Clinical Pharmacology and Drug Therapy

Transcription

1 Oxford Textbook of Clinical Pharmacology and Drug Therapy THIRD EDITION D. G. Grahame-Smith CBE, MBBS, PhD, FRCP Emeritus Professor of Clinical Pharmacology, University of Oxford and J.K. Aronson MBChB, DPhil, FRCP Clinical Reader in Clinical Pharmacology, University of Oxford Honorary Consultant Physician, Oxfordshire Health Authority OXFORD UNIVERSITY PRESS

2 Contents A note about drug nomenclature Consulting authors «SECTION ONE Clinical pharmacology: the scientific basis of drug therapy 1 The four processes of drug therapy 1.1 The pharmaceutical process The pharmacokinetic process The pharmacodynamic process The therapeutic process 5 2 The pharmaceutical process: is the drug getting into the patient? 2.1 Patient compliance/concordance Systemic availability (bioavailability) Special drug formulations 9 3 The pharmacokinetic process: is the drug getting to its site of action? 3.1 Drug absorption and systemic availability Drug distribution Drug metabolism n 3.4 Drug excretion Simple pharmacokinetic calculations The mathematics of pharmacokinetics 29 4 The pharmacodynamic process: is the drug producing the required pharmacological effect? 4.1 The types of pharmacological actions of drugs Stereoisomerism and drug action Graded responses to drugs: the doseresponsive curve in drug therapy 43 5 The therapeutic process: is the pharmacological being translated into a therapeutic effect? 5.1 Translation of the pharmacological effect of a drug into a therapeutic effect during shortterm drug therapy Translation of the pharmacological effect of a drug into a therapeutic effect during longterm drug therapy The aims of drug therapy 53 6 Practical applications of the analysis of drug therapy 6.1 The application of pharmacokinetics to the planning of drug dosage regimens The application of the processes of drug therapy in analysing failure to respond to treatment 6J 7 Monitoring drug therapy 7.1 Monitoring the therapeutic effects of drugs Monitoring the pharmacodynamic effects of drugs Monitoring drug pharmacokinetics (plasma concentration measurement) 71

3 1 CONTENTS 8 Pharmacogenetics and pharmacogenomics 8.1 Pharmacokinetic genetic variations Pharmacodynamic genetic variations S3 9 Adverse reactions to drugs 9.1 History Incidence of adverse drug reactions Classification of adverse drug reactions Dose-related adverse drug reactions Non-dose-related adverse drug reactions Long-term and withdrawal effects causing adverse drug reactions Delayed effects causing adverse drug reactions Surveillance methods used in detecting adverse drug reactions Drug interactions 10.1 Incidence of significant drug interactions Drugs likely to be involved in interactions Pharmaceutical interactions Pharmacokinetic interactions Pharmacodynamic interactions Lists of clinically important drug interactions in 11 Drug therapy in young and old people 11.1 Drug therapy in young people Drug therapy in old people Drug therapy and reproduction 12.1 Hormonal contraception Hormone replacement therapy The treatment of infertility no 12.4 Drug therapy during pregnancy Drug therapy in the termination of pregnancy and in the management of pre-term labour and labour Drug therapy and breastfeeding Patient compliance/concordance 13.1 Factors that affect compliance Methods of measuring compliance Methods of improving compliance Placebos 14.1 Uses and abuses of placebos Factors that influence the response to placebos Mode of action of placebos Adverse effects of placebos Drug discovery and development: the pharmaceutical industry and the regulatory authorities 15.1 Drug discovery Drug development Post-marketing surveillance 150 ISA Advertising Regulatory authorities Local drug and therapeutics committees Drug costs Drug trials 16.1 Definition of a clinical trial The conduct of a clinical trial Ethics The drug history and the clinical examination and investigation of drug effects 17.1 Taking the drug history Clinical examination and investigation of drug effects The importance of good records and communication no SECTION TWO Practical prescribing 18 Principles of prescribing 18.1 The benefit:risk ratio in prescribing Evidence-based medicine How to choose a drug How to write a prescription 19.1 Practical prescription writing Proprietary names versus approved names Prescribing controlled drugs Repeat prescribing Abbreviations Sources of information on drugs 20.1 Pharmaceutical information Pharmacokinetics Pharmacological effects of drugs Therapeutic Pharmacogenetics Adverse effects of drugs Drug interactions Clinical trials Patient compliance Prescribing information Computerized databases Drug information services Bibliography ;9i

