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Pharmacology: Pharmacodynamics: Lignocaine stabilises the neuronal membrane and prevents the initiation and conduction of nerve impulses, thereby effecting local anaesthetic action.
The onset of action occurs within 3-5 minutes on mucous membranes. Its low surface tension ensures an even film over the surface of the mucous membrane so that the lignocaine comes into intimate contact with the total surface. High viscosity ensures sufficiently prolonged contact with the mucous membrane. It is ineffective when applied to intact skin.
Pharmacokinetics: Lignocaine is readily absorbed from the gastrointestinal tract, from mucous membranes, and through damaged skin . The rate of absorption is most rapid after intratracheal administration and the absorption through intact skin is poor. It is weak bases and able to diffuse through connective tissues and cellular membranes at tissue's pH to reach nerve fibre where ionization can occur. In general, its rate and extent of absorption will depend on concentration and total dose administered, the specific site of application and duration of exposure.
Lignocaine is bound to plasma proteins, including α1-acid glycoprotein (AAG). The extent of binding is variable but is about 66%. Plasma protein binding of lignocaine depends in part on the concentrations of both lignocaine and AAG. Any alteration in the concentration of AAG can greatly affect plasma concentrations of lignocaine. The fraction bound decrease with increasing drug concentration. AAG is increased after trauma, surgery, burns, myocardial infarction, in chronic inflammatory disorders such as Crohn's disease and in cancer. Protein binding may therefore be greatly increased in these conditions and reduced in neonates, the nephrotic syndrome and in liver disease when AAG concentrations are lower than normal. This can result in an eightfold variation in the free fraction of lignocaine between these conditions. AAG concentrations may also be reduced by oestrogens leading to a higher free fraction of lignocaine in women than in men and the free fraction is further increased during pregnancy and in women taking oral contraceptives. Protein binding may also be affected by other concomitant drug therapy or smoking.
Lignocaine has biphasic elimination half-life with initial 7 to 30 minutes and terminal 1.5 to 2 hours. Lignocaine is largely metabolised in the liver and any alteration in liver function or hepatic blood flow can have a significant effect on its pharmacokinetics and dosage requirements. First-pass metabolism is extensive and bioavailability is about 35% after oral doses. Metabolism in the liver is rapid and about 90% of a given dose is dealkylated to form monoethylglycinexylidide and glycinexylidide. Both of these metabolites may contribute to the therapeutic and toxic effects of lignocaine and since their half-lives are longer than that of lignocaine. Further metabolism occurs and metabolites are excreted in the urine with less than 10% of unchanged lignocaine. Reduced clearance of lignocaine has been found in patients with heart failure, alcoholic liver disease, or chronic or viral hepatitis.
