Clinical pharmacology, the basics

Clinical Pharmacology: The Basics
D Nicholas Bateman is Reader in Clinical Pharmacology and Consultant Physician at
the Royal Infirmary, Edinburgh, UK, and Director of the Scottish Poisons Information
Bureau. He qualified from Guy’s Hospital, London, and trained at the Royal
Postgraduate Medical School, London and in Newcastle upon Tyne. His research
interests are pharmaco-epidemiology, clinical toxicology and poisons information
systems.

James S McLay is Senior Lecturer in the Department of Medicine and Therapeutics at
the University of Aberdeen, UK. His research interests include the immunological and
growth regulatory functions of the natriuretic peptides and receptors.
Clinical pharmacology encompasses an understanding of how drugs work and their
appropriate use in humans.
Pharmacodynamics
The measurement of the effects of drugs on humans (or, in basic pharmacology,
an organ system) is termed ‘pharmacodynamics’. This term encompasses both
mechanism of action and end-point (e.g. heart rate, blood pressure).
Receptors
The actions of most drugs are mediated by the binding and interaction of drug
molecules with specific molecular substances or macromolecules located on the
cell surface; these are termed ‘receptors’. Some receptor sites are intracellular (e.g.
steroid). The drug–receptor interaction leads to a molecular change in the receptor,
which triggers a chain of events leading to a response. Receptors tend to be highly
specific, interacting with a limited number of structurally related molecules. For some
drugs, the receptor is nonspecific in terms of cell function (e.g. an alkalating agent that
cross-binds molecules within DNA).
Agonists and antagonists
Agonists are drugs that activate a receptor response. Antagonists are drugs that block
receptor response. Examples of such receptor systems include:
• adrenergic (agonist – salbutamol, antagonist – atenolol)
• dopaminergic (agonist – dopamine, antagonist – haloperidol)
• cholinergic (agonist – bethanecol, antagonist – atropine).
Potency
The magnitude of the effect following a drug–receptor interaction usually depends on
the dose of drug given; this relationship is commonly expressed in the form of a dose–
response curve. Onset of response occurs at a threshold dose. For different drugs with
similar actions, use of a dose–response curve allows comparison of:
• potency (the amount of drug necessary to achieve a certain effect
• ED50 (the dose that produces a 50% response, see below)
• efficacy (the maximum possible effect of a drug).
The relative potency of different drugs may be assessed using ED50. Potency has little
clinical relevance, however, because a drug that is more potent than another may also
produce more dose-related adverse effects.
Therapeutic index
The therapeutic index (therapeutic ratio) is the ratio between the toxic dose and the
therapeutic dose of a drug. The closer this ratio is to 1, the more difficult the drug is
to use in clinical practice. The therapeutic index for digoxin, for example, is very low,
whereas that for amoxicillin is extremely high.
Medical use of drugs with a narrow therapeutic index has lead to the concept of
therapeutic drug monitoring, in which the plasma concentration of drug is measured
and the dose adjusted to achieve a desired therapeutic drug concentration (see below).
LD