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Dose response effects of diltiazem on treadmill tolerance in chronic stable angina: a randomized double-blind,
Insights
Diltiazem significantly improves exercise tolerance in patients with stable angina. This calcium channel blocker increases the time to angina onset and maximal exercise duration for up to 8 hours post-dose.
Area of Science:
- Cardiology
- Pharmacology
- Exercise Physiology
Background:
- Stable angina pectoris is a common cardiovascular condition characterized by chest pain during exertion.
- Calcium channel blockers, such as diltiazem, are frequently used to manage angina symptoms.
- Understanding the dose-response relationship and pharmacokinetic profile of diltiazem is crucial for optimizing anti-anginal therapy.
Purpose of the Study:
- To evaluate the effects of a single oral dose of diltiazem on exercise tolerance in patients with stable angina.
- To determine the dose-dependent efficacy and time course of action of diltiazem.
- To correlate plasma diltiazem levels with improvements in exercise capacity.
Main Methods:
- Sixteen patients with stable angina performed treadmill exercise tests.
- Tests were conducted at baseline and at 1, 2, 4, and 8 hours after administration of placebo or single oral doses of diltiazem (30 mg, 60 mg, or 90 mg).
- Exercise parameters, including time to angina onset, ST depression, and maximal exercise, were recorded. Plasma diltiazem levels were also measured.
Main Results:
- Diltiazem significantly prolonged exercise time to angina onset and maximal exercise duration, with effects peaking at 4 hours and lasting up to 8 hours post-dose.
- The 90 mg dose of diltiazem showed a statistically significant increase in the pressure-rate product at angina compared to placebo.
- While mean plasma diltiazem levels correlated with increased exercise tolerance, individual patient correlations were poor.
Conclusions:
- Single oral doses of diltiazem effectively improve exercise tolerance in patients with stable angina.
- The anti-anginal effects are dose-dependent and exhibit a sustained duration of action.
- Pharmacokinetic-pharmacodynamic relationships require further investigation for personalized diltiazem therapy.
Abstract:
Sixteen patients with stable angina underwent treadmill exercise on 4 separate days prior to and at 1, 2, 4 and 8 hours following a single dose of 30 mg, 60 mg or 90 mg of diltiazem or identical placebo. Prolongation of exercise time to the onset of angina, 0.1 mV ST depression and to maximal exercise developed within 2 hours, peaked at 4 hours and persisted for 8 hours. Time to angina at control with placebo and 90 mg of diltiazem was 399 +/- 176 and 368 +/- 193 seconds respectively (X +/- SD) and 4 hours post drug was 474 +/- 216 and 635 +/- 209 seconds respectively (p less than 0.001). The pressure-rate product at angina 4 hours following 90 mg of drug was higher than after placebo (189 +/- 48 and 168 +/- 44 mmHg-1 X 10(-2) respectively). Heart rate increased (127 +/- 24 vs. 117 +/- 19 bpm) while systolic pressure was unchanged (147 +/- 17 and 142 +/- 21 mmHg). During submaximal exercise at a fixed work load, diltiazem, 90 mg, decreased heart rate from 114 +/- 14 to 97 +/- 18 bpm (p less than 0.005), systolic blood pressure from 148 +/- 19 to 135 +/- 18 mmHg (p less than 0.005) and rate-pressure product from 169 +/- 37 to 131 +/- 36 mmHg-1 X 10(-2) (p less than 0.005). Peak diltiazem plasma levels occurred at 4 hours, being 37 +/- 34, 74 +/- 67 and 106 +/- 68 ng/ml for 30, 60 and 90 mg respectively. Drug levels paralleled increased exercise tolerance when mean data were considered; however, correlation on an individual basis was poor.(ABSTRACT TRUNCATED AT 250 WORDS)