A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

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A Textbook of Clinical Pharmacology and Therapeutics FIFTH EDITION JAMES M RITTER MA DPHIL FRCP FMedSci FBPHARMACOLS Professor of Clinical Pharmacology at King’s College London School of Medicine, Guy’s, King’s and St Thomas’ Hospitals, London, UK LIONEL D LEWIS MA MB BCH MD FRCP Professor of Medicine, Pharmacology and Toxicology at Dartmouth Medical School and the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA TIMOTHY GK MANT BSC FFPM FRCP Senior Medical Advisor, Quintiles, Guy's Drug Research Unit, and Visiting Professor at King’s College London School of Medicine, Guy’s, King’s and St Thomas’ Hospitals, London, UK ALBERT FERRO PHD FRCP FBPHARMACOLS Reader in Clinical Pharmacology and Honorary Consultant Physician at King’s College London School of Medicine, Guy’s, King’s and St Thomas’ Hospitals, London, UK PART OF HACHETTE LIVRE UK
First published in Great Britain in 1981 Second edition 1986 Third edition 1995 Fourth edition 1999 This fifth edition published in Great Britain in 2008 by Hodder Arnold, an imprint of Hodden Education, part of Hachette Livre UK, 338 Euston Road, London NW1 3BH http://www.hoddereducation.com ©2008 James M Ritter, Lionel D Lewis, Timothy GK Mant and Albert Ferro All rights reserved. Apart from any use permitted under UK copyright law, this publication may only be reproduced, stored or transmitted, in any form, or by any means with prior permission in writing of the publishers or in the case of reprographic production in accordance with the terms of licences issued by the Copyright Licensing Agency. In the United Kingdom such licences are issued by the Copyright licensing Agency: Saffron House, 6–10 Kirby Street, London EC1N 8TS. Hachette Livre’s policy is to use papers that are natural, renewable and recyclable products and made from wood grown in sustainable forests. The logging and manufacturing processes are expected 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 of going to press, neither the authors nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. In particular, (but without limiting the generality of the preceding disclaimer) every effort has been made to check drug dosages; however it is still possible that errors have been missed. Furthermore, dosage schedules are constantly being revised and new side-effects recognized. For these reasons the reader is strongly urged to consult the drug companies’ printed instructions before administering any of the drugs recommended in this book. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN 978-0-340-90046-8 1 2 3 4 5 6 7 8 9 10 Commissioning Editor: Project Editor: Production Controller: Cover Design: Indexer: Sara Purdy Jane Tod Andre Sim Laura de Grasse John Sampson Typeset in 9/12 pt palatino by Charon Tec Ltd (A Macmillan Company) www.charontec.com Printed and bound in Italy What do you think about this book Or any other Hodder Arnold title Please visit our website: www.hoddereducation.com
Page 2 and 3: A Textbook of Clinical Pharmacology
Page 6 and 7: This fifth edition is dedicated to
Page 8 and 9: CONTENTS FOREWORD PREFACE ACKNOWLED
Page 10 and 11: PREFACE Clinical pharmacology is th
Page 12 and 13: PART I GENERAL PRINCIPLES
Page 14 and 15: CHAPTER 1 INTRODUCTION TO THERAPEUT
Page 16 and 17: SCIENTIFIC BASIS OF USE OF DRUGS IN
Page 18 and 19: AGONISTS 7 100 100 Effect (%) Effec
Page 20 and 21: SLOW PROCESSES 9 100 2 Dose ratio -
Page 22 and 23: CHAPTER 3 PHARMACOKINETICS ● Intr
Page 24 and 25: REPEATED (MULTIPLE) DOSING 13 In re
Page 26 and 27: NON-LINEAR (‘DOSE-DEPENDENT’) P
Page 28 and 29: CHAPTER 4 DRUG ABSORPTION AND ROUTE
Page 30 and 31: ROUTES OF ADMINISTRATION 19 ROUTES
Page 32 and 33: ROUTES OF ADMINISTRATION 21 Transde
Page 34 and 35: ROUTES OF ADMINISTRATION 23 FURTHER
Page 36 and 37: PHASE II METABOLISM (TRANSFERASE RE
Page 38 and 39: ENZYME INDUCTION 27 and lorazepam.
