23A19: Exam Report

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

63% of candidates passed this question.

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.

L2i / 23A19: Describe factors that prolong the action of neuromuscular blocking agents (60% of Marks) Outline the pharmacokinetics and pharmacodynamics of vecuronium (40% of Marks)


Plasma Cholinesterase Deficiency

  • Synthesised in liver
  • Present in plasma, liver, brain, kidney, intestine & pancreas
  • Does not have significant [] in NMJ
  • When Suxamethonium (SUX) is metabolised by Plasma in plasma, its blockade is terminated by the diffusion away from NMJ into ECF
  • Altered levels of plasma cholinesterase significantly prolong the action of SUX
  • Other drugs metabolised by Plasma Cholinesterase that will compete for the enzyme and prolong the effect of SUX include
    • Mivacurium
    • Ester Las
    • Metoclopramide
  • Liver Disease: Plasma cholinesterase levels must by <75% for prolonged SUX effect, therefore hepatic dysfunction severe to reduce levels
  • Pregnancy: associated with reduced plasma cholinesterase levels but does not result in prolonged paralysis due to the increase Vd at term
  • Genetically reduced enzyme function of Plasma Cholinesterase

Phase II Blockade

  • Phase I blockade is due to the slow hydrolysis of SUX (cf ACh).  There is a sustained opening of the receptor ion channels and the end plate remains permeable to Na & K, resulting in sustained depolarisation of postjunctional membrane
  • The depolarised endplate cannot respond to subsequent ACh release and further nerve stimuli are totally ineffective so a depolarising neuromuscular blocked occurs
  • In Phase II blockadel a single large dose (>2mg/kg), repeated doses or infusions of suxamethonium result in post junctional membranes that do not respond normally to ACh even when they have been repolarised (mechanism unknown)
  • Neonates & Myasthenia Gravis pts at high risk of developing Ph II blocks

AMINOSTEROIDS: Determined by peripheral redistribution

Hepatic Disease

  • Vecuronium: increased duration of action due to reduced clearance (deacetylation/biliary excretion)

  • Atracurium / Cisatracurium: no effect

  • Mivacurium: may accumulate in end stage liver disease due to reduced levels of Plasma Cholinesterase

Renal Disease

  • Vecuronium / Rocuronium: modest accumulation and prolongation of block

  • Atracurium, Cisatracurium, Mivacurium: no effect


  • Increases NMJ sensitivity to pancuronium

  • Prolongs duration of neuromuscular blockade for Vecuronium/Pancuronium due to slowing down of hepatic enxyme activity

  • Reduces Hofmann elimination and prolongs Atracurium duration of action


  • Immature hepatic enzymes, reduced biliary clearance


  • Reduced hepatic/renal blood flow and resultant enzyme activity/plasma clearance

NB: Be aware of multiple drug interactions that can potentiate neuromuscular blockade.  These have not been included as the question specifically asks for prolonging duration of action.





  • Competitive antagonism of pre & post junctional nAChR

  • Binding to one/both the a-subunits prevents access by ACh to depolarise the receptor

  • Therefore prevents depolarisation

Onset & Duration

  • Onset 3-5mins

  • Duration 20-35% (until 25% twitch)


  • Does not alter intra-ocular pressure


  • Does not release histamine therefore devoid of circulatory effects

Variability Of Responses


  • Onset quicker (high CO)

  • Duration longer (immature enzymes, reduced biliary clearance)


  • Longer duration (reduced renal & hepatic BF and enzyme activity)

Renal Dysfunction

  • Prolonged t1/2b due to reduced plasma clearance

Hepatic Dysfunction

  • Prolongs t1/2b and longer duration of action



  • IM/IV


  • Vd 250ml/kg

  • Higher lipid solubilty facilitates uptake into hepatocytes

  • PPB 60-90%


  • T1/2b 50mins

  • 40% Hepatic deacetylation to an active but reduced potency metabolites


  • Vd 250ml/kg

  • Higher lipid solubilty facilitates uptake into hepatocytes

  • PPB 60-90%Biliary excretion is the major route of elimination

  • 30% excreted unchanged in urine and as metabolites