Class IA antiarrhythmics

Besides the class I-typical proarrhythmic risk class IA antiarrhythmics possess a marked proarrhythmic risk for the induction of torsade depointes arrhythmia (life-threatening polymorphic ventricular tachycardia observed with most action potential prolonging drugs). 

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. 

S.Y. Kim, and N.L. Benowitz, Poisoning due to class IA antiarrhythmic drugs quini-dine, procainamide and disopyramide. Drug Safety 5 393-420, 1990. 

Class IA antiarrhythmic agents qunidine procainamide (Procan, Procanbid) disopyramide (Norpace)... 

The Vaughan-Williams classification of antiarrhythmic drugs has been criticized for a number of reasons. The classification is based on the effects of drugs on normal, rather than diseased, myocardium. In addition, many of the drugs may be placed into more than one class. For example, the class IA drugs prolong repolarization/refractoriness, either via the parent drug8,9 or an active metabolite,10 and therefore also maybe placed in class III. Sotalol is also a 3-blocker, and therefore fits into class II. Amiodarone inhibits sodium and potassium channels, is a non-competitive inhibitor of 3-receptors, and inhibits calcium... 

UTI, acute exacerbation of chronic bronchitis prophylaxis in transurethral procedures Action Quinolone antibiotic 4- DNA gyrase. Dose 400 mg/d PO w/ renal insuff, avoid antacids Caution [C, -] Interactions w/ cation-containing products Contra Quinolone allergy, children <18 y,T QT interval, i K+ Disp Tabs SE N/V/D, abd pain, photosens, Szs, HA, dizziness, tendon rupture, peripheral neuropathy, pseudomembranous colitis, anaphylaxis Interactions T Effects W/ cimetidine, probenecid T effects OF cyclosporine, warfarin, caffeine i- effects W/ antacids EMS Monitor ECG for TQT interval, esp in pts taking class IA/m antiarrhythmics monitor ECG and BP for signs of hypovolemia and electrolyte disturbances (hypokalemia) d/t D T risk of photosensitivity Rxns OD May cause N/V/D, confusion and Szs symptomatic and supportive... 

Mechanism of action. Na -channel blocking antiarrhythmics resemble most local anesthetics in being cationic amphiphilic molecules (p.206 exception phenytoin, p.191). Possible molecular mechanisms of their inhibitory effects are outlined on p.202 in more detail. Their low structural specificity is reflected by a low selectivity toward different cation channels. Besides the Na channel. Carotid 1C channels are also likely to be blocked. Accordingly, cationic amphiphilic antiarrhythmics affect both the depolarization and repolarization phases. Depending on the substance, AP duration can be increased (Class IA), decreased (Class IB), or remain the same (Class IC). Antiarrhythmics representative of these categories include Class IA—quinidine, procainamide, ajmaline, disopyramide Class IB—lidocaine, mexile-tine, tocainide Class IC—flecainide, propafenone. 

A familial condition associated with increased risk of ventricular arrhythmias may result from mutation in the gene encoding cardiac potassium channels. Class IA and class HI antiarrhythmic drugs may increase the risk of torsades in such patients. 

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