E: CARDIOPULMONARY MEDICATIONS

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. The word arrhythmia can be defined as a lack of rhythm. Some references state they are synonyms for irregular heartbeat, and others define arrhythmia as irregular heartbeat and dysrhythmia as a disturbance to an otherwise normal rhythm. Throughout the text, we have chosen the term dysrhythmia. 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 because dysrhythmias are among the most common causes of preventable sudden cardiac death.⁵²

For many years, 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 extrasystoles which cause patient discomfort or anxiety. However, this approach changed dramatically following publication of the Cardiac Arrhythmia Suppression Trials (CAST and CAST II)²⁸ and more recently with the rise of mechanical interventions, such as ablation therapy and implantable defibrillators. Cardiac Arrhythmia Suppression Trials assessed the ability of three antidysrhythmics to suppress asymptomatic ventricular dysrhythmias considered 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. The CAST II noted similar problems with moricizine.¹⁰² It is 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. Because most patients with atrial fibrillation do not benefit from rhythm conversion compared with control of the ventricular response rate, the use of antidysrhythmics for this indication is less common but is still useful in some populations.⁹¹

In addition to the predictable, mechanism-based adverse effect of each medication, unique and often unanticipated effects also occur.⁸⁷ 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 (found in Chap. 64), have few other medicinal indications. Chap. 15 provides a more detailed description of the electrophysiology of dysrhythmias and a discussion of their genesis. In addition, the toxicities from β-adrenergic antagonists and Ca²⁺ channel blockers, which have indications in addition to dysrhythmia control, are discussed separately in Chaps. 59 and 60. The toxicology of cardioactive steroids such as digoxin is discussed in Chap. 62.

CLASSIFICATION OF ANTIDYSRHYTHMICS

Despite an incomplete understanding of the underlying mechanisms of dysrhythmia formation, an abundance of antidysrhythmics were developed, each ...