Vkorc1

Warfarin

Dihydropyrimidine dehydrogenase

5-Fluorouracil

44-y/o woman

Glucuronosyltransfer- Irinotecan ase (UDPGT-1A1)

49-y/o woman and 63-y/o man

Thiopurine methyl- 6-Mercaptopurine, 6- Several case histories transferase thioguanine, azathioprine

Azathioprine

65-y/o man with heart transplant

Morphine toxicity

Varying degrees of warfarin response

Stomatitis, diarrhea, and pancytopenia

Neutropenia and diarrhea

Severe neutropenia

Severe neutropenia, sepsis

Toxicity attributed to an 20-21

ultrarapid CYP2D6 genotype

Warfarin patients segregate 22

into low-dose (mean mg/day) and high-dose (~7 mg/day) phenotypes

Toxicity attributed to a 23, 24

nonfunctional enzyme due to a point mutation in the splice site

Severe toxicity attributed to a 25 mutant promoter UDPGT1A1*28

Neutropenia and CNS 26

leukemia associated with TPMT deficiency; leukemic relapse associated with elevated TPMT activities

Death due to sepsis acquired 27

after neutropenia clinical interest. CYP2D6 catalyzes the conversion of the prodrug codeine to morphine. Poor metabolizers, who typically carry null alleles of CYP2D6, found in as many as 6% of Caucasians,29 do not obtain pain relief from ingestion of codeine.31 CYP2D6 ultrarapid metabolizers have an enhanced capacity to metabolize codeine to morphine and hence may exhibit an exaggerated response

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