FRCA Notes


Atracurium


  • Atracurium is a benzylisoquinolinium NMBA formed as a mixture of ten stereoisomers, as it has four chiral centres
Atracurium chemical structure

Presentation

  • Colourless solution of 10mg/ml stored at 4'C (i.e. fridge) and pH 4.0
  • It is formed as atracurium besylate and is therefore a base
    • Bases are formed as drug-sulphate/similar e.g. morphine sulphate, bupivacaine hydrochloride, atracurium besylate
    • Acidic drugs are formed as sodium-drug e.g. sodium diclofenac, sodium thiopental

Dosing

  • Single dose 0.5mg/kg provides intubating conditions in 90-120s
  • Can be used as an infusion to maintain neuromuscular blockade on intensive care

  • Is metabolised by two pathways:
    1. Ester-hydrolysis (60%)
    2. Hoffman elimination (minor pathway, 40%)

Ester hydrolysis

  • Non-specific esterases hydrolyse atracurium into:
    • Monoquaternary alcohol
    • Quaternary acid
    • Laudanosine
  • Is accelerated by acidic conditions although changes within the clinical range probably don't affect rate of ester hydrolysis

Hoffman elimination

  • Spontaneous breakdown in a temperature- and pH-dependent fashion into:
    • Monoquaternary acrylate (can cause seizures)
    • Laudanosine
  • Process is slowed by acidosis and hypothermia

Laudanosine

  • Is a glycine antagonist
  • Is a tertiary amine
  • Can cause seizures (in concentrations in excess of those encountered clinically)
  • No neuromuscular blocking properties
  • Rapidly eliminated by renal excretion

Adverse effects

  • Associated with histamine release, which may cause bronchospasm, hypotension and other anaphylactoid symptoms
  • Critical illness myopathy

  • Cis-atracurium is one of the ten stereoisomers in atracurium
  • Safe for use from 2yrs upwards

Uses and presentation

  • Presents as a colourless solution in 2mg/ml or 5mg/ml concentrations and is stored at 4'C
  • Used for induction and maintenance of muscle paralysis at a dose of 0.15 - 0.2mg/kg

  • Is 3-4x more potent than atracurium and therefore has a slower onset time
    • The onset time can be reduced by increasing the dose
    • Cis-atracurium has a low potential for histamine release which makes this viable

Pharmacokinetics

  • Does not undergo ester hydrolysis
  • Metabolism is 100% by Hoffman degradation
  • All metabolites are void of neuromuscular blocking properties
  • No changes to kinetic profile in end-stage renal or hepatic failure