A 4-year-old child receives routine codeine after tonsillectomy and dies of respiratory depression despite receiving an age-appropriate dose. Which pharmacogenomic finding best explains this outcome?
- A UGT2B7 deficiency causing morphine-3-glucuronide accumulation
- B CYP2D6 ultrarapid metabolizer status producing excessive morphine ✓
- C CYP3A4 induction converting codeine to normeperidine
- D Pseudocholinesterase deficiency prolonging codeine action
Correct answer: B. CYP2D6 ultrarapid metabolizer status producing excessive morphine
Explanation
Codeine itself has negligible analgesic activity and is a prodrug, relying on CYP2D6-mediated O-demethylation to morphine. Ultrarapid metabolizers carry duplicated functional CYP2D6 alleles and generate supratherapeutic morphine concentrations, causing fatal respiratory depression in children. This is why codeine is contraindicated after tonsillectomy or adenoidectomy in children under 12 years. Normeperidine is a meperidine metabolite, which kills option C.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.
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