used in metastatic colon cancer),whose toxicity is increased in Gilberts disease. 5A 6-Mercaptopurine (6-MP) is the active metabolite of azathioprine.Bone marrow suppression is more likely in those deficient inthiopurine methyltransferase (0.3 per cent of white population). 78 RENALELIMINATION The kidneys are involved in the elimination of virtually every drug or drugmetabolite. 1G Gentamicin, an aminoglycoside antibacterial drug with a lowtherapeutic index, is predominantly eliminated via the kidney. 2C Probenecidcompetesfortheproximaltubuleactivesecretionoforganicanionshencereducesthetubularsecretionof penicillinandmethotrexate. 3D Urinary alkalinization enhances the excretion of salicylate reducingtoxicity after salicylate/aspirin overdose. 4F Hence salt depletion which causes increased proximal tubular sodiumion reabsorption causes lithium toxicity unless the dose of lithium isreduced. 5B Para-aminohippuric acid is excreted so efficiently that it is completelyextracted from the renal plasma in a single pass through the kidney. 7 9 R E N A L T R A C T 1F Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueoushumour production which is beneficial in glaucoma. It is a weak 37 EMQ ANSWERS diuretic and has a specific role in treating epilepsy associated withmenstruation. 2E Spironolactones active metabolite, canrenone, is an aldosteroneantagonist, which also acts on sex hormone receptors and can causegynaecomastia, menstrual disorders and testicular atrophy. 3G Bendroflumethiazide blocks tubular Na /Cl reabsorption. 4C Furosemide and other loop diuretics enhance aminoglycosideototoxicity through their action on Na

/K /2Cl co-transport in theinner ear. 5A Sildenafil inhibits phosphodiesterase V that inactivates cGMP; glyceryltrinitrate activates guanylate cyclase and the combination can causesevere hypotension. 80 ADVERSE DRUG REACTIONS Adverse drug reactions are unwanted effects caused by normal therapeuticdoses of drugs. 1G Spironolactone acts as a potassium-sparing diuretic through itsantagonism of aldosterone, but also acts on progesterone andandrogen receptors. 2D Osteoporosis is an important adverse effect with chronic use ofprednisolone and all other glucocorticosteroids (diabetes is another). 3C Myositis is a dose-related adverse effect associated with statins andfibrates. 4F SLE-like syndrome is associated with isoniazid, procainamide,hydralazine, chlorpromazine and anticonvulsants. It resembles SLEtogether with a positive antinuclear factor test. It is dose related. Thesedrugs may act as haptens, combining with DNAand forming antigens.The symptoms resolve (sometimes slowly) on drug withdrawal. 5J Tardive dyskinesia is a troublesome adverse effect associatedpredominantly with traditional D 2 -blocking antipsychotic drugs,which follows months or years of continued treatment. 81 MONOCLONALANTIBODIES Monoclonal antibodies are highly specific antibodies derived from one classof cells which recognize one antigen. Receptor affinity is high and toxicity islikely to be due to exaggerated pharmacological action or hypersensitivity. 1J Palivizumab (Synagis ) is used in at-risk infants to prevent seriouslower respiratory-tract disease caused by RSV. At-risk infants includesthose with serious congenital heart disease. CHAPTER 1 GENERAL PRINCIPLES 38 2G Omalizumab (Xolair ) binds to IgE and can be used as additionaltherapy in asthmatics with proven IgE sensitivity to inhaled allergenswhose asthma is inadequately controlled by highdoseglucocorticosteroids (systemic and inhaled); optimal bronchodilatortherapy

(short- and long-acting beta-2 agonists plus anticholinergics)plus oral leukotriene antagonists. 3A Infliximab (Remicade ) inhibits TNF activity and is used inrheumatoid arthritis and psoriatic arthritis in adults who have failedto respond to at least two other disease-modifying agents (e.g.penicillamine and methotrexate). It can also be used in inflammatory bowel disease. 4B Bevacizumab (Avastin ) inhibits VEGF. It is a first-line treatment formetastatic colorectal cancer in combination with 5 fluorouracil plusfolinic acid plus irinotecan (FOLFIRI). 5F Abciximab (ReoPro ) binds to platelet IIb/IIIa receptors blockingfibrinogen binding. It is used as an adjunct to heparin and aspirin inhigh-risk patients undergoing percutaneous coronary intervention. Itcan be used once only to avoid thrombocytopenia. CHAPTER TWO NERVOUSSYSTEM MULTIPLE CHOICE QUESTIONS 82 Benzodiazepines: a) Potentiate the sedative effects of alcohol b) Should only be used as hypnotics for a maximum of 24 weeks c) Suppress rapid eye movement (REM) sleep d) Act by binding to the gamma-aminobutyric acid (GABA)receptorchloride channel complex and facilitate the opening of thechannel in the presence of GABA e) Are anxiolytic 83 Benzodiazepine dependence and withdrawal syndrome: a) Benzodiazepine withdrawal symptoms should be treated with buspirone b) Fits can occur in the first week after withdrawal c) The full withdrawal picture usually appears after an interval of 38weeks d) Perceptual distortions are characteristic e) Shorter-acting benzodiazepines are less likely to cause dependenceand should be substituted for longacting benzodiazepines whenwithdrawing a patient from benzodiazepines 84

Diazepam: a) Has a half-life of less than 20 hours b) Can cause anterograde amnesia c) Is effective in terminating acute dystonia caused by metoclopramide d) Never causes fatal overdose e) The major site of metabolism is the liver 85 Temazepam: a) Has a shorter half-life than diazepam b) Potentiates the effects of alcohol c) Causes no hangover effect 10 hours post dosing d) Is not addictive e) Is more potent than lorazepam CHAPTER 2 NERVOUS SYSTEM 40 86 Clomethiazole (chlormethiazole): a) Is not absorbed orally b) Has a half-life of approximately 10 hours c) In cirrhosis the bioavailability is increased about 10-fold d) High doses cause cardiovascular and respiratory depression e) Is antagonized by ethanol 87 Promethazine: a) Is a GABAagonist b) Is available without prescription c) Causes dry mouth, constipation and reduced sweating d) Liver failure is an absolute contraindication e)

May cause hallucinations 88 Zopiclone: a) Is an ultra short-acting benzodiazepine b) Is the hypnotic of choice in a breastfeeding mother c) Is a more effective anticonvulsant than clonazepam d) Is associated with drug dependence e) Can cause confusion 89 The following drugs may mimic some of the common clinical featuresof schizophrenia: a) Levodopa b) Salbutamol c) LSD d) Diamorphine e) Methylenedioxymethylamphetamine (MDMA, ecstasy) 90 Blockade of central D 2 receptors: a) Parallels the clinical efficacy of the conventional antipsychotic drugssuch as chlorpromazine and haloperidol b) Induces extrapyramidal effects c) Repeated administration of D 2 antagonists causes a reduction in D 2 agonist sensitivity due to an increase in abundance of thesereceptors d) Repeated administration of D 2 antagonists may lead to tardivedyskinesia e) Causes a decrease in cardiac output 91 Adverse effects associated with phenothiazines include: a) Dry mouth

b) Blurred vision c) Postural hypotension d) Impaired temperature control e) Jaundice 41 M ULTIPLE CHOICE QUESTIONS 92 Chlorpromazine: a) Is the first-line treatment for malignant neuroleptic syndrome b) Has a low volume of distribution (approx. 100mL/kg) c) Is predominantly eliminated via the kidneys as unchangedchlorpromazine d) Of the chlorpromazine in plasma, 9095 per cent is bound to plasmaproteins e) Usually once-daily administration is adequate 93 Flupentixol: a) Is particularly effective in mania b) May be given once every 24 weeks via the intramuscular route forchronic schizophrenia c) Is less sedating than chlorpromazine d) Is more prone than chlorpromazine to produce extrapyramidaltoxicity e) Should not be used in patients with porphyria 94 Clozapine: a) Has weak D 2 -blocking activity b) Is effective in up to 60 per cent of patients who have not respondedto phenothiazines c) Is effective against negative as well as positive symptoms d) Rarely causes tardive dyskinesia e) Causes blood dyscrasias more commonly than most antipsychotics 95

Newer atypical drugs such as olanzapine and risperidone: a) Are less effective than traditional antipsychotic drugs against thenegative symptoms of schizophrenia b) Are associated with weight loss c) Bind irreversibly to D 2 receptors d) Are associated with an increased incidence of stroke in elderlypatients with dementia e) Are virtually free from extrapyramidal side-effects at standard doses 96 The following drugs raise synaptic and/or total brain monoamines: a) Cocaine b) Amitriptyline c) Imipramine d) Phenelzine e) Amphetamine CHAPTER 2 NERVOUS SYSTEM 42 97 Tricyclic antidepressants: a) Are more effective in endogenous rather than reactive depression b) Are particularly effective when the depression is associated withpsychomotor and physiological changes c) Onset of therapeutic action is approximately two weeks afterstarting therapy d) Are effective in the management of panic disorder e) Are used for the treatment of nocturnal enuresis in children 98 Antidepressants with sedative properties include: a) Amitriptyline b) Dosulepin c)

Citalopram d) Paroxetine e) Sertraline 99 The following are consistent with tricyclic antidepressant overdose: a) Dilated pupils b) Hyperreflexia c) Sinus tachycardia d) Widened QRS on the ECG e) Convulsions 100 Amitriptyline: a) Is highly lipid soluble b) Is highly protein bound c) Has a low volume of distribution (approx. 100mL/kg body weight) d) Blocks uptake of monoamines into cerebral and other neurons e) Delays gastric emptying 101 Fluvoxamine: a) Inhibits monoamine oxidase (MAO) b) Is a powerful anticholinergic agent c) Is less sedative than trazodone d) Inhibits a CYP450 isoenzyme e) During therapy the blood count should be monitored weekly 102 Fluoxetine: a) Selectively blocks neuronal uptake of noradrenaline b) Is more cardiotoxic than imipramine c) Is less sedative than amitriptyline d)

Is associated with nausea and dyspepsia e) Has a short elimination half-life of 12 hours 43 M ULTIPLE CHOICE QUESTIONS 103 Phenelzine: a) Is a reversible selective inhibitor of MAO-B b) Onset of therapeutic effect is usually within one week c) Is ineffective if used alone in the treatment of depression d) Is sometimes effective in reducing hypochondriacal and hystericalsymptoms e) Is more likely to cause a hypertensive crisis when an indirectlyacting sympathomimetic (e.g. ephedrine) is given concurrentlyrather than a directly acting sympathomimetic (e.g. adrenalinecombined with local anaesthetic) 104 Moclobemide: a) Is a reversible selective inhibitor of MAO-A b) Is effective adjunct therapy in Parkinsons disease c) Has a longer duration of MAO inhibition compared to phenelzineafter stopping therapy d) Causes dry mouth in over 50 per cent of patients e) Is less likely than phenelzine to cause a food (tyramine) interaction 105 The following foodstuffs can cause a hypertensive/hyperthermicreaction during non-selective MAO inhibitor therapy: a) Cheese b) Yoghurt c) Beer d) Marmite e) Grouse 106 Lithium toxicity can be precipitated by: a) Sodium depletion b)

Thiazide therapy c) Angiotensin-converting enzyme (ACE) inhibitors d) Non-steroidal anti-inflammatory drugs (NSAIDs) e) Atenolol 107 Tricyclic antidepressant therapy should not be started within 14 days oftherapy with: a) Citalopram b) lsocarboxazid c) Tranylcypromine d) Moclobemide e) St Johns wort CHAPTER 2 NERVOUS SYSTEM 44 108 Muscarinic antagonists (e.g. procyclidine): a) Are predominantly used in parkinsonism caused by antipsychoticdrugs b) Are least effective in the treatment of tremor c) Are ineffective in the management of post-encephaliticparkinsonism d) Must not be used with levodopa e) May cause confusion in the elderly 109 The following enhance central dopaminergic activity: a) Inhibition of MAO-B b) Bromocriptine c) Apomorphine d) Haloperidol e) Intravenous dopamine 110 Levodopa: a)

Can enter nerve terminals b) Is oxidized by MAO to form dopamine c) Is antagonized by ropinirole d) Metabolism is reduced by entacapone e) May cause dystonic reactions 111 Levodopa: a) Is the amino acid precursor of dopamine b) Improves bradykinesia and rigidity more than tremor c) Levodopa therapy should be initiated with a loading dose d) Should be taken on an empty stomach e) Involuntary movements and psychiatric complications are commonunwanted effects 112 Bromocriptine: a) Stimulates release of endogenous dopamine b) Stimulates postsynaptic D 2 receptors c) Shouldnotbeprescribeduntilthereisinadequateresponsetolevodopa d) Has an antiemetic action e) Inhibits the release of prolactin from the pituitary 113 Selegiline: a) Selectively inhibits MAO-B b) The most common adverse effect is postural hypotension c) Is principally eliminated unchanged in the urine d) Cannot be prescribed concurrently with levodopa e) Cannot be prescribed concurrently with amantadine CHAPTER 2 NERVOUS SYSTEM

54 157 TREATMENTOF MOVEMENTDISORDERS AND DEMENTIA A Botulinum toxin B Procyclidine C Donepezil D Phenelzine E Lamotrigine F Zopiclone G Ropinirole H Buspirone I Thiamine J Neostigmine Select the drug from the above list which is licensed for the indication below: 1 Idiopathic Parkinsons disease 2 Hemifacial spasm 3 Myasthenia 4 Fluphenazine-induced dystonia 5 Alzheimers disease 158 ANALGESICS/PAIN A Fentanyl B Aspirin C Nefopam D Allopurinol E Pregabalin F Indometacin G Morphine H Paracetamol

I Metoclopramide J Ephedrine Link each of 1 to 5 below with the most appropriate item from Ato J: 1 Mild analgesic suitable for children 2 Suitable for acute gout 3 Used by injection for patient-controlled self-administration 4 Overdose causes tinnitus 5 Can be administered as transdermal patch ANSWERS: see pages 6668 55 MCQ ANSWERS ANSWERS MCQ ANSWERS 8 2 a ) TrueBenzodiazepines, whilst being much safer than the b) Truebarbiturates, still have the problems of dependence, c) Truepotentiation of alcohol, respiratory depression in overdose d) T r u e a n d s u p p r e s s i n g R E M s l e e p e) T r u e 8 3 a ) F a l s e B u s p i r o n e i s a n o n - b e n z o d i a z e p i n e a n x i o l yt i c d r u g . I t d o e s not have marked hypnotic, anticonvulsant or musclerelaxant properties. It does not alleviate benzodiazepinewithdrawal symptoms b) T r u e c) F a l s e T h e f u l l w i t h d r a w a l p i c t u r e u s u a l l y a p p e a r s a f t e r a n interval of 38 days d) T r u e e) F a l s e I t i s c o m m o n p r a c t i c e t o s u b s t i t u t e s h o r t e r - a c t i n g w i t h longeracting benzodiazepines (e.g. temazepam todiazepam) to assist withdrawal 8 4 a )

F a l s e U p t o 5 0 h o u r s , t h e a c t i v e d e s m e t h yl m e t a b o l i t e h a s a h a l f life of 36200 hours b) T r u e c) T r u e d) FalseUsually in combination with alcohol or other drugs e) T r u e 8 5 a ) True56 hours in comparison with 2050 hours b) TrueThis combination is a cause of fatal overdose as well a s disinhibited behaviour which may lead to crime or roadtraffic accidents c) FalsePatients must be warned not to drive or operate h e a v y machinery if affected d) FalseTemazepam is a controlled drug e) False 8 6 a ) FalseAbsorption is rapid with peak plasma levels b e i n g obtained at 60 minutes. Clomethiazole undergoes extensivefirst-pass metabolism so oral bioavailability is onlyapproximately 15 per cent b) FalseThe half-life is 50 minutes. The short half-life reduces t h e risk of hangover, ataxia and confusion the next day c) TrueThis results from decreased first-pass metabolism CHAPTER 2 NERVOUS SYSTEM 56 d) TrueFatalities have occurred because of poorly s u p e r v i s e d intravenous infusions. Constant rate infusions lead toaccumulation e) FalseIt potentiates the effects of alcohol although it may be u s e d to treat acute alcohol withdrawal 8 7 a ) FalsePromethazine is an H 1 antihistamine b) T r u e c) TrueAntimuscarinic effects d)

