Pharmacovigilance and Pharmacogenetics Quiz

See Pharmacogenetics. Option A is correct because codeine is a prodrug (a medicine that is only weakly active until the body converts it into its active form). The enzyme CYP2D6 (one of the cytochrome P450 family of liver enzymes that break down or activate many drugs) turns codeine into morphine. An ultra-rapid metaboliser has increased CYP2D6 activity, often because of extra copies of the gene, so a standard dose produces unexpectedly high morphine levels. The result can be opioid toxicity: drowsiness, pinpoint pupils and slow, shallow breathing (respiratory depression), which can be fatal, particularly in children. For this reason the BNF states that codeine is contra-indicated (must not be used) in patients of any age who are known to be ultra-rapid metabolisers. Poor metabolisers show the opposite pattern, with little morphine made and poor pain relief. A simple way to remember it is that the speed of the activating enzyme moves the effect in the same direction: a fast enzyme makes too much active drug, and a slow enzyme makes too little.

• Codeine: a prodrug that the enzyme CYP2D6 turns into morphine.
• Ultra-rapid metaboliser: increased CYP2D6 activity means a standard dose gives unexpectedly high morphine levels.
• Risk: opioid toxicity with respiratory depression, which can be fatal, so the BNF contra-indicates codeine in known ultra-rapid metabolisers.
• Poor metabolisers: little morphine is made, so pain relief is poor.