A Textbook of Clinical Pharmacology and Therapeutics

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5-fluorouracil 375–6 fluoxetine, monoamine oxidase inhibitors and 118 flutamide 384 fluticasone 240 folate 392 antagonism in malaria treatment 364 deficiency 268, 269, 392 Toxoplasma gondii 358 vitamin B 12 deficiency 391 see also antifolate analogues folinic acid methotrexate antagonism 374, 375 methotrexate concentrations requiring 42 follicle-stimulating hormone 307, 312, 317 fomiversen 95 fondaparinux 206 food drug absorption and 19 on first-pass metabolism 29 formularies 4 formulations of drugs bioequivalence 18, 90 elderly patients 60 see also liquid preparations fosamprenavir 356 foscarnet 346 cytomegalovirus 359 eye 427 fosphenytoin 136, 137 framycetin, eye 427 free-radical hypothesis, Parkinson’s syndrome 124 fulvestrant 312, 384 fungi 340 drugs against 340–4 HIV infection 359 skin infections 416 furosemide 275 methotrexate and 375 pulmonary oedema 213 fusidic acid 329 eye 427 on liver 262 fusion inhibitors (HIV) 357 G-protein-linked receptors 7 desensitization 9 G6PD deficiency see glucose 6-phosphate dehydrogenase deficiency GABA (�-aminobutyric acid) 133 gabapentin 138 galantamine 131–2 gallstones drug-induced 69 octreotide 317 ganciclovir 346–7 cytomegalovirus infection 359 eye 427 garlic 97–8 gastrectomy partial, iron absorption 389 vitamin B 12 deficiency 391 gastric emptying see stomach, emptying gastric haemorrhage 252 aspirin 157 gastric lavage 445 gastric ulcers, endoscopy 249 gastrin 247 gastro-oesophageal reflux, pregnancy 49 gastrointestinal tract 247–59 bacteria drug absorption and 20 drug metabolism 29 ‘dialysis’ 446 diseases on drug disposition 34 drug metabolism 28, 29 iron preparations on 390 kidney disease on 35 pharmacokinetics 19–20 gate mechanisms, pain 155 Gaucher’s disease, biotechnology 92 gefitinib 381 gemcitabine 377 gemeprost 311 gemfibrozil 181, 182, 183 gemtuzumab 383 gene therapy 92, 94–5, 96 general anaesthetics 145–54 inhalational 145–8 intravenous 148–9 generalized seizures, drugs for 134 generic drugs 90 prescribing 17–18 genetic variations, first-pass metabolism 29 genistein 100 genital herpes, aciclovir 345 gentamicin 328 eye 427 methotrexate and 375 plasma concentration monitoring 42 geriatrics, polypharmacy (case) 5 germ-line gene therapy 94 GHB (�-hydroxybutyric acid) 442 giant-cell arteritis, prednisolone 169 Giardia lamblia, drugs for 365 Gilbert’s disease 84 ginkgo biloba 99 ginseng 98–9 glargine insulin 286 glaucoma acetazolamide 274 from anticholinergic agents 238 drugs for 425–6 mydriatics and 425 osmotic diuretics 276 glibenclamide 289 elderly patients and 59 gliclazide 289 glitazones 289–90 globalization, drug development 91 glomerular filtration 31 ACEIs 188 children 53 estimated rate 57 heart failure 35 pregnancy 47 renal failure 36 thyroid disease 39 glomerulonephritis, immune-complex, penicillamine 171 glucagon 288 glucan, echinocandins on synthesis 343 glucocorticoids 169, 302–5 for allergic disease 405 as anti-emetics 255 asthma 239 chronic obstructive pulmonary disease 236, 239 dermatitis 413–14 eye 427 hay fever 406 idiopathic thrombocytopenic purpura 395 immunosuppression 400–1 inflammatory bowel disease 255 inhaled 234, 239 for malignant disease 384 requirement reduction 241 thyroid disease 39 see also corticosteroids; hydrocortisone; prednisolone glucosamine 101 INDEX 457 glucose 6-phosphate dehydrogenase deficiency 68–9, 81, 83, 331, 366 glucuronidation 25–7 neonates 28 glutamate 133 glutathione 27, 260 glycerol suppositories 257 glyceryl trinitrate 196–7, 198, 200–1 glycoprotein IIb/IIIa, inhibitors 209 glycylxylidide 223 gold salts 170–1 gonadotrophin-releasing hormone 307 analogues 317–18, 384 gonadotrophins 307, 312, 317 Good Clinical Practice 87 goserelin 312, 317, 318, 384 gout 171–3 granulocyte colony-stimulating factor 394 grapefruit juice 408 Graves’ ophthalmopathy 295 grey baby syndrome, chloramphenicol 328 griseofulvin 344 on spermatozoa 46 growth hormone 316–17 recombinant 92, 316 gynaecomastia, cimetidine 250 H1-receptors 404 antagonists see antihistamines H 2-receptor antagonists 249–51 elderly patients 60 pancreatic enzyme replacement and 250, 259 H 2-receptors 404 H 3-receptors 404 haematinics see folate; iron; vitamin B 12 haematopoietic growth factors 370, 379, 392–4 haemodynamics, nitrates 201 haemolytic anaemia adverse drug reactions 68–9 antibiotics 331 methaemoglobinaemia 83 haemolytic disease of the newborn 400 haemophilias 394–5 desmopressin 278, 395 haemorrhage gastric 252 aspirin 157 liver disease 260 oesophageal varices 261 half-life, drug concentration 12, 13 heparin 206 liver disease 38 repeated dosing and 14 two-compartment models 15 halibut liver oil 265–6 hallucinogens 437 halofantrine 363 haloperidol 112, 114 halothane 146, 147 haptens 400 hay fever 405, 406 heart anthracyclines on 377–8 see also entries beginning cardiac... heart failure 211–16 �-adrenoceptor antagonists 190, 214 pharmacokinetics 34–5 Helicobacter pylori 247–8, 249 helminthic infections 364–6 heparins 205–6 pregnancy 50, 209 hepatic encephalopathy 260–2 hepatitis, viral 348–9 chronic 261 hepatitis B virus 261
