Drug therapy in the elderly

Drug dosage in the elderly requires an understanding of the age-dependent changes in drug disposition and sensitivity. The most important pharmacokinetic alteration is a decline in renal function, the elderly should therefore be treated as renally insufficient patients. Metabolic clearance is primarily reduced with drugs that display high hepatic extraction, whereas the metabolism of drugs with low hepatic extraction usually is not diminished. The reduction of metabolic clearance is especially pronounced in malnourished or frail patients. The water content of the aging body decreases, the fat content rises. Hence the distribution volume of hydrophilic drugs may be reduced in the elderly, resulting in increased plasma concentrations. In contrast, the distribution volume of liphophilic drugs is increased, their plasma concentrations may decrease. Intestinal absorption of most drugs is not altered in the elderly. Aside of these pharmacokinetic changes, one of the characteristics of old age is a progressive decline in counterregulatory (homeostatic) mechanisms. Therefore, drug effects are attenuated less, the responses are usually stronger than in younger subjects, the rate and intensity of adverse effects are higher. Examples of drug actions augmented is this manner are postural hypotension with agents that lower blood pressure, dehydration and electrolyte disturbances in response to diuretics, bleeding complications with oral anticoagulants, hypoglycemia with antidiabetics, and gastrointestinal irritation with non-steroidal antiinflammatory drugs. The brain is an especially sensitive drug target in old age. Psychotropic drugs, anticonvulsants, and centrally acting anti hypertensives may impede intellectual function and motor coordination. Hence drugs should be used restrictively in geriatric patients. (C) 2004 Elsevier Inc. All rights reserved.