Chapter 79: Pharmacogenomics

Question 1

For a recessive allele to produce a recessive phenotype, the individual must have ___ copies

Answer 1

2

Question 2

Specific sequence of nucleotides that code for a single protein

Answer 2

gene

Question 3

What is the most commonly occurring allele

Answer 3

Wild-type

Question 4

Two identical alleles make up a ____ genotype

Answer 4

homozygous

Question 5

Two different alleles make up a ____ genotype

Answer 5

heterozygous

Question 6

The set of unique genes that determine a specific trait in an individual

Answer 6

Genotype

Question 7

An observable trait of the genotype, such as hair color, or an inherited trait that is not outwardly visible, such as sickle cell disease

Answer 7

Phenotype

Question 8

A change in a single nucleotide in a genetic sequence

Answer 8

Single nucleotide polymorphism (SNP)

Question 9

The most common genetic alteration in DNA

Answer 9

SNPs

Question 10

What is responsible for the majority of individual variability in response to a drug

Answer 10

SNP

Question 11

Which type of drug metabolizer has fewer functional enzymes to metabolize a drug substrate

Answer 11

Poor metabolizers

Question 12

Which type of drug metabolizer has more functional enzymes to metabolize a drug substrate

Answer 12

Ultra-rapid metabolizers

Question 13

Abacavir + abacavir containing combo drugs (Triumeq, Epzicom) requires testing for which HLA gene

Answer 13

HLA-B*5701

Question 14

Allopurinol (Zyloprim, Aloprim) requires testing for which HLA gene

Answer 14

HLA-B*5801

Question 15

-Carbamazepine (Tegretol)
-Oxcarbazepine (Trileptal)
-Phenytoin (Dilantin)
-Fosphenytoin (Cerebyx)
require testing for which HLA gene

Answer 15

HLA-B*1502

Question 16

Patients who test positive for HLA-B*5701 with Abacavir + abacavir containing combo drugs (Triumeq, Epzicom) are at increased risk of

Answer 16

fatal hypersensitivity reaction

Question 17

Patients who test positive for HLA-B*5801 with allopurinol are at increased risk of

Answer 17

SJS

Question 18

Patients who test positive for HLA-B*1502 with AEDs are at increased risk of

Answer 18

SJS and TEN

Question 19

Which ethnic group must be tested prior to starting carbamazepine

Answer 19

Asians

Question 20

Which CYP enzyme should be tested prior to Plavix therapy

Answer 20

CYP2C19

prodrug

Question 21

Patients with which star allele(s) are poor metabolizers of Plavix and have increased CV events

Answer 21

*2 and *3

Question 22

Which CYP enzyme should be tested prior to Codeine therapy

Answer 22

CYP2D6

prodrug

Question 23

Which patients will be at increased risk of opioid overdose with codeine therapy

Answer 23

Ultra-rapid metabolizers (due to extensive conversion to morphine)

Question 24

What should be tested prior to warfarin therapy

Answer 24

CYP2C9*2 and *3
VKORC1

Question 25

Patients on warfarin therapy and have CYP2C9*2 and *3 alleles or VCORC1 G>A variant are at increased risk of

Answer 25

bleeding

Question 26

What should be done if a patient on warfarin has CYP2C9*2 and *3 alleles or VCORC1 G>A variant

Answer 26

Start with a lower dose

Question 27

What should be tested prior to trastuzumab (Herceptin) therapy

Answer 27

HER2 gene expression

need HER2 expression for trastuzumab to work

Question 28

What should be tested prior to Cetuximab (Erbitux) therapy

Answer 28

KRAS mutation

Question 29

If a patient is positive for the KRAS mutation, what should be done with cetuximab

Answer 29

It should not be used. Only patients who are KRAS-mutation negative (wild-type) should receive the medication

Question 30

What should be tested prior to azathioprine therapy

Answer 30

TPMT

Question 31

Low or absent TPMT activity with azathioprine therapy increases the risk of

Answer 31

severe, life threatening myelosuppression

Question 32

What should be tested for with capecitabine/5-FU?

Answer 32

DPD deficiency

Question 33

Patients using capecitabine (Xeloda) or fluorouracil and have DPD deficiency are at increased risk of

Answer 33

severe toxicity (diarrhea, neutropenia, neurotoxicity)

Question 34

Key drugs where testing is required or strongly recommended

Answer 34

• Abacavir and any combination products containing abacavir
• Azathioprine
• Carbamazepine
• Cetuximab and other EGFR inhibitors
• Trastuzumab and other HER2 inhibitors

Question 35

Avoid the drug when these pharmacogenomic tests are POSITIVE

Answer 35

• HLA-B testing (increased risk of hypersensitivity)
• KRAS mutation (predicts poor response)