FRCA Notes

Non-depolarising Neuromuscular Blocking Agents

  • All NMBA have at least two charged nitrogen atoms
    • The distance between these two atoms is called the intra-onium distance
    • An intra-onium distance of 12.5 ångström units (1.25nm) gives the highest receptor affinity
    • Drug potency falls if this distance is increased or reduced

  • Non-depolarising NMBA competitively bind the ɑ-subunit of the nAChR at the post-junctional membrane of the NMJ
  • 70% of receptors need to be blocked before neuromuscular blockade can be detected by peripheral nerve stimulators
  • The block provided is a Phase II block
  • Non-depolarising NMBA can be classified by their chemical structure:
    • Aminosteroids
    • Benzoisoquinoliniums

Aminosteroids

Drug Structure Intra-onium distance (nm) Presentation Intubating dose (mg/kg) Duration of effect Metabolites
Rocuronium Monoquaternary 1.9 10mg/ml solution 0.6 - 1.2 Intermediate Excreted (mostly)
unchanged
Vecuronium Monoquaternary 1.9 10mg crystalline powder 0.1 Intermediate Active (3-hydroxy) +
inactive metabolites
Pancuronium Bisquaternary 1.14 2mg/ml solution 0.1 Long Active (3-hydroxy) +
inactive metabolites

Benzoisoquinoliniums

  • Atracurium (and cis-atracurium)
  • Mivacurium
  • Tubocurarine

Other classifications

  • Classification by duration of action:
    • Short: mivacurium
    • Intermediate: rocuronium, vecuronium, atracurium
    • Long: pancuronium

  • Relatively polar molecules that are unable to cross lipid membranes
  • This gives them a relatively small volume of distribution

  • Metabolism varies between molecules:
    • Plasma-based hydrolysis
      • Ester hydrolysis: atracurium (60%)
      • Hoffman degradation: atracurium (40%), cis-atracurium (100%)
      • Plasma cholinesterase: mivacurium
    • Hepatic metabolism: pancuronium, vecuronium
    • Excretion unchanged: rocuronium

  • Multiple factors can influence the duration of effect of non-depolarising agents
Patient factors Drug interaction
Hypothermia
(impaired metabolism)		 Volatiles
(depress somatic CNS reflexes)
Acidosis
(impaired metabolism)		 Calcium channel blockers< br>
Lithium
Magnesium
(BJA, 2021)
Aminoglycosides
Tetracyclines