Anti arrythmics-MOA

Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.

There are five main classes in the Singh Vaughan Williams classification of antiarrhythmic agents:

-Class I agents interfere with the sodium (Na+) channel.

-Class II agents are anti-sympathetic nervous system agents. Most agents in this class are beta blockers.

-Class III agents affect potassium (K+) efflux.

-Class IV agents affect calcium channels and the AV node.

-Class V agents work by other or unknown mechanisms.

With regards to management of atrial fibrillation, Class I and III are used in rhythm control as medical cardioversion agents whilst Class II and IV are used as rate control agents.

Class I agents are divided into three groups (Ia, Ib and Ic) based upon their effect on the length of the action potential.

Ia lengthens the action potential (right shift)

Ib shortens the action potential (left shift)

Ic does not significantly affect the action potential (no shift)

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. 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).

Drugs include: amiodarone, ibutilide, sotalol, dofetilide, and dronedarone. Inhibiting potassium channels, slowing repolarization, results in slowed atrial-ventricular myocyte repolarization.

Class III agents have the potential to prolong the QT interval of the EKG.

Class IV agents are slow 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 don't fit cleanly into categories I through IV.

Some sources use the term "Class V". However, they are more frequently identified by their precise mechanism.

Agents include:

-Digoxin, which decreases conduction of electrical impulses through the AV node and increases vagal activity via its central action on the central nervous system.

-Adenosine

-Magnesium sulfate, which has been used for torsades de pointes.