ANTIARRHYTHMIC DRUGS

LIDOCAINE

Lidocaine is a local anesthetic agent whose antidysrhytmic properties stem from is capability to block the fast inward sodium channels (Class I). The drug interacts with the sodium channel during its inactivated phase and has a fast dissociation rate during the diastolic phase (Class IB). This explains why its effects on the action potential at the normal heart rates are negligible.

The electrophysiologic action of the drug become manifest in partially depolarized cells (ischemia, stretch). In this setting lidocaine decreases conduction velocity (by reducing the amplitude and upstroke velocity of the action potential), abolishes ectopic automaticity (by abolishing late potentials and decreasing phase 4 diastolic depolarization) and increases fibrillation threshold. Its effects on atrial myocardium are negligible. The drug has a minimal negative inotropic action and has no effects on the autonomic nervous system.

Pharmacokinetics

Lidocaine is well absorbed by the gastrointestinal tract, but 80-90% of the dose is inactivated at the first passage by the liver. This precludes the oral route.

Plasma peak (intravenous administration): 30-90 sec

Plasma protein binding: 70%

Metabolism: Lidocaine is actively metabolized by the liver into two major metabolites MEGX and GX. The first metabolite, in turn, is metabolized into the second one. MEGX is 80% as potent as the parent drugs, while GX is nearly ineffective. Both metabolites contribute to the drug’s cerebral toxicity. Significant liver dysfunction or a decreased blood flow (cardiac failure) reduce lidocaine metabolism and can precipitate toxicity. In these conditions drug dosage has to be halved.

Distribution and disposition: Lidocaine disposition follows a three-phase pattern. Phase 1 (peaking): elevated plasma peak and rapid distribution to the highly perfused organs; phase 2 (diffusion): drug diffusion into all tissues with rapid decrease in plasma levels, phase 3 (elimination): hepatic metabolism. Ten per cent of lidocaine and GX are eliminated by the kidney.

Half life: 1.5 hours in normal subject, 3-10 hours in the elderly, in hepatic dysfunction and in low output states.

Drug interactions

Betablockers, cymetidine: reduced hepatic clearance and increased lidocaine plasma levels.

Phenobarbital, Phenytoin, Isoproterenol, Rifampicine: increase clearance and reduced lidocaine plasma levels.

Indications

Lidocaine is the drug of choice in ventricular arrhythmias arising in the setting of acute myocardial ischemia/infarction or digitalis toxicity. It is less effective in chronic arrhythmias or arrhythmias sustained by and anatomical reentrant circuits. Its routine prophylactic use in acute myocardial infarction has been abandoned.

Contraindications

Serious atrio-ventricular conduction disturbances

Severe hepatic insufficiency

Severe hypokalemia

Untoward effects

Cardiac side effects. Proarrhythmic effects (worsening of the ventricular arrhythmia, bradycardia or worsening of preexisting conduction disturbances) are possible but very rare.

Systemic side effects are limited to central nervous system disorders and are related to plasma concentration of the drug and its metabolites: visual disturbances, paraesthesias, lightheadedness, irritability, confusion, mental disorders, seizures.

Dosage

Intramuscular route (rarely used): 4-5 mg/Kg produce therapeutic levels in 15 minutes up to 90-120 minutes.

Intravenous route: 1-2 mg/Kg loading dose (50 mg/min), followed by continuous infusion (1-4 mg/min). A second bolus is necessary after 20 minutes, to maintain adequate plasma levels (see pharmacodinamics). Dose must be reduced up to 50% in elderly patients, low output states and liver insufficiency.

Leopoldo Bianconi
Department of Heart Disease - Division of Cardiology, S. Filippo Neri Hospital - Italy

Home page ANTIARRHYTHMIC DRUGS
Home page EINTHOVEN