Chapter 78: Pharmacogenomics

Question 1

What is Pharmacogenomics?

Answer 1

The science of examining inherited variations in genes that determine a petient’s response to drugs

Question 2

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

Answer 2

2

Question 3

Specific sequence of nucleotides that code for a single protein

Answer 3

gene

Question 4

What is the most commonly occurring allele

Answer 4

Wild-type

Question 5

Two identical alleles make up a _____ genotype

Answer 5

homozygous

Question 6

Two different alleles make up a ____ genotype

Answer 6

heterozygous

Question 7

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

Answer 7

Genotype

Question 8

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 8

Phenotype

Question 9

A change in a single nucleotide in a genetic sequence

Answer 9

Single nucleotide polymorphism (SNP)

Question 10

The most common genetic alteration in DNA

Answer 10

SNPs

Question 11

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

Answer 11

SNP

Question 12

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

Answer 12

Poor metabolizers

Question 13

Poor metabolizers can cause drug levels to ___

Answer 13

increase

Question 14

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

Answer 14

Ultra-rapid metabolizers

Question 15

Ultra-rapid metabolizers can cause drug levels to ___

Answer 15

Decrease

Question 16

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

Answer 16

HLA-B*5701

Question 17

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

Answer 17

HLA-B*5801

Question 18

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

Answer 18

HLA-B*1502

Question 19

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

Answer 19

fatal hypersensitivity reaction

Question 20

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

Answer 20

SJS

Question 21

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

Answer 21

SJS and TEN

Question 22

Which ethnic group must be tested prior to starting carbamazepine?

Answer 22

Asians

Question 23

Which CYP enzyme should be tested prior to Plavix therapy

Answer 23

CYP2C19

Question 24

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

Answer 24

*2 and *3

Question 25

Which CYP enzyme should be tested prior to Codeine therapy

Answer 25

CYP2D6

Question 26

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

Answer 26

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

Question 27

What should be tested prior to warfarin therapy

Answer 27

CYP2C9*2 and *3 ## Footnote VCORC1

Question 28

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

Answer 28

bleeding

Question 29

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

Answer 29

Start with a lower dose

Question 30

What should be tested prior to trastuzumab (Herceptin) therapy

Answer 30

HER2 gene expression

Question 31

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

Answer 31

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 32

What should be tested prior to Cetuximab (Erbitux) therapy

Answer 32

KRAS mutation

Question 33

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

Answer 33

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

Question 34

What should be tested prior to azathioprine therapy

Answer 34

Thiopurine methyltransferase (TPMT)

Question 35

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

Answer 35

severe, life threatening myelosuppression

Question 36

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

Answer 36

severe toxicity (diarrhea, neutropenia, neurotoxicity)

Question 37

Key drugs where testing is required or strongly recommended

Answer 37

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

Question 38

Avoid the drug when these pharmacogenomic tests are POSITIVE

Answer 38

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

Question 39

Avoid the drug when this pharmacogenomic test is NEGATIVE

Answer 39

HER2 expression (indicates poor response)

Question 40

Which drugs require HLA-B*1502?

Answer 40

-Carbamazepine (Tegretol) -Oxcarbazepine (Trileptal) -Phenytoin (Dilantin) -Fosphenytoin (Cerebyx)