Chapter: Modern Pharmacology with Clinical Applications: Pharmacological Management of Chronic Heart Failure

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Mexiletine

Mexiletine (Mexitil) is an antiarrhythmic agent with pharmacological and antiarrhythmic properties similar to those of lidocaine and tocainide. Like tocainide, mex-iletine is available for oral administration.

Mexiletine

Mexiletine (Mexitil) is an antiarrhythmic agent with pharmacological and antiarrhythmic properties similar to those of lidocaine and tocainide. Like tocainide, mex-iletine is available for oral administration.

Electrophysiological Actions

As with other members of class IB, mexiletine slows the maximal rate of depolarization of the cardiac membrane action potential and exerts a negligible ef-fect on repolarization. Mexiletine demonstrates a rate-dependent blocking action on the sodium channel, with rapid onset and recovery kinetics suggesting that it may be more useful for the control of rapid as opposed to slow ventricular tachyarrhythmias.

Hemodynamic Effects

Although its cardiovascular toxicity is minimal, mexile-tine should be used with caution in patients who are hy-potensive or who exhibit severe left ventricular dys-function.

 

Pharmacokinetics

The pharmacokinetic characteristics of mexiletine:

Oral bioavailability : 90%

Onset of action : 0.5–2 hours

Peak response : 2–3 hours

Duration of action : 8–12 hours

Plasma half-life : 10–12 hours

Primary route of metabolism: Hepatic

Primary route of excretion: Primarily biliary; 10% renal

Therapeutic serum concentration : 0.5–2μg /mL

Clinical Uses

Mexiletine is useful as an antiarrhythmic agent in the management of patients with either acute or chronic ventricular arrhythmias. While it is not at present an in-dication for use, there is interest in using mexiletine to treat the congenital long QT syndrome when an abnor-mality in the SCN5A gene (LQTS 3) has been found.

Adverse Effects

A very narrow therapeutic window limits mexiletine use. The first signs of toxicity manifest as fine tremor of the hands, followed by dizziness and blurred vision. Hypotension, sinus bradycardia, and widening of the QRS complex have been noted as the most common unwanted cardiovascular effects of IV mexiletine. The side effects of oral maintenance therapy include re-versible upper gastrointestinal distress, tremor, light-headedness, and coordination difficulties. These effects generally are not serious and can be reduced by down-ward dose adjustment or administering the drug with meals. Cardiovascular adverse effects, which are less common, include palpitations, chest pain, and angina or anginalike pain.

Contraindications

Mexiletine is contraindicated in the presence of cardio-genic shock or preexisting second- or third-degree heart block in the absence of a cardiac pacemaker. Caution must be exercised in administration of the drug to pa-tients with sinus node dysfunction or disturbances of in-traventricular conduction.

Drug Interactions

An upward adjustment in dose may be required when mexiletine is administered with phenytoin or rifampin, since these drugs stimulate the hepatic metabolism of mexiletine, reducing its plasma concentration.

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