Calcium antagonists in geriatric patients: Diltiazem in elderly persons with hypertension

Abstract

Pharmacodynamics and disposition of diltiazem were determined in twelve young (30 to 39 years of age) and twelve elderly (65 to 83 years of age) persons with hypertension after they had received diltiaz,em by rapid intravenous and long-term oral administration. Plasma disappearance half-life of diltiazem increased similarly and significantly in both groups with long-term dosing (young: rapid intravenous, 3.7 ± 0.8 hour; long-term oral, 6.3 ± 1 hour [mean ± SE]; elderly: rapid intravenous, 3.8 ± 0.7 hour; long-term oral, 7.2 ± 2.1 hour; p < 0.01). During long-term therapy both systolic and diastolic blood pressure was significantly lowered from baseline beyond a 12-hour dose interval, with greater decreases in systolic blood pressure in the elderly. Heart rate was decreased with long-term therapy in both groups. Maximal prolongation of PR interval was greater in the young after the intravenous dose (young: 46 ± 28 msec; elderly: 24 ± 11 msec; p < .01), but this effect was not seen with long-term therapy. These data demonstrate that diltiazem administered every 12 hours is an effective antihypertensive agent in both young and elderly patients. (CLIN PHARMACOL THER 1989;45:682-91.) Blood pressure rises with increasing age, and a majority of persons over 65 years of age can be considered hypertensive, depending on the populations examined and the criteria used.' Treatment of the elderly person with hypertension is complicated by concurrent chronic disease states, frequent drug interactions and adverse effects, difficulty in compliance with therapy, and the predominance of systolic hypertension. It has been suggested that calcium entry blockers are particularly beneficial for selected patient populations, such as elderly and black persons with hypertension.' These agents lower peripheral vascular resistance by direct arterial vasodilation, but without reflex sympathetic discharge and activation of the renin-angiotensin-aldosterone axis From the Section

Hemodynamic, Inotropic and Dromotropic Effects of Calcium Antagonists at Rest and during Exercise in Healthy Subjects

“…Diltiazem induced no significant orthostatic reactions, which is in conformity with a recent report on both young and elderly hypertensive patients [17]. Nifedipine gave a marked increase in heart rate and virtually no increase in systolic blood pressure.…”

A comparative study of the steady-state pharmacokinetics of immediate-release and controlled-release diltiazem tablets

“…These interindividual differences could be due to intersubject differences in the disposition and absolute systemic availability of diltiazem. Since the reported intersubject variation in the half-life of intravenous diltiazem is considerably smaller (Montamat et al 1989) than the variation observed here, the interindividual differences in steady-state plasma concentrations we observed probably resulted from variations in both elimination and first-pass metabolism.…”

Drug-Drug Interactions via Mechanism-Based Cytochrome P450 Inactivation: Points to Consider for Risk Assessment from In Vitro Data and Clinical Pharmacologic Evaluation

“…Therefore, the demonstration of mechanism-based CYP3A inactivation by nefazodone [111] coupled with knowledge of a major role for this enzyme in the biotransformation of nefazodone provide insight into the biochemical mechanisms of the nonlinear pharmacokinetics of this drug. Examples of other drugs that display nonstationary pharmacokinetics via autoinactivation of metabolic clearance include the SSRI antidepressant paroxetine [113], a substrate and inactivator of CYP2D6; the macrolide antibiotics erythromycin [114] and clarithromycin [115], and the calcium channel antagonists diltiazem [116] and verapamil [117] which are metabolized by and inactivate CYP3A; and the non-selective CYP substrate and inactivator ticlopidine [118].…”