Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.
Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean differences between age groups reflect the change over time. This is a potentially invalid assumption due to various factors, such as difficulties differentiating chronological age from biological age and selective mortality effects in study cohorts.
The limitations of cross-sectional studies highlight the need for longitudinal pharmacodynamic studies that measure individual rates of aging for specific variables, which are currently rare.
However, changes in pharmacodynamics due to aging alter drug responses. Studies have shown a greater sensitivity to the clinical action of benzodiazepines in older individuals, not attributable to differences in plasma concentrations or drug properties. The exact mechanisms behind this increased sensitivity remain unknown.
Aging is also associated with reduced pharmacodynamic sensitivity to ꞵ-adrenergic drugs, potentially due to impaired signal transduction of ꞵ-receptors and age-associated decreases in Gs activity.
Older patients also exhibit a greater inhibition of synthesis of vitamin K-dependent clotting factors at similar plasma warfarin concentrations compared to younger patients, making age a strong predictor of the anticoagulant effects of warfarin.
Age-related pharmacodynamic changes are less understood due to challenges in measuring drug responses.
Cross-sectional studies providing data on age-related pharmacodynamic differences assume that the average differences between age groups reflect the changes individuals undergo as they age.
Notably, these assumptions may not accurately reflect changes over time due to difficulties in distinguishing between certain parameters.
However, changes in pharmacodynamics due to aging can alter drug responses.
For instance, benzodiazepines show increased sensitivity in older adults. Some cause stronger cognitive and sedative effects, even with unchanged drug levels in the body.
Also, warfarin shows greater inhibition of the synthesis of vitamin K-dependent clotting factors in older patients compared to younger ones at similar plasma concentrations.
Additionally, ꞵ-adrenergic receptor sensitivity declines with age, affecting drug responses.
Factors include impaired signal transduction, downregulation of ꞵ-adrenergic receptors, and decreased activity of Gs proteins. These factors necessitate drug dosage adjustments, with appropriate safety evaluation.
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