Pharmacogenomics

Question 1

1842 First human drug metabolism experiment by Keller showed ________ acid converted in urine to hippuric acid

Answer 1

benzoic acid

Question 2

______________ : study of the relationship between variations in a single gene (or small collection of genes) and variability in drug disposition, response, and toxicity.

Answer 2

pharmacogenetics (PGx)

Question 3

_______________ : study of the relationship between variations in a large collection of genes (up to the whole genome) and variability in drug disposition, response, and toxicity.

Answer 3

pharmacogenomics

Question 4

The liver’s primary mechanism for metabolizing drugs is via a group of cytochrome____________ enzymes

Answer 4

P-450

Question 5

___________: mathematics of the time course of Absorption, Distribution, Metabolism, and Excretion of drugs

Answer 5

pharmacokinetics

Question 6

Drug metabolism is usually monogenic/multigenic?

Answer 6

monogenic

Question 7

Polymorphisms can affect protein function and can make ____________ bimodal or even trimodal

Answer 7

distribution

Question 8

Variable ______________ phenotypes may influence drug dosing, efficacy, and/or toxicity

Answer 8

pharmacokinetic

Question 9

Genetic variants in a metabolizing enzyme can alter enzyme _________, enzyme _________ or inactivate the enzyme

Answer 9

activity, affinity

Question 10

Genetic variants in a metabolizing enzyme can ___________ clearance, ___________ the AUC and ______________half-life

Answer 10

decrease clearance
increase AUC
increase t1/2

Question 11

Duplications/multiplications in a metabolizing enzyme are more rare but can ___________ clearance, ___________ the AUC and ______________half-life

Answer 11

increase clearance
decrease AUC
decrease t1/2

Question 12

The impact of drug metabolizing enzyme gene variants on the pharmacologic effect and toxicity profile of a drug depends, in part, on whether the drug is active in its parent form or is a ___________

Answer 12

prodrug

Question 13

Star nomenclature is typically numbered in order of _____________

Answer 13

discovery

Question 14

1 / (1A/B/C) are typically ____________ allele

Answer 14

reference/normal

Question 15

Some * alleles are defined by the presence of more than 1 variant in _____
Phasing is required

Answer 15

cis

Question 16

Interpretation of phenotype requires knowledge of ____________, not just genotype

Answer 16

diplotype

Question 17

Break down CYP-2-C-19-17
CYP2C192
CYP2C19*3

Answer 17

Superfamily - CYP
Family - 2
Subfamily - C
Gene - 19
Allelic variant *17 increased function
*2 and *3 are no function alleles
= Tier I variants

Question 17

FDA box warning discusses testing of _______________ for Plavix

Answer 17

CYP2C19

Question 18

___________ collects, curates and disseminates knowledge about the impact of human genetic variation on drug responses.”

Answer 18

PharmGKB

Question 19

PharmGKB Clinical Annotation Levels of Evidence

Answer 19

1A/B high, 2A/B moderate, 3 low, 4 preliminary

Question 20

PharmGKB may state that genetic testing for a drug is ____________ or ____________ and that it is _____________ or __________________

Answer 20

required or recommended
actionable or informative

Question 21

CPIC (2009 PGKC and PGRN) stands for ______________ ________________ _______________ _______________

Answer 21

Clinical Pharmacogenetics Implementation Consortium

Question 22

CPIC currently has ______________ guidelines

Answer 22

33

Question 23

_______________ is linked to statin-induced myopathy

Answer 23

SLC01B1

Question 24

SLCO1B1 : Gene expressed at the hepatic ____________ membrane that reabsorbs a variety of chemicals from plasma into the liver

Answer 24

sinusoidal

Question 25

*____ allele of SLC01B1 rs4149056 / p.Val174Ala results in lower transport into liver and decreases clearance of simvastatin = lower dose means that patient has greater exposure to active drug

