A Textbook of Clinical Pharmacology and Therapeutics

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Note: Page numbers in italics refer to figures and tables. � phase 15 ‘ABCD’ rule, antihypertensive drugs 187 abciximab 93, 209 Aberdeen–Dundee intensive monitoring system 65 ablation therapy, cardiac dysrhythmias 222 absence seizures, drugs for 134 absorption of drugs 17, 18 children 52, 54 drug interactions 75 tetracyclines 329, 389 elderly patients 56 eye 21, 423, 429 folate 392 heart failure 34 iron 389 kidney disease on 35 nose 21 oral route 19–20 skin 20–1, 22, 414 children 52, 54 abuse of substances 433–43 acamprosate 441 acarbose 290 accumulation of drugs 13, 14 acetazolamide 274–5, 426 N-acetyl-benzoquinone imine (NABQI) 27 acetyl cysteine 30, 242, 260, 447 acetylation 25 acetylator status 80–1, 82 acetylcholine receptor agonists 7 acetylcholinesterase, deficiency in Alzheimer’s disease 131 acetylcholinesterase inhibitors, adverse effects on lungs 243 ACIC-TP (aciclovir phosphates) 345 aciclovir 345–6 eye 427 herpes simplex in HIV infection 359 skin infections 417 acid secretion, stomach 247, 248 acidic drugs, renal reabsorption 32 acidification of urine 279 acipimox 181 acitretin 416 acne 411–12 drugs causing 418 acquired immune deficiency syndrome see HIV infection acrivastine 405 acromegaly 316–17 activated charcoal 445, 446 activated partial thromboplastin time, heparin therapy 206 active immunity 399 active transport distal renal tubular reabsorption 33 gastrointestinal drug absorption 19–20 acute bronchitis 235 acute coronary syndrome 198, 199 see also myocardial infarction acute intermittent porphyria 81, 84, 154 adalimumab 171 addiction see dependence on drugs adefovir dipivoxil 261, 349 INDEX adenosine 225–6 dipyridamole and 209, 226 adenylyl cyclase 208 β 2-adrenoceptor agonists on 236–7 lithium on 121 Parkinson’s syndrome 124 adjuvant chemotherapy 367 adjuvants (immune) 407 adrenal cortex hormones 302–5 see also corticosteroids suppression 302, 306, 414 tetracosactide test 318 adrenal medulla, hormones 305–6 adrenaline 227, 305 anaphylactic shock 405, 406 cardiopulmonary resuscitation 221 with local anaesthetics 153 adrenoceptor(s) classification 7 eye 424 �-adrenoceptor antagonists 193 on bladder 279 for prostatic obstruction 280 � 2-adrenoceptor agonists 150, 426 �-adrenoceptor antagonists 189–90, 201 for cardiac dysrhythmias 223–4 eye, systemic absorption 429 heart failure 190, 214 hyperthyroidism 294 ischaemic heart disease 198, 199, 201 migraine prophylaxis 143 portal hypertension 261 verapamil and 191, 192, 224, 225 withdrawal 10 � 2-adrenoceptor agonists 236–7 asthma 234 chronic obstructive pulmonary disease 236 adrenocorticotrophic hormone 318 adsorption, on apparent volume of distribution 12 advanced life support 220–1 adverse effects of drugs 3–4, 62–70 children 54–5 combinations to minimize 72 cytotoxic drugs 369–71 drug interactions 73–7 elderly patients 56 on eye 428 on lungs 243 on skin 417–19 see also under skin afterload, cardiac 212 age-related macular degeneration 428 agonists 6, 7 dose–response curves 6 agranulocytosis 69 clozapine 113 AIDS see HIV infection airways obstruction, �-adrenoceptor antagonists 190 akathisia 112, 126 albumin liver disease 37–8, 274 nephrotic syndrome 273 alcohol 439–42 metronidazole and 330, 442 pregnancy 50, 440 procarbazine and 373 sensitivity 80 sleep and 107 withdrawal, antipsychotic drugs and 