Pharmacogenetics in action

Article Outline

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The management of painful crises is one of the challenges in the care of children with sickle cell disease. Some children require significant doses of opiates, and poor pain management is, unfortunately, all too common in this population. This may ultimately result in some of these children and young adults becoming stigmatized as “drug-seeking.”

In the current issue of The Journal, Brousseau et al provide valuable insight into one potential explanation for poor pain control in this disease. These investigators undertook genotyping of CYP2D6, the enzyme responsible for converting codeine to its active metabolite. Although the study design and analysis is complicated, the take-home message is simple. A large number of children whose painful crises are not responding to codeine have a polymorphism of CYP2D6 that would be predicted to result in less active conversion of the drug to its active form. Thus, in at least some of these children, a biologic explanation exists for their apparent unresponsiveness to opiates. The implications of this for patient care are significant, and there now are a number of analgesics which do not depend upon the CYP2D6 mechanism for their action.