Idiosyncratic ADRs

As noted earlier, idiosyncrasy is an unpredictable reaction of any intensity observed in a small number of the individuals. ^1,4 When a drug produces its usual effect on a person at an unexpectedly high dose, the patient is said to be hyporeactive. When a drug produces its effect at an unexpectedly low dosage, the patient is said to be hyperreactive. Some of this diversity in response rates can be attributed to differences in the rate of drug metabolism by the various cytochrome P450 enzymes.

For example, codeine, a pro-drug, is metabolized by demethylation into morphine, its active metabolite, by the cytochrome P450 isoenzyme CYP2D6.²⁰ Isoenzyme CYP2D6 is subject to genetic polymorphism. Up to 10% of patients are poor metabolizers of codeine and do not experience analgesia in response to treatment with codeine. Another 10% of the patients are rapid metabolizers of codeine, i.e., they rapidly convert codeine to morphine and may experience severe toxicity (including death), even with therapeutic doses.