Codeine

[SH4:p115]

Structure

• Substitution of a methyl group for the hydroxyl group on carbon 3 of morphine

Structure-activitiy relationship

• Methyl group substitution
  --> Limits first-pass hepatic metabolism
  --> Improved efficacy with oral administration

NB:

[MCQ:Q148] Codeine has less first pass effect than morphine

Pharmacodynamics

• Less liable for physical dependence than morphine
• Produces minimal sedation, N&V, and constipation
• Even in large dose, apnoea is unlikely.

Pharmacokinetics

Elimination half-time = 3 - 3.5 hours

Metabolism

• About 10% of codeine is demethylated in liver
  --> Becomes morphine
  --> Accounts for analgesic effect
• The remaining codeine is demethylated to
  --> Norcodeine
• Norcodeine is inactive
  --> Excreted by kidney, or conjugated

Clinical

Administration

Not recommended for IV administration
* Due to histamine-induced hypotension

Antitussive

Codeine 15 mg PO

Analgesia

Maximal analgesia occurs with 60mg codeine
* Equivalent to 650mg aspirin