Drug Monitoring And Pharmacogenomics Exam 3

Front 1

Which of the following transporters is most likely to limit bioavailability of digoxin?
a. Breast cancer resistance protein (ABCG2)
b. P‐glycoprotein (ABCB1)
c. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP‐C)
d. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP‐8)
e. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP‐B)
f. Multidrug resistance‐associated protein 2 (MRP2; ABCC2)

Back 1

b. P‐glycoprotein (ABCB1)

Front 2

Breast Cancer Resistance Protein (BCRP) is expressed at the blood‐brain barrier and efficiently transports imatinib. Inhibition of BCRP would be expected to have what effect on the concentration of imatinib achieved in brain tissue relative to plasma?
a. Increased imatinib brain concentration.
b. Decreased imatinib brain concentration.

Back 2

a. Increased imatinib brain concentration.

Front 3

Transport‐based drug interactions with pravastatin are most likely mediated through which of the following transporters?
a. Breast cancer resistance protein (ABCG2)
b. P‐glycoprotein (ABCB1)
c. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP‐C)
d. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP‐8)
e. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP‐B)
f. Multidrug resistance‐associated protein 2 (MRP2; ABCC2)

Back 3

c. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP‐C)

Front 4

The magnitude of CYP enzyme induction caused by rifampin may be affected by genetic variation in which of the following transporters?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MRP2 (ABCC2)
d. OATP1B1 (SLCO1B1)
e. OCTN1 (SLC22A4)
f. None of the above.

Back 4

d. OATP1B1 (SLCO1B1)

Front 5

Antipsychotic‐induced weight gain is associated with polymorphisms in the gene that encodes for which of the following?
a. Arachidonate 5‐lipoxygenase‐activating protein
b. Factor V
c. Leptin
d. Serotonin receptor
e. Major histocompatability complex
f. Vitamin D receptor
g. Vitamin K epoxide reductase

Back 5

d. Serotonin receptor

Front 6

Which of the following BEST summarizes what is known about CYP3A5 and P‐glycoprotein pharmacogenetic associations with calcineurin/ mammalian target of rapamycin inhibitors?
a. Cyclosporine dose requirements are larger in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences sirolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with tacrolimus dose requirements.

b. Cyclosporine dose requirements are smaller in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences tacrolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

c. Cyclosporine dose requirements are not affected by CYP3A5 expression but tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors. P‐glycoprotein genotype may influence cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

d. Cyclosporine dose requirements are not affected by CYP3A5 expression but tacrolimus and sirolimus dose requirements are smaller in CYP3A5 expressors. P‐glycoprotein genotype may influence sirolimus dose requirements, affects the tacrolimus dose requirements only in CYP3A5 expressors, and is not associated with cyclosporine dose requirements.

Back 6

c. Cyclosporine dose requirements are not affected by CYP3A5 expression but tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors. P‐glycoprotein genotype may influence cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

Front 7

Statement #1: Mycophenolic acid acyl‐glucuronide plasma concentrations associate with the UGT1A9 genotype.
Statement #2: Sirolimus nephrotoxicity associates with the ABCB1 genotype.
a. both statements 1 and 2 are true
b. both statements 1 and 2 are false
c. only statement 1 is true
d. only statement 2 is true

Back 7

b. both statements 1 and 2 are false

Front 8

Genetic variation in which of the following targets has NOT been shown to affect the in vitro and/or in vivo pharmacodynamics of an immunosuppressant?
a. Calcineurin
b. Inosine monophosphate dehydrogenase
c. Mammalian target of rapamycin
d. all of the above
e. a and b
f. a and c
g. b and c
h. none of the above

Back 8

f. a and c

Front 9

Statement #1: MRP2 (ABCC2) is involved in enterohepatic circulation of mycophenolic acid.
Statement #2: In kidney‐transplant patients treated with cyclosporine, the ABCB1 genotype of the recipient is more predictive of nephrotoxicity than the ABCB1 genotype of the donor.
a. both statements 1 and 2 are true
b. both statements 1 and 2 are false
c. only statement 1 is true
d. only statement 2 is true

