√ Anaesthesia : 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
    
    
    
    
  
  
  
  

Sumber aciknadzirah.blogspot.com

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