458 INDEX hepatotoxicity 69, 262, 263 halothane 146, 147 non-steroidal anti-inflammatory drugs 169 rifampicin 336 see also paracetamol hepcidin 389 herbal medicines 97–102 heroin (diamorphine) 161, 434, 435, 442 herpes simplex virus infection aciclovir 345 HIV infection 359 skin 417 high-density lipoprotein (HDL) 179 highly active antiretroviral therapy (HAART) 352–3 hirsutism 412 hirudin 206–7 histamine 404–5 atracurium causing release 151 histone deacetylase inhibitors 382 histoplasmosis drugs for 340 HIV infection 359 historical aspects 86 opioids 159 history-taking 4 adverse drug reactions 63 HIV infection 351–60 tuberculosis 338, 359 see also anti-HIV drugs HMG CoA reductase inhibitors see statins hoarseness, inhaled glucocorticoids 239 Hoffmann elimination, atracurium 151 homeopathic medicines 97 hookworm, drugs for 365 hormone replacement therapy (HRT) 311–12, 315 progestogens in 308, 312 hormones for acne 411 for malignant disease 383–4 human normal immunoglobulin 407–8 humanization antibodies 382 recombinant proteins 93 humoral immunity 399 Huntington’s disease 129 hydatid disease, drugs for 365 hydralazine 194 nitrates with 214 slow acetylators 81, 82 hydration, skin 20 hydrocortisone 303–4 anaphylactic shock 405 asthma 239 G6PD deficiency and 83 respiratory failure 242 hydrolysis of drugs 25 �-hydroxybutyric acid (GHB) 442 hydroxychloroquine, rheumatoid arthritis 170 hydroxyphenyl amines 260 5-hydroxytryptamine migraine 142 mood disorders and 116 syndrome 118 see also serotonin-only hypothesis 5-hydroxytryptamine 1 agonists, migraine 142–3 5-hydroxytryptamine 3 receptor antagonists 254 hydroxyurea 377 hyoscine 253 hypercalcaemia 299 diuretics 192 hyperkalaemia 278–9, 280 ACEIs 188 calcium chloride in 227 treatment of heart failure 213 hyperosmolar non-ketotic coma 288 hypersensitivity reactions 399–400 delayed 66–7, 400 glucocorticoids for 400 with histamine release 404–5 vaccine preparations 407 hypertension 185–95 alcoholism 440 diabetes mellitus 286 erythropoietin 396 pregnancy 50 see also antihypertensive drugs hypertensive crises, monoamine oxidase inhibitors 120, 123 hyperthermia, malignant 80, 83–4, 152 hyperthyroidism 292, 293–5 pharmacokinetics 38–9 hyperuricaemia 171–3 hypnotics 105–7, 108, 109 elderly patients 58, 107 hypocalcaemia 300 hypoglycaemia 288 �-adrenoceptor antagonists 190, 214, 224 alcohol 442 hypogonadism, male 313 hypokalaemia 278 diuretics 192, 275 drug-induced 69 elderly patients 59 heart failure 213 liver disease 38, 40 hyponatraemia antidepressants 118, 122 SIADH 277 hypopituitarism, hypothyroidism in 293 hypotension ACEIs 213 poisoning 446 postural 57–8 streptokinase 202 hypothermia 220 hypothyroidism 293 pharmacokinetics 38–9 hypovolaemia 277–8 hypoxia, nitrous oxide 147 hypoxia-inducible factor-1 (HIF) 393 ibuprofen 158 idiopathic thrombocytopenic purpura 395 idiosyncratic drug reactions 62 idoxuridine, eye 427 ifosfamide 372 imatinib 380–1 imidazoles 341–2 imipenem 327 immune-complex glomerulonephritis, penicillamine 171 immune-complex reactions 66, 400 immune responses 399 mediators and blockers 404–6 immunoglobulins (therapeutic) 93, 407–8 immunopharmacology 399–408 immunostimulants 407 immunosuppressive drugs 399, 400–4 inflammatory bowel disease 256 myasthenia gravis 130 plasma concentration monitoring 43 rheumatoid arthritis 170 impotence see erectile dysfunction inclusion criteria, clinical trials 88 incontinence 279 indinavir 356 indometacin 169 on ductus arteriosus 46, 313 induction of enzymes 27–8, 76 anticonvulsants 137 infections alcoholism 440 bacterial, treatment algorithm 324 carbimazole 294 cytotoxic chemotherapy 371 diabetes mellitus 287 eye 427 immunosuppression 400 mycobacterial 334–9 opioid addiction 435 parasites 361–6 skin 416–17 streptococcal, streptokinase and 202 viral 344 hepatitis 261, 348–9 skin 417 see also anti-HIV drugs; antiviral agents; HIV infection see also antibiotics; fungi; urinary tract, infections infective endocarditis, prophylaxis with antibiotics 325 infertility cytotoxic drugs 371 drugs for 312 immunosuppressive drugs 400 inflammation 167 inflammatory bowel disease 255–6 infliximab Crohn’s disease 256 immune diseases 171, 404 psoriasis 415 influenza, antiviral agents for 348 infusion, pharmacokinetics 11–12 inhalational anaesthetics 145–8 inhalers asthma 234 children 54 drug absorption from 21 glucocorticoids 239 asthma 234 insulin via 288 salbutamol 237 inhibition, enzymes 28 inhibitors, receptors 7 injection site reactions, enfuvirtide 357 inotropes, positive 212 insomnia 105–7 insulin(s) 286–8 ‘designer’ 92–3, 286 elderly patients 59 physiology 285 intensive care, sedation 150 intensive monitoring, adverse drug reactions 65 interferon-alfa 2b 385 interferons 348–9 theophylline and 239 viral hepatitis 261 interleukin-2 384, 407 interleukin-11 394 international normalized ratio (INR) 207 paracetamol overdose 447 interstitial nephritis, drug-induced 69, 70, 168 interstitial pneumonitis, bleomycin 385 intra-ocular pressure 425 see also glaucoma intra-uterine devices 310 intracranial pressure halothane and 146 osmotic diuretics 276 intramuscular injection 21 intranuclear receptors 7 intrathecal route 22 baclofen 128 methotrexate 375 morphine 160 intravenous route 22 anaesthetics 148–9
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A Textbook of Clinical Pharmacology
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A Textbook of Clinical Pharmacology
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This fifth edition is dedicated to
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FOREWORD viii PREFACE ix ACKNOWLEDG
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PREFACE Clinical pharmacology is th
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PART I GENERAL PRINCIPLES
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● Use of drugs 3 ● Adverse effe
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and acquired factors, notably disea
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100 Effect (%) 0 0 5 10 1 10 100 (a
