Physiological changes due to age. Pharmacodynamic changes of drug action and implications for therapy.

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The elderly respond differently to drugs than do younger people. Their physiological response is much more variable, and predictability of drug action is much less certain. When all non-pharmacological factors and age-associated pharmacokinetics are taken into account, there is still no full explanation of the potentially altered drug action and increased drug toxicity observed in the elderly. It is only relatively recently that age-associated physiological changes (primary age changes), their interplay with age-associated pathophysiological changes (secondary age changes) and environmental changes (tertiary age changes) have been studied with regard to the effect of those changes on the pharmacodynamics of drug action. In general, age-associated pharmacodynamic changes, i.e. changes in the type, intensity and duration of drug action, have been associated with changes in receptor function (e.g. altered receptor number and affinity, altered second messenger function, altered cell response), changes in the homeostatic mechanisms, and reduced reserve capacity. It is important to realise that these changes, which can differ greatly among patients, may be responsible for an increased incidence of adverse drug reactions and therapeutic failure. They may also mandate a higher dose in some circumstances, as some organs become less responsive to drug action with age.