Problem
One of the genes involved in codeine metabolism is CYP2D6, a component of the cytochrome P-450 family. This enzyme mediates the O-demethylation of codeine to produce morphine. There are over 80 distinct alleles identified for this gene. Many alleles (classified as 'normal' alleles) do not alter enzyme activity levels. Other alleles inactivate CYP2D6 activity ('poor metabolizer' alleles). A few individuals have CYP2D6 genes where a gene duplication event has created an adjacent, a fully functional extra copy of the CYP2D6 gene ('ultrarapid' alleles).
A 62-year-old man with bilateral pneumonia cough does not respond to over-the-counter medication. He is given a standard dosage of oral codeine to relieve the cough. A few days into treatment, the patient becomes unresponsive and develops a life-threatening morphine intoxication.
Discuss why this patient has morphine intoxication, how you treat the intoxication, and how you test for CYP2D6 activity. Would you try any other members of the family? Why or why not? Would you push for different drug sensitivities? If so, what would you consider testing for?