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Dose ratio -1 100 50 The relationsh
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● Introduction 11 ● Constant-ra
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In reality, processes of eliminatio
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lood (from which samples are taken
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● Introduction 17 ● Bioavailabi
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ROUTES OF ADMINISTRATION ORAL ROUTE
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Transdermal absorption is sufficien
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FURTHER READING Fix JA. Strategies
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and thromboxanes are CYP450 enzymes
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and lorazepam. Some patients inheri
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Orally administered drug Parenteral
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● Introduction 31 ● Glomerular
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ACTIVE TUBULAR REABSORPTION This is
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DISTRIBUTION Drug distribution is a
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Detailed recommendations on dosage
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DIGOXIN Myxoedematous patients are
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● Introduction 41 ● Role of dru
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25 20 10 Life-threatening toxicity
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● Introduction 45 ● Harmful eff
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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
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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
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FURTHER READING Dhesi JK, Allain TJ
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Factors involved in the aetiology o
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analgesic. Following its release, t
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antibiotics, such as penicillin or
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predisposes to non-immune haemolysi
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● Introduction 71 ● Useful inte
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Response Therapeutic range Toxic ra
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Table 13.1: Interactions outside th
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Table 13.5: Competitive interaction
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● Introduction: ‘personalized m
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Table 14.2: Variations in drug resp
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lipoprotein (LDL) is impaired. LDL
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Key points • Genetic differences
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• Discovery • • Screening Pre
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Too many statistical comparisons pe
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ETHICS COMMITTEES Protocols for all
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Table 16.1: Recombinant proteins/en
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duration and benefit. Adenoviral ve
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● Introduction 97 ● Garlic 97
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A case report has suggested a possi
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including hypericin and pseudohyper
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PART II THE NERVOUS SYSTEM
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● Introduction 105 ● Sleep diff
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and daytime sleeping should be disc
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Key points • Insomnia and anxiety
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Box 19.1: Dopamine theory of schizo
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The Boston Collaborative Survey ind
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Oral medication, especially in liqu
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e.g. interpersonal difficulties or
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Partial response to first-line trea
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Key points Drug treatment of depres
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Case history A 45-year-old man with
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Levodopa PRINCIPLES OF TREATMENT IN
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• pulmonary, retroperitoneal and
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CHOREA The γ-aminobutyric acid con
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Cholinergic crisis Treatment of mya
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● Introduction 133 ● Mechanisms
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absolute arbiter. The availability
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Table 22.2: Metabolic interactions
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FURTHER ANTI-EPILEPTICS Other drugs
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Case history A 24-year-old woman wh
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Assessment of migraine severity and
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● General anaesthetics 145 ● In
