Sun28November0440PM 50

True / False

Is metabolised primarily in the liver via glucuronidation Correct

Can produce significant respiratory depression in neonates Correct

Is a prodrug that requires conversion to morphine to produce analgesia Incorrect answer selected

Produces no significant analgesia in 4-10% of patients Correct

Is demethylated to morphine by cytochrome P-450 enzymes (CYP2D6) Incorrect answer selected

Explanation

Codeine is readily absorbed from the gastrointestinal tract and metabolised by O- and N-demethylation in the liver to morphine and norcodeine which with codeine are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. The morphine in turn is metabolised into morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) via glucuronidation by phase II metabolism enzyme UDP-glucuronosyl transferase-2B.

Approximately 60% of morphine is converted to M3G, and 6-10% is converted to M6G. M3G is inactive but M6G is reported to be between 4 and 650 times more potent than morphine on the MOP receptor.

When codeine is ingested, it is converted to morphine in the liver by cytochrome P450 2D6 (CYP2D6). Some people have DNA variations that make this enzyme more active, causing codeine to be converted to morphine faster and more completely than in other people. These 'ultra-rapid metabolisers' are more likely to have higher than normal amounts of morphine in their blood after taking codeine. High levels of morphine and M6G can result in respiratory depression/obstruction particularly those with a history of obstructive sleep apnoea.

The estimated number of 'ultra-rapid metabolisers' is generally 1 to 7 per 100 people, but may be as high as 28 per 100 people in some ethnic groups. The converse is the case in Caucasians where up to 10% lack CYP2D6; in these cases codeine is not demethylated to morphine and therefore no significant analgesia is achieved.

Neonates are particularly sensitive to the effects of codeine and other opioids. There are reports of neonates having a respiratory arrest being fed breast milk from 'ultra-rapid metabolisers' of mothers taking codeine.

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Average score: 75.40%

Times answered: 239