Procainamide

Procainamide therapy is the most frequent cause of drug-induced lupus erythematosus. About 100 cases have so far been reported the largest series, 44 cases, was by Blomgren et al. (1972), but there have been several smaller series (Siegel et al. 1967 Hope and Bates 1972 Swerbrick and Grey 1973 Bareis 1974). 

It is difficult to derive an overall figure for the incidence of procainamide-induced lupus erythematosus, mainly due to the difficulty of accurately diagnosing some of the early clinical signs which often cause the patient to stop taking the drug. But in one series more than 10% of patients taking procainamide developed severe lupus erythematosus and another 10% developed a milder form of the syndrome (Fakhro et al. 1967). In the series by Hope and Bates (1972) 3 out of 61 patients who had taken procainamide for more than 4 weeks were found to have the full lupus syndrome, and another 3 had some features of the condition. 

Drug fever has been reported in about 11 patients but the true incidence is likely to be much higher (Robinson 1978). In a prospective study by Kosowsky et al. (1973) 5 out of the 39 patients who started treatment with procainamide developed a fever after 2-18 days. 

Rashes of various types have been reported associated with procainamide, but two cases worthy of special mention are a case of generalized vasculitis reported by Dolan (1968) and a case of digital vasculitis reported by Rosin (1967) both could indicate some immune complex phenomena. Agranulocytosis developing after 26-78 days of treatment with the drug and not clearly dose-related has been reported in 12 cases (Wang and Schuller 1969 Konttinen and Tuominen 1971 Hickson et al. 1972 Hensen 1974). 

The stability of procainamide in glucose infusions may be improved by the addition of sodium bicarbonate. Patients receiving sodium chloride infusions of procainamide are prone to the risk of heart failure due to sodium load.121122 Quinidine gluconate is incompatible with intravenous infusion sets made of PVC due to drug loss by adsorption.123 

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Procainamide. Procainamide hydrochloride is a ben2amide, synthesized to prolong the therapeutic effects of the local anesthetic procaine [59-46-1] (13) (see Anesthetics). The dmg is effective in a wide range of supraventricular and ventricular arrhythmias (14). 

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). 

About 30% of the patients on chronic procainamide dosing develop a systemic lupusfike syndrome consisting of arthralgia, myalgia, skin rash, and fever. Patients who are slow acetylator phenotypes may be prone to this condition. Some may exhibit pleuropneumonic involvement and hepatomegaly... 

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). 

I a With prolongation of action potential Quinidine, Procainamide, Disopyramide, Ajmaline, Prajmaline... 

Further class IA drugs include the open state blockers procainamide and disopyramide with electrophysiolog-ical effects similar to those of quinidine procainamide lacks the antimuscarinic and antiadrenergic effects. Characteristic side effects of procainamide are hypotension and immunological disorders. 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

The drugp disopyramide, procainamide, and quinidine are examples of class I-A drugs. Quinidine depresses... 

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. 

Propranolol may increase procainamide plasma levels. Additive cholinergic effects may occur when procainamide is administered with other drugp with anticholinergic effects. There is the potential of additive cardiodepressant effects when procainamide is administered with lidocaine. When a beta blocker, such as Inderal, is administered with lidocaine, there is an increased risk of lidocaine toxicity. 

ADM INI STERI NG DISOPYRAMID E Disopyramide is administered to tiie patient with a full glass of water either 1 hour before or 2 hours after meals. If patients are receiving procainamide or quinidine tiie manufacturer suggests that disopyramide therapy not be started for 6 to 12 hours after tiie last dose of quinidine and 3 to 6 hours after tiie last dose of procainamide When tiie patient is to switch from taking tiie regular capsules to taking extended-release capsules, 6 hours should lapse after tiie last capsule before therapy is begun with tiie extended-release capsules. 

ADMINISTERING PROCAINAMIDE Adverse reactions with procainamide therapy include nausea, loss of appetite, and vomiting. Small meals eaten frequently may be better tolerated than three full meals. Administering the drug with meals may decrease gastrointestinal effects. 

Remember that the wax matrix of sustained-release tablets of procainamide (Procan SR only) is not absorbed by the body and may be found in the stool. This is normal. 

There is a risk of acute renal failure when iodi-nated contrast material that is used for radiological studies is administered with metformin. Metformin therapy is stopped for 48 hours before and after radiological studies using iodinated material. Alcohol, amiloride, digoxin, morphine, procainamide, quini-dine, quinine ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, and furosemide all increase the risk of hypoglycemia. There is an increased risk of lactic acidosis when metformin is administered with the glucocorticoids. 

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. 

Butacaine Butethuinine Leucinocaine Methotrexate Procainamide Procaine Reboxetine 2>nitrobenzoyl chloride... 

Podrid PJ, Kowey PR, Frishman WF[, et al. Comparative cost-effectiveness analysis of quinidine, procainamide and mexiletine. Am J Cardiol 1991 68 1662-7. 

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