A Textbook of Clinical Pharmacology and Therapeutics

Recommendations

Info

FOREWORD viii PREFACE ix ACKNOWLEDGEMENTS x PART I GENERAL PRINCIPLES 1 1 Introduction to therapeutics 3 2 Mechanisms of drug action (pharmacodynamics) 6 3 Pharmacokinetics 11 4 Drug absorption and routes of administration 17 5 Drug metabolism 24 6 Renal excretion of drugs 31 7 Effects of disease on drug disposition 34 8 Therapeutic drug monitoring 41 9 Drugs in pregnancy 45 10 Drugs in infants and children 52 11 Drugs in the elderly 56 12 Adverse drug reactions 62 13 Drug interactions 71 14 Pharmacogenetics 79 15 Introduction of new drugs and clinical trials 86 16 Cell-based and recombinant DNA therapies 92 17 Alternative medicines: herbals and nutraceuticals 97 PART II THE NERVOUS SYSTEM 103 18 Hypnotics and anxiolytics 105 19 Schizophrenia and behavioural emergencies 110 20 Mood disorders 116 21 Movement disorders and degenerative CNS disease 124 22 Anti-epileptics 133 23 Migraine 142 24 Anaesthetics and muscle relaxants 145 25 Analgesics and the control of pain 155 PART III THE MUSCULOSKELETAL SYSTEM 165 26 Anti-inflammatory drugs and the treatment of arthritis 167 PART IV THE CARDIOVASCULAR SYSTEM 27 Prevention of atheroma: lowering plasma 175 cholesterol and other approaches 177 28 Hypertension 185 29 Ischaemic heart disease 196 30 Anticoagulants and antiplatelet drugs 204 31 Heart failure 211 32 Cardiac dysrhythmias 217 CONTENTS PART V THE RESPIRATORY SYSTEM 33 Therapy of asthma, chronic obstructive pulmonary 231 disease (COPD) and other respiratory disorders 233 PART VI THE ALIMENTARY SYSTEM 245 34 Alimentary system and liver 247 35 Vitamins and trace elements 265 PART VII FLUIDS AND ELECTROLYTES 271 36 Nephrological and related aspects 273 PART VIII THE ENDOCRINE SYSTEM 283 37 Diabetes mellitus 285 38 Thyroid 292 39 Calcium metabolism 297 40 Adrenal hormones 302 41 Reproductive endocrinology 307 42 The pituitary hormones and related drugs 316 PART IX SELECTIVE TOXICITY 321 43 Antibacterial drugs 323 44 Mycobacterial infections 334 45 Fungal and non-HIV viral infections 340 46 HIV and AIDS 351 47 Malaria and other parasitic infections 361 48 Cancer chemotherapy 367 PART X HAEMATOLOGY 387 49 Anaemia and other haematological disorders 389 PART XI IMMUNOPHARMACOLOGY 397 50 Clinical immunopharmacology 399 PART XII THE SKIN 409 51 Drugs and the skin 411 PART XIII THE EYE 421 52 Drugs and the eye 423 PART XIV CLINICAL TOXICOLOGY 431 53 Drugs and alcohol abuse 433 54 Drug overdose and poisoning 444 INDEX 451
FOREWORD John Trounce, who was the senior author of the first edition of this textbook, died on the 16 April 2007. He considered a text in clinical pharmacology suitable for his undergraduate and postgraduate students to be an important part of the programme he developed in his department at Guy’s Hospital Medical School, London. It is difficult to imagine today how much resistance from the medical and pharmacological establishments Trounce had to overcome in order to set up an academic department, a focussed course in the medical curriculum and a separate exam in final MB in clinical pharmacology. In other words, he helped to change a ‘non-subject’ into one of the most important areas of study for medical students. He was also aware of the need for a high quality