4 CONTENTS XMI SECTION THREE The drug therapy of disease 21 Introduction to drug therapy The drug therapy of infectious diseases 22.1 Antibacterial drugs: the treatment of bacterial infections Chemotherapy of viral infections Chemotherapy of protozoal infections A Chemotherapy of helminthic infections Chemotherapy of trematode infections Chemotherapy of fungal infections Prevention of infections using vaccines and immunoglobulins The drug treatment of sexually transmitted diseases The drug therapy of cardiovascular disorders 23.1 Hypertension Angina pectoris Acute myocardial infarction Cardiac arrhythmias Cardiac failure Infective endocarditis Venous thromboembolic disease The drug therapy of respiratory diseases 24.1 The use of oxygen in respiratory disorders Cough Pneumonias Chronic obstructive lung disease Bronchial asthma Pulmonary tuberculosis Inflammatory lung disorders Cystic fibrosis Drug-induced respiratory disorders The drug therapy of gastrointestinal, hepatic, and biliary disorders 25.1 Antacids Antiemetics Peptic ulceration Laxatives Antidiarrhoeal drugs Irritable bowel syndrome Gastrointestinal infections Ulcerative colitis Crohn's disease Drugs and the liver Drug therapy in the treatment of chronic liver disease 29/ Drug treatment of gallstones Drugs and the kidney and the drug therapy of renal, urinary tract, and prostatic disorders 26.1 Diuretic therapy Potassium depletion Hyperkalaemia The place of drugs in the management of acute renal insufficiency The place of drugs in the management of chronic renal insufficiency The drug treatment of glomerulonephritis Drugs in the treatment of urinary tract infection Drug treatment of urinary calculi Drugs and the urinary bladder: the treatment of incontinence, detrusor instability, and enuresis Drug therapy of tumours of the kidney 30<s Drug therapy of prostatic disease Drug-induced renal damage Drugs and dialysis 3/0 27 The drug therapy of endocrine and metabolic disorders 27.1 Disorders of the pituitary gland Disorders of the adrenal gland 3/ Disorders of the thyroid gland 3is 27 A Disorders of calcium metabolism Diabetes mellitus Disorders of lipid metabolism The management of obesity The drug therapy of blood disorders 28.1 Anaemias Myeloproliferative disorders Lymphoproliferative disorders Acute leukaemias Monoclonal gammopathies Drug-induced blood dyscrasias Complications of blood transfusion Blood substitutes The drug therapy of disorders of bones and joints 29.1 Arthritis Gout and hyperuricaemia 35,s 29.3 Musculoskeletal disorders caused by drugs 3MI 29.4 Paget's disease of bone 3oo 29.5 The prevention and treatment of postmenopausal osteoporosis 362

5 xiv CONTENTS 30 The drug therapy of neurological disorders 30.1 Meningitis and encephalitis Parkinson's disease and Parkinsonism Epilepsy Migraine Myasthenia gravis Muscle spasticity Vertigo Trigeminal neuralgia Drug-induced movement disorders The drug therapy of psychiatric disorders 31.1 Mechanisms of action of drugs used in psychiatric disorders The use of psychotropic drugs The relief of pain 32.1 Anatomical and neuropharmacological mechanisms underlying pain sensation Mechanisms of action of analgesics Principles underlying the use of analgesics in the treatment of pain The practical use of analgesics The treatment of intractable pain in terminal malignant disease Postoperative pain General anaesthesia and local anaesthetics 33.1 Premedication Induction of anaesthesia Muscle relaxants A Maintenance of anaesthesia Postoperative medication Local anaesthetics Drug dependence and abuse 34.1 Factors that predispose to drug dependence Opiates Cocaine and amphetamines (including Ecstasy) Cannabis LSD and other psychedelic drugs Solvents and nitrites Alcohol Benzodiazepines 4J Barbiturates Anabolic steroids 41s Tobacco (nicotine) Accounts of drug dependence 4/y 35 The management of poisoning 35.1 The immediate management of the acutely ill patient The detailed management of poisoning Sources of information Agents used in the treatment of poisoning The principles of cancer chemotherapy 36.1 Tumour responsiveness to chemotherapy The actions of chemotherapeutic drugs relevant to the clinical uses Clinical evaluation of tumours before and after treatment Combination chemotherapy Regimens for cancer chemotherapy Adverse effects of drugs used in cancer chemotherapy The practical use of cytotoxic drugs Immunosuppression and the drug therapy of allergies, connective tissue disorders, and primary immunodeficiencies 37.1 Immune disease: pathogenesis and mechanisms of action of drugs The use of glucocorticoids as anti-inflammatory, antiallergic, and immunosuppressive agents The drug therapy of allergic and autoimmune disorders A The management of primary immunodeficiences Immunosuppression in tissue and organ transplantation 455 SECTION FOUR Pharmacopoeia Introductory notes 459 Index to drugs listed in the pharmacopoeia 46i Pharmacopoeia 469 General index 611