T r u e M a y c a u s e c o m a e) T r u e 8 8 a ) F a l s e Z o p i c l o n e i s a n o n - b e n z o d i a z e p i n e h yp n o t i c w h i c h e n h a n c e s b) FalseGABAactivit y. In addition to sedation adverse effects include c) Falsebitter, metallic taste, anorexia, nausea and vomiting, visual d) Truehallucinations, amnesia, aggression and agitation e) T r u e 8 9 a ) TrueOccasionally drug-induced hallucinations/psychosis may b) Falsebe mistaken for schizophrenia. The hypothesis that chronic c) Truecannabis use and LSD can cause schizophrenia is unproven d) False e) T r u e 9 0 a ) T r u e P r o l o n g e d u s e o f D 2 receptor blockers is associated with b) Truethe onset of tardive dyskinesia which may involve c) Falsestructural brain damage and is often irreversible d) T r u e e) False 9 1 a ) T r u e A n t i c h o l i n e r g i c b) T r u e A n t i c h o l i n e r g i c c) TruePeripheral alpha-adrenoceptor blockade d) T r u e H yp o t h e r m i a i n c o l d w e a t h e r , h y p e r t h e r m i a i n h o t w e a t h e r e)

TrueJaundice occurs in 0.5 per cent of patients t a k i n g chlorpromazine. It is due to intrahepatic cholestasis and isa hypersensitivity phenomenon associated witheosinophilia 9 2 a ) F a l s e A n t i p s yc h o t i c d r u g s m a y c a u s e m a l i g a n t n e u r o l e p t i c syndrome. This rare syndrome (hyperthermia, varyingconscious level, rigidity and autonomic dysfunction) may be treated with dantrolene or bromocriptine b) FalseVolume of distribution is large, approximately 22L/ kg c) F a l s e M e t a b o l i s m p r e d o m i n a n t l y b y h e p a t i c m i c r o s o m e s . O v e r 70 metabolites have been identified d) T r u e e) T r u e 57 MCQ ANSWERS 9 3 a ) FalseDepot intramuscular preparations such as flupentixol b) Truedecanoate are valuable in the management of c) Trueschizophrenia for maintenance therapy to ensure d) Truecompliance which is often poor in such patients e) T r u e 9 4 a ) TrueClozapine is an atypical antipsychotic. The term is used b) Trueimprecisely but generally covers those antipsychotic drugs c) Truewhose principal pharmacological effect is not D 2 blockade d) Trueand are rarely associated with extrapyramidal sideeffects e) TrueNeutropenia or agranulocytosis develops in up to 3 p e r cent of patients taking clozapine for 1 year. Althoughdystonias and tardive dyskinesias are rare, clozapine isassociated with fits in 34 per cent of patients and posturalhypotension (particularly after the first dose) 9 5 a )

FalseIn comparison to the conventional antipsychotics where b) Falsepotency is closely related to D 2 receptor blockade, atypical c) Falseantipsychotics bind less tightly to D 2 receptors and have d) Trueadditional pharmacological activity which varies with the e) Truedrug. Efficacy against negative symptoms as w e l l a s f e w e r extrapyramidal side-effects are characteristic. These may bethe result of the transient (hit and run) binding to D 2 receptors. May also block D 4 and 5HT 2 receptors 9 6 a ) TrueTricyclic drugs of the amitriptyline type raise synaptic b) Truestores of NAand 5HT and are antidepressant. MAO c) Trueinhibitors which increase total brain NAand 5HT are also d) Trueantidepressant. Amphetamine and cocaine raise synaptic e) TrueNAand alter mood but are not antidepressant 9 7 a ) T r u e S e e Textbook of Clinical Pharmacology and Therapeutics , b) TrueChapter 20. Although clinical experience is most c) Trueextensive with the tricyclic antidepressants, the sideeffect d) Trueprofile of selective serotonin reuptake inhibitors (SSRIs) is e)

Trueusually less troublesome and these drugs are s a f e r i n overdose 9 8 a ) TrueThe less sedative tricyclic and related antidepressants b) Trueinclude desipramine, imipramine, lofepramine and c) Falsenortriptyline. Protriptyline is a stimulant. The more d) Falsesedative drugs are preferred for agitated and anxious e) Falsepatients, whilst the less sedative are preferred i n withdrawn patients. Citalopram, paroxetine andsertraline are SSRIs. SSRIs are less sedating than mosttricyclic antidepressants. Insomnia occurs in somepatients on SSRIs CHAPTER 2 NERVOUS SYSTEM 58 99 a) TrueTricyclic antidepressant overdoses are commonly fatal. b) TruePatients may die from cardiac dysrh ythmias, convulsions or c) Truedirect CNS depression leading to respiratory arrest/ d) T r u e a s p h y x i a . S e e Textbook of Clinical Pharmacology and e) T r u e Therapeutics , Chapter 54 100 a) TrueAmitriptyline is a sedative tricyclic antidepressant which is b) Trueusually administered as a single nocte dose c) False d) T r u e e) T r u e 101

a) FalseFluvoxamine is an SSRI b) False c) T r u e d) TrueFluvoxamine inhibits CYP1A2 and therefore decreases t h e metabolism of theophylline and warfarin. Both these drugshave a narrow therapeutic index hence their concomitantadministration with fluvoxamine should be avoided ifpossible e) False 102 a) FalseFluoxetine is an SSRI. It is safer in overdose and causes b) Falsefewer antimuscarinic side-effects than the tricyclic c) Trueantidepressants. The most common adverse effects related d) Trueto SSRIs are nausea, dyspepsia, diarrhoea, dry mouth, e) Falseheadache, insomnia and dizziness. Sweating, e r e c t i l e dysfunction and delayed orgasm are well-recognizedassociations 103 a) FalsePhenelzine (and isocarboxazid and tranylcypromine) are b) Falseirreversible non-selective MAO inhibitors c) False d) T r u e e) TrueAdrenaline is metabolized by catecholO -methyltransferase 104 a) TrueMoclobemide is a reversible, competitive, selective MAOA inhibitor b) FalseSelegiline, an MAO-B inhibitor, is used in Parkinsons disease c) False d) F a l s e N o a n t i c h o l i n e r g i c a c t i o n ( c f . t r i c yc l i c a n t i d e p r e s s a n t s ) e)

T r u e 105 a) TruePatients on MAO inhibitors should be given a treatment b) Truecard which lists necessary precautions. Interactions with c) Truefoodstuffs, many proprietary preparations and prescribed d) Truedrugs may cause a hypertensive crisis. Phenotolamine e) Trueand/or labetalol are effective treatment for such a reaction 59 MCQ ANSWERS 106 a) TrueLithium salts have a narrow therapeutic index. Lithium b) Trueconcentrations may rise insidiously and once adverse c) Trueeffects such as tremor, ataxia, dysarthria and nystagmus d) Truedevelop treatment must be stopped whilst the serum e) Falselithium (avoid lithium heparin tubes to collect p l a s m a ) i s measured urgently 107 a) FalseSelective serotonin reuptake inhibitor b) TrueIrreversible non-selective MAO inhibitor c) TrueIrreversible non-selective MAO inhibitor d) FalseReversible selective MAO inhibitor e) FalseSt Johns wort is a herbal remedy which is popular for selftreatment of depression. It is a potent CYP450 enzymeinducer 108 a) TrueMuscarinic antagonists are effective in the treatment of b)

Falseparkinsonian tremor and to a lesser extent rigidity. They c) Falsehave minimal effects on bradykinesia. Although more d) Falsecommonly prescribed to counteract antipsychotic druge) Trueinduced parkinsonism they may be used a l o n e i n idiopathic parkinsonism and postencephaliticparkinsonism if tremor is the predominant symptom 109 a) TrueParkinsonism arises because of deficient dopaminergic b) Truetransmission. Bromocriptine and apomorphine are c) Truedopamine receptor agonists. Acetylcholine is antagonistic d) Falseto dopamine within the striatum e) False 110 a) TrueLevodopa (unlike dopamine) can enter nerve terminals in b) Falsethe basal ganglia where it undergoes decarboxylation to c) F a l s e f o r m d o p a m i n e d) TrueEntacapone is a catecholO -methyltransferase inhibitor e) T r u e 111 a) TrueThe dose of levodopa is titrated upwards, balancing b) Trueefficacy against adverse effects. Nausea and vomiting are c) Falsereduced by the addition of a dopa decarboxylase inhibitor d) Falseand taking the drug after food

e) T r u e 112 a) FalseBromocriptine may be used as an initial treatment in b) TrueParkinsons disease, particularly in younger patients c) F a l s e ( 70 years) or as an adjunct with levodopadopa d) Falsedecarbox ylase combinations in patients with severe motor e) Truefluctuations. There is great inter-individual variation i n i t s efficacy. Ropinirole is another dopamine D 2 receptor agonist CHAPTER 2 NERVOUS SYSTEM 60 113 a) TrueSelegiline, an MAO-B inhibitor, may slow disease b) Falseprogression in idiopathic Parkinsons disease. It usuall y c) Falseallows dose reduction and prolongs the duration of action of d) Falselevodopa. Oral selegiline is well absorbed (100 per cent) and e) F a l s e e x t e n s i v e l y m e t a b o l i z e d i n t h e l i v e r . R a r e l y h yp e r t e n s i o n h a s beenreported.Amantadine(whichstimulatesreleaseofendogenousdopamine)potentiatesitsanti-Parkinsoneffects 114 a) FalseDonepezil is used for Alzheimers disease. Riluzole is used b) Falsein motor neuron disease. Treatment of spasticity is seldom c) Truevery effective, but physiotherapy or limited surgical release d) Trueprocedures have some place. The drugs used to reduce e)

Truespasticity have considerable limitations. D i a z e p a m i s sedative, baclofen is less sedative at equi-effective doses but can cause vertigo, nausea and hypotension. Intrathecal baclofen is currently being evaluated. Dantrolene is lessuseful for spasticity as it markedly reduces muscle power.It is used in the management of neuroleptic malignantsyndrome and malignant hyperthermia 115 a) TrueTardive dyskinesia is thought to result from the b) Truedevelopment of denervation hypersensitivity in c) Truedopaminergic postsynaptic receptors of the nigrostriatal d) Falsepathway following chronic receptor blockade by e) Falseneuroleptics. It is therefore due to a relative preponderance ofdopaminergiceffects.BotulinumtoxinAisoneoftheneurotoxinsproducedby Clostridiumbotulinum andisusedtotreatblepharospasm,certainotherdy stoniasanddy namicequinusfootdeformitiesduetospasticityinambulantpaediatriccerebralpalsypatients.I t blocksthereleaseofacety lcholineattheneuromuscularjunctionandisgivenby localintramuscularinjection.Thisisaspecialistfield! 116 a) TrueMyasthenia gravis is a syndrome of increased muscle b) Truefatigability and weakness of striated muscle and results c) Truefrom an autoimmune process with antibodies to nicotinic d) F a l s e a c e t y l c h o l i n e r e c e p t o r s e) T r u e 117 a) TrueClinically the distinction between a deficiency (myasthenic b) Truecrisis) or an excess (cholinergic crisis) may be difficult and c) Trueimprovement with an injection of the very shortacting d) Trueanticholinesterase edrophonium is diagnostic of e) Falsemyasthenic crisis. Because of its short duration of a c t i o n , any deterioration of a cholinergic crisis is unlikely to haveserious consequences although facilities for artificialventilation must be available. NB: cholinesterase inhibitorscause pupillary constriction 61

MCQ ANSWERS 118 a) TrueAcetylcholinesterase-inhibiting drugs can slow down the b) Trueprogression of mild and moderate Alzheimers disease, but c) Truethe benefit is small and only temporary. Memantine, an d) FalseNMDAreceptor antagonist, inhibits glutamate transmission e) Trueand is licensed for moderate to severe dementia i n Alzheimers disease 119 a) TrueSee Table 2 for choice of drug in various forms of seizure. b) TrueTopiramate has been associated with acute myopia with c) Truesecondary angle-closure glaucoma d) T r u e e) False Table2 Choice of drug in various forms of seizure F o r m o f s e i z u r e F i r s t l i n e S e c o n d l i n e Partial seizures s e c o n d a r y V a l p r o a t e P h e n y t o i n generaliz ed tonic clonic CarbamazepineTopiramates e i z u r e s L a m o t r i g i n e T i a g a b i n e Generalized seizuresP r i m a r y ( t o n i c c l o n i c ) V a l p r o a t e C a r b a m a z e p i n e L a m o t r i g i n e T o p i r a m a t e PhenytoinA b s e n c e s e i z u r e s E t h o s u x i m

i d e L a m o t r i g i n e V a l p r o a t e C l o b a z a m / C l o n a z e p a m M y o c l o n i c j e r k s V a l p r o a t e L a m o t r i g i n e Clobaza m / Clonazepam Note : Other antiepileptics not listed above may be useful. Refer to National Institute forHealth and Clinical Excellence (NICE) guidelines. 120 a) TrueTremor, ataxia and incoordination are dose related. The b) Truegastrointestinal effects can be reduced by the use of an c) F a l s e e n t e r i c c o a t e d f o r m u l a t i o n d) False e) T r u e 121 a) TrueHigh blood concentrations of phenytoin produce a b) Truecerebellar syndrome, involuntary movements and sedation. c) TrueMacrocytic anaemia which responds to folate is common. d) FalseRashes, fever, hepatitis, gum hypertrophy, hirsutism and e) Truelymphadenopathy are all well-recognized adverse e f f e c t s of phenytoin 122 a) TrueAge, body weight, sex and, in particular, saturable b) Falsemetabolism which is under polygenic control, contribute to c) Falsethe wide variation in handling of phenytoin d) False e) T r u e CHAPTER

2 NERVOUS SYSTEM 62 123 a) FalseIn addition to its effectiveness in many forms of epilepsy b) Falseexcept absence seizures, carbamazepine is effective in c) Truetrigeminal neuralgia. It induces its own metabolism, hence d) Falsethe half-life after a single dose is 2560 hours, but on e) Truechronic dosing this falls to 10 hours 124 a) FalseCarbamazepine commonly causes adverse effects but these b) Trueare seldom severe. They are particularly troublesome early c) Truein treatment and may resolvewithout alteration of dose d) Truewhich is probably related to the induction of its own e) Truemetabolism, although pharmacodynamic tolerance i s a l s o a factor. Carbamazepine therapy should be initiated at a lowdose and titrated upwards slowly depending on response.Hyponatraemia is caused by stimulation of antidiuretichormone secretion 125 a) FalseSodium valproate is effective against several forms of b) Trueepilepsy. Adverse effects most commonly involve the c) Falsealimentary system. These include nausea, vomiting and d) Trueabdominal pain (which may be reduced by enteric coated e) Falsetablets). Use in pregnancy is associated with i n c r e a s e d neural tube defects. To reduce the risk of neural tubedefects, folate supplements are advised before and duringpregnancy in women on antiepileptic drugs

126 a) TrueVigabatrin is reserved for the treatment of epilepsy b) Trueunsatisfactorily controlled by more established drugs. It is c) Trueassociated with visual field defects. Onset of symptoms d) Truevaries from one month to several years after starting e) Falsetreatment. Unlike most anticonvulsants it is not metabolized bytheliverandisexcretedunchangedbythekidney 127 a) TrueWomen on long-term enzyme-inducing drugs who are b) Trueunable to use an alternative reliable method of contraception c) Falseshould use an oral contraceptive containing at least 50 g d) Trueethinylestradiol under expert family planning supervision. e) FalseEnzyme induction is also the basis of a n t i c o n v u l s a n t osteomalacia (extremely rare) due to reduced serum25hydroxycholecalciferol 128 a) TrueStatus epilepticus is a medical emergency with a mortality b) Falseof about 10 per cent. Rapid suppression of seizure activity c) Truecan usually be achieved with intravenous lorazepam. d) FalseFalse teeth should be removed, an airway established e) Falseand ox ygen (60 per cent) administered as soon as possible 129 a) TrueUncomplicated febrile seizures have an excellent b)

