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Dose–response relationships may be steep or flat. A steep relationship implies that small changes in dose will produce large changes in clinical response or adverse effects, while flat relationships imply that increasing the dose will offer little clinical advantage (Figure 1.1).

In clinical practice, the maximum therapeutic effect may often be unobtainable because of the appearance of adverse or unwanted effects: few, if any, drugs cause a single pharmacological effect.

The concentration–adverse response relationship is often different in shape and position to that of the concentration–therapeutic response relationship. The difference between the concentration that produces the desired effect and the concentration that causes adverse effects is called the therapeutic index and is a measure of the selectivity of a drug (Figure 1.2).

The shape and position of dose–response curves for a group of patients is variable because of genetic, environmental and disease factors. However, this variability is not solely an expression of differences in response to drugs. It has two important components: the dose–plasma concentration relationship and the plasma concentration–effect relationship.

With the development of specific and sensitive chemical assays for drugs in body fluids, it has been possible to characterise dose–plasma concentration relationships so that this component of the variability in response can be taken into account when drugs are prescribed for patients with various disease states. For drugs with a narrow therapeutic index, it may be necessary to measure plasma concentrations to assess the relationship between dose and concentration in individual patients (see Section ‘Therapeutic drug monitoring’ later).

Figure 1.1 Schematic examples of a drug (a) with a steep dose– (or concentration–) response relationship in the therapeutic range, e.g. warfarin an oral anticoagulant; and (b) a flat dose– (or concentration–) response relationship within the therapeutic range, e.g. thiazide diuretics in hypertension.

Figure 1.2 Schematic diagram of the dose–response relationship for the desired effect (dose–therapeutic response) and for an undesired adverse effect. The therapeutic index is the extent of displacement of the two curves within the normal dose range.