The
Vaughan Williams classification was introduced in 1970 by
Miles Vaughan Williams. Vaughan Williams was a pharmacology tutor at
Hertford College, Oxford. One of his students,
Bramah N. Singh, contributed to the development of the classification system. The system is therefore sometimes known as the
Singh-Vaughan Williams classification. The five main classes in the Vaughan Williams classification of antiarrhythmic agents are: •
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 regard to management of atrial fibrillation, classes I and III are used in rhythm control as medical cardioversion agents, while classes II and IV are used as rate-control agents.
Class I agents The class I antiarrhythmic agents
interfere with the sodium channel. Class I agents are grouped by what effect they have on the Na+ channel, and what effect they have on cardiac
action potentials. Class I agents are called membrane-stabilizing agents, "stabilizing" referring to 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.) Class I agents are divided into three groups (Ia, Ib, and Ic) based upon their effect on the length of the action potential. • Class Ia drugs lengthen the action potential (right shift) • Class Ib drugs shorten the action potential (left shift) • Class Ic drugs do not significantly affect the action potential (no shift) File:Action potential class Ia.svg|Class Ia File:Action potential Class Ib.svg|Class Ib File:Action potential class Ic.svg|Class Ic
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, 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 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 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.
Class V and others 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.
History 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. ==Sicilian gambit classification==