Procainamide

Mechanism of Action

Procainamide is a class 1A anti-arrhythmic that binds to fast sodium channels inhibiting recovery after repolarization. It also prolongs the action potential and reduces the speed of impulse conduction. This action results in decreased myocardial excitability, slowed conduction velocity, and reduced myocardial contractility. It is possible that it acts as a negative inotrope and may cause peripheral vasodilation and hypotension, which may require cardioversion.

Administration

Procainamide is given IV or PO with the onset of action in 10 to 30 minutes. The loading dose is of IV procainamide is 10 to 17 mg/kg and administered at a rate of 20 to 50 mg/min. Alternatively, this may be dosed at 100 mg every 5 minutes in adult patients. The administration of this maintenance dose is from 1 to 4 mg/minute; however, the manufacturer labeling recommends 2 to 6 mg/minute.

Administration of oral procainamide dosing for supraventricular arrhythmia is at 50 mg/kg/24 hours divided into doses every 6 hours.

In the pediatric population, dosing divides into those less than 12 months in which a bolus dose of 7 to 10 mg/kg given over 15 to 30 minutes and those older than 12 months in which a bolus dose of 10 to 15 mg/kg is the regimen. An infusion rate of 20 to 50 mcg/kg/min follows the initial bolus.[6]

Procainamide is metabolized hepatically via acetylation to form N-acetyl procainamide (NAPA) via a substrate of CYP2D6. This compound is then excreted as NAPA. The half-life of procainamide is 2.5 to 5 hrs, and the maximum dose in current recommendations is 17 mg/kg. As such, clinicians may consider decreasing the dosing or frequency of procainamide in cases of hepatic impairment.[7]

Adverse Effects

The adverse effects of procainamide include cardiac toxicity, bradycardia, hypotension, drug-induced lupus erythematosus-like syndrome, and blood dyscrasias. QRS, QTc, and PR prolongation are the most potentially harmful cardiac side effects of procainamide and may become worse when levels of procainamide rise. Serial electrocardiograms are useful for monitoring these toxic effects during treatment with procainamide. Procainamide infusion may also increase the number of premature ventricular contractions in patients.

Another side effect of procainamide is hypotension, more commonly seen at doses of 20 mg/min. Drug-induced lupus erythematosus-like syndrome is rare and occurs due to the creation of positive ANA titers when taking the medication chronically. The symptoms of chronic use may include arthritis, arthralgias, and pleuritis and commonly resolve when usage stops.

Lastly, procainamide is known to cause certain blood dyscrasias. Procainamide has been known to cause bone marrow toxicity, leading to pancytopenia or agranulocytosis; this is usually due to hypersensitivity or varied immunologic mechanisms.[8][9]

Contraindications

Use with caution in patients with heart failure, electrolyte imbalances (particularly hypokalemia and hypomagnesemia), myasthenia gravis patients, and in hepatic or renal impairment. Procainamide also crosses the placenta and may be present in the milk of breastfeeding mothers, and as such, chronic use requires caution in this population.[10]

Monitoring

Procainamide monitoring during therapy of an acute arrhythmia should involve monitoring QRS duration via cardiac monitoring, and the clinician should stop therapy QRS increases by 50% of its original width. Also, blood pressure requires frequent monitoring during treatment.

Toxicity

Toxicity from procainamide overdose is rare as it is usually given IV in a monitored setting. However, it is plausible to administer a toxic dose accidentally or when a patient with renal impairment receives an inaccurate dose. Consultation of a medical toxicologist and regional poison control center is necessary in cases of oral procainamide overdose. Treatment would theoretically be similar to an overdose of other Class 1A antiarrhythmics, including quinidine and disopyramide, in which the patient receives hypertonic sodium bicarbonate to block sodium channels.[11]

Enhancing Healthcare Team Outcomes

There have been several high-quality studies as well as recommendations from the American Heart Association in utilizing procainamide as a viable option to terminate several different arrhythmias. However, procainamide should be used carefully in inpatient settings as it has several side effects that require monitoring. An interprofessional team that includes the treating physician, nurse, and pharmacist can help achieve the best possible outcomes. Care requires coordination between all interprofessional healthcare team members to ensure that everyone involved in the patient's care takes appropriate measures during therapy with procainamide. Cardiovascular monitoring, serial electrocardiograms, and frequent reassessments of the patient’s clinical status will ensure safety during usage. Instruction should be given for possible cardioversion if hypotension, bradycardia, or clinical deterioration occurs.[12] [Level 1]

The coordinated efforts of an interprofessional team will optimize therapeutic results with procainamide while minimizing adverse events. [Level 5]