Opioids and acute pain medicines — formative SAQs

1. Mechanism and unpredictability

Codeine is a prodrug with little intrinsic analgesic activity. About 5 to 10 per cent of a dose is O-demethylated by the cytochrome P450 2D6 (CYP2D6) enzyme into morphine, and it is the morphine that provides the analgesia. Because CYP2D6 activity is genetically determined, the conversion varies enormously between individuals: an ultrarapid metaboliser converts codeine to a dangerous excess of morphine, while a poor metaboliser converts almost none and gets no analgesia. The dose written on the prescription therefore does not predict the opioid the child actually receives, which is why codeine is both ineffective in some and lethal in others. Tramadol shares this mechanism, being converted by CYP2D6 to the active O-desmethyltramadol. [2] [3]

2. Regulatory contraindication and the driving event

Codeine is contraindicated in children under 12 years, and contraindicated for the management of postoperative pain in children and adolescents under 18 years after tonsillectomy or adenoidectomy. Tramadol carries the same restrictions. These were issued as a United States Food and Drug Administration boxed warning and as United Kingdom and European Medicines Agency contraindications. They were driven by a series of deaths from respiratory depression in young children, many of them CYP2D6 ultrarapid metabolisers, following tonsillectomy or adenoidectomy for obstructive sleep apnoea. The risk was judged unacceptable given that paracetamol, NSAIDs, and morphine or oxycodone provide better and safer analgesia. [1] [2]

3. Breastfeeding and a safe plan

The mother should not take codeine while breastfeeding. A breastfeeding mother who is a CYP2D6 ultrarapid metaboliser can generate excess morphine and pass it to her infant through breast milk, with documented cases of neonatal opioid toxicity; the same contraindication applies to tramadol. For her migraine I would advise a non-opioid option reviewed by her own prescriber. For the child, a safe modern post-tonsillectomy plan is scheduled paracetamol and ibuprofen with oral morphine or oxycodone as rescue, given with family safety-netting about over-sedation and airway obstruction, and with confirmation at the prescription that codeine and tramadol are absent. Because he has obstructive sleep apnoea, I would monitor him overnight with oximetry and use the smallest effective opioid dose, avoiding any background infusion. [1] [2] [3]