Page 40 and 41: METABOLISM OF DRUGS BY INTESTINAL O
Page 42 and 43: CHAPTER 6 RENAL EXCRETION OF DRUGS
Page 44 and 45: ACTIVE TUBULAR REABSORPTION 33 ACTI
Page 46 and 47: RENAL DISEASE 35 DISTRIBUTION Drug
Page 48 and 49: LIVER DISEASE 37 Detailed recommend
Page 50 and 51: THYROID DISEASE 39 DIGOXIN Myxoedem
Page 52 and 53: CHAPTER 8 THERAPEUTIC DRUG MONITORI
Page 54 and 55:
DRUGS FOR WHICH THERAPEUTIC DRUG MO
Page 56 and 57:
CHAPTER 9 DRUGS IN PREGNANCY ● In
Page 58 and 59:
PHARMACOKINETICS IN PREGNANCY 47 va
Page 60 and 61:
PRESCRIBING IN PREGNANCY 49 an anti
Page 62 and 63:
PRESCRIBING IN PREGRANCY 51 Case hi
Page 64 and 65:
BREAST-FEEDING 53 METABOLISM At bir
Page 66 and 67:
RESEARCH 55 lifelong effects as a r
Page 68 and 69:
PHARMACODYNAMIC CHANGES 57 DISTRIBU
Page 70 and 71:
EFFECT OF DRUGS ON SOME MAJOR ORGAN
Page 72 and 73:
RESEARCH 61 FURTHER READING Dhesi J
Page 74 and 75:
ADVERSE DRUG REACTION MONITORING/SU
Page 76 and 77:
ADVERSE DRUG REACTION MONITORING/SU
Page 78 and 79:
PREVENTION OF ALLERGIC DRUG REACTIO
Page 80 and 81:
EXAMPLES OF ALLERGIC AND OTHER ADVE
Page 82 and 83:
CHAPTER 13 DRUG INTERACTIONS ● In
Page 84 and 85:
HARMFUL INTERACTIONS 73 Response Re
Page 86 and 87:
HARMFUL INTERACTIONS 75 Table 13.1:
Page 88 and 89:
HARMFUL INTERACTIONS 77 Table 13.5:
Page 90 and 91:
CHAPTER 14 PHARMACOGENETICS ● Int
Page 92 and 93:
GENETIC INFLUENCES ON DRUG METABOLI
Page 94 and 95:
INHERITED DISEASES THAT PREDISPOSE
Page 96 and 97:
INHERITED DISEASES THAT PREDISPOSE
Page 98 and 99:
CLINICAL TRIALS 87 • Discovery
Page 100 and 101:
CLINICAL DRUG DEVELOPMENT 89 Too ma
Page 102 and 103:
GLOBALIZATION 91 ETHICS COMMITTEES
Page 104 and 105:
CELL-BASED AND RECOMBINANT DNA THER
Page 106 and 107:
HUMAN STEM CELL THERAPY 95 duration
Page 108 and 109:
CHAPTER 17 ALTERNATIVE MEDICINES: H
Page 110 and 111:
SOY 99 A case report has suggested
Page 112 and 113:
MISCELLANEOUS HERBS 101 including h
Page 114 and 115:
PART II THE NERVOUS SYSTEM
Page 116 and 117:
CHAPTER 18 HYPNOTICS AND ANXIOLYTIC
Page 118 and 119:
ANXIETY 107 and daytime sleeping sh
Page 120 and 121:
ANXIETY 109 Key points • Insomnia
Page 122 and 123:
SCHIZOPHRENIA 111 Box 19.1: Dopamin
Page 124 and 125:
SCHIZOPHRENIA 113 The Boston Collab
Page 126 and 127:
BEHAVIOURAL EMERGENCIES 115 Oral me
Page 128 and 129:
DEPRESSIVE ILLNESSES AND ANTIDEPRES
Page 130 and 131:
DEPRESSIVE ILLNESSES AND ANTIDEPRES
Page 132 and 133:
LITHIUM, TRYPTOPHAN AND ST JOHN’S
Page 134 and 135:
SPECIAL GROUPS 123 Case history A 4
Page 136 and 137:
PARKINSON’S SYNDROME AND ITS TREA
Page 138 and 139:
PARKINSON’S SYNDROME AND ITS TREA
Page 140 and 141:
MYASTHENIA GRAVIS 129 CHOREA The γ
Page 142 and 143:
ALZHEIMER’S DISEASE 131 Cholinerg
Page 144 and 145:
