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Procainamide was introduced in 1951 as a Class 1a antiarrhythmic agent. Class 1a antiarrythmics, the oldest class of antiarrythmics on the market, are considered membrane-stabilizing agents that work by blocking sodium channels. Agents in this class include quinidine, procainamide, and disopyramide. Although these agents are quite effective in suppressing both atrial and ventricular ectopy, they are associated with significant toxicity, and thus, their use has fallen out of favor. Procainamide is indicated for the treatment of life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia.1 Off-label uses of procainamide include conversion of atrial fibrillation/flutter to sinus rhythm.1,2

Procainamide decreases the ability of incompletely repolarized fibers to generate an active response and delays completion of repolarization. These actions increase the effective refractory period of atrial and ventricular fibers, thereby accounting for its antifibrillatory effects.3 Converting from a unidirectional to a bidirectional block, procainamide decreases reentrant arrhythmias. Procainamide has been proven to be safe and effective against ventricular arrhythmias when administered orally and intramuscularly. Historically, the oral formulation was preferred for less urgent arrhythmias and for long-term maintenance after initial parenteral therapy. Intramuscular administration was reserved for patients unable to tolerate the oral formulation secondary to gastrointestinal toxicity (nausea and vomiting). In addition to the intolerable gastrointestinal adverse effects associated with oral procainamide, other extracardiac effects, including central nervous system symptoms (headache, dizziness, psychosis, hallucinations, and depression), fever, agranulocytosis, rash, myalgias, digital vasculitis, Raynaud's phenomenon, and a systemic lupus-like syndrome, have been reported.3 Toxicity associated with oral formulations of procainamide, availability of alternative antiarrhythmic agents, and the lack of necessity of the drug led to the eventual discontinuation of this dosage form in the mid to late 2000s. Parenteral formulations 500 mg/1 ml in a 2 ml vial remain periodically available. Although undesirable infusion rate related cardiovascular side effects associated with the use of intravenous infusions of procainamide have made this mode of administration unpopular, the use of procainamide as an intravenous bolus remains a viable option. Procainamide exerts electrophysiological effects similar to those of quinidine. However, procainamide lacks quinidine's vagolytic and alpha-adrenergic blocking activity, and as a result, is better tolerated when given intravenously.4


Procainamide produces increases in the QTc interval and widening of the QRS complex in a concentration-dependent manner, usually starting at concentrations >12 mg/mL. Procainamide has been associated with life-threatening arrhythmias such as torsades de pointes and has resulted in sudden cardiac death. N-acetylprocainamide (NAPA), the acetyled metabolite of procainamide, which has been shown to have antiarrhythmic actions of its own, prolongs only the QTc interval.4, 5, and 6 Because NAPA has Class III antiarrhythmic properties, it is of clinical importance to use the total concentrations of both procainamide and NAPA to assess pharmacological activity and toxicity; solely reviewing the procainamide level may be misleading.6



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