Lidocaine (Xylocaine) was introduced as a local anes-thetic and is still used extensively for that purpose . Lidocaine is an effective sodium channel blocker, binding to channels in the inactivated state. Lidocaine, like other IB agents, acts preferentially in diseased (ischemic) tissue, causing conduction block and interrupting reentrant tachycardias.
When administered in normal therapeutic doses (1–5 mg/kg), lidocaine has no effect on the sinus rate.
The electrophysiological properties of lidocaine in atrial muscle resemble those produced by quinidine. Membrane responsiveness, action potential amplitude, and atrial muscle excitability are all decreased. These changes result in a decrease in conduction velocity. However, the depression of conduction velocity is less marked than that caused by quinidine or procainamide. Action potential duration of atrial muscle fibers is not altered by lidocaine at either normal or subnormal ex-tracellular K+ levels. The ERP of atrial myocardium ei-ther remains the same or increases slightly after lido-caine administration.
Lidocaine minimally affects both the conduction ve-locity and the ERP of the A-V node. Lidocaine does not possess anticholinergic properties and will not improve A-V transmission when atrial flutter or atrial fibrillation is present.
Lidocaine reduces action potential amplitude and membrane responsiveness. Significant shortening of the action potential duration and ERP occurs at lower concentrations of lidocaine in Purkinje fibers than in ven-tricular muscle. Lidocaine in very low concentrations slows phase 4 depolarization in Purkinje fibers and de-creases their spontaneous rate of discharge. In higher concentrations, automaticity may be suppressed and phase 4 depolarization eliminated.
It is difficult to suggest a mechanism for lidocaine’s antiarrhythmic action on the basis of its effects on normal ventricular myocardial tissue and His-Purkinje tissue.
Lidocaine does not usually change the PR, QRS, or QT interval, although the QT may be shortened in some pa-tients. The paucity of electrocardiographic changes re-flects lidocaine’s lack of effect on healthy myocardium and conducting tissue.
Lidocaine does not depress myocardial function, even in the face of congestive heart failure, at usual doses.
The pharmacokinetic characteristics of lidocaine:
Oral bioavailability : 30–40%
Onset of action : 5–15 minutes intramuscularly (IM); immediate intravenously (IV)
Peak response : Unknown
Duration of action : 60–90 minutes IM; 10–20 minutes IV
Plasma half-life : 1–2 hours
Primary route of metabolism : 90% hepatic
Primary route of excretion : 10% renal (unchanged), remain der as metabolites
Therapeutic serum : 1.5–5.0 μg/mL concentration
Lidocaine is useful in the control of ventricular arrhyth-mias, particularly in patients with acute myocardial in-farction. Lidocaine is the drug of choice for treatment of the electrical manifestations of digitalis intoxication.
The most common toxic reactions seen after lidocaine ad-ministration affect the CNS. Drowsiness is common, but unless excessive may not be particularly undesirable in patients with acute myocardial infarction. Some patients have paresthesias, disorientation, and muscle twitching that may forewarn of more serious deleterious effects, in-cluding psychosis, respiratory depression, and seizures.
Lidocaine may produce clinically significant hy-potension, but this is exceedingly uncommon if the drug is given in moderate dosage. Depression of an already damaged myocardium may result from large doses.
Contraindications include hypersensitivity to local anesthetics of the amide type (a very rare occurrence), severe hepatic dysfunction, a history of grand mal seizures due to lidocaine, and age 70 or older. Lidocaine is contraindicated in the presence of second- or third-degree heart block, since it may increase the degree of block and can abolish the idioventricular pacemaker re-sponsible for maintaining the cardiac rhythm.
The concurrent administration of lidocaine with cimeti-dine but not ranitidine may cause an increase (15%) in the plasma concentration of lidocaine. This effect is a manifestation of cimetidine reducing the clearance and volume of distribution of lidocaine. The myocardial de-pressant effect of lidocaine is enhanced by phenytoin administration.