A Textbook of Clinical Pharmacology and Therapeutics

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This fifth edition is dedicated to the memory of Professors Howard Rogers and John Trounce, two of the three authors of this textbook’s first edition.
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Page 2 and 3: A Textbook of Clinical Pharmacology
Page 4 and 5: A Textbook of Clinical Pharmacology
Page 8 and 9: FOREWORD viii PREFACE ix ACKNOWLEDG
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
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an anti-analgesic effect when combi
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Case history A 20-year-old female m
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METABOLISM At birth, the hepatic mi
Page 66 and 67:
lifelong effects as a result of tox
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DISTRIBUTION Ageing is associated w
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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
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analgesic. Following its release, t
Page 78 and 79:
antibiotics, such as penicillin or
Page 80 and 81:
predisposes to non-immune haemolysi
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● 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
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lipoprotein (LDL) is impaired. LDL
Page 96 and 97:
Key points • Genetic differences
Page 98 and 99:
• Discovery • • Screening Pre
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Too many statistical comparisons pe
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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
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● Introduction 105 ● Sleep diff
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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
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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
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