A Textbook of Clinical Pharmacology and Therapeutics

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puberty (male), delay 314 puerperium, anticoagulants 209 pulmonary blood flow, anaesthesia 146 pulmonary embolism, heparins for 205 pulmonary eosinophilia 243 pulmonary fibrosis amiodarone 224 drugs causing 243 pulmonary oedema 211, 213 heroin overdose 435 pulmonary surfactants 242 pupil 423 miosis 423, 425–6 see also mydriasis purine antimetabolites 376–7 purpura drugs causing 418 idiopathic thrombocytopenic 395 PUVA (psoralen with UVA light) 414–16 pyrazinamide 335 hepatotoxicity 263 pyridostigmine 130 pyridoxine see vitamin B 6 pyrimethamine malaria 364 Toxoplasma gondii 358–9 pyrimidine antimetabolites 375 quadruple therapy, tuberculosis in HIV infection 359 quinidine, interaction with digoxin 73 quinine 363 pregnancy 48 quinolones 330–1 ‘radiation recall’ 377 radioactive iodine 294–5 randomization, clinical trials 87–8 ranibizumab 428 ranitidine 249–51 ranitidine bismuth citrate tablets 251 rapid acetylators 80 rasagiline 127–8 rasburicase 173 rashes 68 ampicillin 55, 65 rate constant, for elimination (k el) 13 re-entry tachycardia 218 reabsorption, renal 32–3, 76–7 receptor tyrosine kinase inhibitors 381 receptors 6–7 classifications 7 desensitization 9 polymorphisms 82–3 recombinant DNA therapies 92–6 recombinant factor VIII 92, 395 recombinant growth hormone 92, 316 recombinant haematopoietic growth factors 392–4 rectal route 20 children 54 diazepam 54, 140 ‘red man’ syndrome 330 reduction of drugs (metabolic) 25 reflux oesophagitis 252 pregnancy 49 regulation of medicines, United Kingdom 86 rehabilitation, myocardial infarction 200 remifentanil 150, 161 renal artery stenosis, ACEIs 188 renal failure 35–7 from diuretics 280 on drug dosage 33 functional, ACEIs 188 methotrexate 375 repaglinide 289 repeated dosing, pharmacokinetics 13–14 reproductive endocrinology 307–15 hormone antagonists 312 research children 55 clinical trials 5, 64, 86–8, 89–90 elderly patients 60 see also drug development resins, ion-exchange 181, 182, 279 resistance to antibiotics 324–5 to azoles 341 to cytotoxic drugs 369, 370 HIV to therapy 357 malaria to chloroquine 362 respiratory failure 241–2 resuscitation cardiopulmonary 218–21 see also supportive therapy reteplase 199, 202 retinitis, cytomegalovirus 359 retinoids 266 acitretin 416 acne 411–12 teratogenesis 412, 416 retinol (vitamin A) 265–6 retinopathy chloroquine 362 diabetes mellitus 285–6 fibrinolysis and 203 reversible antagonism 8 Reye’s syndrome 54, 157 rhDNase (mucolytic) 242 rhesus-negative mothers, anti-D immunoglobulin 408 ribavirin 347 riboflavin 392 rifabutin, protease inhibitors and 356 rifampicin 335, 336–7 ciclosporin and 402 fluconazole and 342 leprosy 339 on liver 262 protease inhibitors and 356 terbinafine and 343 theophylline and 239 riluzole 129 rimantadine 348 rimonabant 263 Ringer’s lactate solution 277 risedronate 299 risk/benefit 3–4 risperidone 114 ritonavir 356, 360 rituximab 383 rivastigmine 131–2 rizatriptan 143 rocuronium bromide 151 ropivacaine 153 rosiglitazone 290 rosuvastatin 180 ryanodine R1 receptor 83–4, 152 SAHA (vorinostat) 382 salbutamol 21, 236–7 anaphylactic shock 405 respiratory failure 242 salicylates 157 on liver 262 methotrexate and 375 poisoning 448 salmeterol 237 saquinavir 356 sartans see angiotensin receptor blockers satiety factors 263 saturation INDEX 463 enzymes 15 transferrin 390 saturation kinetics, phenytoin 136–7 saw palmetto 100 scabies 417 Schildt plots 9 schistosomiasis, drug for 366 schizophrenia 110–14 sciatic nerve, avoidance in intramuscular injection 21 scurvy 267 seborrhoeic