FRCA Notes


Alfentanil


  • Alfentanil is a synthetic phenylpiperidine derivative

Presentation

  • It is a colourless solution containing 500μg/ml or 5mg/ml alfentanil

Uses

  • As an IV bolus for short-acting analgesia e.g.:
    • At induction, where its rapid onset/offset makes it particular suited to obstetric GA
    • During procedures performed under procedural sedation for periods of stimulation e.g. endoscopy

  • As a continuous infusion e.g.:
    • As a target-controlled infusion for surgical anaesthesia using Maitre or Scott models
    • As a simple infusion on intensive care to facilitate ETT tolerance
    • In palliative care settings, to provide analgesia to those with renal failure in whom morphine or oxycodone is unsuitable

  • A pure MOP receptor agonist
  • Potency 5x that of morphine, but 0.25x that of fentanyl

Absorption

  • pKa 6.5, therefore 89% unionised at pH 7.4
  • Relative lipid solubility vs. morphine: 90x

  • Although it has a lower lipid solubility than fentanyl, its onset of action is quicker than fentanyl's due to:
    • Higher unionised fraction at physiological pH
    • Lower potency = more drug required = higher concentration gradient

Distribution

  • 90-92% plasma protein bound
  • Volume of distribution 0.6/kg

  • Context-sensitive half-time after:
    • 1hr - 30mins
    • 2hrs - 40mins
    • 8hrs - 60mins

Metabolism

  • N-demethylated in the liver by CYP3A4 to noralfentanil
    • As midazolam is also metabolised by CYP3A4, concurrent use increases the elimination half-life of both
  • Metabolites are conjugated and excreted in the urine

Excretion

  • Clearance 6ml/min/kg
  • Elimination half life is 100mins (much shorter than fentanyl (190mins) despite the lower clearance, as it has a lower volume of distribution)