Mechanism of Action

Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby, effecting local anesthetic action. Local anesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.

Onset of Action

After application of XYLOCAINE Viscous 2% (lidocaine hydrochloride), local anesthesia is achieved within 5 minutes. Duration of anesthesia is approximately 20 - 30 minutes. XYLOCAINE Viscous 2% is ineffective when applied to intact skin.

Hemodynamics

Lidocaine, like other local anesthetics, may also have effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach the systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating from the central nervous and cardiovascular systems.

Central nervous system toxicity (see OVERDOSAGE) usually precedes the cardiovascular effects since it occurs at lower plasma concentrations. Direct effects of local anesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.

Pharmacokinetics

Absorption: The rate and extent of absorption depends upon concentration and total dose administered, the specific site of application and duration of exposure. In general, the rate of absorption of local anesthetic agents, following topical application to wound surfaces and mucous membranes is high, and occurs most rapidly after intratracheal and bronchial administration. Lidocaine is also well absorbed from the gastrointestinal tract, although little of the intact drug may appear in the circulation because of biotransformation in the liver.

Distribution: Lidocaine has a total plasma clearance of 0.95 L/min and a volume of distribution at steady state of 91 L.

Lidocaine readily crosses the placenta, and equilibrium in regard to free, unbound drug will be reached. Because the degree of plasma protein binding in the fetus is less than in the mother, the total plasma concentration will be greater in the mother, but the free concentrations will be the same.

The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 µg of free base per mL, 60 to 80 percent of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Metabolism: Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. Only 2% of lidocaine is excreted unchanged. Most of it is metabolized first to monoethylglycinexylidide (MEGX) and then to glycinexylidide (GX) and 2,6-dimethylaniline. Up to 70% appears in the urine as 4-hydroxy- 2,6-dimethylaniline.

Excretion: Lidocaine has an elimination half-life of 1.6 h and an estimated hepatic extraction ratio of 0.65. The clearance of lidocaine is almost entirely due to liver metabolism, and depends both on liver blood flow and the activity of metabolizing enzymes.

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