Xylocaine Pump Spray Mechanism of Action

Pharmacotherapeutic group: Local anaesthetic. ATC code: N01BB02.
Pharmacology: Pharmacodynamics: Xylocaine Pump Spray provides prompt and profound anaesthesia of mucous membranes, which lasts for approximately 10-15 minutes. Anaesthesia usually occurs within 1-3 minutes depending on the area of application (see Dosage & Administration).
Pharmacokinetics: The rate and extent of absorption of lidocaine is dependent upon the concentration and total dose administered, the specific site of application, and the duration of exposure. In general, the rate of absorption following topical administration is most rapid after intratracheal and bronchial administration. Such applications may therefore result in rapidly rising plasma concentrations, with an increased risk of toxic symptoms, such as convulsions. Lidocaine is well absorbed from the gastrointestinal tract, although little of the intact drug appears in the circulation because of biotransformation in the liver.
Normally about 65% of the lidocaine is bound to plasma proteins. The plasma protein binding is predominantly to alpha-1-glycoprotein.
The main elimination pathway of lidocaine is by liver metabolism. De-alkylation to monoethylglycine xylidide (MEGX) is mediated mainly by cytochrome P450 3A4. MEGX is metabolised to 2,6-xylidine and glycine xylidide (GX). 2,6-xylidine is metabolised further by CYP2A6 to 4-hydroxy-2,6-xylidine, which is the major metabolite in the urine (80%) and is excreted as conjugate. MEGX has a convulsant activity equivalent to that of lidocaine, while GX is devoid of convulsant activity. MEGX appears to occur in similar plasma concentrations as the parent substance. The elimination half-life of lidocaine and MEGX following an intravenous bolus dose are approx. 1.5-2 and 2.5 hours respectively.
On account of the rapid hepatic metabolism, the kinetics are sensitive to all alterations in liver function. The half-life can be more than doubled in patients with impaired liver function. Impaired renal function does not affect the kinetics, but can increase the accumulation of metabolites.
Factors such as acidosis and the use of CNS stimulants and depressants affect the levels of lidocaine required to produce systemic effects. Objective manifestation become increasingly apparent with increasing venous plasma levels from 6 μg free base per ml.