CHAPTER 22 ANTI-EPILEPTICS ● Intr
Page 146 and 147:
GENERAL PRINCIPLES OF TREATMENT OF
Page 148 and 149:
GENERAL PRINCIPLES OF TREATMENT OF
Page 150 and 151:
WITHDRAWAL OF ANTI-EPILEPTIC DRUGS
Page 152 and 153:
FEBRILE CONVULSIONS 141 Case histor
Page 154 and 155:
DRUGS USED FOR MIGRAINE PROPHYLAXIS
Page 156 and 157:
CHAPTER 24 ANAESTHETICS AND MUSCLE
Page 158 and 159:
INHALATIONAL ANAESTHETICS 147 is th
Page 160 and 161:
SUPPLEMENTARY DRUGS 149 • Respira
Page 162 and 163:
MUSCLE RELAXANTS 151 NON-DEPOLARIZI
Page 164 and 165:
LOCAL ANAESTHETICS 153 have also pr
Page 166 and 167:
CHAPTER 25 ANALGESICS AND THE CONTR
Page 168 and 169:
DRUGS USED TO TREAT MILD OR MODERAT
Page 170 and 171:
OPIOIDS 159 Key points Drugs for mi
Page 172 and 173:
OPIOIDS 161 increases, correlating
Page 174 and 175:
MANAGEMENT OF POST-OPERATIVE PAIN 1
Page 176 and 177:
PART III THE MUSCULOSKELETAL SYSTEM
Page 178 and 179:
CHAPTER 26 ANTI-INFLAMMATORY DRUGS
Page 180 and 181:
DISEASE-MODIFYING ANTIRHEUMATIC DRU
Page 182 and 183:
HYPERURICAEMIA AND GOUT 171 • Sto
Page 184 and 185:
HYPERURICAEMIA AND GOUT 173 Pharmac
Page 186 and 187:
PART IV THE CARDIOVASCULAR SYSTEM
Page 188 and 189:
CHAPTER 27 PREVENTION OF ATHEROMA:
Page 190 and 191:
PREVENTION OF ATHEROMA 179 responsi
Page 192 and 193:
DRUGS USED TO TREAT DYSLIPIDAEMIA 1
Page 194 and 195:
DRUGS USED TO TREAT DYSLIPIDAEMIA 1
Page 196 and 197:
CHAPTER 28 HYPERTENSION ● Introdu
Page 198 and 199:
DRUGS USED TO TREAT HYPERTENSION 18
Page 200 and 201:
Page 202 and 203:
Page 204 and 205:
OTHER ANTIHYPERTENSIVE DRUGS 193 Ke
Page 206 and 207:
OTHER ANTIHYPERTENSIVE DRUGS 195 Ca
Page 208 and 209:
MANAGEMENT OF STABLE ANGINA 197 Ass
Page 210 and 211:
MANAGEMENT OF UNSTABLE CORONARY DIS
Page 212 and 213:
DRUGS USED IN ISCHAEMIC HEART DISEA
Page 214 and 215:
DRUGS USED IN ISCHAEMIC HEART DISEA
Page 216 and 217:
ANTICOAGULANTS 205 Intrinsic pathwa
Page 218 and 219:
ANTICOAGULANTS 207 that the pharmac
Page 220 and 221:
ANTICOAGULANTS IN PREGNANCY AND PUE
Page 222 and 223:
CHAPTER 31 HEART FAILURE ● Introd
Page 224 and 225:
DRUGS FOR HEART FAILURE 213 The dru
Page 226 and 227:
DRUGS FOR HEART FAILURE 215 therape
Page 228 and 229:
CHAPTER 32 CARDIAC DYSRHYTHMIAS ●
Page 230 and 231:
CARDIOPULMONARY RESUSCITATION AND C
Page 232 and 233:
TREATMENT OF OTHER SPECIFIC DYSRHYT
Page 234 and 235:
SELECTED ANTI-DYSRHYTHMIC DRUGS 223
Page 236 and 237:
Page 238 and 239:
Page 240 and 241:
Page 242 and 243:
PART V THE RESPIRATORY SYSTEM
Page 244 and 245:
CHAPTER 33 THERAPY OF ASTHMA, CHRON
Page 246 and 247:
CHRONIC BRONCHITIS AND EMPHYSEMA 23
Page 248 and 249:
DRUGS USED TO TREAT ASTHMA AND CHRO
Page 250 and 251:
DRUGS USED TO TREAT ASTHMA AND CHRO
Page 252 and 253:
RESPIRATORY FAILURE 241 use in asth
Page 254 and 255:
