FRCA Notes

Codeine and Dihydrocodeine

  • Codeine is 3-methylmorphine, a naturally occurring morphine pro-drug
  • It is 10x less potent than morphine
  • Not suitable for use in severe pain
  • Analgesic at doses of 15-60mg
  • Anti-tussive
  • Anti-diarrhoeal
  • Hypnotic/anxiolytic
  • Use in those <12yrs old restricted because of the risk of morphine toxicity

Absorption

  • The methyl group reduces the 1st pass metabolism and therefore has a higher oral bioavailability (50%) than morphine

Metabolism

  • 5 - 15% is excreted unchanged in the urine
Morphine metabolic pathway
  • O-demethylation to morphine is dependent on non-inducible CYP2D6 enzyme activity
    • Ultrafast metabolisers generate increased amounts of morphine and therefore its (side-) effects
    • Poor metabolisers (enzyme absent in 7-10% of Caucasians, 1-3% of non-Caucasians) experience little analgesia
  • Of codeine's metabolites, only morphine has any significant MOP receptor activity

  • Dihydrocodeine is a synthetic opioid
  • It is structurally similar to codeine although 2x as potent (i.e. 5x less potent than morphine)
  • It has poor (20%) oral bioavailability
  • It is less dependent on CYP2D6 for its effects and has a greater efficacy at the MOP receptor than codeine
  • Its effects are therefore more predictable than codeine
  • Metabolic pathway as for codeine