Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten

Abstract

The existence of cardiac h1- and h2-receptors is evidenced by pharmacologic studies. Despite of the relatively high content of cardiac histamine it is not clarified whether histamine actually plays a physiologic role - apart from pharmacologic effects - in the regulation of myocardial function and coronary blood flow. Under pathophysiologic conditions (during anaphylaxis, surgical procedures, accidents, stress etc.), however, when a local or systemic histamine release occurs both hemodynamic and arrhythmogenic effects are evident. Numerous studies in animal models conclusively demonstrated a role of cardiac histamine as a major mediator of serious arrhythmias. Consequently, a combination of h1- and h2-receptor antagonists (f.e. Dimetinden/Cimetidin) was recommended as a prophylactic treatment against severe anaphylaxis including life-threatening arrhythmias for cardiac patients at risk. There is pharmacologic evidence of both a positive inotropic and chronotropic effect in the human heart via h2-receptor and stimulation of adenylate cyclase. Histamine-induced coronary effects such as vasoconstriction via h1-receptor and coronary dilatation via h2-receptor are not yet sufficiently validated. Studies on the human heart in vitro using coronary strips from explanted hearts and in vivo investigations on the intact coronary system yielded conflicting results. H2-receptor blocking agents cimetidine, ranitidine and famotidine have qualitatively a different pharmocodynamic spectrum of side effects due to differences in chemical structure. Data on cardiac arrhythmias are mostly associated to cimetidine. Symptomatic bradycardia were reported for both ranitidine and cimetidine. A possible negative inotropic effect of famotidine, although presently not validated, requires further studies. Causative and adverse side effects of cimetidine on the cardiovascular system, however, are to be expected extremely seldom due to easily reversible competetive h2-receptor binding. For prophylaxis rapid intravenous injections of h2-blockers, particularly in elder patients with cardiac diseases, should be avoided. Compared to cimetidine, a tendency of explainable difference seems to become apparent for ranitidine and famotidine due to higher receptor affinity.

An Extremely Rare Side Effect of Ranitidine: Junctional Rhythm

“…[3][4][5][6] The underlying mechanism involves the action on the H2 receptors at the sinus node and atrial tissue in the heart. 7,8 Through these receptors, they exert positive chronotropic and inotropic effects on the heart.…”

Synthesis and Dual Histamine H1 and H2 Receptor Antagonist Activity of Cyanoguanidine Derivatives

“…Cardiac arrhythmias induced by activation of H 1 and H 2 receptors are among the most serious consequences of mast cell degranulation. Several studies have shown the effectiveness of a premedication with a combination of H 1 R and H 2 R antagonists, for example dimetindene plus cimetidine [10,17,18,19,20].…”