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.
Many attempts have been made to classify antiarrhythmic agents. The problem arises from the fact that many of the antiarrhythmic agents have multiple modes of action, making any classification imprecise.
Singh Vaughan Williams classification
The Singh Vaughan Williams classification was introduced in 1970. As a doctoral candidate at Oxford University working in the lab of Vaughan Williams, Dr. Bramah Singh determined that amiodarone and sotalol had antiarrhythmic properties and belonged to a new class of antiarrhythmic agents (what would become the class III antiarrhythmic agents). See Singh BN, Vaughan Williams EM (1970). "The effect of amiodarone, a new anti-anginal drug, on cardiac muscle". Br. J. Pharmacol. 39 (4): 657–67. doi:10.1111/j.1476-5381.1970.tb09891.x. PMC 1702721. PMID 5485142.
With regards to management of atrial fibrillation, Class I and III are used in rhythm control as medical cardioversion agents while Class II and IV are used as rate control agents.
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.
|Class||Known as||Examples||Mechanism||Clinical uses in cardiology |
|Ia||fast-channel blockers-affect QRS complex||(Na+) channel block (intermediate association/dissociation)|
|Ib||Can prolong QRS in overdose||(Na+) channel block (fast association/dissociation)|
|Ic||(Na+) channel block (slow association/dissociation)|
Propranolol also shows some class I action
|III||K+ channel blocker|
|IV||slow-channel blockers||Ca2+ channel blocker|
|V||Work by other or unknown mechanisms (Direct nodal inhibition).||Used in supraventricular arrhythmias, especially in Heart Failure with Atrial Fibrillation, contraindicated in ventricular arrhythmias. Or in the case of Magnesium Sulfate, used in Torsades de Pointes.|
Class I agents
Class I agents are called Membrane Stabilizing agents. The 'stabilizing' word is used to describe the decrease of excitogenicity of the plasma membrane which is brought about by these agents. (Also noteworthy is that a few class II agents like propranolol also have a membrane stabilizing effect.)
- 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
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 III agents
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: bretylium, 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
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.
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.
- Digoxin, which decreases conduction of electrical impulses through the AV node and increases vagal activity via its central action on the central nervous system, via indirect action, leads to an increase in acetylcholine production, stimulating M3 receptors on AV node leading to an overall decrease in speed of conduction.
- Adenosine, used intravenously for terminating supraventricular tachycardias. IV adenosine can also be used to differentiate between atrial fibrillation and PSVT
- Magnesium sulfate, an antiarrhythmic drug, but only against very specific arrhythmias  which has been used for torsades de pointes.
Sicilian Gambit classification
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 approximately the 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.
- Action potential
- Cardiac Arrhythmia Suppression Trial (CAST)
- Proarrhythmic agent
- Unless else specified in boxes, then ref is: Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.
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