Back 9

c. only statement 1 is true

Front 10

What information would you use to inform a dosage recommendation for a patient receiving irinotecan for the treatment of colon cancer?
a. Utilize FDA recommended precise dosage reductions for all UGT1A1 variant carriers
b. 7 tandem TA repeats in the promoter of UGT1A1 are associated with increased risk of severe leucopenia
c. 6 tandem TA repeats in exon 4 of UGT1A1 are associated with increased risk of severe leucopenia
d. The prevalence of TA tandem repeat variation within UGT1A1 is greatest in Asian populations

Back 10

b. 7 tandem TA repeats in the promoter of UGT1A1 are associated with increased risk of severe leucopenia

Front 11

Reviewing tamoxifen pharmacogenetic information, which of the following is NOT true?
a. Patients with a high recurrence score as predicted from the Oncotype DX are likely to receive more benefit from tamoxifen than adjuvant chemotherapy
b. CYP2D6 poor metabolizers will likely receive less benefit from tamoxifen
c. Six to 10% of Caucasian populations are classified as CYP2D6 poor metabolizers
d. There is a documented gene‐dose effect regarding tamoxifen metabolite plasma concentrations and CYP2D6

Back 11

a. Patients with a high recurrence score as predicted from the Oncotype DX are likely to receive more benefit from tamoxifen than adjuvant chemotherapy

Front 12

You receive the genotyping analysis for EGFR mutations in a patient with non‐small cell lung cancer, what information would you use to inform a treatment decision?
a. Exon 19 deletions and the L858R mutation have the best data supporting sensitivity to gefitinib
b. Germline mutations are important predictors of gefitinib sensitivity
c. EGFR variants known as double mutants have the best data supporting sensitivity to gefitinib
d. The positive predictive value of EGFR genotyping makes it a poor resource for determining sensitivity to gefitinib

Back 12

a. Exon 19 deletions and the L858R mutation have the best data supporting sensitivity to gefitinib

Front 13

A physician inquires about why pharmacogenetic based dosing for TPMT is important. To appropriately address this question, you state:
a. Wild‐type TPMT results in decreased drug inactivation
b. Variant TPMT carriers are at a greater risk for severe myelosuppression
c. Up to 50% of the population is heterozygous for TPMT variations, and routinely require large dose reductions
d. Mercaptopurine (6‐MP) is inactivated by HGPRT

Back 13

b. Variant TPMT carriers are at a greater risk for severe myelosuppression

Front 14

Drug X is metabolized exclusively by CYP2C8. Drug X exhibits a decreased drug effect in patients who are carriers of the CYP2C8*3 allele. Potential explanations for this genotype effect include all of the following except:
a. The protein coded by CYP2C8*3 has greater specificity for drug X than wild type CYP2C8.
b. Drug X is a prodrug.
c. The CYP2C8*3 allele is in linkage disequilibrium with another variant in the pharmacodynamic target of drug X.
d. The CYP2C8*3 allele increases expression and thus metabolism of drug X.

Back 14

d. The CYP2C8*3 allele increases expression and thus metabolism of drug X.

Front 15

Pharmacogenomics is most applicable to the clinical treatment of which disease?
a. Type 1 diabetes
b. Type 2 diabetes
c. Monogenic diabetes
d. Diabetes insipidus

Back 15

c. Monogenic diabetes

Front 16

Which of the following drugs is paired with a gene that has a variant NOT shown to affect its pharmacokinetics?
a. Glimepride CYP2C9
b. Metformin SLC22A1
c. Nateglinide SLCO1B1
d. Repaglinide CYP2C8

Back 16

c. Nateglinide SLCO1B1

Front 17

Which of the following drugs is paired with a gene that has a variant NOT shown to affect its pharmacodynamics?
a. Glipizide KCNJ11
b. Repaglinide KCNJ11
c. Pioglitazone PPARG
d. Glimepride ABCC8

Back 17

b. Repaglinide KCNJ11

Front 18

Disadvantages of whole genome association studies (GWAS) compared to candidate gene studies include all of
the following except:
a. Large sample size is required
b. Biased by previous findings
c. Replication of the association is essential
d. Expensive

