Age-related changes in the pharmacodynamics of intravenous glyceryl-trinitrate.

Comparable hemodynamic effects were obtained administering a much lower intravenous dose of glyceryl trinitrate (GTN) in elderly than in younger patients. The pharmacodynamics and kinetics of GTN were thus assessed in 2 groups of patients with acute myocardial infarction (group A: ≤ 65 years, 6 patients; group B: ≥ 75 years, 6 patients). The arterial and venous dose-concentration relationship and the associated hemodynamic changes at end-point (EP: 10% reduction in mean systemic arterial pressure) were similar in the 2 groups. However, in older subjects EP was reached at a lower GTN infusion rate (0.11±0.04 vs 0.33±0.11 μg·kg-1·min-1, mean ±S.D.; p<0.001), and with lower arterial and venous drug concentrations (arterial [GTN]: 1.2±0.1 vs 4.6±1.2 ng·ml-1; p<0.01; venous [GTN]: 0.09±0.05 vs 0.35±0.15 ng·ml-1; p<0.05), whereas overall GTN kinetics appeared to be substantially independent of age. Thus, the enhanced efficacy of GTN in advanced age seems to stem mainly from pharmacodynamic changes, which may be the consequence of dampened baroreceptor reflexes, as suggested by a lower heart rate increase per unitary fall in systolic arterial pressure observed in group B (0.12±0.07 vs 0.41±0.29 b·min-1·mmHg-1; p<0.05).