Antiarrhythmic Drugs

Introduction

Overview

• The current status of antiarrhythmic therapy is well summarized by the following excerpt taken from the introductory chapter of a recent symposium proceedings on antiarrhythmic therapy
  

  • "Therapeutic approaches to cardiac arrhythmias continue to change rapidly, as indicated by the recent acceptance of a number of revolutionary concepts. These include (1) the recognition that time-honored antiarrhythmic drugs that act essentially by slowing cardiac conduction (class I agents) may increase mortality despite suppressing cardiac arrhythmias. The result has been a shift to agents that act largely by prolonging cardiac repolarization (class III agents); (2) the realization that radiofrequency catheter ablation may produce permanent cures in many forms of arrhythmia, especially those of supraventricular origin; and (3) the introduction and refinement of the implantable cardioverter-defibrillator (ICD), which has the potential for prolonging survival by terminating ventricular tachycardia and fibrillation (VT/VF)."

History

• Although several of the drugs used to treat cardiac arrhythmias have been used for many years (e.g.- quinidine and digitalis since the early 1900s), most of the agents approved for use today have only been available for a decade or less.

• Research in recent years has provided much information regarding the cellular mechanisms of arrhythmias and the mechanisms by which some of the antiarrhythmic drugs act, but the general approach to antiarrhythmic therapy remains largely empirical.

• The recent results of several clinical trials, including the Cardiac Arrhythmia Suppression Trial (CAST), have indicated that many antiarrhythmic drugs may significantly increase mortality compared to placebo.

Background

• All of the antiarrhythmic drugs act by altering ion fluxes within excitable tissues in the myocardium.

• The three ions of primary importance are Na⁺, Ca⁺⁺, and K⁺. Antiarrhythmic drugs can be classified by their ability to directly or indirectly block flux of one or more of these ions across the membranes of excitable cardiac muscle cells.

Category: Pharmacology Notes