Antiarrhythmics procainamide

ACE INHIBITORS ANTIARRHYTHMICS -PROCAINAMIDE Possible t risk of leukopenia Uncertain at present Monitor FBC before starting treatment, 2-weekly for 3 months after initiation of therapy, then periodically thereafter... 

MUSCLE RELAXANTS -DEPOLARIZING ANTIARRHYTHMICS -PROCAINAMIDE Possibility of t neuromuscular blockade Uncertain procainamide may 1 plasma cholinesterase levels Be aware of the possibility of a prolonged effect of suxamethonium when it is administered to patients taking procainamide... 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

Lldoc ine. Lidocaine hydrochloride, an anilide, was originally introduced as a local anesthetic in 1943 and found to be a potent antiarrhythmic in 1960. The compound is a reverse amide of procainamide. Lidocaine is generally considered to be the dmg of choice in the treatment of ventricular arrhythmias and those originating from digitalis glycoside toxicity (1,2,15—17). 

Fleca.inide, Elecainide acetate, a fluorobenzamide, is a derivative of procainamide, and has been reported to be efficacious in suppressing both supraventricular and ventricular arrhythmias (26—29). The dmg is generally reserved for patients with serious and life-threatening ventricular arrhythmias. Elecainide depresses phase 0 depolarization of the action potential, slows conduction throughout the heart, and significantly prolongs repolarization (30). The latter effect indicates flecainide may possess some Class III antiarrhythmic-type properties (31). 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

When two antiarrhythmic dragp are administered concurrently the patient may experience additive effects and is at increased risk for drug toxicity. When quinidine and procainamide are administered with digitalis, tiie risk of digitalis toxicity is increased. Hiarmacologic effects of procainamide may be increased when procainamide is administered with quinidine When quinidine is administered with the barbiturates or cimetidine, quinidine serum levels may be increased. When quinidine is administered with verapamil, there is an increased risk of hypotensive effects. When quinidine is administered with disopyramide, there is an increased risk of increased disopyramide blood levels and/or decreased serum quinidine levels. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

Patients with mild or no symptoms can be treated initially with antiarrhythmic drugs. IV amiodarone is now recommended as first-line therapy in this situation. Procainamide or lidocaine given IV is a suitable alternative. Synchronized DCC should be delivered if the patient s status deteriorates, VT degenerates to VF, or drug therapy fails. 

Antiarrhythmics representative of these categories include Class lA— quinidine, procainamide, ajmaline, dis-opyramide, propafenone Class IB—lido-caine, mexiletine, tocainide, as well as phenytoin Qass 1C—flecainide. 

The applicability of these results to other populations (eg, those without recent Mis) is uncertain. Considering the known proarrhythmic properties of procainamide and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of procainamide and other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias. 

Terminate IV therapy if persistent conduction disturbances or hypotension develop. As soon as the patient s basic cardiac rhythm appears to be stabilized, oral antiarrhythmic maintenance therapy is preferable (if indicated and possible). A period of approximately 3 to 4 hours (one half-life for renal elimination, ordinarily) should elapse after the last IV dose before administering the first dose of oral procainamide. 

Pharmacology Procainamide, a class lA antiarrhythmic, increases the effective refractory period of the atria, and to a lesser extent the bundle of His-Purkinje system and ventricles of the heart. 

Concurrent antiarrhythmic agents Concurrent antiarrhythmic agents may produce enhanced prolongation of conduction or depression of contractility and hypotension, especially in patients with cardiac decompensation. Reserve concurrent use of procainamide with other Class lA antiarrhythmic agents (eg, quinidine, disopyramide) for patients with serious arrhythmias unresponsive to a single drug and use only if close observation is possible. 

Drugs that may affect procainamide include amiodarone, anticholinergics, antiarrhythmics, beta-blockers, ethanol, histamine H2antagonists, propranolol,... 

Transferring to mexiletine When transferring from other Class I oral antiarrhythmics to mexiletine, based on theoretical considerations, initiate with a 200 mg dose, and titrate to response as described above, 6 to 12 hours after the last dose of quinidine sulfate, 3 to 6 hours after the last dose of procainamide, 6 to 12 hours after the last disopyramide dose or 8 to 12 hours after the last tocainide dose. 

Congenital or acquired QTprolongation Patients with congenital QT prolongation and those taking Class lA (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmic medications should avoid using vardenafil. 

Drugs that may be affected by fluoroquinolones include caffeine, cyclosporine, digoxin, antiarrhythmic agents, bepridil, erythromycin, phenothiazine, tricyclic antidepressants, procainamide, anticoagulants, and theophylline. 

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