Answer 25

*5 SLCO1B1*5

Question 26

Number needed to __________________ is the number of tests that must be performed to affect healthcare

Answer 26

genotype (like number needed to treat)

Question 27

SLC01B1*5 rs4149056 involves a ______ to ________ mutation at 174

Answer 27

Val174Ala

Question 28

_______ is the enzyme that metabolizes fludarabine and capecitabine and is important in GI oncology treatment toxicity

Answer 28

DPYD (dihydropyrimidine dehydrogenase)

Question 29

_______ is the enzyme that metabolizes irinotecan and is important in GI oncology treatment toxicity

Answer 29

UGT1A1 uridine diphosphate (UDP) glucuronosyltransferase 1A1

Question 30

________ and _______ are examples of phase II drug metabolizing enzymes

Answer 30

UGT1A1 and TPMT

Question 31

_______ and _______ are examples of phase I drug metabolizing enzmes

Answer 31

CYP and DPD

Question 32

_______ and ______ metabolize coumadin

Answer 32

CYP2C9 and VKORC1

Question 33

___________ is responsible for metabolizing clopidogrel, voriconazole, PPIs and SSRIs

Answer 33

CYP2C19 (10q23.3)

Question 34

Is clopidogrel an active drug or prodrug?

Answer 34

prodrug

Question 35

Phase I drug metabolism is characterized by _______, ________ and ___________ reactions

Answer 35

oxidation, reduction and hydrolysis

Question 36

Phase II drug metabolism is characterized by ___________ reactions

Answer 36

conjugation

Question 37

____________ is an inducer that increases CYP2B6, 2C8, 2C9, 2C19, 2D6, 3A4, 3A5

Answer 37

rifampin

Question 38

Grapefruit juice and St Johns wort inhibit __________ drug metabolism

Answer 38

CYP3A4

Question 39

___________ is an inducer of CYP1A2

Answer 39

broccoli

Question 40

Two no function alleles makes for a/an __________ metabolizer

Answer 40

poor

Question 41

A normal function allele and a no function allele make for a/an _____________ metabolizer

Answer 41

intermediate

Question 42

Diplotype if no variants are detected (not present or not in the assay design)

Answer 42

*1/*1

Question 43

__________ is a phase I enzyme responsible for metabolizing about 21% of approved medications including warfarin and phenytoin

Answer 43

CYP2D6

Question 44

CYP2D6 has over 130 star ________ as well _________, _________ and ____________ alleles. It is also subject to ________ and _______

Answer 44

alleles, deletions, duplications, hybrid (with pseudogene CYP2D7) induction and inhibition

Question 45

In addition to the phenotype, a CYP2D6 diplotype also has an _________ _________

Answer 45

activity score Ultrarapid >2,25 Normal 1.25-2.25 Intermediate <1.5 Poor metabolizer 0

Question 46

CPIC currently has guidelines for __________ medications with CYP2D6

Answer 46

14 *FDA has 20 tamoxifen (cancer) atomoxetine, SSRI, TCAs (mental health) codeine, tramadol, hydrocodone (pain) ondansetron, tropisetron (pain)

Question 47

Current AMP guidelines for pharmacogenetics takes into account VAF, the existence of ____________ material and testing ___________ feasibility

Answer 47

reference testing feasibility

Question 48

Both phase I enzymes ________ and _______ are on 10q23.3

Answer 48

CYPD26 and CYP2D19

Question 49

The tier I alleles for CYP2C9 include *2, *3, *5, *8 and *11 that have ______ function while *6 has ______ function. This panel covers 75% of African ancestry.

Answer 49

decreased (function) = *2, *3, *5, *6, *8 and *11 No (function) = *6

Question 50

The Tier 1 VKORC1*2 allele is a mutation in the ________ that results in reduced expression of the warfarin target and lower dosing requirement

Answer 50

promoter

Question 51

For Tier 1 warfarin testing, which enzyme acts as the drug target?

Answer 51

VKORC1