Trueprognosis. It is usual to reduce fever using paracetamol, 63 MCQ ANSWERS c) Falseremoval of clothing, tepid sponging and fanning d) False e) False 130 a) TrueOral aspirin, NSAID or paracetamol is effective in the b) Falsetreatment of the headache of acute migraine in nearly c) True75 percent of patients. During a migraine attack, gastric statis d) Trueoccurs, hence the popularity of a combination of aspirin or e) Falseparacetamol with metoclopramide (a dopamine a n t a g o n i s t ) which enhances gastric emptying as well as counteractingthe nausea common in migraine. The value of ergotamineis very limited. There is a risk of peripheral vasospasm 131 a) TrueSumatriptan is a selective agonist of 5HT ID receptors, b) Truewhich are found predominantly in the cranial circulation. c) TruePrepacked dosage vials are available for subcutaneous d) Trueself-injection. Sumatriptan is only 14 per cent available e) Falseafter oral administration. Anasal spray is also a v a i l a b l e . The half-life is 2 hours. Headache recurs after a single dosein 3040 per cent of patients 132 a) FalsePizotifen is given at night as its principal adverse effect b) Falseis drowsiness. It also increases appetite and causes c)

Trueweight gain. Beta blockers potentiate the peripheral d) Truevasoconstriction caused by ergotamine and these drugs e) Trueshould not be given concurrently. Ergotamine must n o t b e used for prophylaxis. Methysergide has 5HT 2 antagonistactivity with partial 5HT agonist activity. It should only beused under specialist hospital supervision. Retroperitonealfibrosis may lead to renal failure 133 a) TrueHalothane is a potent anaesthetic but weak analgesic. It has b) Falsea low therapeutic index. In many centres in the UK c) Truesevoflurane is the inhalation anaesthetic of first choice d) False e) T r u e 134 a) TrueFentanyl is a synthetic opioid and is commonly used as an b) Falseanalgesic supplement. Its short duration of action (peak c) Trueeffect 2030 minutes) is explained by redistribution from d) Falsethe brain. The half-life is 24 hours. It undergoes hepatic e) T r u e m e t a b o l i s m 135 a) FalseNitrous oxide is commonly combined with volatile b) Trueanaesthetics for its analgesic properties. Premixed nitrous c) Trueoxide and oxygen mixtures are used in obstetric practice d) F a l s e a n d b y a m b u l a n c e d r i v e r s e)

False CHAPTER 2 NERVOUS SYSTEM 64 136 a) FalseThiopental sodium, an ultra short-acting barbiturate, is b) Falseused primarily as an induction agent. Propofol is used c) Truefor induction, maintenance of anaesthesia and sedation in d) T r u e i n t e n s i v e c a r e u n i t s e) T r u e 137 a) TrueThe chief aim of premedication is to allay anxiety in the b) Truepatient awaiting surgery. Inadequate premedication may c) Truelead to the administration of larger doses of anaesthetic d) Falsethan would otherwise have been required, resulting in e) Falsedelayed recovery. Neostigmine, an a n t i c h o l i n e s t e r a s e , may be used at the end of a procedure to reverse non-depolarizing muscle relaxants such as tubocurarine.Ketamine is a parenteral anaesthetic which has a widetherapeutic index. Although it is a potent analgesic andsedative it can cause vivid unpleasant hallucinations whichmay recur for months. It increases muscle tone and bloodpressure. It is useful in major disasters for rapid, safeanaesthesia of trapped casualties to carry out proceduressuch as amputation 138 a) TrueAtracurium has a rapid onset of action. It occasionally b) Falsecauses histamine release leading to flushing of the face and c) Truechest, hypotension and rarely bronchospasm. Continuous d) Falseinfusion is popular in intensive care. It is inactivated e)

Falsespontaneously in the plasma, which is a valuable p r o p e r t y in hepatic and renal failure 139 a) FalseOpioids may cause fatal respiratory depression. Even b) Trueepidural opioids can cause respiratory depression and in c) Falsethis situation epidural local anaesthesia and intramuscular d) T r u e N S A I D s a r e p r e f e r r e d e) False 140 a) TrueMalignant hyperthermia is a rare but potentially lethal b) Truecomplication of anaesthesia. It consists of a rapid increase in c) Truebody temperature accompanied by tachycardia and d) Truegeneralized muscle spasm. Severe acidosis and hyperkalaemia e) Trueoccur. Dantrolene reverses the muscle spasm 141 a) TrueSmall unmyelinated fibres are depressed first, hence the b) Falseorder of loss of function is pain, temperature, touch, c) Falseproprioception and motor function. Lidocaine does not d) Falseaffect vascular smooth muscle but is available with e) Trueadrenaline, a vasoconstrictor which prolongs its local e f f e c t . This combination may cause vasospasm and severe digitalischaemia if used for a ring block, hence the combinationis contraindicated in this situation. Bupivacaine is a long-acting local anaesthetic which is often used forperipheral nerve, plexus, epidural and spinal anaesthesia.Toxicity includes cardiac dysrhythmias 142 a) TrueParacetamol probably produces its analgesic effect by b) Falsecentral inhibition of cyclo-ox ygenase. It is antipyretic but c)

T r u e n o t a n t i - i n f l a m m a t o r y d) T r u e e) T r u e 143 a) TrueGastric irritation is reduced by taking aspirin after food b) T r u e c) False d) T r u e e) T r u e 144 a) FalseThe commonest adverse effect associated with salicylates is b) Truedyspepsia. Chronic blood loss from the stomach may be c) Falseasymptomatic. Salicylism which is associated with high d) Trueblood concentrations, consists of tinnitus, deafness, nausea, e) Truevomiting and occasionally abdominal pain and flushing 145 a) TrueIbuprofen is an NSAID which is available without b) Trueprescription. The side-effects are those of all the NSAIDs, of c) Truewhich gastrointestinal irritation is the most common. Selective d) T r u e i n h i b i t o r s o f c y c l o - o x yg e n a s e 2 ( C O X 2 ) , e . g . c e l e c o x i b , m a y e) Trueimprove gastrointestinal tolerance, but are associated with anincreased incidenceofcardiovascularevents 146 a) FalseNefopam is chemically and pharmacologically unrelated to b) Falseopioids and NSAIDs. It is used for moderately severe pain. c)

FalseIt can cause fatal hypertension if prescribed during or d) Truewithin two weeks of cessation of non-selective MAO e) T r u e i n h i b i t o r t r e a t m e n t 147 a) FalseCo-codamol, a compound analgesic of codeine phosphate b) Trueand paracetamol, is widely prescribed. If the codeine c) Falsecontent/tablet is 8mg it is available without prescription. d) FalseWhen taking a drug history one must be aware that many e) Falseover-the-counter remedies contain a surprising m i x t u r e o f pharmacologically active agents, although sometimes inalmost homeopathic quantities 148 a) TrueThe most important use of morphine is pain relief. It is of b) Trueparticular value in palliative care. The use of oral modifiedc) Falserelease preparations allows twice-daily dosing whereas if the d) Truestandard solution is used it needs to be given every 4 hours e) T r u e 149 a) TruePatients with decreased respiratory reserve and b) Truemyxoedema are also more sensitive 65 MCQ ANSWERS CHAPTER 2 NERVOUS SYSTEM 66 c) T r u e d) T r u e e) False

150 a) FalseMorphine increases smooth muscle tone throughout the b) Truegastrointestinal tract and in addition reduces peristalsis c) Truethrough an action on the receptors in the ganglion plexus d) Truein the gut wall which results in constipation. Diamorphine e) Falseis diacetylmorphine. Its actions are similar to those o f morphine but is more potent as an analgesic when given byinjection. It is more soluble than morphine. Diamorphineand 6-acetylmorphine enter the brain more rapidly thanmorphine 151 a) FalsePethidine causes similar respiratory depression and b) Falsevomiting to morphine, but does not release histamine or c) Falsesuppress cough and only uncommonly produces pupillary d) Falseconstriction to the same extent as morphine e) False 152 a) FalseMorphine is a metabolite of codeine. Codeine is used as an b) Falseanalgesic, cough suppressant and antidiarrhoeal agent. The c) Trueplasma half-life is 34 hours. It is metabolized by CYP2D6. d) TrueIt is less effective in patients deficient in CYP2D6 e) T r u e 153 a) TrueIn common with other partial agonists buprenorphine b) Trueoccupies a much larger fraction of the receptors to produce c)

Falseits analgesic effect than does a full agonist. Consequently it d) Truecan precipitate pain and cause withdrawal symptoms in e) Truepatients who have received other opioids and r e l a t i v e l y much larger doses of naloxone are required to displace itfrom receptors in overdosage compared to a full agonist 154 a) TrueNaloxone is a pure competitive antagonist. It has a half-life b) Falseof 1 hour which is less than many opioids c) T r u e d) False e) False EMQ ANSWERS 155 CENTRALLYACTIVE DRUGS 1G Sumatriptan is a 5HT 1 antagonist. Sumatriptan can be given by mouth,subcutaneous injection or as a nasal spray during a migraine attack.Sumatriptan and other 5HT 1 agonists (rizatriptan and zolmitriptan)can cause vasoconstriction in coronary and pulmonary vascular beds. 67 EMQ ANSWERS 2J Valproate is the first-choice anticonvulsant for myoclonic jerks. It iseffective against many forms of epilepsy. 3H Tardive dyskinesias follow months or years of conventional(D 2 blocking) antipsychotic treatment. Anticholinergics aggravatesymptoms. The D 2 blocker should be stopped, but structural changes(possible increased sensitivity of presynaptic dopamine receptors)occur and may be irreversible. An atypical antipsychotic (e.g.aripiprazole) may help alleviate the symptoms and should helpmaintain control of the schizophrenia. 4C An SSRI such as citalopram is usually effective in depression andmuch safer in overdose than a tricyclic antidepressant (e.g.imipramine). 5A

Ashort-acting benzodiazepine such as temazepam is the treatment ofchoice for severe disabling insomnia. 156 DRUG-INDUCED MOVEMENTDISORDERS 1C Salbutamol, a beta 2 agonist, commonly causes a dose-related tremor.Other drug causes include caffeine, thyroxine, SSRIs (e.g. fluoxetine),valproate, lithium and withdrawal from alcohol and benzodiazepines. 2I Phenytoin, an antiepileptic, causes dose-related ataxia with cerebellarsigns including nystagmus (as does alcohol intoxication). 3E Aminoglycosides, e.g. gentamicin, cause 8th nerve damage, which canaffect hearing and balance. 8th nerve toxicity correlates with troughdrug blood levels. 4G The commonest drug causes of proximal myopathy are chroniccorticosteroid therapy and alcoholism. 5B Tendon damage including rupture has been associated withfluoroquinolone (e.g. ciprofloxacin) therapy. Elderly patients and thoseon concurrent corticosteroids are most at risk. 157 TREATMENTOF MOVEMENTDISORDERS AND DEMENTIA 1G Ropinirole is a dopamine receptor agonist which is often used as initialtreatment in younger ( 70 years) patients with parkinsonism. 2A Botulinum toxin (Aand B) is a neurotoxin. It irreversibly blocks therelease of acetylcholine at the neuromuscular junction. It is often usedin cosmetic clinics. 3J Neostigmine and pyridostigmine are cholinesterase inhibitors. 4B Procyclidine is an antimuscarinic of value in treating antipsychoticdrug-induced acute dystonias. 5C Donepezil has a limited effect on slowing the speed of progression ofAlzheimers disease. CHAPTER 2 NERVOUS SYSTEM 68 158 ANALGESICS/PAIN 1H Paracetamol is a mild analgesic and antipyretic which, unlike aspirin,is not associated with Reyes syndrome. Therapeutic doses areextremely well tolerated but overdose can be fatal usually throughhepatic failure. 2F Indometacin, an NSAID, is effective in acute gout. 3G Patient-controlled analgesia using morphine is especially valuable inthe management of post-operative visceral pain.

4B Aspirin overdose is associated with tinnitus. 5A Fentanyl, a potent synthetic opioid, is available as a transdermal patchwhich can provide analgesia for up to 72 hours. CHAPTER THREE MUSCULOSKELETALSYSTEM MULTIPLE CHOICE QUESTIONS 159 Gold salts when used in the treatment of progressive rheumatoidarthritis: a) Are usually administered daily by intravenous injection b) If effective, benefit should be observed after the first week oftreatment c) Produce objective improvement in about 75 per cent of patients d) Can cause skin rashes which can necessitate treatment cessation e) If they cause stomatitis this may be due to neutropenia 160 Penicillamine is used in the management of: a) Rheumatoid arthritis b) Systemic lupus erythematosus (SLE) c) Wilsons disease d) Cystinuria e) Lead poisoning 161 Adverse effects associated with penicillamine include: a) Thrombocytopenia b) Leucopenia c) Immune complex glomerulonephritis d) Loss of taste e) Myasthenia gravis 162 Etanercept: a) Is a humanized monoclonal antibody against tumour necrosis factoralpha (TNF )

b) Can cause life-threatening hypersensitivity reactions c) Has a half-life of 513 days d) Can cause pancytopenia e) Is rarely associated with a demyelinating syndrome CHAPTER 3 MUSCULOSKELETAL SYSTEM 70 163 The following are likely to be effective in the treatment of an acuteepisode of gout: a) Indometacin b) Naproxen c) Alendronate d) Probenecid e) Colchicine 164 The following may cause hyperuricaemia: a) Sulfinpyrazone b) Cytosine arabinoside when treating acute leukaemia c) Bendromethiazide d) Low-dose aspirin e) Bezafibrate 165 Allopurinol: a) Inhibits xanthine oxidase b) May precipitate acute gout c) Is contraindicated in renal failure d) Should not be prescribed with a non-steroidal anti-inflammatorydrug (NSAID) e) Blocks the metabolic inactivation of suxamethonium 166 In a patient with osteoarthritis:

a) Physical exercise and weight loss can be helpful b) NSAIDs are contraindicated c) Gold therapy reverses the pathophysiology of the disease d) Symptoms are exacerbated by bisphosphonates, e.g. alendronate e) Raloxifene may slow disease progression 167 Indometacin causes the following adverse effects: a) Biochemical hepatitis b) Spuriously increased serum creatinine c) Hypokalaemia d) Exacerbates cardiac failure e) Antagonizes the antihypertensive effects of angiotensin-convertingenzyme (ACE) inhibitors Answers: see pages 7273 71 E XTENDED MATCHING QUESTIONS EXTENDED MATCHING QUESTIONS A Colchicine B Azathioprine C Allopurinol D Gold injections E Methotrexate F Methylprednisolone G Hydroxychloroquine H Naproxen I D-penicillamine J Etanercept 168 ARTHRITIS Link each of 1 to 5 below with the most appropriate item from Ato J:

1 Chronic use can cause cirrhosis 2 Used before commencing chemotherapy of leukaemia 3 Licensed for severe ankylosing spondylitis inadequately responsive toconventional therapy 4 Intra-articular injection in rheumatoid arthritis 5 Used in familial Mediterranean fever ANSWERS: see pages 7374 CHAPTER 3 MUSCULOSKELETAL SYSTEM 72 ANSWERS MCQ ANSWERS 159 a) FalseGold (as sodium aurothiomalate) is usually administered b) Falseas weekly intramuscular injections or by mouth daily. c) TrueBenefit is not anticipated for at least six weeks. Blood d) Truedyscrasias and glomerular injury (nephrotic syndrome) e) Trueoccur and monitoring of blood counts and urine i s performed monthly. Rashes may progress toexfoliation 160 a) TruePenicillamine, a breakdown product of penicillin, is given b) Falseby mouth. In rheumatoid arthritis clinical improvement is c) Trueanticipated only after 612 weeks. It is contraindicated in d) TrueSLE. Apart from its immunosuppressive action, it also e) Truechelates certain heavy metals (Cu, Pb, etc.) 161 a) TrueThe toxicity of penicillamine is such that it should only be b)

