SM46_Pharmacogenomics Flashcards
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The use of pharmacogenomics can result in lower risks for ________, a major cause of mortality
Adverse drug reactions (ADRs). This is because you can personalize medicine using genomic information
Genetically based variability in drug responses can be attributed to genes affecting either _______ or _____
pharmacodynamics (direct effect on molecular target) or pharmacokinetics (plasma or tissue drug concentration)
For standard drugs, low metabolizing capacity may cause……
decreased elimination rate (poor) and increased toxicity risk (poor and intermediate)
For pro-drugs, low metabolizing capacity may cause….
decreased activation (Poor) and reduced effectiveness (poor and intermediate)
For standard drugs, rapid metabolizing capacity causes….
increased elimination rate, reduced effectiveness
For pro-drugs, rapid metabolizing capacity causes…
increased activation, increased toxicity risk
Genetic variants of drug metabolizing enzymes can result in only normal function, reduced function and increased function (true or false)
False, it can also result in non-function
True or False:
Genetic variants of drug metabolizing enzymes can result from single SNPs, multiple SNPs, or copy number variants with entire gene deletion/duplication
True
Metabolizing enzyme responsible for metabolism of codeine to active form, morphine
CYP2D6
Phenotype of 1) ultra rapid metabolizer and 2) poor metabolizers of Codeine
Ultra rapid: risk of excessive sedation and life-threatening respiratory depression
Poor: poor analgesic effect
Metabolizing enzyme with clinical relevance in metabolism of clopidogrel
CYP2C19
Phenotype of poor metabolizers of clopidogrel
no bioactivation of clopidogrel –> less anti-platelet effect –> greater risk for recurrent thrombosis, myocardial infarction, cardiovascular death
Omeprazole is a _____ inhibitor used to treat ____
Gastric proton pump inhibitor used to treated peptic ulcer and gastroesophageal reflux disease (GERD) by lowering gastric acidity
What CYPs metabolize omeprazole and other gastric proton pump inhibitors
CYP3A4, CYP2C19
Poor metabolizers vs ultra rapid metabolizers of CYP2C19 (in regards to gastric proton pump inhibitors)
Ultra rapid: high drug clearance from plasma and less efficacious lowering of gastric acidity
Poor: Higher plasma concentrations of drug and more robust reduction in gastric acidity
Things that thiopurine drugs treat
Leukemia, rheumatic disease, inflammatory bowel disease, solid organ transplant
Conversion of thiopurine drugs to thioguanine nucleotides is slowed by what enzyme?
thiopurine methyltransferase (TPMT) which methylates the compound
Accumulation of thioguanine nucleotides (metabolized form of thiopurine drugs) occurs because of low activity of what and what does it result in?
Reduced TPMT activity, results in bone marrow suppression (myelosuppression), increased risk for life-threatening infection (sepsis)
______ ______ therapy for cancer is prone to resistance via tyrosine kinase domain mutations in tumor cells
EGFR inhibitor (gefitinib, erlotinib). On the other hands, some cells express mutations with increased sensitivity to inhibitors –> excellent response to treatment
Therapeutic benefit and adverse effects of warfarain
therapeutic: prevention of thrombosis
adverse: excessive anticoagulation and bleeding
What enzyme does warfarin inhibit
vitamin K oxidoreductase (VKORC1) – involved in biosynthesis of clotting factors
Explain pharmacodynamic and pharmacokinetic effects of warfarin (related to mutations)
Reduced function variants of CYP2C9 enzyme –> slowed elimination of warfarin –> potentiated anticoagulation (pharmacokinetic)
VKORC1 mutations –> influences efficacy and dose requirements for warfarin (pharmacodynamic effect)
