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Cardiovascular Pharmacology Concepts

Richard E. Klabunde, PhD

Clinical Disorders:

Therapeutic Classes:

Mechanism Classes:

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Vaughan-Williams Classification of Antiarrhythmic Drugs

Antiarrhythmic drugs comprise many different drug classes and have several different mechanisms of action. Furthermore, some classes and even some specific drugs within a class are effective with only certain types of arrhythmias. Therefore, attempts have been made to classify the different antiarrhythmic drugs so by mechanism. Although different classification schemes have been proposed, the first scheme (Vaughan-Williams) is still the one that most physicians use when speaking of antiarrhythmic drugs.

The following table shows the Vaughan-Williams classification and the basic mechanism of action associated with each class. Note that Class I drugs are further broken down into subclasses because of subtle, yet important differences in their effects on action potentials. Clicking on the "Class" or "Basic Mechanism" will take you to a page describing the drugs that comprise that class.

Class Basic Mechanism Comments
I sodium-channel blockade Reduce phase 0 slope and peak of action potential.
IA    - moderate Moderate reduction in phase 0 slope; increase APD; increase ERP.
IB    - weak Small reduction in phase 0 slope; reduce APD; decrease ERP.
IC    - strong Pronounced reduction in phase 0 slope; no effect on APD or ERP.
II beta-blockade Block sympathetic activity; reduce rate and conduction.
III potassium-channel blockade Delay repolarization (phase 3) and thereby increase action potential duration and effective refractory period.
IV calcium-channel blockade Block L-type calcium-channels; most effective at SA and AV nodes; reduce rate and conduction.

Abbreviations: APD, action potential duration; ERP, effective refractory period; SA, sinoatrial node; AV, atrioventricular node.

The Vaughan-Williams classification has severe limitations. When initially conceived, there were relatively few antiarrhythmic drugs and our understanding of their mechanisms was rudimentary at best. Now with many more antiarrhythmic drugs, and with a much greater yet still incomplete understanding of drug mechanisms, this classification system breaks down especially for the Class I and III drugs. Many of these drugs have mechanisms of action that are shared with drugs found the other classes. For example, amiodarone, a Class III antiarrhythmic, also has sodium and calcium-channel blocking actions. Many of the Class I compounds also affect potassium channels. Some of these drugs, it could be argued, could fit in just as well as a different class than the one that they may be assigned. For this reason, different sources of information may classify some antiarrhythmic drugs differently than other sources.

The drugs that make up the different classes differ in their efficacy (and sometimes safety) for different types of arrhythmias. The following table provides an overview of drug classes and associated arrhythmias. Antiarrhythmic agents that are not included in the Vaughan-Williams scheme are also shown in the table.

Condition Drug Comments
Sinus tachycardia Class II, IV Other underlying causes may need treatment
Atrial fibrillation/flutter Class IA, IC, II, III, IV
Ventricular rate control is important goal; anticoagulation is required
Paroxysmal supraventricular tachycardia Class IA, IC, II, III, IV
AV block atropine Acute reversal
Ventricular tachycardia Class I, II, III  
Premature ventricular complexes Class II, IV
magnesium sulfate
PVCs are often benign and do not require treatment
Digitalis toxicity Class IB
magnesium sulfate

Revised 3/19/10

DISCLAIMER: These materials are for educational purposes only, and are not a source of medical decision-making advice.