Back 18

b. Biased by previous findings

Front 19

Which of the following does NOT describe/apply to candidate gene approach in pharmacogenetic investigations?
a. is useful in the study of genetic influences on a complex trait or disease state
b. evaluates genetic influence of genes that are likely to be involved or ‘usual suspects’
c. includes scanning the genome to discover genetic variations associated with a trait or disease state
d. candidate genes include those that may affect the pharmacokinetic or pharmacodynamic response to drugs
e. all of the above describe/apply to the candidate gene approach

Back 19

c. includes scanning the genome to discover genetic variations associated with a trait or disease state

Front 20

Which of the following would be a candidate gene or gene product for pharmacogenetic investigation within a disease state?
a. drug targets
b. metabolism enzymes
c. drug transporters
d. gene products that mediate adverse drug reactions
e. all of the above

Back 20

e. all of the above

Front 21

Which enzyme has a clear phenotypic/genotypic relationship for metabolic status and number of functional
alleles?
a. CYP1A2
b. CYP2D6
c. CYP3A4
d. UGT1A4
e. UGT1A6

Back 21

b. CYP2D6

Front 22

What characteristics are required of a trait or disease state to allow for pharmacogenetic investigation?
1. the disease should be a Mendelian disease, or caused by a single mutation
2. high variability in drug response among individuals
3. validated measures
4. high prevalence
5. clinically available pharmacogenetic tests
a. 1, 2, and 3
b. 1, 2, 3, and 5
c. 2, 3, and 5
d. 2, 3, and 4
e. all of the above

Back 22

d. 2, 3, and 4

Front 23

Genetic variation of CYP2D6 has been associated with pain and opioid response. How is this explained?
a. increased metabolic activity causes increased opiate clearance and decreased analgesia
b. decreased metabolic activity causes decreased opiate clearance and increased analgesia
c. increased metabolic activity causes increased conversion to active metabolites and increased analgesia
d. decreased metabolic activity causes decreased conversion to active metabolites and increased analgesia
e. all of the above

Back 23

c. increased metabolic activity causes increased conversion to active metabolites and increased analgesia

Front 24

What black box warning involving pharmacogenetics was recently added to the prescribing information of carbamazepine?
a. CYP2C9 for increased incidence of suicidal ideation
b. P‐gp for increased seizure activity
c. SCN1A for increased risk of stroke
d. HLA‐B for increased dermatologic reactions
e. UGT2B7 for increased risk of neutropenia

Back 24

d. HLA‐B for increased dermatologic reactions

Front 25

An example of genetic variation within the efflux transporter P‐glycoprotein and phenobarbital in which serum concentrations were identical between groups, but efficacy varied between groups. Which of the following explain this?
a. increased P‐glycoprotein activity was associated with increased transport into the blood‐brain barrier and increased CSF concentrations
b. increased P‐glycoprotein activity was associated with increased transport out of the blood‐brain barrier and decreased CSF levels
c. decreased P‐glycoprotein activity was associated with increased transport into the blood‐brain barrier and increased CSF concentrations
d. decreased P‐glycoprotein activity was associated with increased transport out of the blood‐brain barrier and decreased CSF levels
e. all of the above

Back 25

b. increased P‐glycoprotein activity was associated with increased transport out of the blood‐brain barrier and decreased CSF levels

Front 26

Which of the following is/are FALSE regarding P‐glycoprotein (P‐gp)?
a. P‐gp transports drugs out of cells
b. P‐gp contributes to drug resistance
c. P‐gp is present at the blood‐brain barrier
d. P‐gp can affect efficacy of drugs
e. all of the above are true regarding P‐glycoprotein

Back 26

e. all of the above are true regarding P‐glycoprotein

Front 27

True/False
The Genetic Information Nondiscrimination Act of 2008 (GINA) prohibits discrimination in health coverage and employment on the basis of genetic information. However, the protections do not apply to genetic information collected or acquired as part of research, defined as genetic services or participation in clinical research that includes genetic services (genetic testing, counseling, or education) by an individual or family member.

