Defi ne antiarrhythmic drugs and their utility • Categorize antiarrhythmics based on the mode of action • Describe the synthesis, mode of action, and dose administered from each class of anti-arrhythmicsAntiarrhythmic Drugs17.1 INTRODUCTIONAntiarrhythmic drugs are medicines that correct irregular heartbeats and slow down hearts that beat too fast. The heart is a muscle that works like a pump. It is divided into four chambers, two atria at the top of the heart and two ventricles at the bottom. The heart beats (contracts) when an electrical impulse from the heart’s ‘natural pacemaker”—the sinoatrial (SA) node—moves through it. The normal sequence begins in the right atrium, spreads throughout the atria, and to the atrioventricular (AV) node. From the AV node, the impulse travels down a group of specialized fi bres (His—Purkinje system) to all parts of the ventricles. This exact route must be followed for the heart to pump properly. As long as electric impulse is transmitted normally, the heart pumps and beats at a regular pace. A normal heart beats 60–100 times a minute. The term arrhythmia refers to any change from the normal sequence of electrical impulses, causing abnormal heart rhythm. This can cause the heart to pump less effectively. The rhythm of heart contractions depends on many parameters: condition of pacemaker cells and the conduction system, myocardial blood fl ow, and other factors; consequently, arrhythmia can originate for different reasons that are caused by disruptions in electrical impulse generation or conduction. They can be caused by heart disease, myocardial ischemia, electrolytic and acid–base changes, heart innerva-tions problems, intoxication of the organism, and soon.
Some arrhythmias are life-threatening medical emergencies that can result in cardiac arrest and sud-den death. Others cause aggravating symptoms such as an abnormal awareness of heart beat (palpi-tations), and may be merely annoying. Others may not be associated with any symptoms at all, but predispose towards potentially life-threatening stroke or embolus. Drugs used for treating arrhythmia can have an effect on the electrical conduction system of the heart, its excitability, automatism, the size of the effective refrac-tory period, and adrenergic and cholinergic heart inner-vations. Accordingly, compounds of various chemical classes can restore heart-rate disturbances. As already noted, arrhythmia originates from problems forming electric impulses and propagating them to the heart, or when both of these happen simultaneously, which can be accomplished by transferring Na + , K + , and Ca 2+ ions through cell membranes. Therefore, the mechanism of action of many antiarrhythmic drugs consists of block-ing Na + and Ca + ion channels of the myocardium, which prolongs the time necessary for restoration after being activated by these channels, and which in turn acts on the electrical conduction system of the heart, its excitability, automatism, and so on.17.2 CLASSIFICATION Antiarrhythmic drugs are classifi ed according to their electrophysiological properties. 1. Class I agents : A. Class IA: Quinidine, Procainamide, Disopyramide, Cifenline B. Class IB: Lidocaine, Phenytoin, Tocainide, Mexiletine C. Class IC: Encainide, Flecainide, Propafenone 2. Class II agents : β-adrenoreceptor antagonists 3. Class III agents : Amiodarone, Bretylium, Acecainide 17.2.1 Class I AgentsMechanism of action: Drugs belonging to this group form complexes with lipoproteins of cell mem-branes of the myocardia, thus blocking Na + channel conductivity and the fl ow of Na + into the cell, and facilitate the release of K + from myocardial cells, which as a result leads to a weak suppression of depo-larization of myocardial cells, reduction of repolarization time, and a slowing of the propagation of excitation. • Drugs such as encainide, fl ecainide, and propafenone in class IC slowly dissociate from the Na + channel, causing slowing down of the conduction time of the impulse through the heart.