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

Poor metabolizers can cause drug levels to ___

Answer 12

increase

Question 13

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

Answer 13

Ultra-rapid metabolizers

Question 14

Ultra-rapid metabolizers can cause drug levels to ___

Answer 14

Decrease

Question 15

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

Answer 15

HLA-B*5701

Question 16

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

Answer 16

HLA-B*5801

Question 17

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

Answer 17

HLA-B*1502

Question 18

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

Answer 18

fatal hypersensitivity reaction

Question 19

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

Answer 19

SJS

Question 20

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

Answer 20

SJS and TEN

Question 21

Which ethnic group must be tested prior to starting carbamazepine

Answer 21

Asians

Question 22

Which CYP enzyme should be tested prior to Plavix therapy

Answer 22

CYP2C19

Question 23

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

Answer 23

*2 and *3

Question 24

Which CYP enzyme should be tested prior to Codeine therapy

Answer 24

CYP2D6

Question 25

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

Answer 25

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

Question 26

What should be tested prior to warfarin therapy

Answer 26

CYP2C9*2 and *3

VCORC1

Question 27

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

Answer 27

bleeding

Question 28

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

Answer 28

Start with a lower dose

Question 29

What should be tested prior to trastuzumab (Herceptin) therapy

Answer 29

HER2 gene expression

Question 30

If a tumor is HER2 negative, what should be done with trastuzumab

Answer 30

It should not be used since the drug will not be effective. Trastuzumab is HER2 inhibitor, so if the tumor is negative for the gene, it won’t be useful

Question 31

What should be tested prior to Cetuximab (Erbitux) therapy

Answer 31

KRAS mutation

Question 32

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

Answer 32

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

Question 33

What should be tested prior to azathioprine therapy

Answer 33

TPMT

Question 34

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

Answer 34

severe, life threatening myelosuppression

Question 35

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

Answer 35

severe toxicity (diarrhea, neutropenia, neurotoxicity)

Question 36

Key drugs where testing is required or strongly recommended

Answer 36

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

Question 37

Avoid the drug when these pharmacogenomic tests are POSITIVE

Answer 37

• HLA-B testing (increased risk of hypersensitivity)

- KRAS mutation (predicts poor response)

Question 38

Avoid the drug when this pharmacogenomic test is NEGATIVE

Answer 38

HER2 expression (indicates poor response)