Mark W Bowie1, Patricia W Slattum. 1. Department of Pharmacy, University of Virginia Medical Center, Charlottesville, Virginia 23298-0533, USA.
Abstract
BACKGROUND: Older individuals experience physiologic changes in organ function related to aging or to specific disease processes. These changes can affect drug pharmacodynamics in older adults. OBJECTIVE: The goal of this article was to review age-related changes in pharmacodynamics and their clinical relevance. METHODS: PubMed and International Pharmaceutical Abstracts were searched (January 1980-June 2006) for the following combination of terms: pharmacodynamic and elderly, geriatric or aged. References cited in other reviews were also evaluated. The current review focused on age-related pharmacodynamic changes in agents affecting the central nervous system (CNS), cardiovascular, and endocrine functions. RESULTS: Older adults frequently demonstrate an exaggerated response to CNS-active drugs. This is in part due to an underlying age-related decline in CNS function and in part due to increased pharmacodynamic sensitivity for some benzodiazepines, anesthetics, and opioids. The most important pharmacodynamic differences with age for cardiovascular agents are the decrease in effect for beta-adrenergic agents. This decline in response in vascular, cardiac, and pulmonary tissue may be due to a decrease in Gs protein interactions. Most studies indicate there is no decrease in cx-receptor sensitivity with age. Angiotensin-converting enzyme inhibitors do not show age-related differences in elderly patients. With the dihydropyridine calcium channel blockers, there was a slight increase in effect for older adults, but this was only for treatment-naive patients and was transient. Nondihydropyridines did not show an age- associated change in pharmacodynamic effect; however, in the elderly, there appeared to be a decrease in the PR interval prolongation normally seen with these agents. Studies of diuretics indicated that the changes in diuretic and natriuretic effects seen in the elderly were associated with pharmacokinetic changes and were not pharmacodynamic in nature. There was a lack of consistent evidence regarding whether sulfonylureas show age-related changes in pharmacodynamic effect. CONCLUSIONS: There is a general trend of greater pharmacodynamic sensitivity in the elderly; however, this is not universal, and these age-related changes must be investigated agent-by-agent until further research yields greater understanding of the molecular mechanisms underlying the aging process.
BACKGROUND: Older individuals experience physiologic changes in organ function related to aging or to specific disease processes. These changes can affect drug pharmacodynamics in older adults. OBJECTIVE: The goal of this article was to review age-related changes in pharmacodynamics and their clinical relevance. METHODS: PubMed and International Pharmaceutical Abstracts were searched (January 1980-June 2006) for the following combination of terms: pharmacodynamic and elderly, geriatric or aged. References cited in other reviews were also evaluated. The current review focused on age-related pharmacodynamic changes in agents affecting the central nervous system (CNS), cardiovascular, and endocrine functions. RESULTS: Older adults frequently demonstrate an exaggerated response to CNS-active drugs. This is in part due to an underlying age-related decline in CNS function and in part due to increased pharmacodynamic sensitivity for some benzodiazepines, anesthetics, and opioids. The most important pharmacodynamic differences with age for cardiovascular agents are the decrease in effect for beta-adrenergic agents. This decline in response in vascular, cardiac, and pulmonary tissue may be due to a decrease in Gs protein interactions. Most studies indicate there is no decrease in cx-receptor sensitivity with age. Angiotensin-converting enzyme inhibitors do not show age-related differences in elderly patients. With the dihydropyridine calcium channel blockers, there was a slight increase in effect for older adults, but this was only for treatment-naive patients and was transient. Nondihydropyridines did not show an age- associated change in pharmacodynamic effect; however, in the elderly, there appeared to be a decrease in the PR interval prolongation normally seen with these agents. Studies of diuretics indicated that the changes in diuretic and natriuretic effects seen in the elderly were associated with pharmacokinetic changes and were not pharmacodynamic in nature. There was a lack of consistent evidence regarding whether sulfonylureas show age-related changes in pharmacodynamic effect. CONCLUSIONS: There is a general trend of greater pharmacodynamic sensitivity in the elderly; however, this is not universal, and these age-related changes must be investigated agent-by-agent until further research yields greater understanding of the molecular mechanisms underlying the aging process.
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