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is the theoretical concern of a ‘
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• Respiratory system - apnoea fol
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Competitive antagonists (vecuronium
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have also proved useful in combinat
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● Introduction 155 ● Pathophysi
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ASPIRIN (ACETYLSALICYLATE) Use Anti
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Key points Drugs for mild pain •
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increases, correlating with the hig
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• If possible, use oral medicatio
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PART III THE MUSCULOSKELETAL SYSTEM
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● Introduction: inflammation 167
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Chapter 33). All NSAIDs cause wheez
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• Stomatitis suggests the possibi
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Pharmacokinetics Allopurinol is wel
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PART IV THE CARDIOVASCULAR SYSTEM
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esponsible for the strong predilect
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Ezetimibe Fat Muscle Dietary fat In
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educed). The risk of muscle damage
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Each of these classes of drug reduc
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AT 1 receptor) produce good 24-hour
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Table 28.2: Examples of calcium-cha
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Key points Drugs used in essential
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Case history A 72-year-old woman se
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Assess risk factors Investigations:
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Persistent ST segment elevation Thr
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Mechanism of action GTN works by re
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Because of the risks of haemorrhage
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Intrinsic pathway XIIa XIa the acti
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that the pharmacodynamic response i
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used with apparent benefit in acute
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The drugs that are most effective i
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therapeutic plasma concentration ca
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● Common dysrhythmias 217 ● Gen
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BASIC LIFE SUPPORT CARDIOPULMONARY
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arrest. The electrocardiogram is li
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should be given to insertion of an
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Drug interactions Amiodarone potent
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effect when treating sinus bradycar
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Case history A 24-year-old medical
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PART V THE RESPIRATORY SYSTEM
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CHAPTER 33 THERAPY OF ASTHMA, CHRON
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STEP 5: CONTINUOUS OR FREQUENT USE
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Adenylyl cyclase Table 33.1: Compar
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Drug interactions Although synergis
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use in asthma has declined consider
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α 1-antitrypsin deficiency, neutro
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PART VI THE ALIMENTARY SYSTEM
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● Peptic ulceration 247 ● Oesop
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PEPTIC ULCERATION 249 • With rega
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Ranitidine has a similar profile of
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Vestibular stimulation ? via cerebe
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cortical centres affecting vomiting
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• in hepatocellular failure to re
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Ciprofloxacin is occasionally used
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withdrawal), small doses of benzodi
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Table 34.7: Dose-independent hepato
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● Introduction 265 ● General ph
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dinucleotide (NAD) and nicotinamide
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Table 35.1: Common trace element de
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PART VII FLUIDS AND ELECTROLYTES
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● Introduction 273 ● Volume ove
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Key points Diuretics Diuretics are
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is sometimes caused by drugs, notab