115 see also alcoholism alcohol dehydrogenase 25 alcoholism 440–2 thiamine 266 aldesleukin (interleukin-2) 384, 407 aldosterone 305 aldosterone antagonists 193, 305 heart failure 214 myocardial infarction 200 alefacept 415 alemtuzumab 383 alfentanil 150, 161 alginate, reflux oesophagitis 252 alkalinization of urine 279 alkalosis, loop diuretics 275 alkylating agents 372–3 aplastic anaemia 395 allergic asthma 233 omalizumab for 241 allergic rhinitis 405, 406 allergy adverse drug reactions 63, 66–7 lungs 243 mediator blocking 405–6 allopurinol 172–3 ciclosporin and 402 6-mercaptopurine and 173, 376–7 allylamines 343 alopecia androgenic 412 cytotoxic drugs 371 drugs causing 418 alprostadil cavernosal injection 315 ductus arteriosus 313 alteplase 199, 202 alternative medicines 97–102 altitude sickness, acetazolamide 274 aluminium hydroxide 250 Alzheimer’s disease 131–2 amantadine elderly patients 58 influenza 348 Parkinson’s disease 126 amikacin 328 plasma concentrations 42 amiloride 276 hyperkalaemia 280 �-aminobutyric acid (GABA) 133 aminoglutethimide 384 aminoglycosides 327–8 ciclosporin and 402 eye 427 plasma concentration monitoring 42 platinum compounds and 374 renal failure 37 urinary tract infections 33 5-aminolevulinic acid synthetase, induction 84
452 INDEX aminophylline 238 plasma concentration monitoring 43 4-aminoquinolines 362–3 8-aminoquinolines 364 aminosalicylates 255 amiodarone 221, 224–5 interaction with warfarin 208 monitoring 42–3 amitriptyline, migraine prophylaxis 144 amlodipine 191 ammonia 260 ammonium chloride 279 amoxicillin 326 amphetamines 438–9 on appetite 263 urinary pH and 32 amphotericin 341 ciclosporin and 402 flucytosine with 344 ganciclovir and 347 platinum compounds and 374 ampicillin 326 rash 55, 65 amprenavir 356 amyl nitrate 442 amyotrophic lateral sclerosis 129 anabolic steroids 314 abuse 442 for aplastic anaemia 395 ciclosporin and 402 anaemia see aplastic anaemia; folate; haemolytic anaemia; iron; vitamin B 12 anaesthesia 145–54 � 2-adrenoceptor agonists 150 benzodiazepines 149 on fetus 46 H 2-receptor antagonists 250 inhalational 145–8 intravenous 148–9 malignant hyperthermia 80, 83–4, 152 muscle relaxants 150–2 opioids 149–50 pregnancy 48–9 premedication 150 see also local anaesthesia analgesics 156–64 migraine 142 myocardial infarction 198 nitrous oxide as 147 postoperative 163–4 pregnancy 48 terminal care 162–3 anandamide 7 anaphylaxis 404, 405, 406 anastrazole 384 Ancylostoma duodenale, drugs for 365 androgens 313–14 baldness 412 angina 196–8 unstable 196, 198–200 angioplasty, coronary 197–8, 199, 200 angiotensin-converting enzyme inhibitors 187–8 ciclosporin and 402 elderly patients 59 heart failure 213 ischaemic heart disease 199, 200, 201 renal failure 37 angiotensin receptor blockers 188–9 elderly patients 59 heart failure 213–14 ischaemic heart disease 199–200, 201 anidulafungin 343 animal studies 4, 87 anion-exchange resins 181, 182 anorectic drugs 262–4 antacids 249, 250 mycophenolate mofetil and 403 reflux oesophagitis 252 tetracyclines and 329 antagonists 6, 8–9 competitive 8, 9, 10 on effect of partial agonists 9 dose–response curves 6 anterior pituitary hormones 316–18 anthracyclines 377–8 anti-androgens 314, 318 anti-Bcl-2 oligonucleotide 382 anti-CD3 antibody 403 anti-D immunoglobulin 408 anti-dysrhythmic drugs classification 218, 219 plasma concentration monitoring 42–3 anti-emetics 253–5 with cytotoxic drugs 