Gainof Function Polymorphisms Leading to an ADR

This is liable to be important when the drug itself is inactive but has an active metabolite responsible for its pharmacological and toxicological activities. An example is codeine, which is frequently used for the treatment of pain. About 10% of codeine undergoes O-demethylation to morphine, which is responsible for the analgesia. This biotransformation is performed by CYP2D6. Thus, poor metabolizers experience no pain relief from using codeine, whereas in ultrarapid metabolizers, which constitute between 1% and 30% of the population depending on ethnicity (69,70), the rate of conversion to the active metabolite may be greater leading potentially to increased respiratory, psychomotor, and pupillary effects (71,72). However, whether this is true in reality needs specific studies in ultrarapid metabolizers.

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