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. The sodium channels of the nerve membrane are considered a receptor for local anesthetic molecules.

Onset of Action

The onset of action is 1-5 minutes following infiltration and 5-15 minutes following other types of administration. The duration of anesthesia depends on the concentration of lidocaine used, the dose, and the type of block. The 2% solution will last 1½-2 h when given epidurally, and up to 5 hours with peripheral nerve blocks. With the 1% concentration, there is less effect on motor nerve fibres and the duration of action is shorter. The addition of epinephrine decreases the rate of absorption, reducing toxicity and increasing the duration of effect.

Hemodynamics

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

Central nervous system toxicity (see SYMPTOMS AND TREATMENT OF 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. Indirect cardiovascular effects (hypotension, bradycardia) may occur after epidural administration depending on the extent of the concomitant sympathetic block.

Pharmacokinetics and Metabolism

Lidocaine is completely absorbed following parenteral administration. The rate of absorption depends on the dose, route of administration, and the vascularity of the injection site. The highest peak plasma levels are obtained following intercostal nerve block (approximately 1.5 μg/mL per 100 mg injected) while abdominal subcutaneous injections give the lowest (approximately 0.5 μg/mL per 100 mg injected). Epidural and major nerve blocks are intermediate.

Absorption is considerably slowed by the addition of epinephrine, although it also depends on the site of injection. Peak plasma concentrations are reduced by 50% following subcutaneous injection, by 30% following epidural injection and by 20% following intercostal block if epinephrine 5 μg/mL is added.

Lidocaine shows complete and biphasic absorption from the epidural space with half lives of the two phases in the order of 9.3 min and 82 min respectively. The slow absorption is the rate limiting factor in the elimination of lidocaine, which explains why the apparent terminal half-life is longer after epidural administration. Absorption of lidocaine from the subarachnoid space is monophasic with an absorption half-life of 71 min.

Lidocaine has a total plasma clearance of 0.95 L/min, a volume of distribution at steady state of 91 L, a terminal 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.

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.

Lidocaine readily crosses the placenta, and equilibrium with regard to the unbound concentration is rapidly reached. The degree of plasma protein binding in the fetus is less than in the mother, which results in lower total plasma concentrations in the fetus.

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