Vecuronium Pharmacology

Master answer

FACTORS

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)
  • hypercalcaemia results in shortened blockade
  • hypocalcaemia potentiates blockage
  • magnesium
    • stabilise membranes and decrease release and sensitivity to ACh
  • potassium
    • hypokalaemia leads to membrane hyperpolarisation (decreased drug effect)
    • hyperkalaemia has the reverse effect
• pathology
  • myasthenia gravis patients have defective nACh receptors
  • eaton-lambert syndrome patients have decreased ACh release
  • burns – leads to receptor mediated resistance to non depolarising NMBD

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)
  • women have higher lipid content which may lead to reduced effect site conc
• metabolism
  • hepatic failure may lead to decreased metabolism of a drug – pancuronium
• excretion
  • renally excreted drugs, especially minimally metabolised vecuronium, rocuronium

Pharmaceutical / Drug Interactions

• Increase effect
  • aminoglycosides – decreased prejunctional ACh release
  • volatile anaesthetics – mechanism not well understood
  • frusemide – potassium effect, may interfere with cAMP and ACh release
• decrease effect
  • anticonvulsants – may develop resistance to pancuronium, vecuronium

JC 2019

Answer by JC