MEDICINAL CHEMISTRY

6. Anti-arrhythmic Agents
Introduction
Certain disease and the effect of some drugs are usually responsible affecting the rhythm
and the normal heart rate. These cardiac arrhythmia may be caused from disorders in the
normal mechanical activity of the heart depends upon a specific sequence of electrical
activation for all myocardial cells during each beat, beginning first at the SA node and
ending with depolarization of the ventricle. Thus arrhythmia may arise due to alteration
in, Conduction Automaticity Refractory period of the myocardial cells.
Antiarrhythmic drugs may be defined as drugs that are capable of reverting any
irregular cardiac rhythm or rate to normal. Antiarrhythmic agents are also termed as
antidysrhythmic drugs or antifibrillatory drugs. The 'ideal' antiarrhythmic drug should
have the following properties:
(i) High efficiency in controlling symptoms and improving survival in both
supraventricular and ventricular arrhythmias.
(ii) No negative effect.
(iii) Favourable effect on myocardial oxygen consumption.
(iv) Both oral and intravenous activity.
(v) Wide therapeutic range.
Classification of Antiarrhythmic drugs
Vaughan Williams & Singh gave four class systems for Antiarrhythmic agents and
further proposed modified sub-grouping of class I drug was done by D.C. Harrison.
Class I: Membrane stabilizing agents (Na + channel blockers). These classes of
drugs are found to interfere directly with depolarization of the cardiac membrane.
Class IA: Prolongs action potential duration e.g. Quinidine, Procainamide,
Disopyramide and moricizine.
Class IB: Shortens action potential duration e.g. Lidocaine, Phenytoin, Tocainide
and Mexiletine.
Class IC: Have no effect on action potential duration (i.e., slow phase O
depolarization), e.g. Encainide, Flecainide, Indecainide and propaferone.
Class II: β- adrenergic Blockers e.g. Propranolol, Metoprolol
Class III: Drugs that prolongs the action potential duration. e.g. Amiodaron,
Bretylium tosylate.
Class IV: Calcium Channel Blockers e.g Verapamil, Diltiazem, Nifedipine
Class I Antiarrhythmic Drugs: Class I drugs are generally local anesthetics acting on
nerve and myocardial membranes to slow conduction by inhibiting phase 0 of the action
potential. Myocardial membranes show the greatest sensitivity. Class I drugs decrease
the maximal rate of depolarization without changing the resting potential. They also
increase the threshold of excitability; increase the effective refractory period, decrease