DRUG-INDUCED PULMONARY DISEASE 243
Page 256 and 257:
PART VI THE ALIMENTARY SYSTEM
Page 258 and 259:
CHAPTER 34 ALIMENTARY SYSTEM AND LI
Page 260 and 261:
PEPTIC ULCERATION 249 • With rega
Page 262 and 263:
PEPTIC ULCERATION 251 Ranitidine ha
Page 264 and 265:
ANTI-EMETICS 253 Vestibular stimula
Page 266 and 267:
INFLAMMATORY BOWEL DISEASE 255 cort
Page 268 and 269:
CONSTIPATION 257 • in hepatocellu
Page 270 and 271:
PANCREATIC INSUFFICIENCY 259 Ciprof
Page 272 and 273:
LIVER DISEASE 261 withdrawal), smal
Page 274 and 275:
DRUGS THAT MODIFY APPETITE 263 Tabl
Page 276 and 277:
CHAPTER 35 VITAMINS AND TRACE ELEME
Page 278 and 279:
VITAMIN C(ASCORBIC ACID) 267 dinucl
Page 280 and 281:
TRACE ELEMENTS 269 Table 35.1: Comm
Page 282 and 283:
PART VII FLUIDS AND ELECTROLYTES
Page 284 and 285:
CHAPTER 36 NEPHROLOGICAL AND RELATE
Page 286 and 287:
DIURETICS 275 Key points Diuretics
Page 288 and 289:
VOLUME DEPLETION 277 is sometimes c
Page 290 and 291:
DRUGS THAT AFFECT THE BLADDER AND G
Page 292 and 293:
DRUGS THAT AFFECT THE BLADDER AND G
Page 294 and 295:
PART VIII THE ENDOCRINE SYSTEM
Page 296 and 297:
CHAPTER 37 DIABETES MELLITUS ● In
Page 298 and 299:
DRUGS USED TO TREAT DIABETES MELLIT
Page 300 and 301:
Page 302 and 303:
Page 304 and 305:
ANTITHYROID DRUGS 293 deficiency. P
Page 306 and 307:
SPECIAL SITUATIONS 295 fertility. I
Page 308 and 309:
CHAPTER 39 CALCIUM METABOLISM ● I
Page 310 and 311:
BISPHOSPHONATES 299 effective in li
Page 312 and 313:
CINACALCET 301 Further reading Bloc
Page 314 and 315:
ADRENAL CORTEX 303 Table 40.1: Acti
Page 316 and 317:
ADRENAL MEDULLA 305 injection may b
Page 318 and 319:
CHAPTER 41 REPRODUCTIVE ENDOCRINOLO
Page 320 and 321:
FEMALE REPRODUCTIVE ENDOCRINOLOGY 3
Page 322 and 323:
FEMALE REPRODUCTIVE ENDOCRINOLOGY 3
Page 324 and 325:
MALE REPRODUCTIVE ENDOCRINOLOGY 313
Page 326 and 327:
MALE REPRODUCTIVE ENDOCRINOLOGY 315
Page 328 and 329:
ANTERIOR PITUITARY HARMONES AND REL
Page 330 and 331:
POSTERIOR PITUITARY HARMONES 319 FU
Page 332 and 333:
PART IX SELECTIVE TOXICITY
Page 334 and 335:
CHAPTER 43 ANTIBACTERIAL DRUGS ●
Page 336 and 337:
COMMONLY PRESCRIBED ANTIBACTERIAL D
Page 338 and 339:
Page 340 and 341:
Page 342 and 343:
Page 344 and 345:
Page 346 and 347:
PRINCIPLES OF MANAGEMENT OF MYCOBAC
Page 348 and 349:
FIRST-LINE DRUGS IN TUBERCULOSIS TH
Page 350 and 351:
MYCOBACTERIUM LEPRAE INFECTION 339
Page 352 and 353:
ANTIFUNGAL DRUG THERAPY 341 POLYENE
Page 354 and 355:
ANTIFUNGAL DRUG THERAPY 343 therapy
Page 356 and 357:
ANTIVIRAL DRUG THERAPY (EXCLUDING A
Page 358 and 359:
ANTIVIRAL DRUG THERAPY (EXCLUDING A
Page 360 and 361:
INTERFERONS AND ANTIVIRAL HEPATITIS
Page 362 and 363:
CHAPTER 46 HIV AND AIDS ● Introdu
Page 364 and 365:
ANTI-HIV DRUGS 353 Table 46.1: Exam