Trueused by clinicians with experience of the drug and with c) T r u e m e t i c u l o u s p a t i e n t m o n i t o r i n g d) T r u e e) T r u e 162 a) FalseEtanercept is a recombinant protein that has two s o l u b l e TNF receptors joined to an Fc fragment; this is in contrastto infliximab, a humanized murine monoclonal againstTNF used in Crohns disease. Both are licensed for thetreatment of adult rheumatoid arthritis b) TrueLike all proteins it can cause hypersensitivity reactions c) TrueIt has a long half-life in plasma and is administered e v e r y two weeks d) TrueIt can cause bone marrow suppression (all lineages) a n d sepsis e) T r u e R a r e l y, d e m y e l i n a t i n g s yn d r o m e s l i k e m u l t i p l e s c l e r o s i s have been reported with its use 163 a) TrueAcute gout is treated by anti-inflammatory analgesic b) Trueagents. Colchicine is an alternative in those unable to c) Falsetolerate NSAIDs but commonly causes diarrhoea. d) FalseAlendronate is a bisphosphonate used in the e) Truemanagement of Pagets disease. B i s p h o s p h o n a t e s are also used to treat hypercalcaemia of pregnancy. Theymay be used in the prevention of postmenopausalosteoporosis 73 EMQ ANSWERS 164 a) FalseUric acid is the end product of purine metabolism in humans, b) Trueand gives rise to problems because of its limited solubility. c) TrueCytosine arabinoside causes massive cell death and increased

d) T r u e u r i c a c i d p r o d u c t i o n . D i u r e t i c s , l o w - d o s e s a l i c yl a t e s a n d e) F a l s e p yr a z i n a m i d e i n h i b i t t u b u l a r e x c r e t i o n o f u r i c a c i d 165 a) TrueAllopurinol is used as long-term medication to treat b) Truepatients with recurrent gout. By inhibiting xanthine c) Falseoxidase it decreases uric acid production. It potentiates d) Falseazathioprine by blocking inactivation of its active e) Falsemetabolite 6-mercaptopurine 166 a) T r u e b) FalseNSAIDs are probably one of the most widely used c) Falsetreatments although paracetamol, because of its superior d) Falsetolerance in the elderly, should be tried first e) FalseRaloxifene is used in the treatment and prevention o f postmenopausal osteoporosis 167 a) TrueCan cause transaminitis b) F a l s e R e d u c e s g l o m e r u l a r f i l t r a t i o n r a t e ( G F R ) a n d t r u l y c a u s e s an increase in serum creatinine by diminishingvasodilatory prostaglandins in the renal bed c) FalseReduces renal potassium excretion thus leads t o hyperkalaemia d) T r u e R e d u c e s N a e x c r e t i o n l e a d i n g t o i n c r e a s e d f l u i d r e t e n t i o n and fluid overload e) T r u e EMQ ANSWERS 168 ARTHRITIS 1E Methotrexate is one of the most frequently used disease-modifyingantirheumatic drugs (DMARDs) in rheumatoid arthritis.Myelosuppression is another potentially fatal adverse effect.

2C As well as being used in the prophylaxis of gout, allopurinol isused before commencing chemotherapy of rapidly dividingmalignancies where killing a large number of tumour cellsincreases nucleic acid breakdown so increasing production ofurate which can precipitate in the renal tract. Allopurinolprevents this (xanthine is much more water soluble than urate). 3J Inhibitors of TNF can reactivate latent tuberculosis as cancorticosteroids and other immunosuppressants. CHAPTER 3 MUSCULOSKELETAL SYSTEM 74 4F Intra-articular corticosteroids, e.g. methylprednisolone, are valuable toreduce pain, increase mobility and reduce deformity in one or a few joints in a rheumatoid arthritis flare. 5A Colchicine, in addition to its use in the treatment and prophylaxis ofgout, is also effective in the treatment of familial Mediterranean fever. CHAPTER FOUR CARDIOVASCULARSYSTEM MULTIPLE CHOICE QUESTIONS 169 The following are modifiable risk factors for the genesis ofatheromatous plaque: a) Smoking b) Obesity c) Dyslipidaemia d) Glucose intolerance e) Hypertension 170 Colestyramine: a) Causes a fall in plasma cholesterol b) Increases fecal excretion of bile acids c) Reduces absorption of folic acid d) Causes diarrhoea in diabetic autonomic neuropathy e) Reduces pruritus in incomplete biliary obstruction 171 Bezafibrate: a) Lowers plasma triglyceride

b) Is ineffective post cholecystectomy c) Inhibits lipoprotein lipase d) Is indicated in alcohol-induced hyperlipidaemia e) Potentiates the effects of warfarin 172 Simvastatin, an HMG-CoA(3-hydroxy-3-methyl-glutaryl-CoA)reductase inhibitor: a) Lowers low-density lipoprotein (LDL) cholesterol b) Is particularly useful in heterozygous familialhypercholesterolaemia c) Acts locally on HMG-CoAreductase in the intestine d) Is associated with myositis/myopathy e) Is ineffective if prescribed with ezetimibe CHAPTER 4 CARDIOVASCULAR SYSTEM 76 173 The following can cause hypertension: a) Corticosteroid therapy b) Oral contraception c) Alcohol withdrawal d) Amphetamines e) Ergotamine 174 Thiazide diuretics when used in the management of uncomplicatedessential hypertension: a) Reduce the risk of stroke b) Are natriuretic c) Potassium supplements are usually required d) Reduce plasma renin e) Are associated with impotence 175

Beta-adrenoceptor antagonists: a) Are indicated in patients with stable heart failure b) Prolong life in survivors of myocardial infarction c) Improve performance of sprinters d) The antihypertensive effect is antagonized by non-steroidalanti-inflammatory drugs (NSAIDs) e) May cause life-threatening bronchospasm in asthmatics 176 The following drugs when used as monotherapy in the management ofhypertension are likely to be less effective in Afro-Caribbean than inwhite patients: a) Atenolol b) Enalapril c) Bendroflumethiazide d) Amlodipine e) Diltiazem 177 Ramipril, an angiotensin-converting enzyme (ACE) inhibitor: a) Reduces concentrations of angiotensin II b) Increases concentrations of bradykinin c) Increases noradrenaline release from sympathetic nerveterminals d) Increases aldosterone secretion e) Causes hypokalaemia 178 Irbesartan (an angiotensin-11 receptor antagonist) is contraindicated in: a) Left ventricular failure b) Asthma c) Bilateral renal artery stenosis d) Pregnancy e) Diabetic nephropathy 77 M

ULTIPLE CHOICE QUESTIONS 179 Nifedipine, a dihydropyridine calcium channel blocker: a) Dilates veins more than arteries b) Can be combined with beta blockers in the management ofhypertension c) Increases plasma calcium concentration d) Is contraindicated in asthma e) Raises the plasma concentration of cholesterol 180 Nifedipine in comparison to verapamil is more likely to: a) Worsen angina b) Cause ankle swelling unresponsive to diuretics c) Have negative inotropic effects d) Cause flushing and headache e) Cause constipation 181 Doxazosin: a) Is a selective reversible 1 receptor antagonist b) Should always be prescribed with a beta blocker to prevent reflextachycardia c) Is associated with first-dose hypotension d) ReducesplasmaLDL/high-densitylipoprotein(HDL)cholesterolratio e) Can cause urinary incontinence in women with pre-existing pelvicpathology 182 Sodium nitroprusside: a) Is administered by intravenous infusion b) Prolonged administration can lead to cyanide poisoning c) Has a half-life of about one week d) Reduces cardiac pre-load

e) Reduces cardiac afterload 183 Methyldopa: a) Causes central 2 agonist effects b) Causes drowsiness and fatigue c) Pyrexia is an adverse effect d) Is associated with Coombs-positive haemolytic anaemia e) Asingle missed dose can cause profound rebound hypertension 184 The following hypotensive combinations are rational when a singledrug has not been effective in treating essential hypertension: a) Thiazide and candesartan b) Thiazide and ramipril in an asthmatic c) Amiloride and ramipril in an asthmatic who has gout d) Nifedipine and verapamil in a man who has had thiazide-inducedimpotence, seconddegree heart block and captopril-induced rash e) Ramipril and doxazosin in a man with prostatism CHAPTER 4 CARDIOVASCULAR SYSTEM 78 185 The following drug effects have been correctly paired with the nameddrug: a) Hydralazine drug-induced systemic lupus erythematosus (SLE) b) Minoxidil hirsutism c) Captopril first-dose hypotension d) Atenolol tremor e) Candesartan cough 186 Management of acute ST elevation myocardial infarction (STEMI)should usually include: a)

24 per cent oxygen b) Intravenous opiate with an antiemetic c) Aspirin d) Some measure to open the coronary atery (e.g. angioplasty) e) Lidocaine (lignocaine) 187 The management of unstable angina usually includes: a) Aspirin b) Glyceryl trinitrate (GTN) c) Low molecular weight heparin d) Salbutamol e) Beta-adrenoceptor antagonist 188 GTN: a) Relaxes vascular smooth muscle b) Is associated with tolerance more commonly with transdermal GTNpatches than sublingual GTN c) Is volatile d) Is more selective for arteriolar than for venous smooth muscle e) May relieve the pain of oesophageal spasm 189 Beta-adrenoceptor antagonists: a) Increase cardiac tissue cyclic adenosine monophosphate (cAMP) b) Competitively antagonize the receptor-mediated effects ofadrenaline and noradrenaline c) Non-competitively antagonize several of the actions of thyroxine d) Decrease peripheral vascular resistance e) Reduce renin secretion 190 The following drugs may reduce the risk of recurrence or death postmyocardial infarction:

a) Aspirin b) Beta blockers c) Dexfenfluramine d) Sildenafil e) Statins 79 M ULTIPLE CHOICE QUESTIONS 191 Verapamil is used: a) For prophylaxis of angina b) To treat hypertension c) To treat ventricular tachycardia d) To prevent cerebral vasospasm following subarachnoidhaemorrhage e) To treat left ventricular failure 192 Acalcium channel blocker such as amlodipine or nifedipine is preferredto a beta blocker such as atenolol to treat hypertension and angina inpatients who also have: a) Chronic bronchitis b) Peripheral vascular disease c) Heart block d) Diabetes e) Anxiety 193 Aspirin: a) Reduces the risk of stroke in patients with transient ischaemicattacks b) Predisposes to peptic ulceration c) Irreversibly inhibits fatty acid cyclo-oxygenase d) Has no effect on bleeding time e) Needs to be given twice daily to prevent platelet cyclo-oxygenaseresynthesis within the dose interval

194 Streptokinase: a) Is derived from streptococci b) Reduces the acute mortality of myocardial infarctiononly if administered within 4 hours of the onset ofchest pain c) Is contraindicated if the patient is taking regular NSAIDtherapy d) Is administered by intravenous infusion e) Should not be given to patients over the age of 60 years 195 Alteplase: a) Is a prodrug that liberates streptokinase b) Heparin must not be administered within 24 hours of alteplaseinfusion c) Should only be administered if pulmonary artery pressure can bemeasured d) Is indicated in the treatment of pulmonary embolism e) Is contraindicated if aspirin has been administered in the last24 hours CHAPTER 4 CARDIOVASCULAR SYSTEM 80 196 The following are relative contraindications to the use of streptokinasein acute myocardial infarction: a) Therapy with streptokinase from 5 days to 12 monthspreviously b) Stroke due to cerebral thrombosis in the last six months c) Concurrent hormone replacement therapy for menopausalsymptoms d) Pulmonary disease with cavitation e) Penicillin allergy 197 Unfractionated heparin: a) Binds to antithrombin III b) Inhibits the action of thrombin c)

Is monitored in the laboratory by measurement of activated partialthromboplastin time (APTT) d) Is less effective in patients with inherited or acquired deficiency ofantithrombin III e) Is reversed by protamine sulphate 198 Low molecular weight heparin (LMWH) prophylaxis to prevent deepvein thrombosis/pulmonary embolism in major surgery: a) Must be started one week before surgery b) Is via twice-daily intramuscular injection c) Is more likely to be of value in an obese man of 50 than in a slimman of 30 d) Unfractionated heparin should be substituted for LMWH in renalfailure e) Concomitant antibiotics are contraindicated 199 The following are recognized adverse effects of unfractionated heparintherapy: a) Osteoporosis b) Alopecia c) Thrombocytopenia d) Diarrhoea e) Fetal cleft palate 200 The following statements are correct: a) Thrombocytopenia is more commonly associated withunfractionated heparin than LMWH b) LMWH is eliminated solely by renal excretion c) Neither heparin nor LMWH cross the placenta d) Fondaparinux selectively binds and inhibits factor Xa e) Hirudin is a direct thrombin inhibitor 81 M ULTIPLE CHOICE QUESTIONS 201 Warfarin: a) Prevents the hepatic synthesis of the vitamin K-dependentcoagulation factors II, VII, IX and X

b) Is structurally closely related to vitamin K c) Should initially be given as a subcutaneous loading dose d) During life-threatening bleeding can be reversed by vitamin K andfresh frozen plasma e) Anticoagulant effect is monitored by measurement of theprothrombin time/international normalized ratio (INR) 202 The following are relative or absolute contraindications to warfarintherapy: a) First trimester of pregnancy b) Prosthetic heart valves c) Space-occupying CNS lesion d) Concurrent digoxin therapy e) Glucose 6-phosphate dehydrogenase (G6PD) deficiency 203 The following inhibit the metabolism of warfarin: a) Cimetidine b) Fluvoxamine c) St Johns wort d) Carbamazepine e) Smoking 204 The following inhibit platelet activation and/or aggregation: a) Warfarin b) Heparin c) Thromboxane A 2 d) Prostacyclin (epoprostenol) e) Dipyridamole 205 Clopidogrel: a) Is a direct inhibitor of glycoprotein IIb and IIIa

b) The antiplatelet effect lasts the life of the platelet c) Is usually given by intravenous bolus in acute coronary syndrome d) Is a prodrug, requiring conversion in the liver to its active metabolite e) Prolongs the QTc (QT interval on the ECG corrected for heart rate)predisposing to ventricular tachycardia 206 Prostacyclin (epoprostenol): a) Relaxes pulmonary and systemic vasculature b) Is the principal endogenous prostaglandin of large- and medium-sized blood vessels c) Is an effective anticoagulant d) Is contraindicated in haemodialysis e) Increases diastolic pressure CHAPTER 4 CARDIOVASCULAR SYSTEM 82 207 The principal beneficial effect in heart failure of the following drugs isto reduce preload (left ventricular filling pressure): a) Digoxin b) Furosemide c) Dobutamine d) GTN e) Sodium nitroprusside 208 Thefollowingdrugsatstandardtherapeuticdosesaggravateheartfailure: a) Imatinib (a tyrosine kinase inhibitor) b) Verapamil c) Daunorubicin d) Ibuprofen e) Bendroflumethiazide

209 In acute pulmonary oedema the following are usually appropriate: a) Sublingual nifedipine b) Lie the patient supine c) Oxygen d) Intravenous loop diuretic e) Intravenous morphine 210 Intravenous furosemide: a) Causes natriuresis b) Causes kaliuresis c) Has an indirect vasodilator effect d) Diuresis begins 1020 minutes after an intravenous dose e) High doses are ototoxic 211 ACE inhibitors: a) Are positive inotropes b) Increase afterload c) Increase preload d) May cause cough e) Should be given parenterally in acute heart failure 212 The following statements concerning drugs in heart failure are correct: a) The combination of furosemide (a loop diuretic) and ramipril (anACE inhibitor) should be avoided b) Candesartan (an angiotensin-II receptor antagonist) is generally better tolerated than captopril (an ACE inhibitor) c) Beta blockers are contraindicated in heart failure d) The combination of loop diuretic, ACE inhibitor and spironolactonemust always be avoided because of the risk of hyperkalaemia e)

