Plotting the logarithm of drug dose against drug response typically produces a sigmoidal dose–response curve (Fig. 1). Progressive increases in drug dose (which, for most drugs, is proportional to the plasma drug concentration) produce increasing response, but only within a relatively narrow range of dose; further increases in dose beyond this range produce little extra effect. The following characteristics of the drug response are useful in comparing different drugs:

- Efficacy describes the extent to which a drug can produce a target-specific response when all available receptors or binding sites are occupied (i.e. Emax on the dose–response curve). A full agonist can produce the maximum response of which the receptor is capable, while a partial agonist at the same receptor will have lower efficacy. Therapeutic efficacy describes the effect of the drug on a desired biological endpoint and can be used to compare drugs that act via different pharmacological mechanisms (e.g. loop diuretics induce a greater diuresis than thiazide diuretics and so have greater therapeutic efficacy).

- Potency describes the amount of drug required for a given response. More potent drugs produce biological effects at lower doses, so they have a lower ED₅₀ . A less potent drug can still have an equivalent or greater efficacy if it is given in higher doses.

Fig1. Dose–response curve. The green curve represents the beneficial effect of the drug. The maximum response on the curve is the E_max  and the dose (or concentration) producing half this value (E_max /2) is the ED₅₀  (or EC₅₀) . The red curve illustrates the dose–response relationship for the most important adverse effect of this drug. This occurs at much higher doses; the ratio between the ED₅₀  for the adverse effect and that for the beneficial effect is the ‘therapeutic index’, which indicates how much margin there is for prescribers when choosing a dose that will provide beneficial effects without also causing this adverse effect. Adverse effects that occur at doses above the therapeutic range are normally called ‘toxic effects’, while those occurring within the therapeutic range are ‘side-effects’ and those below it are ‘hyper-susceptibility effects’.

The dose–response relationship for a specific drug varies between patients because of variations in the many determinants of pharmacokinetics and pharmacodynamics. In clinical practice, the prescriber is unable to construct a dose–response curve for each individual patient. Therefore, most drugs are licensed for use within a recommended range of doses that is expected to reach close to the top of the dose–response curve for most patients. However, it is sometimes possible to achieve the desired therapeutic efficacy at doses towards the lower end of, or even below, the recommended range.

 Therapeutic index

The adverse effects of drugs are often dose-related in a similar way to the beneficial effects, although the dose–response curve for these adverse effects is normally shifted to the right (see Fig. 1). The ratio of the ED₅₀ for therapeutic efficacy and for a major adverse effect is known as the ‘therapeutic index’. In reality, drugs have multiple potential adverse effects, but the concept of therapeutic index is usually based on adverse effects that might require dose reduction or discontinuation. For most drugs, the therapeutic index is greater than 100, but there are some notable exceptions with therapeutic indices of less than 10 (e.g. digoxin, warfarin, insulin, phenytoin, opioids). The doses of such drugs have to be titrated carefully for individual patients to maximise benefits, but avoid adverse effects.

مواضيع ذات صلة

Drug elimination

Drug distribution

السلفوناميدات

Antibiotic Resistance

البنسيلينات Penicillins

المضادات الحيوية المثبطة لصناعة الجدار الخلوي

Aminoglycosides and spectinomycin

β-lactam antibiotics

مضادّات الببتيد الدهنية وغليكو ببتيد الدهنية الحيوية

التجميع الإنزيمي للبتيد السباعي للفانكوميسين وكلوروإرموميسين (chloroermomycin)

تعديلات السلسلة الجانبية في مضادّات الكيفالوسبورين: أجيال متعددة

Drug targets and mechanisms of action