Page 366 and 367:
ANTI-HIV DRUGS 355 NON-NUCLEOSIDE A
Page 368 and 369:
OPPORTUNISTIC INFECTIONS IN HIV-1-S
Page 370 and 371:
ANTI-HERPES VIRUS THERAPY 359 salva
Page 372 and 373:
CHAPTER 47 MALARIA AND OTHER PARASI
Page 374 and 375:
MALARIA 363 Pharmacokinetics Chloro
Page 376 and 377:
HELMINTHIC INFECTION 365 Table 47.2
Page 378 and 379:
CHAPTER 48 CANCER CHEMOTHERAPY ●
Page 380 and 381:
COMMON COMPLICATIONS OF CANCER CHEM
Page 382 and 383:
DRUGS USED IN CANCER CHEMOTHERAPY 3
Page 384 and 385:
Page 386 and 387:
Page 388 and 389:
Page 390 and 391:
Page 392 and 393:
Page 394 and 395:
Page 396 and 397:
Page 398 and 399:
PART X HAEMATOLOGY
Page 400 and 401:
CHAPTER 49 ANAEMIA AND OTHER HAEMAT
Page 402 and 403:
HAEMATINICS - IRON, VITAMIN B 12 AN
Page 404 and 405:
HAEMATOPOIETIC GROWTH FACTORS 393 S
Page 406 and 407:
IDIOPATHIC THROMBOCYTOPENIC PURPURA
Page 408 and 409:
PART XI IMMUNOPHARMACOLOGY
Page 410 and 411:
CHAPTER 50 CLINICAL IMMUNOPHARMACOL
Page 412 and 413:
IMMUNOSUPPRESSIVE AGENTS 401 Ag Ant
Page 414 and 415:
IMMUNOSUPPRESSIVE AGENTS 403 Table
Page 416 and 417:
CHEMICAL MEDIATORS OF THE IMMUNE RE
Page 418 and 419:
IMMUNOGLOBULINS AS THERAPY 407 DRUG
Page 420 and 421:
PART XII THE SKIN
Page 422 and 423:
CHAPTER 51 DRUGS AND THE SKIN ● I
Page 424 and 425:
DERMATITIS (ECZEMA) 413 Avoid preci
Page 426 and 427:
PSORIASIS 415 Emollients Improving
Page 428 and 429:
ADVERSE DRUG REACTIONS INVOLVING TH
Page 430 and 431:
ADVERSE DRUG REACTIONS INVOLVING TH
Page 432 and 433:
PART XIII THE EYE
Page 434 and 435:
CHAPTER 52 DRUGS AND THE EYE ● In
Page 436 and 437:
DRUGS USED TO CONSTRICT THE PUPIL A
Page 438 and 439:
DRUGS USED TO TREAT INFLAMMATORY DI
Page 440 and 441:
CONTACT LENS WEARERS 429 Table 52.6
Page 442 and 443:
PART XIV CLINICAL TOXICOLOGY
Page 444 and 445:
CHAPTER 53 DRUGS AND ALCOHOL ABUSE
Page 446 and 447:
OPIOID/NARCOTIC ANALGESICS 435 Tabl
Page 448 and 449:
DRUGS THAT ALTER PERCEPTION 437 whi
Page 450 and 451:
CENTRAL DEPRESSANTS 439 Peak plasma
Page 452 and 453:
CENTRAL DEPRESSANTS 441 Key points
Page 454 and 455:
MISCELLANEOUS 443 FURTHER READING G
Page 456 and 457:
INTENTIONAL SELF-POISONING 445 Tabl
Page 458 and 459:
INTENTIONAL SELF-POISONING 447 Tabl
Page 460 and 461:
CRIMINAL POISONING 449 Commission o
Page 462 and 463:
INDEX Note: Page numbers in italics
Page 464 and 465:
INDEX 453 atrial fibrillation 217,
Page 466 and 467:
INDEX 455 Cushing’s syndrome 302
Page 468 and 469:
INDEX 457 5-fluorouracil 375-6 fluo
Page 470 and 471:
INDEX 459 children 54 diazepam 108
Page 472 and 473:
INDEX 461 non-steroidal anti-inflam
Page 474 and 475:
INDEX 463 puberty (male), delay 314
Page 476:
INDEX 465 tolerance 9, 433 benzodia
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