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or with potassium-sparing diuretics
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Greger R, Lang F, Sebekova, Heidlan
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PART VIII THE ENDOCRINE SYSTEM
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in prefilled injection devices (‘
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Metformin should be withdrawn and i
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FURTHER READING American Diabetes A
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deficiency. Potassium iodide (3 mg
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fertility. It is contraindicated du
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● Introduction 297 ● Vitamin D
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effective in life-threatening hyper
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Further reading Block GA, Martin KJ
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Table 40.1: Actions of cortisol and
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injection may be useful, but if don
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CHAPTER 41 REPRODUCTIVE ENDOCRINOLO
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elease by the pituitary via negativ
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Treatment with depot progestogen in
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infusion using an infusion pump to
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significant proportion of men who r
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with symptoms caused by the release
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FURTHER READING Birnbaumer M. Vasop
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PART IX SELECTIVE TOXICITY
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● Principles of antibacterial che
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2. transfer of resistance between o
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Pharmacokinetics Absorption of thes
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Mechanism of action Macrolides bind
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asic quinolone structure dramatical
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Case history A 70-year-old man with
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PRINCIPLES OF MANAGEMENT OF MYCOBAC
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Pharmacokinetics Absorption from th
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MYCOBACTERIUM LEPRAE INFECTION Lepr
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POLYENES AMPHOTERICIN B Uses Amphot
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therapy is adequate though more fre
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NUCLEOSIDE ANALOGUES ACICLOVIR Uses
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Table 45.3: Summary of available ac
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Uses Interferon-α when combined wi
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● Introduction 351 ● Immunopath
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Table 46.1: Examples of combination
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NON-NUCLEOSIDE ANALOGUE REVERSE TRA
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FUSION INHIBITORS Uses Currently, e
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salvage therapy include azithromyci
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● Malaria 361 ● Trypanosomal in
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Pharmacokinetics Chloroquine is rap
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Table 47.2: Drug therapy of non-mal
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Table 48.1: Classification of commo
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Polymorph count/mm 3 (a) (b) 10 000
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doses are used to prepare patients
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Adverse effects Methotrexate Inhibi
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Table 48.7: Summary of clinical pha
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Table 48.9: Summary of the clinical
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Plasma membrane Signal transduction
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Table 48.10: Monoclonal antibodies
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INTERFERON-ALFA 2B Interferon-alfa
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PART X HAEMATOLOGY
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● Haematinics - iron, vitamin B 1
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one marrow to produce red cells. Th
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EPO Erythroid precursors Erythrocyt
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Therapeutic principles The extent o
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PART XI IMMUNOPHARMACOLOGY
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● Introduction 399 ● Immunity a
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Key points Antigen recognition Expr
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Table 50.1: Novel anti-proliferativ
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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: ● Introduction 433 ● Pathophysi
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 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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