The combination of hydralazine and nitrates is of demonstratedefficacy in Africanorigin patients 83 M ULTIPLE CHOICE QUESTIONS 213 Dobutamine: a) Is a sympathomimetic amine b) Is predominantly a 1 -receptor agonist c) Increases blood pressure via vasoconstriction d) Should not be given at the same time as loop diuretics e) Increases myocardial oxygen consumption 214 The following drugs can cause sinus tachycardia: a) Esmolol b) Theophylline c) Ephedrine d) Amphetamine e) Verapamil 215 Lidocaine: a) Is a class 1b agent that blocks cardiac Na channels, reducing therate of rise of the cardiac action potential and increasing theeffective refractory period b) Is epileptogenic c) Is a positive inotrope d) Is usually administered as an intravenous bolus followed byinfusion e) Is the drug of first choice for supraventricular tachycardia 216 The following drugs prolong the QT interval and/or cause torsades depointes: a)

Erythromycin b) Pimozide c) Foscarnet d) Tacrolimus e) Disopyramide 217 Amiodarone: a) Is effective in resistant atrial fibrillation or flutter b) Is effective in preventing recurrent ventricular fibrillation c) Is contraindicated in WolffParkinsonWhite (WPW)syndrome d) May be given intravenously via a central line e) Prolongs the QT interval 218 The following adverse effects are associated with amiodarone: a) Visual disturbances (e.g. coloured halos) b) Hyperthyroidism c) Hypothyroidism d) Pulmonary fibrosis e) Photosensitivity CHAPTER 4 CARDIOVASCULAR SYSTEM 84 219 Amiodarone: a) Is highly lipid soluble b) Has an apparent volume of distribution of approximately 5000L c) Is predominantly eliminated by the kidney d) Accumulates in the heart e) Has a half-life of 3 weeks 220

Sotalol: a) Is effective in supraventricular and ventricular dysrhythmias b) Is not effective when given by mouth c) The dose should be reduced in renal impairment d) May cause torsade de pointes e) Is a less potent negative inotrope than amiodarone 221 Intravenous verapamil: a) May terminate supraventricular tachycardia b) Must not be given to patients receiving beta blockers c) Reduces digoxin excretion d) One must delay DC cardioversion at least 2 hours after a dose e) Shortens the PR interval on the ECG 222 Adenosine: a) Is used to terminate ventricular tachycardia b) Is contraindicated in regular broad complex tachycardia c) Dilates bronchial smooth muscle d) Is associated with chest pain e) Circulatory effects last 2030 seconds 223 Digoxin: a) Reduces the ventricular rate in atrial fibrillation b) Is contraindicated in second-degree heart block c) Is the treatment of choice in atrial fibrillation in a patient with WPWsyndrome d) Induced dysrhythmias may be terminated by magnesium e) 80 per cent of administered digoxin is excreted unchanged in the bile 224 A70-year-old woman has recurrent, symptomatic ventriculartachycardia following an acute myocardial infarction in spite of DCconversion and lidocaine. The following may be effective:

a) Amiodarone b) Atropine c) Verapamil d) Adenosine e) Isoprenaline 85 M ULTIPLE CHOICE QUESTIONS 225 The following are indications for transvenous pacing: a) Asymptomatic sinus bradycardia post inferior myocardial infarction b) First-degree heart block post inferior myocardial infarction c) Aheart rate of 34bpm at rest in an athlete with second-degree(Mobitz type 1) heart block d) Asymptomatic congenital complete heart block e) Blackouts associated with bradycardia in sick sinus syndrome 226 The following dysrhythmias are correctly paired with their first-linetreatment: a) Ventricular fibrillation synchronized DC cardioversion b) Ventricular fibrillation unsynchronized DC cardioversion c) Ventricular tachycardia post myocardial infarction esmolol d) Rapid chronic (established) atrial fibrillation flecainide e) Drug-induced torsade de pointes disopyramide Answers: see pages 8997 CHAPTER 4 CARDIOVASCULAR SYSTEM 86 EXTENDED MATCHING QUESTIONS A Simvastatin B Recombinant hirudin C Tranexamic acid

D Epoprostenol (prostacyclin) E Estradiol F Fenofibrate G Warfarin H Colestyramine I Tissue plasminogen activator J Ezetimibe Link each of 1 to 5 below with the most appropriate item from Ato J: 1 Useful combined with a statin 2 Inhibition of platelet aggregation during haemodialysis 3 Lowers serum triglyceride and cholesterol concentrations 4 Causes malabsorption of fat-soluble vitamins 5 Myalgia 228 HYPERTENSION227 ATHEROMA AND THROMBOSIS A Labetalol B Minoxidil C Doxazosin D Methyldopa E Atenolol F Spironolactone G Candesartan H Trandolapril I Bendroflumethiazide J Amlodipine Select the drug from the list above most appropriate to prescribe to the patientsdescribed below. In each patient the current blood pressure is above target. 1

A40-year-old Afro-Caribbean man who has poorly controlledhypertension having stopped bendroflumethiazide, which causedimpotence 2 A70-year-old white man who takes losartan and amlodipine and whohas symptoms from prostatic hyperplasia 3 A50-year-old hypertensive man who has hyperaldosteronism due to bilateral adrenal hyperplasia who is currently on no therapy 4 A50-year-old white man who has type II diabetes and asthma. Hecurrently takes gliclazide, simvastatin and inhaled beclomethasone. Hewas on trandolapril, but this was associated with a troublesome cough 5 A50-year-old Afro-Caribbean woman who developed marked lowerlimb oedema on amlodipine 87 E XTENDED MATCHING QUESTIONS A Ramipril B Warfarin C Tissue plasminogen activator D Glyceryl trinitrate E Magnesium F Nifedipine G Verapamil H Nicorandil I Simvastatin J None of the above Which of the above drugs is useful in each of the following clinical situations? 1 Acute treatment of an angina attack in a 65-year-old man withischaemic chest pain following exertion 2 Acute treatment of anterior ST-elevation myocardial infarction in apreviously healthy 60-year-old man 3 Long-term treatment of left ventricular dysfunction in a 65-year-oldwoman post myocardial infarction 4

Long-term prevention of cardiac events in an asymptomatic 67-year-oldwoman with a 10-year history of type 2 diabetes and a total cholesterolof 5.0mmol/L 5 Prevention of angina in a 78-year-old man with widespread diffusecoronary artery disease, not amenable to percutaneous coronaryintervention or surgery, who is having troublesome exertional anginadespite combination treatment with a long-acting nitrate, beta blockerand calcium antagonist 230 ANTICOAGULANTS AND ANTIPLATELETDRUGS229 ISCHAEMIC HEARTDISEASE A Aspirin B Warfarin C Intravenous heparin D Subcutaneous enoxaparin E Dipyridamole F Clopidogrel G Aspirin clopidogrel H Aspirin dipyridamole I Aspirin clopidogrel subcutaneousenoxaparin J Clopidogrel dipyridamole Which drug or drug combination is appropriate for each of the followingscenarios? 1 Treatment of a 68-year-old man with known ischaemic heart disease,admitted to hospital with unstable angina 2 Treatment of a 65-year-old woman, known to have mitral stenosissecondary to childhood rheumatic fever, who is otherwise well andpresents with a two-week history of atrial fibrillation 3 Immediate treatment of a 30-year-old man, normally well, who presentswith a suspected deep vein thrombosis following a long-haul flight 4

Immediate treatment of a 70-year-old woman, known to havepancreatic carcinoma and renal impairment (creatinine 300 mol/L),who presents with a suspected deep vein thrombosis 5 Treatment of a 55-year-old man with known stable angina pectoris, on beta blocker treatment, who is allergic to aspirin CHAPTER 4 CARDIOVASCULAR SYSTEM 88 A Daunorubicin B Infliximab C Amlodipine D Digoxin E Bisoprolol F Glyceryl trinitrate G Ibuprofen H Verapamil I Amiloride J Furosemide Link each of 1 to 5 below with the most appropriate item from Ato J: 1 Improves survival in stable heart failure 2 Positive inotrope 3 Contraindicated in heart failure because a strong negative inotrope 4 Causes hypokalaemia 5 Cardiotoxic 232 CARDIAC DYSRHYTHMIAS231 HEARTFAILURE A Intravenous adenosine B Intravenous lidocaine C Oral disopyramide D

Direct current cardioversion E Oral sotalol F Intravenous digoxin G Intravenous verapamil H Oral mexiletine I Intravenous atropine J None of the above Which of the above is appropriate for each clinical situation below? 1 Prevention of paroxysmal atrial fibrillation in an otherwise well60-year-old man 2 Treatment of supraventricular tachycardia in a 28-year-old woman,otherwise well, where vagal manoeuvres have failed 3 Treatment of symptomatic supraventricular tachycardia in a 22-year-old woman with brittle asthma, where vagal manoeuvres have failed 4 Treatment of symptomatic sinus bradycardia (rate 35/minute) in a62-year-old man with an acute inferior myocardial infarction 5 Treatment of frequent asymptomatic ventricular ectopic beats in a65-year-old man with an acute anterior myocardial infarction ANSWERS: see pages 97100 89 MCQ ANSWERS ANSWERS MCQ ANSWERS 169 a) TrueAtheroma is the commonest cause of ischaemic heart b) Truedisease, stroke and peripheral vascular disease c) T r u e d) T r u e e) T r u e 170 a) TrueThe anion-exchange resins colestyramine and colestipol are b)

T r u e n o t a b s o r b e d i n t o t h e s ys t e m i c c i r c u l a t i o n a n d b i n d b i l e a c i d s c) Falsein the gut lumen inhibiting reabsorption of bile salts and d) Falsecholesterol. They have been almost completely superseded e) Trueby statins in the management of h y p e r c h o l e s t e r o l a e m i a . Colestyramine causes malabsorption of fatsolublevitamins, and is used to treat pruritus in patients withincomplete biliary obstruction. Side-effects includeflatulence, constipation and nausea 171 a) TrueThe fibrates stimulate lipoprotein lipase and reduce plasma b) Falsetriglyceride. They also tend to reduce LDLcholesterol and to c) Falseraise HDLcholesterol. They can cause myositis which is d) Falsemore common in alcoholics, patients with impaired renal e) Truefunction and in patients on concurrent H M G - C o A reductase inhibitors (statins). Other adverse effects includenausea and abdominal discomfort 172 a) TrueHMG-CoAreductase is the rate-limiting step in cholesterol b) Truebiosynthesis from acetate. HMG-CoAreductase inhibitors c) Falseare ineffective in rare patients with homozygous familial d) Truehypercholesterolaemia as they cannot make LDLreceptors. e) F a l s e E z e t i m i b e i s u s e d i n c o m b i n a t i o n w i t h d i e t a n d s t a t i n s for severe hypercholesterolaemia or when statins arecontraindicated 173 a) TrueAlthough hypertension is usually essential (i.e. idiopathic), b) Truethe possibility of secondary hypertension must always be c)

Trueconsidered. Equally important is the confirmation or d) Truerejection of persistent hypertension by repeated measures e) True(blood pressure is very variable) and the i d e n t i f i c a t i o n o f other treatable risk factors such as diabetes, smoking,hypercholesterolaemia and obesity 174 a) TrueThiazide diuretics (e.g. bendroflumethiazide) remain b) Truea logical first choice for treating older patients and CHAPTER 4 CARDIOVASCULAR SYSTEM 90 c) FalseAfro-Caribbean patients with mild hypertension unless d) Falsecontraindicated by some co-existent disease, and are also e) Truevaluable in patients with more severe h y p e r t e n s i o n i n combination with other therapy 175 a) T r u e T h e r e l a t i v e l y c a r d i o s e l e c t i v e -adrenoreceptor antagonists, b) Trueatenolol and metoprolol, are no longer used as first-line c) Falsetreatment of hypertension in the UK. They are particularly d) Truevaluable in patients with additional pathology, such as e) Trueangina or heart failure (e.g. metoprolol, carvedilol), o r w h o have survived a myocardial infarction. Atenolol is a polardrug and undergoes renal elimination whilst metoprolol isnon-polar and is metabolized by CYP450 2D6 176 a) TrueAfro-Caribbean patients are less likely to have high b)

Truecirculating renin levels, hence beta blockers and ACE c) Falseinhibitors are less likely to be effective. This difference d) Falseis statistical and based on large populations. Both ACE e) Falseinhibitors and beta blockers can be effective in i n d i v i d u a l Afro-Caribbean patients but a thiazide or calcium channelantagonist is usually the antihypertensive of first choice 177 a) TrueACE inhibitors inhibit the conversion of inactive angiotensin b) TrueI to active angiotensin II, a powerful vasoconstrictor, and also c) Falseinhibit the breakdown of the vasodilator peptides such as d) Falsebradykinin. ACE inhibitors are of particular value in e) Falsetreating diabetic hypertensive patients as they s i g n i f i c a n t l y slow down the progressive renal impairment typical inthese patients 178 a) FalseAngiotensin-II receptor antagonists, unlike ACE inhibitors, do b) Falsenot inhibit the breakdown of bradykinin, hence dry cough is c) Truea much less common adverse effect. In bilateral renal artery d) Truestenosis glomerular filtration is dependant on angiotensin-IIe) Falsemediated efferent arteriolar vasoconstriction 179 a) FalseNifedipine is used in the management of Raynauds b) T r u e s yn d r o m e , h yp e r t e n s i o n a n d a n g i n a . M o d i f i e d - r e l e a s e t a b l e t s c) Falseare preferred. Amlodipine is a once-daily calcium channel d) Falseblocker with similar pharmacodynamic properties e) False

180 a) TrueNifedipine, unlike verapamil, has little effect on the b) Trueconducting system of the heart. It can worsen angina due to c) Falsea reflex tachycardia whilst verapamil causes a bradycardia. d) TrueBoth drugs are effective arterial dilators. Verapamil is a much e) Falsemore potent negative inotrope and has a greater i n h i b i t o r y effect on intestinal peristalsis 91 MCQ ANSWERS 181 a) TrueNon-specific alpha blockers such as phenoxybenzamine b) F a l s e c a u s e p r o f o u n d p o s t u r a l h yp o t e n s i o n a n d r e f l e x t a c h y c a r d i a . c) TrueDoxazosin does not block presynaptic 2 receptors that are d) Truenormally stimulated by released noradrenaline and which e) Trueinhibit further transmitter release. This is a n e g a t i v e feedback pathway hence there is little reflex tachycardiawith doxazosin although first-dose hypotension is aproblem; therefore start with a low dose, usually at night 182 a) TrueSodium nitroprusside is valuable in treating hypertensive b) Trueencephalopathy and in the management of certain types of c) Falseshock when it is combined with positive inotropes. d) TrueContinuous blood pressure monitoring is essential as it e) Truecauses profound hypotension. It has a half-life o f l e s s t h a n 10 minutes

183 a) TrueAlthough generally safe and not contraindicated in asthma b) Trueand pregnancy, methyldopa is often poorly tolerated. The c) Truedose should be slowly titrated upwards. Drowsiness and d) T r u e f a t i g u e m a y b e i n t o l e r a b l e w h e n u s e d c h r o n i c a l l y. I t i s a w e l l e) Falserecognized (but uncommon) cause of drug fever a n d Coombs-positive haemolytic anaemia 184 a) TrueDiuretics worsen symptoms of bladder neck obstruction, b) T r u e w h e r e a s 1 antagonists improve such symptoms as well as c) Falsesynergizing with ACE inhibitors d) False e) T r u e 185 a) TrueMore common in slow acetylators b) TrueFluid retention is also a problem c) T r u e W o r s e i f o n d i u r e t i c s d) F a l s e M a y r e d u c e t r e m o r e) F a l s e F i r s t - d o s e h y p o t e n s i o n c a n o c c u r s o u s e s a m e p r e c a u t i o n s as with an ACE inhibitor 186 a) FalseThe highest concentration of oxygen available should be b) Trueused unless there is coincident pulmonary disease with CO 2 c) Trueretention. Aspirin and opening the occluded artery (either d)

