Cognitive toxicity of drugs used in the elderly

Abstract

The aged are an extremely heterogeneous population that is growing worldwide, included are healthy and agile individuals in their early sixties, as well as an increasing number of people over the age of 35. Pharmacotherapy is expected to continue its prominent role in the medical management of a wide range of conditions that affect older people. Adverse consequences of all kinds complicate the use of medications, and such events seem to increase in incidence with polypharmacy. Cognitive impairment can occur during the course of treatment with a wide range of medications and can have a variety of presentations, Both the number of concurrent medications that older individuals routinely use and physiologic changes in these patients render them more susceptible to developing cognitive toxicity. Most of the frequently implicated medications carry documentation of their ability to cause cognitive disturbances in their package labeling, suggesting that the level of vigilance for adverse effects during the course of their use should always be high. Such caution can be used to guide appropriate drug treatment of the aged so that clinicians do not need to opt for undertreatment to avoid toxicity.

Keywords: adverse drug reaction; cognitive toxicity; elderly; risk factor.

Figure 1.. Actual and projected demographic data from the US population' shown as a representative example of cross-national demographic shifts. Ciosed circles connected by solid lines are the actual numbers of individuals aged 65 years or older, with anticipated numbers projected to the year 2030. In parentheses are the numbers expressed as a percentage of the total population. By 2030, it is expected that 70 million Americans will be aged 65 years or older, comprising 20% of the total population. Reproduced from reference 1: Profile of older Americans: 2000. Washington, DC: Administration on Aging. June 2001. www.aoa.dhhs.gov/aoa/stats/profile/. Copyright © 2001, Administration on Aging.

Figure 2.. Consequences of reduced clearance in the elderly. For any given drug, impairment of the capacity for drug elimination (reduced clearance) will cause an elevation in steady-state concentrations (C_ss) with a resulting increase in the likelihood of toxicity. Reduced clearance also may cause a prolongation of elimination half-life, and a consequent delay in the rate of attainment of the steady-state condition. An increase in volume of distribution (V_d) may also contribute to a prolongation of elimination half-life.

Figure 3.. Mean (±SE) plasma chlordiazepoxide concentrations in a series of young and elderly male volunteers who received a single 50-mg intravenous dose of chlordiazepoxide hydrochloride. Note the slower elimination of chlordiazepoxide in the elderly group.

Figure 4.. Mean (±SE) values of chlordiazepoxide elimination half-life (left) and clearance (right) in young and elderly male volunteers as determined in the study described in Figure 3 . The asterisk (*) indicates a statistically significant difference between young and elderly groups.