Of all prescription medications, about 30% are taken by the elderly even though they comprise only 14% of the population. Nonprescription medications, which often are used as much as or more than prescription medications, also are disproportionately consumed by older individuals.

The gastrointestinal absorption of medications generally does not change with advancing age, despite the theoretical possibility that medications requiring acidification in the stomach may be absorbed less well because of the higher frequency of atrophic gastritis and reduced gastric acid. Drug distribution changes significantly with advancing age because medications distribute to fat or muscle. As muscle mass declines with advancing age, fat increases as a proportion of total body weight. As a result, older individuals are more sensitive to the effects of water-soluble drugs and have prolonged effects from lipophilic drugs.

The decline in renal function with normal aging reduces the clearance of many drugs, especially digoxin, aminoglycosides, and cimetidine. Hepatic metabolism also may decline with age. Oxidative reactions, so-called phase 1 reactions, become impaired with normal aging, whereas phase 2 reactions (conjugation and glucuronidization) are relatively spared. A clinical example is that diazepam, which requires phase 1 and phase 2 metabolism, has a prolonged half-life with advancing age, but oxazepam, which requires only phase 2 reactions to be metabolized, does not.

The overall impact of these pharmacokinetic changes is that the half-life, which is proportional to the volume of distribution divided by drug clearance, increases for many lipophilic drugs. Poorly nourished or frail elderly persons may have a low serum albumin level. The normal age-related decline in the serum albumin level is clinically insignificant. When the albumin level is less than 3 g/dL, however, drug levels have to be interpreted based on their binding to albumin.

The elderly are more sensitive to many medications after they are absorbed. The brain appears to be increasingly sensitive to many compounds, including opiates, benzodiazapines, and neuroleptics. As a result, lower doses create equivalent effects to higher doses in younger individuals. Warfarin, which acts primarily on the liver, should be used at lower doses in the elderly to maintain normal anticoagulation profiles because the aging liver is increasingly sensitive to blockage of vitamin K-dependent systems.

The elderly are at higher risk for nonadherence to prescribed regimens. Factors influencing nonadherence include the cost of medications, inadequate patient education about their medications, unacceptable side effects, and the complexity of the medical regimen. Individuals who take more than three prescription drugs have lower compliance.

Perhaps the most important phenomenon in multiple drug regimens in older individuals is the progressive accumulation of anticholinergic effects, including dry mouth, constipation, poor vision, urinary retention, balance disorders, and cognitive difficulties. Drug classes include neuroleptics, antispasmodics, antianxiety agents, antihistamines, and medications used for urinary incontinence.