Truewith thrombolytic therapy or angioplasty) have an additive e) Falsebeneficial effect on reduction of infarct size a n d improvement in survival. There is evidence of some benefitfrom early treatment with ACE inhibitors post infarction inpatients with left ventricular dysfunction 187 a) TruePatients with unstable angina require urgent admission, b) Trueurgent antiplatelet therapy (aspirin and clopidogrel) plus CHAPTER 4 CARDIOVASCULAR SYSTEM 92 c) Trueantithrombotic therapy (usually low molecular weight d) Falseheparin). GTN (usually by infusion in this indication) is often e) Trueeffective in relieving pain, but does not significantly a l t e r outcome 188 a) TrueGTN is generally best used as acute prophylaxis (i.e. b) Trueimmediately before undertaking strenuous activity). The c) Truespray has a longer shelf-life but is more expensive than the d) Falsesublingual GTN. GTN is subject to extensive presystemic e) Truemetabolism if swallowed. Longer-acting oral n i t r a t e s ( e . g . isosorbide mononitrate) are effective as regularprophylactic therapy 189 a) FalseBeta blockers slow the heart, are negatively inotropic (but b) Truemetoprolol, bisoprolol, carvedilol and nebivolol may be of c) Truevalue in stable heart failure) and reduce arterial blood d)

Falsepressure, are antidysrh ythmic, increase peripheral vascular e) Trueresistance, reduce plasma renin activity and p r e d i s p o s e t o bronchoconstriction 190 a) TrueModifiable risk factors should be sought and attended to. b) TrueStopping smoking is particularly important. ACE inhibitors c) Falseare recommended for patients with left ventricular d) F a l s e d y s f u n c t i o n e) T r u e 191 a) TrueIn addition to hypertension and angina, verapamil is used to b) Truetreat supraventricular tachycardia. Nimodipine helps c) Falseprevent cerebral vasospasm and nifedipine is used in d) F a l s e R a y n a u d s s y n d r o m e e) False 192 a) TrueThe commonest side-effects of nifedipine and amlodipine are b) Trueflushing and headache. They have no significant effect on the c) T r u e c o n d u c t i o n s y s t e m o f t h e h e a r t d) T r u e e) False 193 a) T r u e T h r o m b o x a n e ( T X ) A 2 is the main cyclo-oxygenase product b) Trueof activated platelets and is proaggregatory and a c) T r u e v a s o c o n s t r i c t o r

d) False e) False 194 a) TrueStreptokinase combines with plasminogen to form an b) Falseactivator complex that converts remaining free plasminogen c) Falseto plasmin which dissolves fibrin. The potential benefit d) Truelessens with delay but the value of treatment within 24 hours e) F a l s e i s w e l l e s t a b l i s h e d 93 MCQ ANSWERS 195 a) FalseAlteplase is a direct-acting plasminogen activator b) F a l s e I m m e d i a t e h e p a r i n f o l l o w i n g a l t e p l a s e i s n e c e s s a r y t o prevent re-occlusion c) False d) TrueAlso indicated in acute myocardial infarction and a c u t e ischaemic stroke (under specialist neurologists) e) False 196 a) TrueImmune reactions are important with streptokinase and its b) Trueprodrug anistreplase. It seems unlikely that mild infections c) Falsesuch as sore throats reduce its efficacy. Recent dental d) Trueextraction is considered a contraindication e) False 197 a) TrueUnfractionated heparin binds to antithrombin III, the b)

Truenaturally occurring inhibitor of thrombin and of the other c) Trueserine proteases (factors IXa, Xa and XIa), enormously d) Truepotentiating its inhibitory action e) T r u e 198 a) FalseProphylactic once-daily subcutaneous LMWH reduces the b) Falserisk of thromboembolism associated with major surgery. c) TrueLaboratory monitoring of coagulation is not necessary in d) Trueroutine clinical use. The benefit normally outweighs the e) Falseincreased risk of bleeding in major orthopaedic surgery 199 a) TrueThe commonest adverse effect is bleeding. This can be b) Truetreated by stopping the infusion (if relevant), local c) Truecompression, protamine sulphate and, if severe and d) Falsecontinues in spite of the above, fresh frozen plasma e) False 200 a) TrueLMWH is preferred to heparin unless renal failure is b) T r u e p r e s e n t c) T r u e d) TrueFondaparinux, a synthetic pentasaccharide, has b e e n shown to be superior to unfractionated heparin or LMWHfor thromboprophylaxis in some studies e)

T r u e 201 a) TrueWarfarin is the most commonly prescribed oral b) Trueanticoagulant. It usually takes at least 3 days to achieve c) Falseadequate anticoagulation. If more rapid action is required d) Trueintravenous heparin and oral warfarin are used until the I N R is in the usual therapeutic range (23 for most indications) e) TrueHeparin only influences the INR if the APTT is 2.5 timesthe control. The laboratory can allow for this by the in vitro addition of protamine CHAPTER 4 CARDIOVASCULAR SYSTEM 94 202 a) TrueOther contraindications include active bleeding, blood b) Falsedyscrasias with haemorrhagic diatheses, dissecting c) Trueaneurysm of the aorta and recent CNS surgery. Aspirin and d) Falsewarfarin should not be used together routinely, although e) Falsetrials of low-dose combination therapy are in progress 203 a) TrueWarfarin has a narrow therapeutic range and steep b) Truedoseresponse curve. It is metabolized by CYP450. c) F a l s e C i m e t i d i n e , a n H 2 blocker used to reduce gastric acid d) Falseproduction, and fluvoxamine, a selective serotonin reuptake e)

Falseinhibitor (SSRI) antidepressant, both inhibit C Y P 4 5 0 . St Johns wort, carbamazepine and smoking induceCYP450. The INR must be monitored to reduce both therisk of bleeding and inadequate anticoagulation 204 a) F a l s e T h r o m b o x a n e A 2 is synthesized by activated platelets and b) Trueacts on platelet receptors to cause further activation and c) Falsepropagation of the aggregate. It also acts on vascular smooth d) Truemuscle to cause vasoconstriction. Heparin inhibits thrombin, e) Truewhich is a platelet agonist, as well as causing coagulation 205 a) FalseClopidogrel is combined with aspirin to treat patients with b) Trueacute coronary syndrome/myocardial infarction and c) Falsefollowing percutaneous coronary intervention with stent d) Trueplacement. It may be substituted for aspirin in other e) Falseindications as an antiplatelet drug if aspirin is p o o r l y tolerated 206 a) TrueProstacyclin may be used to prevent coagulation in b) Trueextracorporeal circuits. It causes flushing, headache, reduced c) Truediastolic pressure, increased pulse pressure and usually a d) Falsereflex tachycardia. Occasionally vagally mediated e) Falsebradycardia and hypotension occur 207 a) FalseThe major influences on preload are blood volume and b)

T r u e c a p a c i t a n c e v e s s e l t o n e c) False d) T r u e e) False 208 a) TrueNegative inotropes, direct cardiac toxins (e.g. daunorubicin) b) Trueand drugs that cause salt retention (e.g. NSAIDs) aggravate c) Trueheart failure. Excessive tachycardia does not allow d) Truesufficient time for the ventricle to fill in diastole e) False 209 a) FalseIn addition to helping relieve the acute anxiety and b) Falsediscomfort associated with acute pulmonary oedema, opioids 95 MCQ ANSWERS c) T r u e d i l a t e c a p a c i t a n c e v e s s e l s d) T r u e e) T r u e 210 a) T r u e L o o p d i u r e t i c s i n h i b i t N a /K /2Cl co-transport in the b) Truethick ascending c) T r u e d) T r u e e) T r u e

limb

of Henles

loop

211 a) FalseACE inhibitors and angiotensin-II antagonists act as b) Falsearterial and venous vasodilators in cardiac failure, c) F a l s e p r o l o n g i n g s u r v i v a l d) T r u e e) False 212 a) FalseSpironolactone can cause life-threatening hyperkalaemia, b) Truehowever if renal function is not appreciably impaired c) Falseand serum potassium monitored, the addition of d) Falsespironolactone to the loop diuretic/ACE inhibitor e) Truecombination is usually beneficial. Although beta b l o c k e r s are negative inotropes, several trials have shown thatcareful addition of beta blockers to other treatments (e.g.ACE inhibitors) improve survival 213 a) TrueDobutamine is a positive inotrope used predominantly in b) Truecardiogenic shock. Hypovolaemia must be corrected before c) F a l s e i t s u s e d) False e) T r u e 214 a) FalseThe management of sinus tachycardia is directed to the b) Trueunderlying cause (e.g. pain, anxiety, left ventricular failure, c) Trueasthma, thyrotoxicosis) and iatrogenic factors. Of calcium d)

Trueantagonists, verapamil causes bradycardia, dihyropyridines e) Falsecan cause reflex tachycardia, and diltiazem seldom c a u s e s appreciable changes in heart rate. Esmolol is a beta blockerwith a very short duration of action 215 a) TrueLidocaine has a narrow therapeutic index but is used for the b) T r u e t r e a t m e n t o f v e n t r i c u l a r t a c h yc a r d i a a n d f i b r i l l a t i o n ( p o s t D C c) Falsecardioversion). It is also used as a local anaesthetic d) T r u e e) False 216 a) TrueAprolonged QT interval predisposes to torsade b) Truede pointes, a form of ventricular tachycardia c) TrueUsed for cytomegalovirus (CMV) retinitis and p a t i e n t s with acquired immunodeficiency syndrome (AIDS) CHAPTER 4 CARDIOVASCULAR SYSTEM 96 d) TrueAn immunosuppressant whose adverse effects i n c l u d e cardiomyopathy e) T r u e 217 a) TrueAmiodarone, a class III agent, is highly effective in both b) Truesupraventricular and ventricular arrhythmias. It is not a c) Falsenegative inotrope in contrast to most antidysrhythmic d) T r u e a g e n t s e) T r u e 218 a)

TrueAdverse effects are many and varied and are common b) Truewhen plasma amiodarone concentration exceeds 2.5mg/L. c) TrueMost are reversible on stopping treatment, but this is not true d) T r u e o f p u l m o n a r y f i b r o s i s e) T r u e 219 a) TrueAmiodarone is highly protein bound and is slowly excreted b) T r u e b y t h e l i v e r . A n t i d ys r h yt h m i c a c t i v i t y m a y p e r s i s t f o r s e v e r a l c) Falsemonths after stopping treatment d) T r u e e) T r u e 220 a) T r u e S o t a l o l i s a -adrenoreceptor antagonist (class II) with b )Falseadditional class III antidysrhythmic activity c) T r u e d) T r u e e) False 221 a) TrueVerapamil slows intracardiac conduction affecting in b) Trueparticular the atrioventricular (AV) node but also the c) Truesinoatrial (SA) node. It is a potent negative inotrope. It d) Falseshould be avoided in WPW as it can increase conduction e) Falsethrough an accessory pathway

222 a) F a l s e A d e n o s i n e i s u s e d t o t e r m i n a t e s u p r a v e n t r i c u l a r t a c h yc a r d i a b) False(SVT). It is particularly useful diagnosticall y in patients with c) F a l s e r e g u l a r b r o a d c o m p l e x t a c h yc a r d i a w h i c h i s s u s p e c t e d o f d) Truebeing SVT with aberrant conduction. If adenosine terminates e) Truethe bradycardia the AV node is involved 223 a) TrueThe main use of digoxin as an antidysrhythmic is to control b) Truethe ventricular rate (and hence improve cardiac output) in c) F a l s e p a t i e n t s w i t h a t r i a l f i b r i l l a t i o n . D r u g s c a u s i n g h yp o k a l a e m i a d) T r u e a g g r a v a t e d i g o x i n t o x i c i t y e) False 224 a) TrueIsoprenaline, a beta agonist, is likely to be dysrh ythmogenic b) Falseand will increase myocardial oxygen consumption. 97 EMQ ANSWERS c) FalseVerapamil is a potent negative inotrope and is only effective d) F a l s e i n S V T e) False 225 a) FalseBradycardia and first-degree heart block are common post b) Falseinferior myocardial infarction. If the bradycardia causes c) Falsesymptoms 0.6mg atropine intravenously is usually effective d) False e)

T r u e 226 a) FalseIf causing immediate cardiovascular embarrassment, DC b) Truecardioversion is indicated in ventricular tachycardia. c) FalseOtherwise, if intravenous lidocaine is ineffective, or oral d) Falseprophylaxis is required, amiodarone may be used. e) FalseIntravenous magnesium sulphate has been r e c o m m e n d e d for torsades de pointes. It also has a major role in eclampsiafor the prevention of recurrent seizures EMQ ANSWERS 227 ATHEROMA AND THROMBOSIS 1J Ezetimibe blocks cholesterol absorption and is useful when combinedwith a statin. (Specialists sometimes combine fibrates with statins but this is not routine as there is an increased risk of adverseeffects.) 2D Epoprostenol (prostacyclin) is used to inhibit platelet aggregationduring haemodialysis. It can also be used in primary pulmonaryhypertension. 3F Fenofibrate, bezafibrate and gemfibrozil are used mainly for patientswith mixed dyslipidaemia with severely raised triglycerides,especially if they are poorly responsive to statins. 4H Colestyramine used to be combined with a statin but has beenrendered largely obsolete by ezetimibe because of its inconvenienceand adverse effects. Colestyramine is indicated for pruritus associatedwith partial biliary obstruction and primary biliary cirrhosis, diarrhoeaassocated with Crohns disease, ileal resection, vagotomy, diabeticvagal neuropathy and radiation. 5A Simvastatin is very well tolerated but myalgia is its most commonadverse effect (see Textbook of Clinical Pharmacology and Therapeutics ,Chapter 27). CHAPTER 4 CARDIOVASCULAR SYSTEM 98 228 HYPERTENSION See Textbook of Clinical Pharmacology and Therapeutics , Chapter 28. 1J

