Question 19

Describe factors that prolong the action of neuromuscular blocking agents (60% of Marks) Outline the pharmacokinetics and pharmacodynamics of vecuronium (40% of Marks)

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College Answer

The first part of the question required a description of the factors prolonging neuromuscular blockade which would include a description of the reasoning behind the prolongation. Many candidates missed the important factors and most did not include any explanation. Some candidates confused the causes of "delayed onset" and "prolonged action". For vecuronium mechanism of action all the details were expected, superficial explanations did not score well. The following key words were expected to be included in the mechanism description; competitive binding/ Nicotinic ACH (N2)/alpha subunit/post synaptic. In pharmacokinetics, details on hepatic metabolism to active metabolites, renal and biliary excretion along with accurate values of the volume of distribution, protein binding and half-life were expected to score full marks. These facts were frequently lacking in candidate answers.


This question is very similar to Question 6 from the first paper of 2021, which asked the exact same things, but in a different order. The pass rate has improved from 13% to 20%, suggesting that people are still not using any vecuronium in their practice, or that, upon reading the past papers, the idea that vecuronium might come up again seemed implausible.

Factors prolonging neuromuscular blockade:

  • Impaired clearance (renal or hepatic dysfunction, hypothermia)
  • Factors which increase the potency of vecuronium:
    • Factors that reduce the synthesis or storage of acetylcholine
      • Hemicholinium
      • Vesamicol
    • Factors that decrease acetylcholine release
      • Foetal/neonatal motor endplates
      • General anaesthetic agents (volatiles)
      • Regional local anaesthesia
      • Frusemide
      • Calcium channel blockers
      • Aminoglycosides
    • Factors that partially depolarise the motor endplate
      • Hypermagnesemia
      • Hypocalcemia
      • Hypokalemia
    • Factors that reduce the number of acetylcholine receptors, such as myasthenia gravis (for depolarising agents, this slows the onset)

Now, as for vecuronium:

Class Non-depolarising NMJ blocker
Chemistry Aminosteroid
Routes of administration IV or IM only
Absorption Poor absorption; minimal oral bioavailability
Solubility pKa=8.97; good water solubility
Distribution VOD= 0.2L/kg, 77% protein-bound
Target receptor Nicotinic acetylcholine receptors at the neuromuscular junction
Metabolism Perhaps 5% is metabolised; one of the metabolites has about 80% of the potency of the parent drug (3-desacetylvecuronium)
Elimination 30-40% is cleared by the liver and into the bile (good lipid solubility); another 30% is renally eliminated as unchanged drug
Time course of action Half-life 110 minutes
Mechanism of action Nondepolarising neuromuscular junction blocker (competitive antagonist of acetylcholine); by binding to the nicotinic acetylcholine receptor, this agent blocks the binding of acetylcholine, and prevents the cation channel from opening, thus preventing the depolarisation of the motor endplate.
Clinical effects Nondepolarising neuromuscular junction blockade; also:
- Minimal ganglionic effects
- Minimal vagolytic effect (slight increase in HR)
- Minimal sympathomimetic effect (slight increase in HR)
- Minimal histamine release (only slightly more than pancuronium)
Single best reference for further information Miller et al (1984)