Chapter 6 - Intro to Pharcogenomics

Question 1

Pharmacogenomics is

Answer 1

identification of the genetic attributes of an individual that lead to variable responses to drugs OR study of genetic differences among people, impact that differences have on uptake/effectiveness/toxicity/metabolism of drugs

Question 2

Pharmacogenomics (PGx) are

Answer 2

Genetic polymorphisms that occur in a patient population

Question 3

All DNA in an individual cell is called the

Answer 3

Genome

Question 4

Single-Nucleotide Polymorphisms contribute to

Answer 4

Allotypic Phenotype variations

Question 5

Genetic polymorphism is expressed in

Answer 5

1% or more of the population

Question 6

Wild-Type Gene

Answer 6

Standard allele found in the population

Question 7

What will PGx do

Answer 7

enhance drug therapy, maximize efficacy, target drugs only to patients that are going to respond, avoid ADR, and decrease cost to healthcare system

Question 8

The 4 phenotype effects of genetic polymorphisms are

Answer 8

Poor metabolizer, Intermediate Metabolizer, Extensive Metabolizer, and UIltrarapid Metabolizer

Question 9

Poor Metabolizer (PM)

Answer 9

Lack working enzyme

Question 10

Intermediate Metabolizer (IM)

Answer 10

heterozygous have 1 variant and 1 working wild allele
o These both slow drug metabolism
Can cause accumulation of prodrug and possibly active drug – Lower dose

Question 11

Extensive Metabolizer (EM)

Answer 11

2 working allele, Standard expression

Question 12

Ultrarapid Metabolizer (UM)

Answer 12

more than one functioning copy of enzyme
o Fast metabolism. Patient will require higher dose

Question 13

What are the 3 most polymorphic forms of p450

Answer 13

CYP2D6, CYP2C9, CYP2C19 make up 40% of hepatic phase 1 metabolism

Question 14

CYP2D6 is responsible for ____% of drug metabolism

Answer 14

19% of drug metabolism

Question 15

CYP2D6 acts on

Answer 15

SSRI, Tricyclic antidepressants (TCA), beta blockers, calcium channel blockers, theophyline, and Tamoxifen

Question 16

Specific considerations for CYP2D6 on opioids?

Answer 16

UM may not experience effects of codeine, PM may be unable to convert to active form
Pediatric - Due to faster activation, can be lethal

Question 17

CYP2C9 acts on

Answer 17

Tolbutamide, warfarin, phenytoin, NSAIDS, Losartan, celecoxib, glipizide

Question 18

CYP2C9 variants can affect warfarin dosing how?

Answer 18

Variants of CYP2C9 reduce clearance, requiring lower dosing

Question 19

CYP3A4 is responsible for ____% of drug metabolism

Answer 19

50% of drug metabolism

Question 20

CYP3A4 acts on

Answer 20

Azole Antifungals, Calcium Channel Blockers, Antihistamines, HMG Co-A reductaser inhibitors, Antiepileptics, Antimicrobials, and corticosteroids

Question 21

What would grapefruit do to CYP3A4?

Answer 21

Inhibits enzyme action

Question 22

P-Glycoprotein (Pgp)

Answer 22

Membrane-bound, ATP bound transport system; efflux of xenobiotics from cell to extracellular fluid (usually against concentration gradient)

Question 23

Increased expression of P-Glycoprotein (Pgp) causes

Answer 23

Greater efflux from cell

Question 24

When should you test PGx before prescribing?

Answer 24

Pt is on 4+ drugs
Not responding as expected
Adult over 65
Narrow therapeutic range and severe consequence of failure
Over 40 with 2 chronic conditions
FHx
Personal/family interest in genetics
Proactive patient

Question 25

What are the 3 tiers of PGx

Answer 25

1: Required and Center for Medicare/Medicaid (CMS) is willing to pay
Ex. Cetuximab, Maraviroc, Dasatinib
2: Recommended
Carbimazepine: Asian ancestry had high risk of Steven-Johnsons/Toxic epidermal Necrolysis
3: Not recommended, not reimbursed