textbook in clinical pharmacology that could also be used by nurses, pharmacists, pharmacology science students and doctors preparing for higher qualifications. (For example, it has been said that nobody knows more about acute pharmacology than an anaesthetist.) The present edition of the textbook reflects the advances in therapeutics since the publication of the fourth edition. It is interesting to follow in all the editions of the book, for example, how the treatment of tumours has progressed. It was about the time of the first edition that Trounce set up the first oncology clinic at Guy’s Hospital in which he investigated the value of combined radiation and chemotherapy and drug cocktails in the treatment of lymphomas. John Trounce was pleased to see his textbook (and his subject) in the expert hands of Professor Ritter and his colleagues. Roy Spector Professor Emeritus in Applied Pharmacology, University of London
Page 2 and 3: A Textbook of Clinical Pharmacology
Page 4 and 5: A Textbook of Clinical Pharmacology
Page 6 and 7: This fifth edition is dedicated to
Page 10 and 11: PREFACE Clinical pharmacology is th
Page 12 and 13: PART I GENERAL PRINCIPLES
Page 14 and 15: ● Use of drugs 3 ● Adverse effe
Page 16 and 17: and acquired factors, notably disea
Page 18 and 19: 100 Effect (%) 0 0 5 10 1 10 100 (a
Page 20 and 21: Dose ratio -1 100 50 The relationsh
Page 22 and 23: ● Introduction 11 ● Constant-ra
Page 24 and 25: In reality, processes of eliminatio
Page 26 and 27: lood (from which samples are taken
Page 28 and 29: ● Introduction 17 ● Bioavailabi
Page 30 and 31: ROUTES OF ADMINISTRATION ORAL ROUTE
Page 32 and 33: Transdermal absorption is sufficien
Page 34 and 35: FURTHER READING Fix JA. Strategies
Page 36 and 37: and thromboxanes are CYP450 enzymes
Page 38 and 39: and lorazepam. Some patients inheri
Page 40 and 41: Orally administered drug Parenteral
Page 42 and 43: ● Introduction 31 ● Glomerular
Page 44 and 45: ACTIVE TUBULAR REABSORPTION This is
Page 46 and 47: DISTRIBUTION Drug distribution is a
Page 48 and 49: Detailed recommendations on dosage
Page 50 and 51: DIGOXIN Myxoedematous patients are
Page 52 and 53: ● Introduction 41 ● Role of dru
Page 54 and 55: 25 20 10 Life-threatening toxicity
Page 56 and 57: ● Introduction 45 ● Harmful eff
Page 58 and 59:
vagina in girls in their late teens
Page 60 and 61:
an anti-analgesic effect when combi
Page 62 and 63:
Case history A 20-year-old female m
Page 64 and 65:
METABOLISM At birth, the hepatic mi
Page 66 and 67:
lifelong effects as a result of tox
Page 68 and 69:
DISTRIBUTION Ageing is associated w
Page 70 and 71:
DIGOXIN Digoxin toxicity is common
Page 72 and 73:
FURTHER READING Dhesi JK, Allain TJ
Page 74 and 75:
Factors involved in the aetiology o
Page 76 and 77:
analgesic. Following its release, t
Page 78 and 79:
antibiotics, such as penicillin or
Page 80 and 81:
predisposes to non-immune haemolysi
Page 82 and 83:
● Introduction 71 ● Useful inte
Page 84 and 85:
Response Therapeutic range Toxic ra
Page 86 and 87:
Table 13.1: Interactions outside th
Page 88 and 89:
Table 13.5: Competitive interaction
Page 90 and 91:
● Introduction: ‘personalized m
Page 92 and 93:
Table 14.2: Variations in drug resp
Page 94 and 95:
lipoprotein (LDL) is impaired. LDL
Page 96 and 97:
Key points • Genetic differences