dermatitis 413 sedation, intensive care 150 seizures 133 children 54 ciclosporin 408 febrile 140 see also epilepsy selective oestrogen receptor modulators and downregulators 384 selective serotonin (5HT) reuptake inhibitors 117–18, 122 elderly patients 58 poisoning 448 selegiline 127–8 self-poisoning 444–9 sensitivity of receptors, manipulation 9–10 serology, adverse drug reactions 63 serotonin-noradrenaline reuptake inhibitors (SNRI) 116, 118 serotonin-only hypothesis, depression 116 serum sickness 66 severe combined immunodeficiency disease, gene therapy 95 sevoflurane 147 shingles, aciclovir 345 shock anaphylaxis 404, 405, 406 volume depletion 277–8 shock lung 241 short stature 316 SIADH (syndrome of inappropriate antidiuretic hormone) 276–7 sibutramine 263 sick sinus syndrome 223 signal transduction 8 sildenafil 315 azoles and 350 nitrates and 442 simvastatin 180, 182 Singh–Vaughan–Williams classification, antidysrhythmic drugs 218, 219 single-bolus doses, pharmacokinetics 12–13 single nucleotide polymorphisms 79 sinus bradycardia 223 sirolimus 403 micafungin on 343 plasma concentration monitoring 43 skin 411–19 adverse drug reactions 66–7, 68 amiodarone 224 drug absorption 20–1, 22, 414 children 52, 54 provocation testing 63 sleep 105–7 elderly patients 58 slow-reacting substance of anaphylaxis 240 slow-release preparations 18, 20 aspirin 157 overdose 445 small intestine, disease on drug disposition 34 smoking 438–9 atheroma 179 peptic ulcer 248 pregnancy 50, 438
464 INDEX sodium ketoacidosis 287 laxative abuse 258 lithium and 122 liver disease 38 see also volume overload sodium bicarbonate as antacid 250 aspirin poisoning 448 calcium chloride and 227 ketoacidosis 287 magnesium salts and 228 tricyclic antidepressant poisoning 448 urine alkalinization 279 sodium fusidate see fusidic acid Na � –K � ATPase, digoxin on 215, 226 sodium valproate 135 migraine prophylaxis 143 solifenacin 279 solubility anaesthetics 145 see also lipid-solubility of drugs; watersolubility of drugs solvent abuse 442 somatomedin 316 somatostatin 316 oesophageal varices 261 somatropin 92, 316 Somogyi effect 288 sorafenib 382 sotalol 222, 225 soy 99–100 spasticity 128 specificity of drugs 6 spermatozoa drugs on 46 storage before chemotherapy 371 spina bifida, anticonvulsants 49 spironolactone 40, 193, 214, 276, 305 splenectomy, idiopathic thrombocytopenic purpura 395 sputum, viscosity reduction 242 St John’s wort 100–1, 102, 122 ST-segment-elevation myocardial infarction 198–200 staphylococci, antibiotic resistance 326 statins 180–2 azoles and 350 familial hypercholesterolaemia 83 ischaemic heart disease 197 on liver 262 myocardial infarction 200 statistics, clinical trials 88–9 status epilepticus 136, 139, 140 stavudine 354 steady-state concentrations 11 stem cell therapy 95–6 stents, coronary 197 Stevens Johnson syndrome 68, 419, 428 stilbestrol, on fetus 47 stimulant laxatives 257 Stokes–Adams attacks 217 stomach acid secretion 247, 248 emptying 34 migraine 34, 142 neonates 52 pregnancy 47 renal disease on pH 35 see also entries beginning gastric... stones prevention with thiazides 276 see also gallstones streptococcal infections, streptokinase and 202 streptokinase 199, 202 streptomycin 335, 337–8 stress incontinence 279 stroke, hormone replacement therapy 311 Strongyloides stercoralis, drug for 365 strontium ranelate 300 subcutaneous route 21–2 sublingual route 20 substance abuse 433–43 sucralfate 252 suicide genes 94, 95 sulfadiazine, Toxoplasma gondii 358 sulfamethoxazole, pregnancy 51 sulfasalazine 19, 170, 255 sulfinpyrazone 173 sulindac 37, 168 sulphation 27 sulphhydryl group effects, ACEIs 