Procainamide (Pronestyl, Procan SR) is a derivative of the local anesthetic agent procaine. Procainamide has a longer half-life, does not cause CNS toxicity at thera-peutic plasma concentrations, and is effective orally. Procainamide is a particularly useful antiarrhythmic drug, effective in the treatment of supraventricular, ven-tricular, and digitalis-induced arrhythmias.
Table 16.2 describes the direct, indirect, and net actions of procainamide on cardiac electrophysiology.
The hemodynamic alterations produced by pro-cainamide are similar to those of quinidine but are not as intense. Alterations in circulatory dynamics vary ac-cording to the cardiovascular state of the individual. The hypotensive effects of procainamide are less pro-nounced after intramuscular administration and seldom occur after oral administration.
The pharmacokinetic characteristics of procainamide:
Oral bioavailability : 75–95%
Onset of action : 5–10 minutes
Peak response : 60–90 minutes
Duration of action : 4–10 hours
Plasma half-life : 2.5–4.5 hours
Primary route of metabolism: Hepatic; active metabolite
Primary route of excretion: 50–60% renal (unchanged)
Therapeutic serum concentration: 4–10 μg /mL
Procainamide is an effective antiarrhythmic agent when given in sufficient doses at relatively short (3–4 hours) dosage intervals. Procainamide is useful in the treatment of premature atrial contractions, paroxysmal atrial tachy-cardia, and atrial fibrillation of recent onset. Procainamide is only moderately effective in converting atrial flutter or chronic atrial fibrillation to sinus rhythm, although it has value in preventing recurrences of these arrhythmias once they have been terminated by direct current (DC) cardioversion.
Procainamide can decrease the occurrence of all types of active ventricular dysrhythmias in patients with acute myocardial infarction who are free from A-V dis-sociation, serious ventricular failure, and cardiogenic shock. About 90% of patients with ventricular prema-ture contractions and 80% of patients with ventricular tachycardia respond to procainamide administration.
Although the spectrum of action and electrophysio-logical effects of quinidine and procainamide are simi-lar, the relatively short duration of action of pro-cainamide has tended to restrict its use to patients who are intolerant of or unresponsive to quinidine.
Acute cardiovascular reactions to procainamide admin-istration include hypotension, A-V block, intraventricu-lar block, ventricular tachyarrhythmias, and complete heart block. The drug dosage must be reduced or even stopped if severe depression of conduction (severe pro-longation of the QRS interval) or repolarization (severe prolongation of the QT interval) occurs.
Long-term drug use leads to increased antinuclear antibody titers in more than 80% of patients; more than 30% of patients receiving long-term procainamide ther-apy develop a clinical lupus erythematosus–like syn-drome. The symptoms may disappear within a few days of cessation of procainamide therapy, although the tests for antinuclear factor and lupus erythematosus cells may remain positive for several months.
Procainamide, unlike procaine, has little potential to produce CNS toxicity. Rarely, patients may be confused or have hallucinations.
Contraindications to procainamide are similar to those for quinidine. Because of its effects on A-V nodal and His-Purkinje conduction, procainamide should be ad-ministered with caution to patients with second-degree A-V block and bundle branch block. Procainamide should not be administered to patients who have shown procaine or procainamide hypersensitivity and should be used with caution in patients with bronchial asthma. Prolonged administration should be accompanied by hematological studies, since agranulocytosis may occur.
The inherent anticholinergic properties of procainamide may interfere with the therapeutic effect of cholinergic agents. Patients receiving cimetidine and procainamide may exhibit signs of procainamide toxicity, as cimetidine inhibits the metabolism of procainamide. Simultaneous use of alcohol will increase the hepatic clearance of pro-cainamide. Procainamide may enhance or prolong the neuromuscular blocking activity of the aminoglycosides with the potential of producing respiratory depression. The simultaneous administration of quinidine or amio-darone may increase the plasma concentration of pro-cainamide.