Xylocaine Injection Mechanism of Action

Pharmacology: Lignocaine, like other local anaesthetics, causes a reversible blockade of impulse propagation along nerve fibres by preventing the inward movement of sodium ions through the nerve membrane. Local anaesthetics of the amide-type are thought to act within the sodium channels of the nerve membrane.
Local anaesthetic drugs may have similar 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 mainly from the CNS and cardiovascular system.
Central nervous system toxicity usually precedes the cardiovascular effects as it occurs at lower plasma concentrations. Direct effects of local anaesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.
Indirect cardiovascular effects eg, hypotension and bradycardia, may occur after epidural or spinal administration depending on the extent of the concomitant sympathetic block.
Pharmacokinetics: Lignocaine has a rapid onset and a medium duration of action. The onset of action is 1-5 min following infiltration and 5-15 min following other types of administration.
The rate of absorption depends upon the dose, the route of administration and the vascularity of the injection site. Intercostal blocks give the highest peak plasma concentrations (approximately 1.5 mcg/mL for every 100 mg injected), while abdominal SC injections give the lowest (approximately 0.5 mcg/mL/100 mg injected). Epidural and major nerve block produce peak plasma levels intermediate between these.
Absorption of lignocaine from the epidural space occurs in 2 phases; the 1st phase is in the order of 9 min and the 2nd is approximately 82 min. The slow absorption is the rate-limiting step in the elimination of lignocaine, which also explains the apparent elimination half-life (t_1/2) following epidural injection is longer than after IV administration.
The plasma binding of lignocaine is dependent on drug concentration and the fraction bound decreases with increasing concentration. At concentrations of 1-4 mcg of free base/mL, 60-80% of lignocaine is protein bound. Binding is also dependent on the plasma concentration of the α₁-acid glycoprotein.
Lignocaine crosses the blood-brain and placental barriers by passive diffusion. Since the degree of plasma protein-binding in the foetus is less than in the mother, although free lignocaine concentrations will be the same, the total plasma concentration will be greater in the mother.
Lignocaine has a total plasma clearance of 0.95 L/min, a volume of distribution at steady-state of 91 L, an elimination t_1/2 of 1.6 hrs and an estimated hepatic extraction ratio of 0.65. Approximately 90% of a parenteral dose of lignocaine is rapidly metabolised in the liver by de-ethylation to form monoethylglycinexylidide (MEGX) and glycinexylidide (GX) followed by cleavage of the amide bond to form xylidine and 4-hydroxyxylidine which are excreted in the urine. Less than 10% of a dose is excreted unchanged in the urine.
The principal metabolites, MEGX and GX, also possess pharmacological activity. The rate of metabolism of lignocaine appears to be limited by liver blood flow which may be reduced in patients after acute myocardial infarction and/or congestive heart failure. The rate of lignocaine metabolism may also be reduced in patients with liver or hepatic tissue necrosis, possibly because of altered perfusion.
The duration of action depends upon the concentration used, the dose given, the nerves to be blocked and the status of the patient. The 2% solution will produce an effect for 1½-2 hrs when given epidurally and up to 5 hrs when given as a peripheral nerve block. When used in a 1% concentration, there is less effect on motor nerve fibres and the duration of effect is shorter.