Mechanism of Action
The drug exerts electrophysiological effects on the heart similar to quinidine. The primary mechanism involves blocking sodium ($Na^+$) and potassium ($K^+$) channels, which prevents cell membrane depolarization. This leads to the prolongation of phase 0 (depolarization), phase 3 (repolarization), and phase 4 of the action potential. Procainamide also possesses moderate ganglion-blocking activity.
Pharmacological Effects and Differences from Quinidine
Compared to quinidine, procainamide has important differences:
- Lesser depression of myocardial contractility (less pronounced negative inotropic effect).
- Less pronounced anticholinergic (vagolytic) properties.
- Complete absence of $\beta$-blocking activity.
Procainamide can concentrate in saliva at levels exceeding plasma concentrations (the saliva-to-plasma ratio is 3.5), allowing for non-invasive monitoring.
Indications
Indications for use are identical to quinidine:
- Ventricular and supraventricular tachyarrhythmias;
- Extrasystoles.
Dosing regimen: Administered orally in doses ranging from 0.25 to 1.0 g (maximum daily dose is 4.0 g). Administered intravenously as an IV push of 0.1 g; for repeated administrations, the cumulative maximum daily dose is 1.0 g.
Side Effects
Main side effects include:
- Hemodynamic: marked decrease in blood pressure (hypotension) due to ganglion-blocking activity.
- Cardiac: impaired myocardial conduction.
- Extracardiac: gastrointestinal disturbances (nausea, vomiting, diarrhea) and neurological disorders (up to seizures).
Genetic polymorphism plays a major role: the presence of "slow" and "fast" acetylators determines the rate of hepatic metabolism. In patients with an N-acetyltransferase deficiency ("slow acetylator" phenotype, found in up to 50% of the Caucasian population), the risk of adverse reactions increases sharply. In renal failure, there is a high risk of active metabolite (N-acetylprocainamide) accumulation.
Metabolism and Excretion
Procainamide undergoes hepatic metabolism involving amidase enzymes (hydrolysis of the amide bond). This produces the active metabolite — N-acetylprocainamide (NAPA), which is excreted by the kidneys more slowly than the parent compound. The drug is also excreted by salivary glands via passive diffusion.