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16 Cards in this Set
- Front
- Back
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Pharmacokinetics and dynamics may be altered by variations in genes for?
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drug metabolizing enzymes, drug targets, transporters, DNA repair enzymes
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Cytochrome P450 enzymes
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>50 isoenzymes (diff genes) highly polymorphic
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What P450 enzyme metabolizes 25% of Rx (eg tamoxifen)
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CYP2D6
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What P450 enzyme metabolizes 5% of Rx (eg warfarin)?
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CYP2C9
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What happens to endoxifen concentrations after SSRI admin? Why?
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Lower endoxifen conc; affects efficacy because SSRIs are potent CYP2D6 inhibitors.
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When is hemorrhagic risk highest for warfarin dosage?
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first two weeks
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Where is warfarin's role in the clotting cascade?
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CYP2C9 --> warfarin --> VKOR --> inhibits activation of vit K --> inactive factors --> can't clot
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What happens if CYP2C9 is underactive?
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warfarin sensitivity
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What does CYP2C9 do?
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metabolizes >90% active warfarin
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What is VKOR?
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vitamin K epoxide reductase; inhibited by warfarin, important for replenishment of vit K
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What are variant alleles of VKOR?
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VKORC1 snps gene associated with resistance to warfarin
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What is R98W and VKCFD2?
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Vit K clotting factor def type 2; VKORC1 gene variant that highly decreases enzyme activity and has clinical spontaneous bleeding; autosomal recessive
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Where are the common snps associated with altered response warfarin?
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non coding region
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What is a set of closely linked alleles inherited as a unit?
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haplotypes
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Due to linkage disequilibrium, identification of a SNP associated witha phenotypic effects tells us what?
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only the region wherein the causal genetic change resides; such as the noncoding region
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How can a snp in an intron or UT region be causal?
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through mediation of mRNA structure/stability/translation
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