ABSTRACT
Local anaesthetic (LA) molecules bind specifically to sodium channel proteins in axonal membranes of neurons near the injection site, with essentially no effects centrally unless given in overdose. Local anaesthetics are all weak bases, and exist in vivo in both their ionized and unionized forms. The degree of ionization depends on the pH of the solution they exist in and on their own pKa (the pH at which the ionized and unionized forms exist in equal concentrations). They act by blocking the sodium channels that generate action potentials. The local anaesthetic molecule which is deposited outside the nerve fibre must cross the lipid axon membrane to exert its effect. Hence, the molecule must exist in its unionized form and be lipid soluble. The more lipid soluble the drug, the more potent it will be. Also, as different local anaesthetics have different pKa values, they will consequently have different speeds of onset of action.
