Local anaesthetics

Vivian Imbriotis | June 19, 2026

Classification of local anaesthetics

  • Esters \(\to\) surface action (cocaine), short action (procaine), long action (tetracaine)
  • Amides \(to\) medium action (lidocaine), long action (bupivacaine, ropivacaine)
  • All are weak bases (ionized below their pKa) with pKa ~8

Mechanism of action

  • Unionized form diffuses across neuronal cell membrane \(\to\) becomes ionized in more acidic ICF
  • Binds to open state of fast sodium channel \(\to\) stabilize in inactive state
  • Use-dependance = more frequent firing \(\to\) more efficacious block
  • Preferentially affect pain and temperature sensation because C-fibers are unmyelinated

Class: Local anaesthetic and class 1b antiarrhythmic

Pharmacuetics: colorless liquid, stored in acidic pH to remain soluble. 1% and 2% formulations common.

Dose: max subcut dose 3mg/kg; with adrenaline 7mg/kg. 1mg/kg IV dose for antiarrhythmic effect -> 1mg/kg/hr infusion. CC/CNS ratio 7:1 (plasma level for CNS toxicity << that for CVS toxicity).

A: 35% OBA

D: 0.9L/kg, 70% protein bound

M: Completely hepatically metabolised \(\to\) inactive metabolites

E: No renal elimination. T1/2=15 minutes IV, 1 hour subcut, duration of action \(\approx\) 1 half life

Mechanism:

  • Unionized form diffuses across excitable cell membrane \(\to\) becomes ionized in more acidic ICF
  • Binds to open state of fast sodium channel \(\to\) stabilize in inactive state
  • Use-dependance = more frequent firing \(\to\) more efficacious block

Effects:

  • Preferentially affect pain and temperature sensory fibers because C-fibers are unmyelinated
  • Regional anaesthsia
  • Motor block with higher exposure
  • CNS effects - visual disturbamces, perioral numbness, progressing to seizure, coma.
  • CVS effects - tachycardia and hypertension \(to\) bradycardia, negative inotropy, vasodilation, arrhythmia. QRS prolongation.

Lidocaine

  • Fast onset (<5 minutes)
  • Short duration ~1 hour
  • CC/CNS 7:1

Bupivicaine

  • Slow onset (15 minutes)
  • Longest duration ~18 hours
  • Most cardiotoxic, CC/CNS 3:1

Ropivacaine

  • Slow onset (15 minutes)
  • Intermediate duration (~10 hours)
  • Medium cardiotoxicity, CC/CNS 5:1