FRCA Notes


Diamorphine


  • Diamorphine is an ester, a di-acetylated morphine derivative with a potency 2x that of morphine
  • It is a pro-drug with no affinity for opioid receptors - active metabolites are responsible for its effects
  • As with all opioids it is a weak base
Diamorphine chemical structure

Presentation

  • Tablets are available but not in the UK
  • A white powder containing 5mg, 10mg, 30mg, 100mg or 500mg of the hydrochloride salt, which is dissolved to form a solution for administration

Uses/doses

  • Largely an analgesic, although can be used to treat dyspnoea e.g. in palliative care settings

  • Neuraxial doses:
    • Intrathecal: 300-400micrograms
    • Epidural: 1-3mg

Absorption

  • pKa 7.6
  • 37% unionised at pH 7.4

  • Reduced oral bioavailability due to extensive 1st pass metabolism
  • Has a relatively high lipid solubility and therefore is well absorbed from the GI tract and can be used effectively by a SC route

  • Has a higher lipid solubility than morphine, therefore
    • Diamorphine has a more rapid onset than morphine
    • Has a shorter duration of action
    • Is less likely to cause (late) respiratory depression than morphine

Distribution

  • 40% plasma protein bound
  • Volume of distribution: 350L
  • Plasma half-life 5mins

Metabolism

  • Undergoes ester-hydrolysis by plasma and tissue esterases in the liver, plasma and CNS
  • Active metabolites are morphine and 6-monoacetylmorphine, which are both MOP receptor agonists

Excretion

  • 50-60% of an administered dose appears in the urine as morphine derivatives
  • 0.13% is excreted unchanged
  • Elimination half-life 3mins
  • The clearance of the morphine component is 3.1 ml/min/kg

  • Largely similar to morphine/that of a typical opioid
  • Produces significantly more euphoria than other opioids, hence its place as a drug of abuse (heroin)