Clinical Pharmacology and Therapeutics

October 2020

The following have contributed substantially to the writing, revision and rewriting of the chapters for this tenth edition.

Andrea LlanoNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 1, Pharmacodynamics and pharmacokinetics

Gerard A. McKayNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 1, Pharmacodynamics and pharmacokinetics Chapter 2, Clinical trials and drug development Chapter 10, Drugs and endocrine disease

Alan CameronCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 2, Clinical trials and drug development

Matthew R. WaltersCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 2, Clinical trials and drug development

Ailsa BrownScottish Medicines Consortium, Glasgow, UK Chapter 3, Pharmacoeconomics: the economic evaluation of new drugs

Kenneth PatersonNHS Greater Glasgow and Clyde, Glasgow, UK (formerly) Chapter 3, Pharmacoeconomics: the economic evaluation of new drugs

Neil D. RitchieNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 4, Practical prescribing Chapter 9, Infection

Rosemary HaddockNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 5, Gastrointestinal system

Adrian StanleyNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 5, Gastrointestinal system

Kieran DochertyCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 6, Cardiovascular system

Ninian LangNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 6, Cardiovascular system

Malcolm ShepherdNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 7, Respiratory system

Azmil Abdul‐RahmanCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 8, Nervous system

Jamie HerronCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 8, Nervous system

Sam LeightonCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 8, Nervous system

Jonathan CavanaghCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 8, Nervous system

Celia JacksonNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 9, Infection

Heather BlackNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 9, Infection

Emma JohnsNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 10, Drugs and endocrine disease

Ceilidh GrimshawNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 11, Genitourinary system

Caroline BruceCollege of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK Chapter 12, Malignant disease

Charlie GourleyCollege of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK Chapter 12, Malignant disease

Mark RaffertyNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 13, Drugs and the blood

Hanna JohnssonCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 14, Musculoskeletal system Chapter 15, Immunopharmacology

Iain McInnesCollege of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Chapter 14, Musculoskeletal system Chapter 15, Immunopharmacology

Sharon IrvineRoyal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool, UK Chapter 16, Travel medicine

Malcolm SimNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 17, Analgesia and anaesthesia

Mohammed Al‐HaddadNHS Greater Glasgow and Clyde, Glasgow, UK Chapter 17, Analgesia and anaesthesia

James DearNHS Lothian, Edinburgh, UK Chapter 18, Poisoning and drug overdose

A 50‐year‐old obese man with type 2 diabetes, hypertension and hyperlipidaemia has made arrangements to see his general practitioner to review his medications. He is on three different drugs for his diabetes, four different anti‐hypertensives, a statin for his cholesterol and a dispersible aspirin. These medications have been added over a period of 2 years despite him not having any symptoms and he feels that if anything they are giving him symptoms of fatigue and muscle ache. He has also read recently that aspirin may actually be bad for patients with diabetes. He is keen to know why he is on so many medications, if the way he is feeling is due to the medications and whether they are interfering with the action of each other. What knowledge might help the general practitioner deal with this?

A basic knowledge of the mechanism of action of drugs and how the body deals with drugs allows the clinician to prescribe safely and effectively. Prior to the twentieth century, prescribing medication was based on intelligent observation and folklore with medical practices depending largely on the administration of mixtures of natural plant or animal substances. These preparations contained a number of pharmacologically active agents in variable amounts (e.g. powdered bark from the cinchona tree, now known to contain quinine, being used by natives of Peru to treat ‘fevers’ caused by malaria).

During the last 100 years, an increased understanding has developed of biochemical and pathophysiological factors that influence disease. The chemical synthesis of agents with well‐characterised and specific actions on cellular mechanisms has led to the introduction of many powerful and effective drugs. Additionally, advances in the detection of these compounds in body fluids have facilitated investigation into the relationships between the dosage regimen, the profile of drug concentration against time in body fluids, notably the plasma, and corresponding profiles of clinical effect. Knowledge of this concentration–effect relationship, and the factors that influence drug concentrations, underpin early stages of the drug development process.

The variability in the relationship between dose and response is a measure of the sensitivity of a patient to a drug. This has two components: dose–concentration (pharmacokinetics) and concentration–effect (pharmacodynamics)

Pharmacokinetics describes the processes of drug absorption, distribution, metabolism and excretion

Clinical pharmacology seeks to explore the factors that underlie variability in pharmacodynamics and pharmacokinetics for the optimization of drug therapy in individual patients

More recently, the development of genomics and proteomics has provided additional insights and opportunities for drug development with new and more specific targets. Such knowledge will replace the concept of one drug and/or one dose fitting all.