Sun28November0628PM 7

A 65-year-old woman has been admitted to the Emergency Department with signs of opioid toxicity.

She has been taking 60 mg co-codamol six hourly for cancer pain. Her glomerular filtration rate is measured as 30 ml/minute.

Which one of the following metabolites of codeine is likely to be the principal cause of her clinical signs?

(Please select 1 option)

Norcodeine

Morphine-6-glucuronide Correct

Codeine-6-glucuronide

Morphine

Morphine-3-glucuronide

Explanation

The conversion of codeine into norcodeine by the cytochrome (CYP3A4) and into codeine-6-glucuronide by glucuronidation usually represents 80% of codeine clearance, and conversion of codeine to morphine by CYP2D6 represents only 10% of codeine clearance.

Morphine is further metabolised to morphine-3-glucuronide and morphine-6-glucuronide. Morphine and morphine-6-glucuronide have opioid activity. Morphine-6-glucuronide is thought to be 45-360 times more potent than morphine and is much more likely to accumulate in patients with renal impairment.

Glucuronides are eliminated by the kidney and are thus susceptible to accumulation in renal failure.

Codeine-6-glucuronide, norcodeine and morphine-3 glucuronide have no opioid activity.

Morphine excretion is not significantly affected by renal insufficiency.

Answer Statistics

1

7%

2

64%

3

4%

4

15%

5

12%

Times answered: 245