Class+IB+antiarrhythmics

Class IB antiarrhythmics


 * Background:** The publication of the results of the Cardiac Arrhythmia Suppression Trials in 1989 [296] and 1992 [297] and other studies suggesting increased mortality associated with the use of antiarrhythmic drugs caused the medical community to reevaluate the choice and use of pharmacologic agents for the management of many serious arrhythmias. As a result, antiarrhythmic agents have been replaced in some cases (e.g., life-threatening ventricular arrhythmias) by implantable defibrillator devices. Antiarrhythmic drugs are still used as primary therapy for many supraventricular arrhythmias, but their use as primary therapy for prevention of ventricular arrhythmias has declined since the publication of the trials mentioned above.

The Vaughan-Williams (V-W) classification system traditionally has been used to classify antiarrhythmic drugs.[298] This scheme places the available agents into one of four classes: I, II, III, or IV. The V-W system, however, has two limitations. First, although all drugs within a single class might possess a similar electrophysiologic action, they do not necessarily exert all of the same actions. The second limitation of the V-W classification system is that some agents have multiple electrophysiologic activities that complicate the placement of a drug into a single (e.g., amiodarone) or any (e.g., adenosine) category.[299]

Class IB antiarrhythmic agents include: lidocaine, mexiletine, and tocainide. The class IB drugs are primarily used to treat ventricular arrhythmias.


 * Mechanism of Action:** Class I agents are membrane-active drugs that act on the sodium channel and slow the maximal rate of depolarization or Vmax as measured by phase 0 of the action potential. Blockade of the sodium channel results in reduced automaticity, delayed conduction, and prolonged refractory periods. The class I agents have been further classified into three subcategories: 1A, IB, and IC. The differences among these subgroups lie in the nature of their inhibition of the sodium ion channel. 'On-off receptor kinetics' refers to the affinity of drug binding to the sodium channel ('on kinetics'). 'Off kinetics' describes the rapidity of dissociation of the drug from the sodium channel. The class I agents also may be characterized by the mechanism by which they inhibit the sodium channel.[295]

The class IB agents, lidocaine and its oral congeners mexiletine and tocainide, exhibit rapid 'on-off' sodium-channel receptor kinetics and therefore minimal effects on depolarization. Class IB agents inhibit the fast sodium channel (Class I effect) while shortening the action potential duration in non-diseased tissue. Unlike Class IA agents such as quinidine, Class IB agents are not associated with QT prolongation or torsades de pointes.


 * Distinguishing Features:** Lidocaine is the prototypical class IB agent and is the only drug in this class not administered orally. However, orally effective derivatives of lidocaine have been developed including tocainide (1984) and mexiletine (1986). The class IB drugs are primarily used to treat ventricular arrhythmias; however they do not favorably improve mortality compared with placebo. Class IB agents are ineffective for the treatment of atrial arrhythmias.

Lidocaine is used for the treatment of acute, life-threatening ventricular arrhythmias. Although lidocaine has historically been used as a first-line antiarrhythmic agent for ventricular arrhythmias, lidocaine is now considered a second choice behind other alternative agents for the treatment of ventricular arrhythmias by the ECC/AHA 2000 guidelines for cardiopulmonary resuscitation.[2999] The revised ACLS guidelines suggest IV amiodarone be considered prior to administration of lidocaine for ventricular fibrillation or pulseless ventricular tachycardia, based on greater supporting data for amiodarone.[2999] In addition, lidocaine has been shown to be ineffective for prophylaxis of arrhythmias in post-myocardial infarction patients.[301] [2999] Lidocaine side effects primarily involve CNS effects such as dizziness, ataxia, tremor, or seizures at higher dosage or plasma concentrations. Plasma lidocaine levels can be monitored to guide dosage during continuous lidocaine infusions. Lidocaine has relatively few adverse circulatory effects, presumably because the clearance of lidocaine is rapid in comparison to that of other class I antiarrhythmic agents.

Tocainide and mexiletine are oral congeners of lidocaine which are used to treat sustained life-threatening ventricular arrhythmias. Dose-dependent side effects for these agents primarily include the GI and CNS systems.