Pharmacology Notes

Although codeine (3-methylmorphine) is widely used, its place in therapy is uncertain. It is a weak opioid, but is metabolised by cytochrome P450 2D6 to morphine, which may result in most of its analgesic action. Approximately 7% to 10% of Caucasians and 1% to 2% of Asians are poor metabolisers of codeine to morphine, and have no detectable analgesic effect from codeine. In these individuals there is no benefit and some potential harm in increasing the dose because codeine itself can cause constipation and drowsiness.

The lowest dose of codeine producing significant analgesia is not well defined. In acute pain of moderate intensity, studies suggest that on average a dose of 30 mg of codeine is required to produce an analgesic effect. For persistent pain, the lowest effective dose should always be used. The recommended dose for codeine is 30 to 60 mg every 4 to 6 hours. At doses of 60 mg, codeine may be associated with severe constipation, dizziness and drowsiness. Exceeding the recommended daily dose of codeine is unlikely to provide additional analgesia and increases the risk of restlessness and excitement.

Codeine has a longer elimination half-life (3 to 4 hours) and greater oral bioavailability than morphine. Otherwise its actions and adverse effects are similar to morphine. 

. Constipation is frequent and often distressing (and may limit dosage); with chronic use, co-administration of laxatives is necessary. Codeine shares all the properties of other opioids, including the potential for dependence.