Home | | Modern Medical Toxicology | Procainamide - Antiarrhythmic Cardiovascular Poison

Chapter: Modern Medical Toxicology: Cardiovascular Poisons: Diurets, Antihypertensives and Antiarrhythmics

Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail

Procainamide - Antiarrhythmic Cardiovascular Poison

Procainamide is classified as a Vaughn Williams’ Class IA antiarrhythmic agent. In contrast, its active metabolite, N-acetylprocainamide (NAPA; acecainide) has been described as a Class III antiarrhythmic drug.

Procainamide

Procainamide is classified as a Vaughn Williams’ Class IA antiarrhythmic agent. In contrast, its active metabolite, N-acetylprocainamide (NAPA; acecainide) has been described as a Class III antiarrhythmic drug. Procainamide is an antiarrhythmic agent with electrophysiologic properties similar to that of quinidine. Its primary effects on the heart are to decrease electrical impulse conduction velocity through atrial and ventricular tissue manifested by a widened QRS and PR interval in the ECG, and to prolong the effective refractory period. While N-acetylprocainamide retains some of the same clinical effects as procainamide, it has a slightly different electrophysiologic profile. It increases the effective refractory period with a selective lengthening of the action potential by prolonging repolarisation. There is no effect on depolarisation, which is thought to result from its inability to block fast sodium channels and depress phase 4 depolarisation. Thus, the drug has been described as a Class III antiarrhythmic.

Uses

·              To suppress ventricular ectopy.

·              To suppress atrial and ventricular tachyarrhythmias.

Toxicokinetics

Procainamide can be given orally but absorption is often delayed in overdose situations. The apparent volume of distri-bution is 1.7 to 2.22 L/kg. Peak plasma level: 1 to 2 hours; protein binding: 15%. It is metabolised by the liver and under-goes biotransformation by acetylation to N-acetylprocainamide (NAPA) which is pharmacologically active. Excretion occurs in the urine (approximately 40 to 60% procainamide and 84% NAPA are excreted unchanged in the urine). Elimination half-life is approximately 8 hours.

Adverse Effects and Clinical (Toxic) Features

The usual oral adult dose of procainamide is 1 gram initially, followed by 50 mg/kg/day in divided doses every 3 hours. Therapeutic range for procainamide serum levels varies from 6 to 14 mcg/ml (25.5 to 59.5 mmol/L).

Adverse Effects:

·              Nausea, vomiting, diarrhoea, anorexia.

·              Drowsiness, blurred vision, paraesthesias, hallucina-tions. Toxic psychosis has been reported.

·              Proarrhythmic events :  torsade de pointes, ventriculartachycardia, and fibrillation.

·              Skin rash.

·              Thrombocytopenia.

·              Drug-induced systemic lupus erythematosus (SLE), characterised by fever, arthralgias, myalgias, pleural effusion and pain, and serositis.

·              Elevated liver enzyme and serum bilirubin levels have been reported.

Overdose results in arrhythmias (ventricular tachycardia, junctional tachycardia), conduction abnormalities (QRS and QTc prolongation), torsade de pointes, hypotension, mental status depression, seizures, anticholinergic effects, respiratory depression, nausea, vomiting and diarrhoea.

 

Treatment

·      Monitoring drug levels of procainamide and its active metabolite, N-acetyl procainamide, may be helpful in diagnosis of procainamide toxicity.

·      Decontamination : stomach wash and activated charcoal.

·      Elimination enhancement: haemoperfusion, continuousarteriovenous haemofiltration, or continuous arteriovenous haemodiafiltration. Resin haemoperfusion or haemodialysis are the methods of choice for removal of procainamide and N-acetylprocainamide.

·      Continuous ECG monitoring, airway and circulatory support, and IV access.

·      Sodium bicarbonate or sodium lactate may help in reversing the sodium blockade. Cardiac toxicity often responds to intravenous sodium bicarbonate. A reasonable starting dose is 1 to 2 mEq/kg as an intravenous bolus repeated as needed to reverse QRS widening and arrhythmias and maintain an arterial pH of 7.45 to 7.55. Monitor serial ECGs, arterial blood gases and serum potassium.

·      Lignocaine: 1 to 1.5 mg/kg IV push. For refractory VT/VF an additional bolus of 0.5 to 0.75 mg/kg can be given over 3 to 5 minutes. Total dose should not exceed 3 mg/kg or more than 200 to 300 mg during a one hour period. Only bolus therapy is recommended during cardiac arrest. Once circulation has been restored begin maintenance infusion of 1 to 4 mg/min. If arrhythmias recur during infusion, repeat 0.5 mg/kg bolus, and increase the infusion rate incremen-tally (maximal infusion rate is 4 mg/min). For a child: 1 mg/kg initial bolus intravenously; followed by a continuous infusion of 20 to 50 mcg/kg/min.

 

Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail


Copyright © 2018-2020 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.