The antianginal effects ofbeta-adrenoceptor antagonists are achieved by a reduction in myocardial oxygen demand. This is a rational approach to treatment in patients whose angina is caused by a fixed stenosis. However, dynamic coronary vasospasm is an important factor in patients with chronic stable angina. Nifedipine increases myocardial oxygen supply by reducing coronary vascular tone and is a logical approach to treatment in these patients. For monotherapy of angina, nifedipine is less effective than the beta-adrenoceptor antagonists, but the combination has additive effects in reducing the frequency of anginal episodes and improving exercise tolerance.
Plasma concentrations of nifedipine are closely related to clinical efficacy, and the variable first-pass metabolism of the drug leads to wide interindividual differences in peak concentrations and duration of action. Increasing the size of individual doses of nifedipine carries a risk of enhanced side effects due to high peak plasma concentrations. Optimal treatment may be more appropriately achieved in some patients by a slow release formulation, but with an increased frequency of administration.
KEY WORDS. beta-adreneceptor antagonist, nifedipine, angina pectoris
Considerable advances have been made in the pharmacologic management of angina pectoris during the last 20 years. Improved understanding of the pathophysiological mechanisms that produce myocardial ischemia has led to a more rational and effective approach to treatment. Beta-adrenoceptor antagonists are well established for the prophylactic management of chronic stable angina pectoris [1-3], but even with optimal doses some patients will require additional treatment to achieve adequate control of symptoms. Slow-channel calcium blockers are increasingly used in this situation as an alternative to long-acting nitrates. The calcium antagonists are a heterogenous group of compounds, and of these the dihydropyridine derivatives, such as nifedipine, have properties that make them particularly suitable for combination with betaadrenoceptor antagonists. Increasing numbers of dihydropyridine derivatives are now undergoing investigation, and it is therefore opportune to review their efficacy in this situation.