Pharmacology of Mexiletine

Pharmacology
Indication	For the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.
Pharmacodynamics	Mexiletine is a local anesthetic, antiarrhythmic agent (Class Ib), structurally similar to lidocaine, but orally active. Mexiletine has fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. It shortens the action potential duration, reduces refractoriness, and decreases Vmax in partially depolarized cells with fast response action potentials. Mexiletine either does not change the action potential duration, or decreases the action potential duration.
Mechanism of action	Mexiletine, like lidocaine, inhibits the inward sodium current required for the initiation and conduction of impulses, thus reducing the rate of rise of the action potential, Phase 0. It achieves this reduced sodium current by inhibiting sodium channels. Mexiletine decreases the effective refractory period (ERP) in Purkinje fibers in the heart. The decrease in ERP is of lesser magnitude than the decrease in action potential duration (APD), which results in an increase in the ERP/APD ratio. It does not significantly affect resting membrane potential or sinus node automaticity, left ventricular function, systolic arterial blood pressure, atrioventricular (AV) conduction velocity, or QRS or QT intervals
Absorption	Well absorbed (bioavailability 90%) from the gastrointenstinal tract.
Volume of distribution	5 to 7 L/lg
Protein binding	50-60%
Metabolism	Primarily hepatic (85%) via CYP2D6 and CYP1A2 (primarily CYP2D6).
Route of elimination	Approximately 10% is excreted unchanged by the kidney. The urinary excretion of N-methylmexiletine in man is less than 0.5%.
Half life	10-12 hours
Clearance	Not Available
Toxicity	Symptoms of overdose include nausea, hypotension, sinus bradycardia, paresthesia, seizures, bundle branch block, AV heart block, asystole, ventricular tachyarrythmia, including ventricular fibrillation, cardiovascular collapse, and coma.