All local anaesthetics are weak bases with the majority in the ionised form at physiological pH (7.35-7.45)
Balance of ionised and non-ionised forms dependent on pKa for that LA and the pH of the tissues/fluid it is in
pKa defined as pH of a solution in which the LA is in equilibrium (expressed in the Henderson-Hasselbalch equation)
Only the non-ionised form of LA is ‘active’ and able to enter the cell
It is the ionised form within the cell which binds to Na+ channels
The lower the pKa the higher the proportion of LA in the non-ionised form hence a more rapid onset due to better absorption into the nerve.
The lower the pKa the better the absorption into the nerve
Higher pKa results in a longer duration of block
Inflamed/Infected tissues have a lower pH (5-6) and therefore LA mainly ionised, unable to enter cell, and unlikely to be effective in preventing pain transmission
Sodium bicarbonate can be added to LA solutions to raise the pH and therefore increase the speed of onset
Potency of LA dependent on lipid solubility
Duration of action dependent on binding to plasma proteins
LA which bind more easily to plasma proteins have longer duration of action and lower risk of toxicity
Lower pH reduces affinity for protein binding and increases risk of toxicity
Two main types (defined by the linkage between the hydrophilic and lipophillic groups)
Esters:
Rapid metabolism by plasma cholinesterases hence are short acting
Up to 1/3 of patients have allergic reaction due to similarity to para-aminobenzoic acid (PABA) structure
Unstable in solution and degrades
pKa 8.5-8.9
e.g. Cocaine, Benzocaine, Tetracaine, Procaine
Amides:
Slow hepatic metabolism
Lower risk of allergy but more likely to cause malignant hyperthermia
Allergies are rare and are more likely due to preservatives rather than LA itself
