Clinical Pharmacology and Therapeutics

1 Cover

2 Title Page Clinical Pharmacology and Therapeutics Lecture Notes Edited by Gerard A. McKay Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde Glasgow, UK Matthew R. Walters College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow, UK Neil D. Ritchie Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde Glasgow, UK Tenth Edition

3 Copyright Page

4 Preface

5 Contributors

6 Part 1: Principles of clinical pharmacology 1 Pharmacodynamics and pharmacokinetics Introduction Principles of drug action (pharmacodynamics) Mechanism of drug action Principles of pharmacokinetics Principles of drug elimination Clinical pharmacokinetics: dosage individualisation Clinical examples of therapeutic drug monitoring Influence of renal function on pharmacokinetics and pharmacodynamics Prescribing for the young and the elderly Drugs in pregnant and breastfeeding women 2 Clinical trials and drug development Introduction Drug discovery Models of drug development Clinical trials 3 Pharmacoeconomics: the economic evaluation of new drugs Introduction – why do we need economic evaluations? Economic evaluation Perspective Costs Linking costs to benefits Cost‐minimisation analysis Cost‐effectiveness analysis Cost–benefit analysis Cost–utility analysis Why use CUA and QALYs? How are the constituent parts of QALYs estimated? How is cost‐effectiveness then assessed? Sensitivity analysis Pharmacoeconomics and decision‐making REFERENCES 4 Practical prescribing Good prescribing: questions to ask yourself before prescribing a drug Writing the prescription: practical aspects General pointers on good prescribing Adverse drug reactions Drug allergy Drug interactions Emergency prescribing

7 Part 2: Aspects of prescribing 5 Gastrointestinal systemIntroduction Gastro‐oesophageal reflux disease Drugs used in the treatment of gastro‐oesophageal reflux disease Drugs used in the treatment of gastro‐oesophageal reflux disease Drugs that inhibit gastric acid secretion Drugs that act on oesophageal and/or gastric motility Peptic ulcer Drugs used in the treatment of peptic ulcer Drugs used in the treatment of peptic ulcer Drug combinations to eradicate H. pylori Nausea and vomiting Drugs used in treatment of vomiting Diarrhoea and constipation Inflammatory bowel disease Drugs used in the treatment of inflammatory bowel disease – (box/flow chart for management of IBD) New treatments (often second line) Drugs adversely affecting gastrointestinal function 6 Cardiovascular systemIntroduction Angina pectoris and acute coronary syndromes Cardiac arrhythmia Class I agents Class II agents Class III agents Class IV agents Adenine nucleotides Heart failure Neuroendocrine antagonists Drugs with a positive inotropic effect Drugs affecting preload Drugs affecting preload and afterload General principles of management of heart failure Long‐term management of chronic heart failure Primary and secondary prevention of cardiovascular disease 7 Respiratory systemIntroduction Diseases of airflow obstruction Management of asthma and COPD Treatment of chronic airways disease Treatment of acute airways disease Management of acute asthma Management of acute exacerbations of COPD Other therapy for airways diseases Notes on other respiratory diseases Disease targeted treatment 8 Nervous systemIntroduction Epilepsy Pathophysiology Aetiology of seizures Anti‐epileptic drugs in common use Anti‐epileptic drug therapy in pregnancy Headache Migraine Acute treatment of migraine attack Migraine prophylaxis Antimigraine drugs in common use Medication‐overuse headache Cerebrovascular disease Infections of the nervous system Drug‐induced neurological disorders Neuroinflammatory disorders Movement disorders Drugs used for parkinsonism Treatment of psychiatric disorders Antipsychotic drugs Antidepressants Mood‐stabilising agents Anxiolytics Hypnotic drugs and the treatment of insomnia Drug‐induced psychiatric disorder Abuse of psychoactive drugs Treatment of dementia 9 InfectionIntroduction Principles of anti‐infective treatment Antibacterial drugs Antituberculous drugs Antifungal drugs Antiviral drugs Hepatitis B (HBV) Hepatitis C (HCV) 10 Drugs and endocrine diseaseDiabetes mellitus Thyroid disease Hypothyroidism Obesity Bone metabolism Pituitary and adrenal cortex disease 11 Genitourinary systemDrugs for bladder outlet obstruction Drugs for overactive bladder Drugs for prostate cancer Drugs for erectile dysfunction Drugs and the reproductive system 12 Malignant disease Introduction Chemotherapy Targeted therapy: signal transduction inhibitors 13 Drugs and the blood Introduction Anticoagulant drugs Thrombolytic agents Anaemia and haematinics Drug‐induced blood conditions 14 Musculoskeletal system Principles of management Principles of drug treatment Drugs used in gout and pseudogout 15 Immunopharmacology Introduction Drugs that suppress immune responses Corticosteroids 16 Travel medicineIntroduction Principles of immunisation Vaccines used for preventing infection in travellers Malaria prevention and treatment Treatment of other common imported parasitic infections 17 Analgesia and anaesthesiaIntroduction Pathophysiology of pain Management of pain Opioids Adjunctive agents Anaesthesia Critical care considerations 18 Poisoning and drug overdose Introduction General approach to the poisoned patient The management of specific complications Features of common drug overdose Summary