370 migraine 142 with opioids 163 pregnancy 48–9 anti-epileptic drugs see anticonvulsants anti-HIV drugs 353–7 interaction with garlic 98 anti-oestrogens, for malignant disease 384 anti-parkinsonian drugs, elderly patients 58 anti-progestogens 311 anti-proliferative immunosuppressants 402–3 anti-sense oligonucleotides 95 antibiotics 323–33 acne 411 antacids and 249 chronic obstructive pulmonary disease 236 combinations 72 cytotoxic 377–8 in cytotoxic chemotherapy 371 elderly patients 59 eye infections 427 pregnancy 48 warfarin and 208 see also aminoglycosides anticholinergic drugs 114, 128 chronic obstructive pulmonary disease 236 mydriatics 425 see also muscarinic receptors, antagonists anticholinesterases 130, 131–2 reversal of muscle relaxants 151 anticoagulants 204, 205–8 combined oral contraceptives and 310 DC cardioversion 221 pregnancy 50, 209 sulphonamides and 330 thyroid disease 39 anticonvulsants 133–41 interaction with corticosteroids 74 plasma concentration monitoring 42 pregnancy 49 antidepressants 116–23 drug interactions 118 elderly patients 58 see also tricyclic antidepressants antidiuretic hormone 276–7 antagonists 318 antidotes 72, 446, 447 antifolate analogues 374–5 antihistamines 241, 405–6 eye 427 for vomiting 253–4 antihypertensive drugs 186–95 elderly patients 58 non-steroidal anti-inflammatory drugs and 168 antilymphocyte globulin 403 antiplatelet drugs 208–9 antipseudomonal penicillins 326 antipsychotic drugs 111–15 antiretroviral agents see anti-HIV drugs antithrombin III 206 antithyroid drugs 39, 293–5 �1-antitrypsin deficiency 242–3 antitussives 242 antiviral agents 344–9 eye 427 influenza 348 nucleoside analogues 345–7 pregnancy 48 see also anti-HIV drugs anxiety 107–9 anxiolytics 105, 106, 107–9 aorta, dissecting aneurysms, �-adrenoceptor antagonists 189–90 aplastic anaemia 69, 395 chloramphenicol 328, 395 apnoea, suxamethonium sensitivity 80, 81–2, 152 apolipoprotein A 179 apparent volume of distribution 12 pregnancy 47 appetite stimulation 264 appetite-suppressing drugs 262–4 apraclonidine 426 aqueous humour circulation 425 arachidonic acid 268 cytochrome P450 enzymes on 24–5 metabolism 168 arachis oil 257 aripiprazole 114 aromatase inhibitors 312, 384 arrhythmias see cardiac dysrhythmias artemether 364 artenusate 364 Arthus reactions 66, 400 arylaminoalcohols 363 ascariasis, drugs for 366 ascites 40 ascorbic acid see vitamin C aspergillosis, drugs for 340 aspirin 157–8 antacids and 249 asthma 157, 243 children and 54 ischaemic heart disease 65, 198, 199, 200, 201–2, 208 migraine 142 nicotinic acid and 183 poisoning 448 thyroid crisis and 295 warfarin and 208 asthma 233–5, 236–41 �-adrenoceptor antagonists 190 adverse effects of drugs 243 aspirin 157, 243 cough 55 non-steroidal anti-inflammatory drugs and 168–9, 243 asystole 221 ataxia see cerebellar ataxia atazanavir 356 atenolol 224 birth weight 45 atheroma 177–84 diabetes mellitus 286 atopic dermatitis 413 atorvastatin 180 atovaquone malaria prophylaxis 362 Pneumocystis carinii 358 zidovudine and 354 ATP binding cassette proteins (ABC proteins) 82 atracurium 150, 151
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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
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: ● 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 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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