188 sulphonamides 330 kernicterus 73 methotrexate and 330, 375 sulphonylureas 289 SIADH 277 sulphonamides and 330 sulphoxidation 81 sumatriptan 142–3 sunitinib 382 supersensitivity 10 supportive therapy self-poisoning 445–6 see also resuscitation supraventricular dysrhythmias 217–18, 221–2, 229 surfactants, pulmonary 242 surrogate markers 41 surveillance, adverse drug reactions 63–6 sustained-release preparations see slow-release preparations suxamethonium 150–1, 152 pentamidine and 358 sensitivity 80, 81–2, 152 syndrome of inappropriate antidiuretic hormone (SIADH) 276–7 synergy 72 syntometrine 313 systemic absorption eye 423, 425, 426 nose 21 skin 20–1, 22, 52, 54, 414 systemic lupus erythematosus, drug-induced 69 systolic hypertension, elderly patients 195 T-lymphocytes, transplantation 95 tachycardia–bradycardia syndrome 223 tachycardias 217, 221–3 supraventricular 217–18, 221–2, 229 ventricular 218, 222–3 tacrolimus 402 Taenia spp., drugs for 365 tamoxifen 312, 384 genistein on 100 tamsulosin 280 tapeworms, drugs for 365 tardive dyskinesia 112 taxanes 379–80 tears 423 teicoplanin 330 telithromycin 332 hepatotoxicity 263 telomeres 367 temazepam 108, 150 tenecteplase 199, 202 teniposide 379 tenofovir 354 teratogenesis 46–7, 55 aciclovir 345 anticonvulsants 49 carbimazole 294 co-trimoxazole 51 cytotoxic drugs 371 detection 48 immunosuppressive drugs 400 retinoids 412, 416 ribavirin 347 vitamin A 266 warfarin 50 terbinafine 343 terbutaline 237 teriparatide 300 terlipressin, oesophageal varices 261 terminal disease, analgesics 162–3 testosterone 313–14 tetrabenazine 129 tetracaine 154 tetracosactide 318 tetracyclines 329 acitretin and 416 acne 411 eye 427 iron absorption 329, 389 on liver 262 thalidomide 46, 64, 86, 385 theophylline 238–9 adenosine and 226 ciprofloxacin and 331 pharmacokinetics in heart failure 35 plasma concentration monitoring 42, 43 therapeutic drug monitoring 41–4 anticonvulsants 134–5 digoxin 215 lithium 121 pregnancy 49 therapeutic index 41 thiacetazone 338 thiamine (vitamin B 1) 266 thiazides 192, 275–6 see also bendroflumethiazide thiazolidinediones 289–90 thiopental 148, 442 thiopurine-S-methyltransferase 79, 84, 376 threadworm, drugs for 365 thrombocytopenia adverse drug reactions 68 idiopathic 395 thromboembolism combined oral contraceptives 309 hormone replacement therapy 311 thrombolytic therapy (fibrinolytics), ischaemic heart disease 199, 202–3 thrombopoietin 394 thrombosis 204–5 thromboxane A 2 208 thymectomy, myasthenia gravis 130 thyroid crisis 295 thyroid gland 292–6 amiodarone 224 disease on pharmacokinetics 38–9 drugs affecting 295 thyroid stimulating hormone 292 thyroxine 293 thyroid disease 39 weight reduction 264 tiaconazole 342 tiagabine 138 tibolone 312 tics 129 time to peak plasma concentration (T max) 18 tinea 416 tiotropium 238 tipranavir 356 tissue binding, drug displacement 73 tissue to plasma concentration ratios 41–2 tobramycin 328 tocopherol (vitamin E) 268 tolbutamide 289 see also CYP2C9 polymorphism
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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
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DRUGS THAT ENHANCE IMMUNE SYSTEM FU
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PART XII THE SKIN
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● 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 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 476: tolerance 9, 433 benzodiazepines 10
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A Textbook of Clinical Pharmacology and Therapeutics

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