Pharmacodynamic basis for altered drug action in the elderly.

The elderly have the highest incidence of medical and psychiatric disorders. These conditions frequently occur simultaneously and are often chronic, lasting the lifetime of the individual. Consequently, the elderly require more medications than do younger patients. Consumption of over-the-counter drugs is considerable among the aged. There is considerable evidence that the elderly patient in most cases responds differently to drugs than do young adults. Many factors contribute to these differences. Among them are reduced protein binding, reduced biotransformation, diminished renal elimination, changes in receptor density or affinity, or both, diminished receptor adaptability, changes in the coupling between receptors and effector systems, impairment of responding organs resulting from the pathologic state, reduction in the reactivity of homeostatic mechanisms, and the aging process itself. These components may have different weight, depending on the drug and the individual considered. Because of the physiologic age-related changes in the distribution and elimination of drugs and in the sensitivity to medications, adverse side effects develop frequently in the elderly. Accordingly, dosages and dosage intervals must be adjusted carefully. In addition, since the elderly often take multiple medications, they frequently experience ADRs. Psychotropic drugs are often involved in such interactions and cause twice the incidence of side effects in elderly patients as they do in younger patients. Drug-nutrient and drug-drug interactions, programs to enhance patient compliance, and sociogenic factors should be taken into account in any well-designed dose regimen for the elderly. Physician awareness of problems that exist in the elderly population's use of drugs is essential if rational drug therapy for the aged is to evolve. The proper use of drugs in the elderly largely depends on taking into account both the pharmacokinetic and the pharmacodynamic properties of the drug and how these parameters are altered with age; such information can be obtained only by investigating drug action in older people.