Thiazide diuretics are associated with erectile dysfunction whichis reversible on stopping the thiazide. Calcium channel blockers(e.g. amlodipine) and thiazide diuretics are the antihypertensivesof first choice in Afro-Caribbean patients. 2C Doxazosin has postsynaptic 1 -blocking activity and is an effectivehypotensive agent. First-dose hypotension is a potential problem.It relaxes smooth muscle in benign prostatic hyperplasia improvingflow rate and reducing obstructive symptoms. 3F Spironolactone competes with aldosterone for its intracellularreceptors. Its indications include Conns syndrome, secondaryhyperaldosteronism in ascites and resistant, low renin hypertension.Hyperkalaemia is a potential problem, particularly if on anotherpotassiumsparing drug (e.g. an ACE inhibitor such as trandolapril),or if there is renal impairment. 4G Candesartan is an angiotensin II blocker. Unlike ACE inhibitors it doesnot inhibit the breakdown of bradykinin, the likely cause of an ACEinhibitor-induced cough. 5I Although not sinister, ankle oedema is a troublesome adverse effect ofcalcium channel blockers (less common with verapamil). Thiazides areoften effective in Afro-Caribbean patients. Metabolic adverse effectsinclude hypokalaemia, hyperglycaemia, hypercalcaemia andhyperuricaemia. 229 ISCHAEMIC HEARTDISEASE 1D Sublingual GTN is an effective and convenient acute treatment forangina. 2C Recombinant tissue plasminogen activator (alteplase) is an effectivethrombolytic. 3A Long-term use of ACE inhibitors (e.g. ramipril) post myocardialinfarction in patients with left ventricular dysfunction preventscardiac remodelling and subsequent worsening of heartfailure. 4I Numerous large studies have shown statins to be beneficial inreducing future cardiac events in this situation. 5H Nicorandil combines activation of the potassium K ATP channel withvasodilator (nitric oxide donor) actions. 99 EMQ ANSWERS 230 ANTICOAGULANTS AND ANTIPLATELETDRUGS 1I Aspirin clopidogrel

subcutaneous enoxaparin (an LMWH)approximately halves the likelihood of myocardial infarction inpatients with acute coronary syndrome. 2B Warfarin would reduce the risk of stroke in this patient with mitralstenosis and atrial fibrillation. 3D Subcutaneous enoxaparin is an effective and convenient (once-dailysubcutaneous injection) acute treatment in suspected deep veinthrombosis. 4C Unfractionated heparin has been replaced by LMWH for mostindications but remains important in patients with impaired or rapidlychanging renal function. 5F Clopidogrel is an inactive prodrug that is converted in the liver to anactive metabolite that binds to and irreversibly inhibits platelet ADPreceptors, thereby inhibiting platelet aggregation and arterialthrombotic disease. 231 HEARTFAILURE Heart failure occurs when the heart fails to deliver adequate oxygenated bloodto the tissues during exercise, or in severe cases, at rest. 1E Bisoprolol, and other -adrenoreceptor antagonists, although negativeinotropes can improve survival in heart failure, if the dose is titratedcarefully. This improvement is probably through antagonism ofcounter-regulatory sympathetic activation. 2D Digoxin inhibits Na /K ATPase causing an increase in intracellularCa 2 which results in a positive inotropic effect, although its mainvalue is in reducing ventricular rate in rapid atrial fibrillation. 3H Verapamil is a strong negative inotrope. 4J Furosemide, a loop diuretic, causes hypokalaemia which predisposesto dysrhythmias. 5A Daunorubicin, ethanol, imatinib, gefitinib and trastuzumab are cardiactoxins. 232 CARDIAC DYSRHYTHMIAS 1E Sotalol is a -adrenoreceptor antagonist which additionally hassubstantial class III activity. 2A Intravenous adenosine is used to terminate SVT. Adenosine A 1 receptors block AV nodal conduction. CHAPTER 4

CARDIOVASCULAR SYSTEM 100 3G Intravenous verapamil is used to terminate SVT in patients who arenot haemodynamically compromised if adenosine is contraindicated.Verapamil is a calcium channel blocker. 4I Atropine, a selective antagonist of acetylcholine at muscarinicreceptors, accelerates the heart rate by inhibiting vagal tone. 5J Asymptomatic ventricular ectopic beats post anterior myocardialinfarction do not require any drug therapy. Trials of anti-dysrhythmicdrugs in this situation have shown that they are more likely to increasemortality. CHAPTER FIVE RESPIRATORYSYSTEM MULTIPLE CHOICE QUESTIONS 233 The following should be administered to an otherwise healthy 27-year-old male with acute severe asthma: a) Intravenous midazolam b) Nebulized salbutamol c) Intravenous glucocorticosteroids d) Nebulized salmeterol e) Continuous high percentage oxygen ( F iO 2 3540 per cent) 234 Beta 2 agonists (e.g. salbutamol, terbutaline, salmeterol): a) Relax bronchial smooth muscle b) Inhibit release of mast cell and other inflammatory mediators c) Reduce heart rate d) Cause pulmonary vasoconstriction e) Decrease intracellular cyclic adenosine monophosphate (cAMP) 235 Pharmacodyamic properties of salmeterol include: a)

Tremor b) Exacerbation of atrial dysrhythmias c) Hyperkalaemia d) Prolonged pharmacodynamic effects allowing twice-daily dosing e) Seizures 236 Omalizumab: a) Is contraindicated in patients with IgE-mediated sensitivity toinhaled allergen b) Is used to treat severe acute attacks c) Is administered by subcutaneous injection d) Inhibits warfarin metabolism via CYP2C9 e) Cannot be used in children CHAPTER 5 RESPIRATORY SYSTEM 102 237 Ipratropium bromide: a) Is administered intravenously b) Causes bronchodilatation because of its antagonistic effects at thecholinergic M 2 /M 3 receptors c) Has a more rapid onset of bronchodilatation than beta 2 agonists d) Has a bitter taste e) May precipitate glaucoma in high doses 238 Adverse effects associated with the use of theophyllineinclude: a) Cardiac dysrhythmias b) Convulsions c)

Oral candidiasis d) Headache e) Nausea and vomiting 239 In acute severe asthma hydrocortisone: a) Is usually given via the intravenous route b) Subjective improvement following steroid administration takes3060 minutes c) Is contraindicated in growing children d) Is contraindicated in pregnancy e) Should not be administered until at least two doses of nebulizedsalbutamol have been administered without significant evidence ofsustained bronchodilatation 240 Administration of fluticasone via a metered dose inhaler: a) Allows reduction in the maintenance dose of oral prednisolone inchronic asthma b) More of the dose is swallowed than enters the lungs c) Does not cause hypothalamo-pituitary-adrenal suppression at adose of 2000 g/day d) Has a lower systemic bioavailability than beclomethasone e) In children, causes reversible inhibition of long bone growth at highdoses 241 Inhaled sodium cromoglicate: a) Is effective in alleviating an acute episode of allergicasthma b) Has no benefit in preventing exercise-induced bronchospasm c) Prevents antigenantibody combination d) Inhibits mediator release from mast cells e) Causes cardiac dysrhythmias by prolonging the QTc 103 M ULTIPLE CHOICE QUESTIONS 242 Montelukast: a)

Is a competitive antagonist at the Cys LT 1 receptor b) Can be given orally c) Is usually taken once daily at bedtime d) May be associated with ChurgStrauss syndrome e) Is not beneficial to patients with antigen-induced asthma 243 The following drugs can produce pulmonary fibrosis: a) Methotrexate b) Bleomycin c) Busulphan d) Lisinopril e) Amiodarone 244 Pulmonary eosinophilia is caused by the following drugs: a) Methysergide b) Aspirin c) Nitrofurantoin d) Carmustine (BCNU) e) Sulfasalazine 245 The following agents if given to an asthmatic are likely to causecatastrophic bronchospasm: a) Carvedilol b) Losartan c) Adenosine d) Lidocaine (lignocaine) e) Bethanecol 246

The following drugs are used as standard of care when treating apatient with type II (hypoxic hypercanic) respiratory failure: a) 35 per cent oxygen b) Doxapram c) Salbutamol d) Methylprednisolone e) Dantrolene Answers: see pages 105107 CHAPTER 5 RESPIRATORY SYSTEM 104 EXTENDED MATCHING QUESTIONS A Salbutamol B Salmeterol C Tiotropium D Methylprednisolone E Montelukast F Sodium cromoglicate G Theophylline H Omalizumab I Cetirizine J Zafirlukast Select the drug whose mechanism of action is described below: 1 Inhibits transcription of proinflammatory cytokines 2 Binds to the Fc portion of IgE 3 Inhibits H 1 but not H 2 receptors 4

Modulates the firing of respiratory C fibres 5 Competitively inhibits M 2 and M 3 muscarinic receptors 248 RESPIRATORYDRUGS ADVERSE EFFECTS247 RESPIRATORYDRUGS MECHANISM OF ACTION A Terbutaline B Formoterol C Azithromycin D Dexamethasone E Montelukast F Nedocromil G Theophylline H Omalizumab I Loratadine J Codeine Select the drugs most frequently associated with the adverse effects described below: 1 Seizures 2 Apnoea 3 QTc prolongation 4 Hypertension 5 Anaphylaxis ANSWERS: see page 108 105 MCQ ANSWERS ANSWERS MCQ ANSWERS 233 a) FalseNever give anxiolytics/sedatives in acute asthma.

b) TrueIntravenous fluids are administered to correct/prevent c) Truedehydration. Antibiotics are administered if there is d) Falsehistory/signs of infection. Refractory cases require an e) T r u e i n t r a v e n o u s s h o r t - a c t i n g b e t a 2 agonist (salbutamol) or as alast resort theophylline. If these are inadequate,intermittent positive pressure ventilation is required.Nebulized salmeterol is not available and its onset of bronchodilation is too slow to be used acutely 234 a) T r u e B e t a 2 agonists stimulate the 2 receptor which via linked b) TrueG-proteins increases adenylyl cyclase activity and increases c) Falseintracellular cAMP. They cause a tachycardia and d) F a l s e v a s o d i l a t a t i o n e) False 235 a) T r u e B e t a 2 agonists are generally well tolerated when given by b) Trueinhalation. Salmeterol, a long-acting beta 2 agonist, is c) Falseinhaled twice daily and reduces the need for shorteracting d) Trueagents and possibly the dose of inhaled corticosteroids. e) F a l s e B e t a 2 agonists cause hypokalaemia

236 a) FalseOmalizumab is a recombinant humanized IgG 1 monoclonal b) Falseanti-IgE antibody. It is used in paediatric patients (12 or c) Trueolder) who have allergic/atopic asthma refractory to d) Falsemaximal regular therapy. If there is no improvement in 16 e) Falseweeks it should be discontinued, see NICE guidelines 2007 237 a) FalseInhaled antimuscarinic drugs such as ipratropium and b) Truetiotropium (long acting once daily) are effective as acute c) Falseand maintenance bronchodilator therapy in asthma. Their d) Trueaction is slower in onset than that of beta 2 agonists. High e) Truedoses usually via a nebulizer may precipitate a c u t e glaucoma or urinary retention 238 a) TrueTheophylline has a narrow therapeutic index and its b) Truepharmacokinetics show considerable interindividual c) Falsevariation. Because of hepatic metabolism it is prone to a d) Truenumber of drugdrug interactions which may lead to e) Truetoxicity (see Table 3). Its main side-effects a r e gastrointestinal, cardiovascular and CNS CHAPTER 5 RESPIRATORY SYSTEM

106 239 a) TrueObjective improvement does not occur until 6 hours and is b) Falsemaximal 13 hours after the start of intravenous glucocortic) Falsecosteroid treatment in asthma. This delay is due to the d) Falsepharmacodynamics of glucocorticoids which work via e) Falsemodifying transcription of certain genes and thus a f f e c t i n g their protein synthesis. They should be administered earlyin acute asthma 240 a) TrueSystemic adverse events are rarely significant with inhaled b) Trueglucocorticoids unless the dose exceeds e.g. 1000 g of c) Falsefluticasone or its equivalent. They are invaluable in the d) Falseprophylaxis of asthma and have been shown to reduce e) Trueasthma deaths and exacerbations in patients with c h r o n i c obstructive pulmonary disease (COPD) 241 a) FalseSodium cromoglicate is administered by inhalation of a b) Falsepowder. Used prophylactically it can prevent type I and c) Falsetype III allergic reactions and exercise-induced asthma. Table3 Factors influencing theophylline clearance Factors decreasing theophylline Factors increasing theophyllineclearance and suggested initial clearance and suggested initialdose* adjustment (assuming dose* adjustment (assumingn o r m a l d o s e i s 1 0 0 % ) n o r m a l d o s e i s 1 0 0 % )

C o n g e s t i v e c a r d i a c f a i l u r e ( 4 0 % ) H y p e r t h y r o i d i s m ( 1 5 0 % ) H e p a t i c d i s e a s e , c i r r h o s i s ( 4 0 % ) M a r i j u a n a ( 1 5 0 % ) N e o n a t e s ( 6 0 % ) S m o k i n g ( 1 5 0 % ) P n e u m o n i a ( 7 0 % ) C h a r c o a l b a r b e c u e d m e a t ( 1 3 0 % ) Old age (80%)D r u g s D r u g s Azole-antifungals Carbamazepine (150%)( e . g . k e t o c o n a z o l e e t c . ) ( 5 0 % ) P h e n y t o i n ( 1 5 0 % ) C i m e t i d i n e ( 5 0 % ) R i f a m p i c i n ( 1 5 0 % ) Fluoroquinolones High protein, low carbohydrate( e . g . c i p r o f l o x a c i n ) ( 5 0 % ) d i e t ( 1 5 0 % ) C h l o r a m p h e n i c o l ( 7 5 % ) E t h a n o l ( c h r o n i c ) ( 1 2 0 % ) Erythromycin (75%)Flu vaccine and interferon (75%)Propranolol (70%)*Subsequent dose adjustment to be made in the light of plasma concentrationmonitoring, which should be carried out more frequently in the circumstanceslisted. The suggested adjustments are obviously very approximate, and dependon the extent of exposure to the various agents. 107 MCQ ANSWERS d) TrueIt is very safe although approximately 1:10000 experience a e) F a l s e c o u g h o r h o a r s e n e s s 242 a) TrueIt is a potent, oral, once-daily inhibitor of cysteinyl b) T r u e l e u k o t r i e n e s a t t h e C y s L T 1 receptor. Thus its main action is c) Trueto antagonize the potent proinflammatory effects of d) Trueleukotrienes. It causes about a 510 per cent increase in e)

F a l s e b a s e l i n e F E V 1 but this takes about 1 hour to manifest. About5 per cent of patients develop a reversible transaminitis 243 a) TrueSeveral cytotoxics, particularly if given with or following b) Trueradiation, cause a severe pulmonary fibrosis that may not c) Truebe reversible. Angiotensin-converting enzyme (ACE) d) Falseinhibitors but not the angiotensin II receptor blockers e) True(ARBs)) are associated with a dose-dependent c h r o n i c d r y cough thought to be related to bradykinin accumulation 244 a) FalseMethysergide causes retroperitoneal fibrosis. Aspirin b) True(and nitrofurantoin, imipramine, isoniazid, penicillins, c) Truesulfonamides and streptomycin) has been associated with d) Falsepulmonary eosinophilia. Carmustine causes pulmonary e) T r u e f i b r o s i s 245 a) TrueCarvedilol is a non-selective beta blocker w h o s e indications include hypertension, angina and, as adjunctto other agents, symptomatic chronic heart failure. Theinitial dose for this indication is a quarter of the otherindications b) False c) TrueAdenosine causes bronchoconstriction by s t i m u l a t i n g adenosine receptors d) False e) TrueBethanecol and carbachol are acetylcholine a n a l o g u e s a n d increase cholinergic (parasympathetic) tone 246 a) F a l s e U s e l o w F iO

2 (e.g. 2224 per cent) and titrate upwards based on blood gas response/clinical response b) FalseAnaleptics are no longer used unless m e c h a n i c a l ventilation is unavailable or contraindicated c) T r u e d) T r u e e) FalseDantrolene is a muscle relaxant; this would w o r s e n respiratory failure CHAPTER 5 RESPIRATORY SYSTEM 108 EMQ ANSWERS 247 RESPIRATORYDRUGS MECHANISM OF ACTION 1D Corticosteroids bind to its receptor in the cytoplasm, which thenmoves to the nucleus where it binds to DNAsuppressing thetranscription of certain genes such as interleukins and tumour necrosisfactor (TNF) and enhancing transcription of beta 2 receptors, ACE andother anti-inflammatory entities. 2H Omalizumab binds to the Fc receptor portion of IgE and blocks IgE,interacting with its receptor on inflammatory cells and reducescirculating IgE concentrations. 3I Second-generation antihistamines are competitive antagonists at theH 1 receptor without significant binding to other receptors includingthe gastric H 2 , muscarinic and serotonin receptors. 4F Sodium cromoglicate whose precise anti-inflammatory mechanism isnot clearly defined modulates the firing of cough C fibres. 5C Tiotropium is a competitive antagonist at respiratory muscarinicreceptors and blocks parasympathetic effects on bronchiolar smoothmuscle. 248 RESPIRATORYDRUGS ADVERSE EFFECTS 1G Theophylline adverse effects are usually dose (concentration)dependent with mainly gastrointestinal disturbances at low toxicconcentrations, then CVS (dysrhythmias etc.) at moderately toxicconcentrations and CNS stimulation at high toxic concentrations. 2J Opiates are agonists and directly suppress the respiratory centre,leading to apnoea. 3B

