PHARM: Precision Medicine: Clinical Pharmacogenomics Flashcards Preview

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Flashcards in PHARM: Precision Medicine: Clinical Pharmacogenomics Deck (16):
1

What is precision medicine?

A form of medicine that uses info about a person's genes, proteins, and environment to prevent, diagnose, and treat disease

2

What gene variant is responsible for variation in susceptibility to doxorubicin-induced cardiotoxicity in breast cancer treatment?

G671V in ABCC1 transporter

3

What is pharmacogenomics?

The science of determining how genetic variability influences physiological response to drugs, from absorption and metabolism to pharmacological action and therapeutic effect

4

What are the two broad classes of genetic variance?

Germline variance (changes in inherited DNA) and Somatic variance (changes that occurred w/in the individual

5

What is the target of Gleevec? What is it used to treat?

Targeted against the mutant BCR-Abl tyrosine kinase protein found in chronic myelogenous leukemia

6

What CYP450 is affected by St. John's Wort and how does this affect metabolism of drugs metabolized by the enzyme?

St. John's Wort induces CYP3A4 and can cause rapid metabolism of drugs cleared by the enzyme, decreasing their effectiveness

7

What CYP450 is affected by grapefruit juice and how does this affect metabolism of drugs metabolized by the enzyme?

CYP3A4 is inhibited by grapefruit juice causing the substrates of the enzyme not to be metabolized, increasing exposure to the drug and causing potentially dangerous side effects

8

How is warfarin primarily metabolized and how does it exert its anticoagulant effect?

Metabolized primarily via CYP2C9 and exerts its effect by inhibiting vitamin K epoxide reductase complex, subunit 1 (VKORC1)

9

What polymorphisms affect Warfarin metabolism and how?

CYP2C9*1 confers normal warfarin metabolism, CYP2C9*2 reduces metabolsim by 30%, CYP2C9*3 reduces metabolism by 90%, and VKORC1 SNP 1639 produces leess VKORC1

10

How is clopidogrel metabolized and how does it exert its function?

Clopidogrel is a prodrug that is activated by CYP2C19 and irreversibly inhibits platelet ADP receptor P2RY12

11

What polymorphisms affect clopidogrel metabolism and how?

CYP2C19*1 confers normal metabolsim, CYP2C19*2 and *3 confer poor metabolism, and CYP2C19*17 confers hyper metabolism

12

How does metformin work? What effects does it elicit?

Metformin acts in the liver to activate AMPK which decreases blood glucose, LDL, and triglycerides and increases insulin sensitivity

13

What SNPs are relevant to Metformin metabolism/ efficacy?

SNP rs2289669 G>A in the SLC47A1/MATE1 transporter (transports metformin out of liver) inactivates the transporter, keeping metformin in the liver longer and increasing its effectiveness

14

How is 5-fluorouracil dosed? How does it act? How is it metaboized?

Dosed as a prodrug that is converted to 5-fluoro-2-deoxyuridine monophosphate to inhibit thymidylate synthase. More than 80% of 5-FU is inactivated by dihydropyrimidine dehydrogenase (DPD)

15

What genetic variants are responsible for variance in 5-FU efficacy?

Patients with low DPD activity cannot efficiently inactivate 5-FU, causing accumulation of 5-FdUMP and potentially dangerous side effects; Patients with tandem repeats in the promoter of the thymidylate synthase are chemoresistant to inhibition by 5-FU therapy

16

What pharmacogenetics microarray-based test is FDA approved for the diagnostic analysis of CYP2D6 and CYP2C19?

Roche AmpliChip CYP450