Procainamide

• Overview:

  • Local anesthetic (procaine) analog

  • Long-term use avoided because of lupus-related side effect

• Metabolism:

  • Elimination: renal excretion & hepatic metabolism; by contrast to procaine, procainamide is highly resistant to hydrolysis by plasma esterases.

  • 40%-60% excreted unchanged (renal)

  • Renal dysfunction requires procainamide dosage reduction

  • Hepatic metabolism -- acetylation

    • cardioactive metabolite: N-acetylprocainamide (NAPA);

    • NAPA accumulation may lead to Torsades de pointes

    • Quinidine and Procainamide similar: electrophysiological properties.

    
    

  • • Possibly somewhat less effective in suppressing automaticity; possibly more effective in sodium channel blockade in depolarized cells

    • Useful in acute management of supraventricular and ventricular arrhythmias.

      • Drug of second choice for management of sustained ventricular arrhythmias (in the acute myocardial infarction setting)

      • Effective in suppression of premature ventricular contractions & paroxysmal ventricular tachycardia rapidly following IV administration

  • Most important difference compared quinidine: procainamide does not exhibit vagolytic (antimuscarinic) activity.

• • • • Procainamide is less likely to produce hypotension, unless following rapid IV infusion

    • Ganglionic-Blocking Activity

• Side Effects/Toxicities

  • Long term use is associated with side effects, including a drug-induced, reversible lupus erythematosus-like syndrome which occurs at a frequency of 25% to 50%.

    • Consists of serositis, arthralgia & arthritis

    • Occasionally: pluritis, pericarditis, parenchymal pulmonary disease

    • Rare: renal lupus

    • Vasculitis not typically present (unlike systemic lupus erythematosus)

    • Positive antinuclear antibody test is common; symptoms disappear upon drug discontinuation

    • In slow acetylators the procainamide-induced lupus syndrome occurs more frequently and earlier in therapy than in rapid acetylators.

  • Nausea, Vomiting -- most common early, noncardiac complication

Hondeghem, L.M. and Roden, D.M., "Agents Used in Cardiac Arrhythmias", in Basic and Clinical Pharmacology, Katzung, B.G., editor, Appleton & Lange, 1998, pp 216-241; Stoelting, R.K., "Cardiac Antidysrhythmic Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 331-343

Category: Pharmacology Notes