Aging and susceptibility to drug-induced orthostatic hypotension

OBJECTIVE: To test the hypothesis that the short-term effect of transbuccal nitroglycerin (glyceryl trinitrate, 0.0625 to 1.5 mg) on orthostatic cardiovascular responses would predict the effect of a diuretic (5 mg bendroflumethiazide daily for 1 week), particularly in elderly subjects who may be at higher risk for orthostatic hypotension. METHODS: This was a randomized crossover study. Participants were 17 elderly (age range, 63 to 84 years) and 15 younger (age range, 19 to 35 years) healthy ambulant volunteers. Interventions and measures of outcome included blood pressure (BP; in millimeters of mercury) and heart rate (HR; in beats per minute) changes with standing, which were measured before administration of medication and after each drug treatment. RESULTS: Subjects in the elderly and younger groups had different BP and HR changes (mean percentage change) at 1 minute after standing in all three study phases (unmedicated, elderly: BP, -4%/+1%; HR, +12%; young: BP, +2%/+12%; HR, +27%; p = 0.06 for BP, p less than 0.01 for HR; bendroflumethiazide, elderly: BP, -9%/-3%; HR, +17%; young: BP, +1%/+11%; HR, +33%; p less than 0.05 for all; nitroglycerin (0.25 mg), elderly: BP, -15%/-12%; HR, +21%; young: BP, -6%/+7%; HR, +38%; p less than 0.05 for all). The incremental orthostatic effects of the two drugs were similar in the two age groups and were positively correlated (r = 0.65, p less than 0.001) in individual subjects. CONCLUSIONS: Individual susceptibility to drug-induced orthostatic hypotension depends on a combination of the age-related unmedicated orthostatic response and the additional drug effect, which is independent of age. The BP response to standing after administration of nitroglycerin may be useful in predicting the effect of other drugs known to influence orthostatic BP control.