β-Adrenergic Blockers as Antiarrhythmic and Antifibrillatory Compounds: An Overview

Abstract

Beta-Adrenergic blockers have a wide spectrum of action for controlling cardiac arrhythmias that is larger than initially thought. Data from the past several decades indicate that, as an antiarrhythmic class, beta-blockers remain among the very few pharmacologic agents that reduce the incidence of sudden cardiac death, prolong survival, and ameliorate symptoms caused by arrhythmias in patients with cardiac disease. As a class of compounds, beta-blockers have a fundamental pharmacologic property that attenuates the effects of competitive adrenergic receptors. However, the net clinical effects of the different beta-receptor blockers may vary quantitatively because of variations in associated intrinsic sympathomimetic agonism and in their intrinsic potency for binding to beta-receptors. These individual compounds also differ in their selectivity for beta(1)- and beta(2)-receptors. Metoprolol is a beta(1)-selective blocker, whereas carvedilol is a nonselective beta(1)- and beta(2)-blocker, an antioxidant, and has a propensity to inhibit alpha(1)-receptors and endothelin. Evolving data from controlled and uncontrolled clinical trials suggest that there are clinically significant differences among this class of drugs. Recent evidence also suggests that the antiarrhythmic actions of certain beta-receptor blockers such as carvedilol and metoprolol extend beyond the ventricular tissue to encompass atrial cells and help maintain sinus rhythm in patients with atrial fibrillation, especially in combination with potent antifibrillatory agents such as amiodarone. This introduction provides a current perspective on these newer developments in the understanding of the antiarrhythmic and antifibrillatory actions of beta-blockers.

Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart

“…[10][11][12][13][14][15] Data from the past several decades indicate that β-AR blockers remain among the very few pharmacologic agents that reduce the incidence of sudden cardiac death and arrhythmias in patients with cardiac diseases. 44 Our findings may support the hypothesis of the anti-arrhythmic effects of β-AR blockers, possibly through the suppression of non-GJ substrates. This hypothesis is under investigation.…”

Adrenergic control of a constitutively active acetylcholine-regulated potassium current in canine atrial cardiomyocytes

“…The present observations point to the potential role of constitutive acetylcholineregulated current as a mediator of adrenergic effects on atrial APD and arrhythmias. β-Adrenoceptor blocking drugs can prevent AF [47]. β-Adrenergic modulation of constitutive acetylcholine-regulated K + current may contribute to this action.…”

Influence of Plasma Protein Binding on Pharmacodynamics: Estimation of In Vivo Receptor Affinities of β Blockers Using a New Mechanism-Based PK–PD Modelling Approach

“…The b-blockers S(À)-atenolol, S(À)-metoprolol, S(À)-propranolol and timolol were selected as model drugs since they vary widely in plasma protein binding, ranging from almost no plasma protein binding for atenolol ($3%) to high plasma protein binding for propranolol ($95%), and furthermore differ widely in affinity for the b-adrenoceptor (mM-nM), and in lipophilicity. [10][11][12][13] Another advantage is the readily available PD endpoint (i.e., heart rate under isoprenaline-induced tachycardia) in both humans and animals. 14 In the current study, mechanism-based PD modelling was used for the analysis of the interaction between isoprenaline and the individual b-blockers.…”