Pharmacology of acute effort angina

Abstract

From the pharmacologic point of view, each of the major types of antianginal agents--calcium antagonists, beta-blockers, and nitrates--seem to act at least in part by an improvement of the myocardial blood supply. The recently elucidated mechanism of action of nitrates, acting on a common pathway with the endothelium-derived relaxation factor (EDRF), suggests an important role for guanylate cyclase and cyclic GMP in maintaining coronary artery patency in patients with coronary atheroma. The efficacy of calcium antagonists, even in effort-induced angina, is in accord with a current hypothesis that physical exercise in the presence of coronary stenosis can cause relative coronary vasoconstriction, or at the least, failure of full dilation. Therefore, calcium antagonists all act, at least in part, on the "supply" side of the supply-demand equation. Beta-adrenergic blockers appear to have as their major mode of action a reduction of heart rate, which not only reduces the oxygen demand but, through an anti-ischemic effect, also appears to improve the endocardial blood supply (in relation to the heart rate). Thus beta-blockade indirectly enhances the supply side of the equation. The intriguing situation arises whereby all three major types of antianginal compounds may also act by a common mechanism of anginal relief, namely, improvement in the coronary blood supply, in addition to the diverse mechanisms specific to each type of compound. That conclusion does not mean the the "demand" side of the equation can be ignored. Rather, the critical importance of a reduced myocardial blood supply in the production of anginal syndromes is highlighted.

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

“…Accordingly, agents that reduce HR without affecting ventricular contractility are of major clinical interest for the treatment of ischemic heart disease and heart failure. 3 HR reduction can be achieved with β-adrenoceptor antagonists or rate-limiting calcium channel blockers; however, these agents may exert concomitant negative inotropic and hypotensive effects, 4 potentially exacerbating myocardial ischemia.…”

Electrophysiological effects of S 16257, a novel sino‐atrial node modulator, on rabbit and guinea‐pig cardiac preparations: comparison with UL‐FS 49

“…As heart rate is one of the major determinants of myocardial oxygen consumption (Laurent et al, 1956;Sonnenblick et al, 1968), agents able to reduce sinus heart rate are of major interest for the treatment of ischaemic heart diseases. This can be achieved with P-adrenoceptor antagonists or some calcium channel blockers; however, these agents may exert concomitant negative inotropic and hypotensive effects (Opie, 1989; Kern et al, 1989), potentially deleterious during ischaemia. Recently the pharmacological properties of a novel class of substances, specific bradycardic agents (SBAs), have been described (Kobinger & Lillie, 1987).…”

Effects of the two enantiomers, S‐16257‐2 and S‐16260‐2, of a new bradycardic agent on guinea‐pig isolated cardiac preparations

“…Bradycardic agents, i.e. fi-adrenoceptor blocking agents and calcium channel blockers are frequently used in the treatment of effort-induced angina pectoris (Cruickshank & Prichard, 1987;Opie, 1989). However, these drugs also exhibit negative inotropic and hypotensive effects which may antagonize the beneficial effects of the bradycardia on myocardial blood flow by unmasking a-adrenoceptor vasoconstrictor mechanisms or increasing the extracellular component of coronary resistance (via an increase in left ventricular end-diastolic pressure) and reducing coronary artery perfusion pressure, respectively.…”