Pharmacodynamic Effects of R-(-) and S-(+) Tocainide in Patients with Chronic Ventricular Arrhythmias.
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Tocainide is a primary amine analog of lidocaine which, in contrast to lidocaine, can be administered both orally and intravenously. Orally administered tocainide is effective in suppressing both chronic stable ventricular arrhythmias and life treatening ventricular arrhythmias refractory to conventional antiarrhythmic drug therapy. Intravenously administered tocainide has been used successfully in the treatment of ventricular arrhythmias after acute myocardial infarction. Tocainide is a Class 1B antiarrhythmic agent that shortens the action potential duration and the effect refractory periods of the atria, atrioventricular node, and ventricles. It has little effect on sinus nodal automaticity or intracardiac conduction. Although PR and QRS intervals are usually unchanged, tocainide may reduce the QT interval. Cardiac hemodynamic effects are minor, even in patients with moderate left ventricular dysfunction or those also receiving a beta-adrenergic agonist. The chemical structure of tocainide includes an asymmetric center and the drug is used clinically in the racemic form. Although the antiarrhythmic properties of the tocainide enantiomers have not been studied in man, the R-- enantiomer is three times more potent than the S- isomer as an antiarrhythmic agent in a mouse model and smaller differences in antiarrhythmic activity between the enantiomers have been demonstrated in coronary-ligated dogs.
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