Drug Pharmacology and Aging

Drugs often have more pronounced effects in older patients. The cause can be either pharmacodynamic, in which case the target organ (often the brain) is more sensitive to a given drug tissue level, or pharmacokinetic, in which case a given dose of drug commonly produces higher blood levels in older patients.
Typically, the initial blood concentration of bolus drugs is higher in older patients, partly because of a mildly contracted blood volume. Despite the typically enhanced effect of bolus drugs on older patients, there is a general impression that bolus drugs take longer to achieve that greater effect. (The reasons are unclear.)
The most prominent pharmacokinetic effect of aging is a decrease in drug metabolism because of both a decrease in clearance and an increase in Vd_ss (increase in body fat). In addition, elderly patients often take a host of chronic medications, a setup for drug interactions as well as for inhibition of drug metabolism.
1. Drugs with primarily renal elimination experience decreased metabolism because of reductions in GFR with aging. The net effect on drug metabolism is typically a doubling of the elimination half-life between old and young adults. In the case of diazepam, the half-life in hours is roughly equal to the patient's age.
2. The concept of the context-sensitive half-time (time necessary for a 50% [or any desired percent] decrease in plasma concentration after termination of an infusion) is often increased in elderly patients.