Altered pharmacodynamics in the elderly.

The importance of age-related changes in drug sensitivity is increasingly appreciated. More conclusive evidence is now being presented in combined kinetic and dynamic studies. The type, intensity, and duration of drug action may be affected, ranging from therapeutic failure to major drug toxicity. Alterations in physiologic and homeostatic systems, including the autonomic system, baroreceptors, thermoregulation, and balance, have been described. These may explain the propensity to postural hypotension, falls, hypothermia, and confusion, particularly following drug-induced decrements in these systems. Studies on the sensitivity to individual drugs produce a varied picture emphasizing the danger of generalizations. An increased sensitivity to many agents affecting the central nervous system, including benzodiazepines, halothane, metoclopramide, and narcotic analgesics, is becoming apparent. For the latter this may also be accompanied by an age-associated qualitative difference in toxicity. Whereas there is conclusive evidence of a reduced responsiveness to propranolol, the data are conflicting for calcium antagonists. The increased hypotensive response to ACE inhibitors is more likely due to kinetic factors. The anticoagulant response to warfarin is enhanced. Evidence is also emerging of a wide divergence in the sensitivity of different systems to the same drug--with aging the inotropic effect of theophylline is increased, but the bronchodilator response is decreased. It is becoming clear also that there is a need to separately study certain subgroups of the elderly population.