Formoterol like other long-acting beta 2 agonists prolongs QTc and canalso cause hypokalaemia which can exacerbate QTc prolongation. 4D Corticosteroids in anti-inflammatory systemic doses cause an increasein vascular resistance and sodium retention which both lead to anincrease in blood pressure. 5H Omalizumab is a recombinant humanized monoclonal antibody toIgE, but as with all monoclonals can cause severe acute and delayedanaphylactic reactions. (It has a long terminal elimination half-life ofapproximately 21 days.) CHAPTER SIX ALIMENTARYSYSTEM MULTIPLE CHOICE QUESTIONS 249 The following stimulate gastric acid secretion: a) Vagal stimulation b) Gastrin c) Acetylcholine stimulation of the M 1 receptor d) Histamine stimulation of the H 2 receptor e) Increased intracellular cyclic adenosine monophosphate (cAMP) 250 Prostaglandin E 2 : a) Is the principal prostaglandin synthesized in the stomach b) Stimulates gastric acid secretion c) Causes vasoconstriction of submucosal blood vessels d) Biosynthesis is inhibited by aspirin e) Biosynthesis is inhibited by rectal indometacin 251 Helicobacter pylori : a) Is strongly linked to the development of carcinoma of the colon b)

Is a bacterium that is strongly linked to the development andrecurrence of peptic ulcer disease c) Is usually found in the gastric antrum d) Is uncommon in asymptomatic patients e) Colonization of the stomach is inhibited by corticosteroids 252 The following accelerate healing in gastric ulcers: a) Diclofenac b) Stopping smoking c) Corticosteroids d) Ranitidine e) Sucralfate CHAPTER 6 ALIMENTARY SYSTEM 110 253 Antacids: a) Large doses heal gastric ulcers more frequently than duodenalulcers b) Standard doses reduce gastric acidity for approximately 4 hours c) Magnesium salts tend to cause diarrhoea d) Aluminium salts tend to cause a diuresis e) Magnesium and aluminium salts reduce the rate and extent ofabsorption of phenytoin 254 Cimetidine therapy is associated with: a) Transient increase in serum prolactin b) Irreversible gynaecomastia c) Mental confusion in the elderly d) Asystole after rapid intravenous injection e) Reversible rise in serum creatinine 255 Eradication of

H. pylori following a positive breath test is recommendedin the following situations: a) Duodenal ulcer b) Gastric ulcer c) Patients requiring long-term proton pump inhibitor treatment d) Severe gastritis e) Mucosa-associated lymphoid tissue lymphoma 256 In comparison to cimetidine, ranitidine: a) Does not bind to androgen receptors b) Is less likely to cause gynaecomastia c) Penetrates the bloodbrain barrier to a lesser extent d) Is not available for parenteral use e) Has a lower affinity for CYP450 257 Omeprazole: a) Is an irreversible inhibitor of the hydrogen/potassium adenosinetriphosphatase locus of the gastric parietal cell b) Reduces gastric acid secretion c) Is the drug of choice in ZollingerEllison syndrome d) Has a plasma half-life of approximately 1 hour e) Requires dose reduction in renal failure 258 Omeprazole enhances the effects of the following drugs throughinhibition of drug metabolism: a) Atenolol b) Amoxicillin c) Captopril d) Warfarin e) Phenytoin 111

M ULTIPLE CHOICE QUESTIONS 259 Problems associated with proton pump inhibitors include: a) Masking symptoms of gastric cancer b) Diarrhoea, nausea and vomiting c) Increased risk of gastrointestinal infection d) Headache e) Prolonged QT interval on ECG 260 Misoprostol: a) Is a synthetic analogue of prostaglandin E b) Inhibits cyclo-oxygenase c) Causes vasodilatation in the submucosa d) Is rapidly and nearly completely absorbed e) Is contraindicated in pregnancy 261 Bismuth chelate (tripotassium dicitratobismuthate): a) Precipitates at acid pH b) Stimulates mucus production c) Has a direct toxic effect on H . pylori d) Causes pale stools e) Causes nausea 262 Sucralfate: a) Requires systemic absorption for anti-ulcer activity b) Contains aluminium c) Is effective in healing gastric ulcers d)

Is contraindicated in pregnancy e) Is associated with constipation 263 The following drugs are used to prevent motion sickness: a) Hyoscine b) Promethazine c) Cinnarizine d) Metoclopramide e) Chlorpromazine 264 Cyclizine: a) Is a dopamine receptor antagonist b) Is effective in morphine-induced vomiting c) Is a proven teratogen d) Causes dry mouth e) Causes drowsiness CHAPTER 6 ALIMENTARY SYSTEM 112 265 Metoclopramide: a) Is most effective in centrally mediated vomiting b) Is ineffective in drug-induced nausea c) Increases the rate of gastric emptying d) Should be avoided for 34 days following gastrointestinal surgery e) High doses block 5HT 3 receptors 266 Ondansetron: a) Is a phenothiazine b)

Is not absorbed after oral administration c) Is effective in preventing nausea and vomiting due to cancerchemotherapy and radiotherapy d) Is ineffective in ciplastin-induced nausea e) 1 per cent of patients have dystonic reactions 267 In ulcerative colitis: a) Intravenous hydrocortisone is of proven value in the treatment ofacute colitis b) Oral corticosteroids are first line for maintenance treatment c) Localized rectal disease often responds to prednisoloneenemas/suppositories d) In severe colitis codeine should be used e) Fibre is contraindicated 268 Sulfasalazine: a) Is a prodrug b) Is used for maintenance treatment of ulcerative colitis c) Is effective in small bowel Crohns disease d) Should be avoided in glucose 6-phosphate dehydrogenase (G6PD)deficiency e) Should be avoided in salicylate hypersensitivity 269 Adverse effects associated with sulfasalazine include: a) Blood dyscrasias b) Oligospermia c) StevensJohnson syndrome d) Systemic lupus erythematosus (SLE)-like syndrome e) Hepatitis 270 Mesalazine: a) Is a prodrug consisting of a dimer of two 5-aminosalicylic acidmolecules b) Dissolves at the pH found in the terminal ileum and colon c)

Is contraindicated in sulphonamide hypersensitivity d) Is associated with oligospermia e) Is associated with interstitial nephritis 113 M ULTIPLE CHOICE QUESTIONS 271 Infliximab: a) Inhibits tumour necrosis factor (TNF) b) Can only be administered on one occasion due to antibodyproduction c) Is licensed for management of irritable bowel syndrome d) Can be used for maintenance therapy in Crohns disease andulcerative colitis e) Should not be used in a patient who has been treated withcorticosteroids within the previous 12 months 272 The following drugs cause constipation: a) Amiodarone b) Amitriptyline c) Amoxicillin d) Misoprostol e) Metformin 273 Lactulose: a) Is a chemical stimulant to the colon b) Produces its effect 1012 hours after an oral dose c) Requires colonic bacteria for activity d) Should not be administered concurrently with bran e) Is contraindicated in liver failure 274 Loperamide: a) Decreases intestinal transit time b)

Increases bulk of gut contents c) Requires systemic absorption for activity on the bowel d) Causes pupil constriction e) Causes hypersalivation 275 Treatment of hepatic encephalopathy includes: a) Dietary protein restriction b) Emptying the lower bowel c) Oral lactulose d) Prophylactic vitamin K e) Oral methionine 276 The emergency drug therapy of portal hypertension and oesophagealvarices may include: a) Terlipressin b) Chenodeoxycholic acid c) Calcitonin d) Octreotide e) Isoprenaline CHAPTER 6 ALIMENTARY SYSTEM 114 277 The following drugs are associated with cholestatic jaundice/hepatitis: a) Ondansetron b) Methotrexate c) Synthetic oestrogens d) Chlorpromazine e) Rifampicin 278 The following are licensed in the UK for the management of obesity: a)

Orlistat b) Sibutramine c) Thiazide diuretics d) Pizotifen e) Dexamphetamine 279 Rimonabant: a) Inhibits insulin secretion b) Systemic absorption is minimal c) Has been associated with pulmonary hypertension d) Is contraindicated in, and may cause, depression e) Is metabolized by CYP3A4 Answers: see pages 116120 115 E XTENDED MATCHING QUESTIONS EXTENDED MATCHING QUESTIONS 280 ALIMENTARYSYSTEM A Gemcitabine B Capecitabine C Etoposide D Adefovir dipivoxil E Loperamide F Ondansetron G Olsalazine H Lansoprazole I Mebeverine J Ribavarin and peginterferon alfa Match the drug from the list above with the mode of action/indication below: 1 Serotonin (5HT

3 ) receptor blockade 2 Symptomatic treatment of acute diarrhoea 3 Maintenance of remission of ulcerative colitis 4 Chemotherapy for patients with advanced or metastaticadenocarcinoma of the pancreas 5 Chronic hepatitis C ANSWERS: see page 121 CHAPTER 6 ALIMENTARY SYSTEM 116 ANSWERS MCQ ANSWERS 249 a) T r u e S e e F i g . 2 b) T r u e c) T r u e d) T r u e e) T r u e Vagal stimulationAcetylcholineParietal cellM 1 -receptorH 2 -receptorGastrinreceptorGastrinGastrinreceptorCa 2 Ca 2 ATPHistamineHistaminestomachlumencAMPH ATPProton pumpH K K Cl Mast cell Fig. 2

Mechanisms regulating hydrochloric acid secretion. Ca 2+ ,calcium;ATP,adenosine triphosphate; cAMP, cyclic adenosine monophosphate; K + , potassium;Cl , chloride 117 MCQ ANSWERS 250 a) T r u e P r o s t a g l a n d i n E 2 is an important gastroprotective mediator. b) FalseIt inhibits secretion of acid, promotes secretion of protective c) Falsemucus and causes vasodilation of submucosal blood d) T r u e v e s s e l s e) T r u e 251 a) False Helicobacter pylori is strongly linked to the development b) Trueand recurrence of duodenal ulcer. Possible linkage to c) Truegastric carcinoma is under investigation d) False e) False 252 a) FalseNon-steroidal anti-inflammatory drug ( N S A I D ) , ulcerogenic b) TrueMore effective in preventing recurrence of duodenal u l c e r s than H 2 blockers c) F a l s e U l c e r o g e n i c d) T r u e H 2

blocker e) T r u e 253 a) FalseAntacids are available without prescription and produce b) Falseprompt but transient pain relief in patients with peptic c) Trueulceration. Aluminium salts cause constipation d) False e) T r u e 254 a) TrueChronic cimetidine therapy causes reversible b) Falsegynaecomastia in 0.10.2 per cent of patients. It is c) Truegenerally well tolerated. Cimetidine blocks the tubular d) T r u e s e c r e t i o n o f c r e a t i n i n e e) T r u e 255 a) TrueEradication should be confirmed, preferably by urea breath b) Truetest at a minimum of four weeks post treatment c) T r u e d) T r u e e) T r u e 256 a) T r u e A l l t h e H 2 -receptorblockerscurrentlyavailableintheUKare b) Trueeffective in peptic ulceration and are well tolerated. There c) Trueis most experience with cimetidine and ranitidine

d) False e) T r u e 257 a) TrueOmeprazole, a proton pump inhibitor, is effective in b) Truereducing gastric acid secretion and in spite of its short half-life c) Trueonly has to be administered once daily since it acts d) T r u e i r r e v e r s i b l y e) False CHAPTER 6 ALIMENTARY SYSTEM 118 258 a) FalseFor drugs such as phenytoin and warfarin which have a b) Falsenarrow therapeutic index this is clinically significant c) False d) T r u e e) T r u e 259 a) TrueThere are currently five proton pump inhibitors licensed in b) Truethe UK: esomeprazole, omeprazole, lansoprazole, c) T r u e p a n t o p r a z o l e a n d r a b e p r a z o l e d) T r u e e) False 260 a) TrueMisoprostol inhibits gastric acid secretion, causes b) Falsevasodilatation in the submucosa and stimulates production c)

Trueof protective mucus. It contracts uterine muscle and causes d) T r u e a b o r t i o n e) T r u e 261 a) TrueSeveral studies show bismuth chelate to be as active as b) Truecimetidine in the healing of duodenal and gastric ulcers c) Trueafter 48 weeks of treatment. It is, however, associated with d) Falsefrequent minor adverse effects. Ranitidine bismuth chelate can e) Truebe substituted for a proton pump inhibitor as part of tripletherapy for the eradication of H. pylori 262 a) FalseSucralfate, a basic aluminium salt, becomes a sticky b) Trueadherent paste in the presence of acid which retains antacid c) Trueefficacy and apparently coats the floor of ulcer craters d) False e) T r u e 263 a) TrueMuscarinic antagonist; NB: anticholinergic side-effects b) T r u e H 1 blocker minor antimuscarinic action c) T r u e H 1 blocker minor antimuscarinic action d) FalseDopamine receptor antagonist e) FalseChlorpromazine is not used for motion sickness 264 a) F a l s e C y c l i z i n e i s a n H

1 blocker with additional antimuscarinic b) Trueactions. Its indications are nausea, vomiting, vertigo, c) Falsemotion sickness and labyrinthine disorders d) T r u e e) T r u e 265 a) FalseRelatively ineffective in motion sickness and other forms o f centrally mediated vomiting b) False c) TrueIncreases the rate of absorption of oral drugs d) T r u e e) TrueEffective in some patients in preventing cisplatini n d u c e d nausea and vomiting

Search Search History: Searching... Result 00 of 00 00 results for result for p. Clinical-Pharmacology-and-Therapeutics-MCQ Download or Print Add To Collection 19.4K Reads 76 Readcasts 32 Embed Views

Published by Syed Saqib Jalal

b73b86888d50f72a44b013da63d043f288321223

Following

Search TIP Press Ctrl-FF to search anywhere in the document. Sections

INTRODUCTION GENERAL PRINCIPLES MULTIPLE CHOICE QUESTIONS MULTIPLE CHOICE QUESTIONS EXTENDED MATCHING QUESTIONS ANSWERS NERVOUS SYSTEM MULTIPLE CHOICE QUESTIONS CARDIOVASCULAR SYSTEM RESPIRATORY SYSTEM ALIMENTARY SYSTEM ENDOCRINE SYSTEM SELECTIVE TOXICITY THE SKIN AND THE EYE CLINICALTOXICOLOGY PRACTICE EXAMINATION PROBLEM SOLVING QUESTIONS

Info and Rating Category: Uncategorized. Rating: (1 Rating) Upload Date: 03/04/2011 Copyright: Attribution Non-commercial Tags: This document has no tags. ebook download or read book online. Flag document for inapproriate content Download and print this document

Read offline in your PDF viewer Edit this document in Adobe Acrobat, Notepad Keep a copy in case this version is deleted from Scribd Read and print without ads Email the file

Choose a format to download in

.PDF

.TXT Download Recommended

244 p. MCQ Pharmacology Badal Shah 3309 Reads

6 p.

general pharmacology mcq Shrikant Thakur 1159 Reads

136 p. MCQ Pharmacology Ibrahim Negm 8056 Reads

42 p. mcq pharmacology jul2001 v3 Anaesthesia Blog 2011 Reads Next

Featured

450 p. Contagious Crown Publishing Group $24.95

30 p. Processed Food & America Simon and Schuster

24 p. Strange Case of John Ashcroft Crown Publishing Group

610 p. Cold War's Dangerous Legacy Vintage Books / Anchor Books $16.95 Next

Comments
a

Post comment Zamir Siddiqui4 months ago Reply 00 Excellent and hard work,Thank You sir Fadi Rushrush24 days ago Replydelete 00 like scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. scribd. About

About Scribd Blog Join our team! Contact Us

Premium

Premium Reader Scribd Store

Advertise with us

Get started AdChoices

Support

Help FAQ Press

Partners

Publishers Developers / API

Legal

Terms Privacy Copyright

Copyright 2013 Scribd Inc. Language: English