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Heart rhythm medication

Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a class of drugs that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia. Many attempts have been made to classify antiarrhythmic agents. Many of the antiarrhythmic agents have multiple modes of action, which makes any classification imprecise.

The cardiac myocyte has two general types of action potentials: conduction system and working myocardium. The action potential is divided into 5 phases and shown in the diagram. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium channel inactivation and the repolarizing efflux of potassium ions. The characteristic plateau ("2") results from the opening of voltage sensitive calcium channels. Each phase utilizes different channels and it is useful to compare these phases to the most common classification system — Vaughan Williams — described below.

Class II agents are conventional beta blockers. They act by blocking the effects of catecholamines at the β1 adrenergic receptors, thereby decreasing sympathetic activity on the heart, which reduces intracellular cAMP levels and hence reduces Ca2+ influx. These agents are particularly useful in the treatment of supraventricular tachycardias. They decrease conduction through the AV node. Class II agents include atenolol, esmolol, propranolol, and metoprolol.

Class III agents predominantly block the potassium channels, thereby prolonging repolarization. Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re entrant arrhythmias. (The re entrant rhythm is less likely to interact with tissue that has become refractory). The class III agents exhibit reverse use dependence (their potency increases with slower heart rates, and therefore improves maintenance of sinus rhythm). Inhibiting potassium channels results in slowed atrial ventricular myocyte repolarization. Class III agents have the potential to prolong the QT interval of the EKG, and may be proarrhythmic (more associated with development of polymorphic VT). Class III agents include: bretylium, amiodarone, ibutilide, sotalol, dofetilide, vernakalant, and dronedarone.

Class IV agents are slow non dihydropyridine calcium channel blockers. They decrease conduction through the AV node, and shorten phase two (the plateau) of the cardiac action potential. They thus reduce the contractility of the heart, so may be inappropriate in heart failure. However, in contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility. Class IV agents include verapamil and diltiazem.

Since the development of the original Vaughan Williams classification system, additional agents have been used that do not fit cleanly into categories I through IV. Such agents include:
Adenosine is used intravenously for terminating supraventricular tachycardias. Digoxin decreases conduction of electrical impulses through the AV node and increases vagal activity via its action on the central nervous system. Via indirect action, it leads to an increase in acetylcholine production, stimulating M2 receptors on AV node leading to an overall decrease in speed of conduction. Magnesium sulfate is an antiarrhythmic drug, but only used against very specific arrhythmias such as torsades de pointes.

The initial classification system had 4 classes, although their definitions different from the modern classification. Those proposed in 1970 were: but was supported by experimental data presented by Vaughan Williams (1970). The figure illustrating these findings was also published in the same year by Singh and Vaughan Williams. Drugs acting like diphenylhydantoin (DPH): mechanism of action unknown, but others had attributed its cardiac action to an indirect action on the brain; this drug is better known as antiepileptic drug phenytoin.

Another approach, known as the "Sicilian gambit", placed a greater approach on the underlying mechanism. It presents the drugs on two axes, instead of one, and is presented in tabular form. On the Y axis, each drug is listed, in roughly the Singh Vaughan Williams order. On the X axis, the channels, receptors, pumps, and clinical effects are listed for each drug, with the results listed in a grid. It is, therefore, not a true classification in that it does not aggregate drugs into categories.