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Pharmacology of local anaesthetics

 

  • 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
      • Stable in solution (longer storage possible)
      • pKa 7.6-8.1
      • e.g. Lidocaine, Bupivacaine, Prilocaine

 

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