Neuromuscular Blockade — Block Potentiation

Non depolarising neuromuscular blockers

• act by non-competitive binding to the nicotinic ACh receptor on the motor end plate
• this prevents the action of ACh at the motor end plate and stops muscle excitation
• aminosteroids – rocuronium, pancuronium, vecuronium
• isoquinolones – atracurium, cisatracurium
• the pharmacodynamic response is dependent on the number of receptors occupied
  • dose dependent according to the laws of mass action
  • >70% to elicit a response

The factors which alter the response (number of receptors occupied) may be separated into

• pharmacodynamic factors
• pharmacokinetic factors
• pharmaceutical and drug interaction factors

Pharmacodynamic factors

• Decreased pH increases the affi­nity of non depolarising NMB
• Electrolyte disturbances
  • Ca disturbances affect the release of ACh from the presynaptic terminal (triggered by Ca)
    • hypocalcaemia potentiates blockage
  • magnesium
    • hypomagnesemia
  • potassium
    • hyperkalaemia leads to increased drug effect

Pharmacokinetic factors (affect the amount of drug reaching the receptor)

• Absorption
  • dose given (higher dose – more receptors occupied)
• Distribution
  • lipid soluble drugs such as vecuronium may accumulate in lipid rich tissue (esp infusion)
  • Patients with decreased lipid content may lead to increased effect site conc
• Metabolism
  • hepatic failure may lead to decreased metabolism of a drug – pancuronium
  • deranged pH changes the metabolism of the isoquinolones which use Hoffmann elim
• Excretion
  • renally excreted drugs, especially minimally metabolised vecuronium, rocuronium

Pharmaceutical/ drug interactions

• storage of the drug (isoquinolones must be stored at 4 degrees to maintain potency)
• aminoglycosides – decreased prejunctional ACh release
• volatile anaesthetics – mechanism not well understood
• frusemide – potassium effect, may interfere with cAMP and ACh release

JC 2019

Answer by JC