Page 98 and 99:
• Discovery • • Screening Pre
Page 100 and 101:
Too many statistical comparisons pe
Page 102 and 103:
ETHICS COMMITTEES Protocols for all
Page 104 and 105:
Table 16.1: Recombinant proteins/en
Page 106 and 107:
duration and benefit. Adenoviral ve
Page 108 and 109:
● Introduction 97 ● Garlic 97
Page 110 and 111:
A case report has suggested a possi
Page 112 and 113:
including hypericin and pseudohyper
Page 114 and 115:
PART II THE NERVOUS SYSTEM
Page 116 and 117:
● Introduction 105 ● Sleep diff
Page 118 and 119:
and daytime sleeping should be disc
Page 120 and 121:
Key points • Insomnia and anxiety
Page 122 and 123:
Box 19.1: Dopamine theory of schizo
Page 124 and 125:
The Boston Collaborative Survey ind
Page 126 and 127:
Oral medication, especially in liqu
Page 128 and 129:
e.g. interpersonal difficulties or
Page 130 and 131:
Partial response to first-line trea
Page 132 and 133:
Key points Drug treatment of depres
Page 134 and 135:
Case history A 45-year-old man with
Page 136 and 137:
Levodopa PRINCIPLES OF TREATMENT IN
Page 138 and 139:
• pulmonary, retroperitoneal and
Page 140 and 141:
CHOREA The γ-aminobutyric acid con
Page 142 and 143:
Cholinergic crisis Treatment of mya
Page 144 and 145:
● Introduction 133 ● Mechanisms
Page 146 and 147:
absolute arbiter. The availability
Page 148 and 149:
Table 22.2: Metabolic interactions
Page 150 and 151:
FURTHER ANTI-EPILEPTICS Other drugs
Page 152 and 153:
Case history A 24-year-old woman wh
Page 154 and 155:
Assessment of migraine severity and
Page 156 and 157:
● General anaesthetics 145 ● In
Page 158 and 159:
is the theoretical concern of a ‘
Page 160 and 161:
• Respiratory system - apnoea fol
Page 162 and 163:
Competitive antagonists (vecuronium
Page 164 and 165:
have also proved useful in combinat
Page 166 and 167:
● Introduction 155 ● Pathophysi
Page 168 and 169:
ASPIRIN (ACETYLSALICYLATE) Use Anti
Page 170 and 171:
Key points Drugs for mild pain •
Page 172 and 173:
increases, correlating with the hig
Page 174 and 175:
• If possible, use oral medicatio
Page 176 and 177:
PART III THE MUSCULOSKELETAL SYSTEM
Page 178 and 179:
● Introduction: inflammation 167
Page 180 and 181:
Chapter 33). All NSAIDs cause wheez
Page 182 and 183:
• Stomatitis suggests the possibi
Page 184 and 185:
Pharmacokinetics Allopurinol is wel
Page 186 and 187:
PART IV THE CARDIOVASCULAR SYSTEM
Page 188 and 189:
Page 190 and 191:
esponsible for the strong predilect
Page 192 and 193:
Ezetimibe Fat Muscle Dietary fat In
Page 194 and 195:
educed). The risk of muscle damage
Page 196 and 197:
Page 198 and 199:
Each of these classes of drug reduc
Page 200 and 201:
AT 1 receptor) produce good 24-hour
Page 202 and 203:
Table 28.2: Examples of calcium-cha
Page 204 and 205:
Key points Drugs used in essential
Page 206 and 207:
Case history A 72-year-old woman se
Page 208 and 209:
Assess risk factors Investigations:
Page 210 and 211:
Persistent ST segment elevation Thr
Page 212 and 213:
Mechanism of action GTN works by re
Page 214 and 215:
Because of the risks of haemorrhage
Page 216 and 217:
Intrinsic pathway XIIa XIa the acti
Page 218 and 219:
that the pharmacodynamic response i
Page 220 and 221:
used with apparent benefit in acute
Page 222 and 223:
Page 224 and 225:
The drugs that are most effective i
Page 226 and 227:
therapeutic plasma concentration ca
Page 228 and 229:
● Common dysrhythmias 217 ● Gen
Page 230 and 231:
BASIC LIFE SUPPORT CARDIOPULMONARY
Page 232 and 233:
arrest. The electrocardiogram is li
Page 234 and 235:
should be given to insertion of an
Page 236 and 237:
Drug interactions Amiodarone potent
Page 238 and 239:
effect when treating sinus bradycar
Page 240 and 241:
Case history A 24-year-old medical
Page 242 and 243:
PART V THE RESPIRATORY SYSTEM
Page 244 and 245:
CHAPTER 33 THERAPY OF ASTHMA, CHRON
Page 246 and 247:
STEP 5: CONTINUOUS OR FREQUENT USE
Page 248 and 249:
Adenylyl cyclase Table 33.1: Compar
Page 250 and 251:
Drug interactions Although synergis
Page 252 and 253:
use in asthma has declined consider
Page 254 and 255:
α 1-antitrypsin deficiency, neutro
Page 256 and 257:
PART VI THE ALIMENTARY SYSTEM
Page 258 and 259:
● Peptic ulceration 247 ● Oesop
Page 260 and 261:
PEPTIC ULCERATION 249 • With rega
Page 262 and 263:
Ranitidine has a similar profile of
Page 264 and 265:
Vestibular stimulation ? via cerebe
Page 266 and 267:
cortical centres affecting vomiting
Page 268 and 269:
• in hepatocellular failure to re
Page 270 and 271:
Ciprofloxacin is occasionally used
Page 272 and 273:
withdrawal), small doses of benzodi
Page 274 and 275:
Table 34.7: Dose-independent hepato
Page 276 and 277:
● Introduction 265 ● General ph
Page 278 and 279:
dinucleotide (NAD) and nicotinamide
Page 280 and 281:
Table 35.1: Common trace element de
Page 282 and 283:
PART VII FLUIDS AND ELECTROLYTES
Page 284 and 285:
● Introduction 273 ● Volume ove
Page 286 and 287:
Key points Diuretics Diuretics are
Page 288 and 289:
is sometimes caused by drugs, notab
Page 290 and 291:
or with potassium-sparing diuretics
Page 292 and 293:
Greger R, Lang F, Sebekova, Heidlan
Page 294 and 295:
PART VIII THE ENDOCRINE SYSTEM
Page 296 and 297:
Page 298 and 299:
in prefilled injection devices (‘
Page 300 and 301:
Metformin should be withdrawn and i
Page 302 and 303:
FURTHER READING American Diabetes A
Page 304 and 305:
deficiency. Potassium iodide (3 mg
Page 306 and 307:
fertility. It is contraindicated du
Page 308 and 309:
● Introduction 297 ● Vitamin D
Page 310 and 311:
effective in life-threatening hyper
Page 312 and 313:
Further reading Block GA, Martin KJ
Page 314 and 315:
Table 40.1: Actions of cortisol and
Page 316 and 317:
injection may be useful, but if don
Page 318 and 319:
CHAPTER 41 REPRODUCTIVE ENDOCRINOLO
Page 320 and 321:
elease by the pituitary via negativ
Page 322 and 323:
Treatment with depot progestogen in
Page 324 and 325:
infusion using an infusion pump to
Page 326 and 327:
significant proportion of men who r
Page 328 and 329:
with symptoms caused by the release
Page 330 and 331:
FURTHER READING Birnbaumer M. Vasop
Page 332 and 333:
PART IX SELECTIVE TOXICITY
Page 334 and 335:
● Principles of antibacterial che
Page 336 and 337:
2. transfer of resistance between o
Page 338 and 339:
Pharmacokinetics Absorption of thes
Page 340 and 341:
Mechanism of action Macrolides bind
Page 342 and 343:
asic quinolone structure dramatical
Page 344 and 345:
Case history A 70-year-old man with
Page 346 and 347:
PRINCIPLES OF MANAGEMENT OF MYCOBAC
Page 348 and 349:
Pharmacokinetics Absorption from th
Page 350 and 351:
MYCOBACTERIUM LEPRAE INFECTION Lepr
Page 352 and 353:
POLYENES AMPHOTERICIN B Uses Amphot
Page 354 and 355:
therapy is adequate though more fre
Page 356 and 357:
NUCLEOSIDE ANALOGUES ACICLOVIR Uses
Page 358 and 359:
Table 45.3: Summary of available ac
Page 360 and 361:
Uses Interferon-α when combined wi
Page 362 and 363:
● Introduction 351 ● Immunopath
Page 364 and 365:
Table 46.1: Examples of combination
Page 366 and 367:
NON-NUCLEOSIDE ANALOGUE REVERSE TRA
Page 368 and 369:
FUSION INHIBITORS Uses Currently, e
Page 370 and 371:
salvage therapy include azithromyci
Page 372 and 373:
● Malaria 361 ● Trypanosomal in
Page 374 and 375:
Pharmacokinetics Chloroquine is rap
Page 376 and 377:
Table 47.2: Drug therapy of non-mal
Page 378 and 379:
Page 380 and 381:
Table 48.1: Classification of commo
Page 382 and 383:
Polymorph count/mm 3 (a) (b) 10 000
Page 384 and 385:
doses are used to prepare patients
Page 386 and 387:
Adverse effects Methotrexate Inhibi
Page 388 and 389:
Table 48.7: Summary of clinical pha
Page 390 and 391:
Table 48.9: Summary of the clinical
Page 392 and 393:
Plasma membrane Signal transduction
Page 394 and 395:
Table 48.10: Monoclonal antibodies
Page 396 and 397:
INTERFERON-ALFA 2B Interferon-alfa
Page 398 and 399:
PART X HAEMATOLOGY
Page 400 and 401:
● Haematinics - iron, vitamin B 1
Page 402 and 403:
one marrow to produce red cells. Th
Page 404 and 405:
EPO Erythroid precursors Erythrocyt
Page 406 and 407:
Therapeutic principles The extent o
Page 408 and 409:
PART XI IMMUNOPHARMACOLOGY
Page 410 and 411:
● Introduction 399 ● Immunity a
Page 412 and 413:
Key points Antigen recognition Expr
Page 414 and 415:
Table 50.1: Novel anti-proliferativ
Page 416 and 417:
Key points Treatment of anaphylacti
Page 418 and 419:
DRUGS THAT ENHANCE IMMUNE SYSTEM FU
Page 420 and 421:
PART XII THE SKIN
Page 422 and 423:
● Introduction 411 ● Acne 411
Page 424 and 425:
DERMATITIS (ECZEMA) PRINCIPLES OF T
Page 426 and 427:
SPECIALISTS ONLY SPECIALISTS ONLY E
Page 428 and 429:
TREATMENT OF OTHER SKIN INFECTIONS
Page 430 and 431:
effect of too high a dose of UVB in
Page 432 and 433:
PART XIII THE EYE
Page 434 and 435:
● Introduction: ocular anatomy, p
Page 436 and 437:
to cause pupillary dilatation, name
Page 438 and 439:
Table 52.3: Antibacterial agents us
Page 440 and 441:
Table 52.6: Common drug-induced pro
Page 442 and 443:
PART XIV CLINICAL TOXICOLOGY
Page 444 and 445:
Page 446 and 447:
Table 53.2: Central nervous system
Page 448 and 449:
which provide anonymized data to th
Page 450 and 451:
Peak plasma levels after smoking ci
Page 452 and 453:
Key points Acute effects of alcohol
Page 454 and 455:
FURTHER READING Goldman D, Oroszi G
Page 456 and 457:
Table 54.2: Common indications for
Page 458 and 459:
Table 54.5: Antidotes and other spe
Page 460 and 461:
Commission on Human Medicines (CHM)
Page 462 and 463:
Note: Page numbers in italics refer
Page 464 and 465:
atrial fibrillation 217, 221 digoxi
Page 466 and 467:
Cushing’s syndrome 302 cyclic ade
Page 468 and 469:
5-fluorouracil 375-6 fluoxetine, mo
Page 470 and 471:
children 54 diazepam 108 iron prepa
Page 472 and 473:
non-steroidal anti-inflammatory dru
Page 474 and 475:
puberty (male), delay 314 puerperiu
Page 476:
tolerance 9, 433 benzodiazepines 10
show all

A Textbook of Clinical Pharmacology and Therapeutics

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?