64: Antidysrhythmics

HISTORY AND EPIDEMIOLOGY

The term dysrhythmia encompasses an array of abnormal cardiac rhythms that range in clinical significance from merely annoying to instantly life threatening. Antidysrhythmics include all medications that are used to treat any of these various dysrhythmias. The importance of dysrhythmia management in the modern practice of medicine cannot be overstated, as dysrhythmias are among the most common causes of preventable sudden cardiac death.⁴²

For a long time antidysrhythmics were considered among the most rational of the available cardiac medications. This well-earned reputation related to their high efficacy at reducing the incidence of malignant dysrhythmias. Similarly, they are effective at controlling discomforting rhythm disorders. However, this approach changed dramatically following publication of the Cardiac Arrhythmia Suppression Trials (CAST and CAST II),²³ and, more recently, with the rise of mechanical interventions, such as ablation therapy and implantable defibrillators. CAST assessed the ability of three antidysrhythmics to suppress asymptomatic ventricular dysrhythmias known to be harbingers of sudden death. The original CAST was discontinued in 1989 before completion, when encainide and flecainide, two of the study medications, not only failed to prevent sudden death but actually increased overall mortality. CAST II noted similar problems with moricizine.⁹² It has since become clear that the enhanced mortality associated with many antidysrhythmics is a result of their prodysrhythmogenic effects and that virtually all medications of this group carry such risk. Since patients with atrial fibrillation do not benefit from rhythm conversion compared to control of the ventricular response rate, the use of antidysrhythmics for this indication is now uncommon.⁸⁰

In addition to the predictable, mechanism-based adverse effect of each medication, unique and often unanticipated effects also occur.⁷⁵ Experience with overdose of many of these medications is limited, and management is generally based on the underlying pharmacologic principles, existing case reports, and the experimental literature. This chapter focuses on the medications that serve primarily as antidysrhythmics and, with the exception of lidocaine (Chap. 67), have few other medicinal indications. Chapter 16 provides a more detailed description of the electrophysiology of dysrhythmias and a discussion of their genesis. In addition, the toxicities from Ca²⁺ channel blockers and β-adrenergic antagonists, which have indications in addition to dysrhythmia control, are discussed separately in Chaps. 61 and 62.

CLASSIFICATION OF ANTIDYSRHYTHMICS

Despite an incomplete understanding of the underlying mechanisms of dysrhythmia formation, an abundance of antidysrhythmics have been developed, each attempting to alter specific electrophysiologic components of the cardiac impulse generating or conducting system.

Antidysrhythmics modify impulse generation and conduction by interacting with various membrane Na⁺, K⁺, and Ca²⁺ channels. Generally, antidysrhythmics manifest electrophysiologic effects either through alteration of the channel pore or, more commonly, by modification of its gating mechanism (Fig. 64–1). Unfortunately, given their exceedingly complex mechanisms of action, the descriptive terms used to explain their ...