Pharmacogenomics II Flashcards
what are the gene polymorphisms that affect pharmacokinetics?
metabolic enzymes: CYP2D6 CYP2C19 CYP2C9 DPD TPMT
drug transporters:
solute carrier organic anion transporter 1B1
tamoxifen, codeine, and paroxetine are metabolized by what enzyme?
CYP2D6
what drugs are metabolized by CYP2D6?
tamoxifen
codeine
paroxetine
patients who are poor metabolizers for CYP2D6 will have what response to tamoxifen? why?
low
cannot be converted to active form
women with ER positive breast cancer need to be screened for what polymorphism?
CYP2D6
what is the effect of CYP2D6 on codeine?
activation to active compound (morphine)
what is the effect of CYP2D6 on tamoxifen?
activation to active compound (4-OH tamoxifen)
what is the effect of CYP2D6 on paroxetine (SSRI)?
metabolism to less active compound
clopidogrel, omeprazole, and lansoprazole are metabolized by what enzyme?
CYP2C19
which drugs are metabolized by CYP2C19 enzyme?
clopidogrel
omeprazole
lansoprazole
what is the effect of CYP2C19 on clopidogrel?
activation
what might be a good alternative to clopidogrel therapy in patients with inactive CYP2C19 alleles?
asdf
what is the effect of CYP2C19 on omeprazole?
inactivation
CYP2C19 poor metabolizers will have what omeperazole serum levels?
high
what enzyme is responsible for warfarin metabolism?
CYP2C9
what is the effect of CYP2C9 on warfarin?
clears warfarin
CYP2C9 poor metabolizers will show what levels of warfarin?
high
polymorphisms in what proteins affect 5-FU?
DPD
TYMS
polymorphisms in what protein affects 6-MP?
TPMT
what is the function of DPD?
reduces toxicity of 5-FU by inactivating it
decreased DPD leads to what? are these changes pharmacokinetic or pharmacodynamic?
increased adverse effects of 5-FU
pharmacodynamic
what is the function of TPMT?
inactivates 6-MP
polymorphism causing a decrease in activity of SLC01B1 leads to what?
high levels of simvastatin
polymorphism at the ADRB2 gene has what affect on albuterol therapy?
decreased
polymorphisms in what proteins increases the risk of venous thromboembolisms with oral contraceptive use?
factor V leiden
prothrombin
individuals with a polymorphism in HLA-B 57:01 protein have a high risk of hypersensitivity (stevens johnson syndrome) when given what drug?
abacavir
individuals with a polymorphism in HLA-B 57:01 protein have what response when given abacavir?
hypersensitivity (stevens johnson syndrome)
alpha interferon therapy is used for what condition?
HCV
