SM46_Pharmacogenomics

Question 1

The use of pharmacogenomics can result in lower risks for ________, a major cause of mortality

Answer 1

Adverse drug reactions (ADRs). This is because you can personalize medicine using genomic information

Question 2

Genetically based variability in drug responses can be attributed to genes affecting either _______ or _____

Answer 2

pharmacodynamics (direct effect on molecular target) or pharmacokinetics (plasma or tissue drug concentration)

Question 3

For standard drugs, low metabolizing capacity may cause……

Answer 3

decreased elimination rate (poor) and increased toxicity risk (poor and intermediate)

Question 4

For pro-drugs, low metabolizing capacity may cause….

Answer 4

decreased activation (Poor) and reduced effectiveness (poor and intermediate)

Question 5

For standard drugs, rapid metabolizing capacity causes….

Answer 5

increased elimination rate, reduced effectiveness

Question 6

For pro-drugs, rapid metabolizing capacity causes…

Answer 6

increased activation, increased toxicity risk

Question 7

Genetic variants of drug metabolizing enzymes can result in only normal function, reduced function and increased function (true or false)

Answer 7

False, it can also result in non-function

Question 8

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

Answer 8

True

Question 9

Metabolizing enzyme responsible for metabolism of codeine to active form, morphine

Answer 9

CYP2D6

Question 10

Phenotype of 1) ultra rapid metabolizer and 2) poor metabolizers of Codeine

Answer 10

Ultra rapid: risk of excessive sedation and life-threatening respiratory depression

Poor: poor analgesic effect

Question 11

Metabolizing enzyme with clinical relevance in metabolism of clopidogrel

Answer 11

CYP2C19

Question 12

Phenotype of poor metabolizers of clopidogrel

Answer 12

no bioactivation of clopidogrel –> less anti-platelet effect –> greater risk for recurrent thrombosis, myocardial infarction, cardiovascular death

Question 13

Omeprazole is a _____ inhibitor used to treat ____

Answer 13

Gastric proton pump inhibitor used to treated peptic ulcer and gastroesophageal reflux disease (GERD) by lowering gastric acidity

Question 14

What CYPs metabolize omeprazole and other gastric proton pump inhibitors

Answer 14

CYP3A4, CYP2C19

Question 15

Poor metabolizers vs ultra rapid metabolizers of CYP2C19 (in regards to gastric proton pump inhibitors)

Answer 15

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

Question 16

Things that thiopurine drugs treat

Answer 16

Leukemia, rheumatic disease, inflammatory bowel disease, solid organ transplant

Question 17

Conversion of thiopurine drugs to thioguanine nucleotides is slowed by what enzyme?

Answer 17

thiopurine methyltransferase (TPMT) which methylates the compound

Question 18

Accumulation of thioguanine nucleotides (metabolized form of thiopurine drugs) occurs because of low activity of what and what does it result in?

Answer 18

Reduced TPMT activity, results in bone marrow suppression (myelosuppression), increased risk for life-threatening infection (sepsis)

Question 19

______ ______ therapy for cancer is prone to resistance via tyrosine kinase domain mutations in tumor cells

Answer 19

EGFR inhibitor (gefitinib, erlotinib). On the other hands, some cells express mutations with increased sensitivity to inhibitors –> excellent response to treatment

Question 20

Therapeutic benefit and adverse effects of warfarain

Answer 20

therapeutic: prevention of thrombosis
adverse: excessive anticoagulation and bleeding

Question 21

What enzyme does warfarin inhibit

Answer 21

vitamin K oxidoreductase (VKORC1) – involved in biosynthesis of clotting factors

Question 22

Explain pharmacodynamic and pharmacokinetic effects of warfarin (related to mutations)

Answer 22

Reduced function variants of CYP2C9 enzyme –> slowed elimination of warfarin –> potentiated anticoagulation (pharmacokinetic)

VKORC1 mutations –> influences efficacy and dose requirements for warfarin (pharmacodynamic effect)