8 Index

9 End User License Agreement

1 Chapter 1 Table 1.1 P450 inhibitors involved in drug interactions. Table 1.2 Major enzymes displaying genetic polymorphism. Table 1.3 Examples of target ranges. Table 1.4 Factors influencing theophylline clearance and therefore dose requireme... Table 1.5 Predicted steady‐state digoxin concentrations for clinical scenario... Table 1.6 Predicted steady‐state phenytoin concentrations for clinical scenar... Table 1.7 Drugs that can cause liver damage. Table 1.8 Drugs that are known to be teratogenic. Table 1.9 Data from UK epilepsy and pregnancy register 2005. Table 1.10 Influence of anti‐epileptic drug treatment on rates of congenital malf... Table 1.11 Special considerations to be made when prescribing in pregnancy. Table 1.12 Drugs safe for breastfeeding mothers. Table 1.13 Commonly used drugs that should be avoided in women who are breastfeed...

2 Chapter 3 Table 3.1 Utility values from selected published studies. Table 3.2 Cost per QALY gained figures from selected published studies (refer... Table 3.3 An example of how QALYs are calculated.

3 Chapter 4 Table 4.1 Examples of different types of drug reaction. Table 4.2 Examples of pharmacokinetic interactions.

4 Chapter 5 Table 5.1 Drugs that may adversely affect gastrointestinal function. Table 5.2 Common drug‐related gastrointestinal symptoms.

5 Chapter 6Table 6.1 Examples of the pharmacological properties and route of elimination...Table 6.2 Classification of anti‐arrhythmic drug actions.Table 6.3 Aetiology/management of heart failure.Table 6.4 Drugs used to treat heart failure.Table 6.5 Indications and contraindications for the major classes of antihype...Table 6.6 Clinical classification of calcium antagonist drugs.Table 6.7 Drugs acting on the renin–angiotensin system.Table 6.8 Angiotensin II (AT 1) receptor antagonists used in hypertension.Table 6.9 Classification and site of action of diuretics.Table 6.10 Summary of the actions of lipid‐lowering drugs.Table 6.11 Clinical conditions in which low‐dose aspirin is of proven benefit...

6 Chapter 7Table 7.1 Inhaled agents used in airways disease.Table 7.2 Main groups of drugs used to treat airflow obstruction.

7 Chapter 8Table 8.1 Therapy for convulsive status epilepticus.Table 8.2 Anti‐epileptic drugs.Table 8.3 Drug‐induced neurological disorders.Table 8.4 Neuroinflammatory disorders.Table 8.5 Symptomatic treatment of chronic neurological disability.Table 8.6 Commonly used antiparkinsonian drug therapy.Table 8.7 Anxiolytic drugs and dose range used.Table 8.8 Benzodiazepine hypnotic drugs.Table 8.9 Drug‐induced psychiatric disorder.