Back 27

False

Front 28

Haga and Burke (Genet Med. 2008 Jun;10(6):391‐5) proposed a classification scheme for pharmacogenetic tests in order to identify and prioritize the policy issues that will need to be addressed to ensure appropriate delivery of pharmacogenetics testing. Which of the following is NOT one of the criteria they proposed as a basis for classification of a pharmacogenetics test?
a. Whether the test is intended to address a current specific clinical question or to provide
information for future clinical care
b. Whether the test identifies an acquired or inherited variant
c. Whether the test results are portable and retrievable
d. Whether the test reveals ancillary clinical information

Back 28

c. Whether the test results are portable and retrievable

Front 29

TRUE (A) or FALSE (B). The Genetic Information Nondiscrimination Act (GINA) of 2008 protects Americans against discrimination based on their genetic information when it comes to health insurance AND employment.

Back 29

True

Front 30

Pravastatin pharmacokinetics is affected by genetic variation in which of the following transporters?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MDR1 (ABCB1)
d. MRP2 (ABCC2)
e. MRP3 (ABCC3)
f. OATP1B1 (SLCO1B1)
g. OATP1B3 (SLCO1B3)
h. OATP2B1 (SLCO2B1)
i. OCTN1 (SLC22A4)
j. None of the above

Back 30

f. OATP1B1 (SLCO1B1)

Front 31

A polymorphism in the ABCB1 gene, which encodes for the transporter P‐glycoprotein, that results in reduced activity (i.e., reduced transporter function) would be predicted to have which of the following effects on digoxin pharmacokinetics?
a. Decreased bioavailability and decreased renal clearance.
b. Increased bioavailability and increased renal clearance.
c. Decreased bioavailability and increased renal clearance.
d. Increased bioavailability and decreased renal clearance.
e. Genetic variation in ABCB1 would not affect digoxin pharmacokinetics.

Back 31

d. Increased bioavailability and decreased renal clearance.

Front 32

Which of the following have genetic polymorphims that associate with variation in phenytoin response due to alterations in pharmacokinetics or pharmacodynamics?
a. CYP2C9
b. CYP2C19
c. P‐glycoprotein
d. SCN1A
e. all of the above
f. a and b
g. a and c
h. a and d
i. none of the above

Back 32

e. all of the above

Front 33

The efficacy of phenobarbital in epilepsy was shown to be worse in carriers of the wild type allele for P‐glycoprotein (3435 C>T) as compared to carriers of the variant allele. However, serum blood phenobarbital concentrations were the same. Why was the efficacy worse?
a. The wild type P‐glycoprotein has negative effects on neurotransmitters, which would not show a difference in phenobarbital concentrations
b. Although the serum blood concentrations were the same, the CSF concentrations were different due to differences in drug efflux at the blood‐brain barrier
c. The 3435 C>T SNP of P‐glycoprotein is known to be linked to SNPs of the GABA receptor, which would not affect Phenobarbital concentrations
d. All of the above
e. None of the above

Back 33

b. Although the serum blood concentrations were the same, the CSF concentrations were different due to differences in drug efflux at the blood‐brain barrier

Front 34

Recently, a Black Box Warning was added for serious dermatologic reactions in patients who carry HLA‐B*1502. This warning is specific for :
a. phenytoin in patients of African ancestry
b. phenytoin in patients of Asian ancestry
c. carbamazepine in patients of African ancestry
d. carbamazepine in patients of Asian ancestry
e. all of the above
f. none of the above

Back 34

d. carbamazepine in patients of Asian ancestry

Front 35

The cytochrome 450 (CYP) enzyme with the most evidence of association with antidepressants is?
a. CYP1A2
b. CYP2C9
c. CYP2D6
d. CYP2C19
e. CYP3A4

Back 35

c. CYP2D6

Front 36

The treatment of schizophrenia could potentially benefit from pharmacogenetics because:
a. The current treatment response is poor
b. The presentation of the disease is highly variable in individuals
c. Validated scales for symptoms and side effects are available
d. The drug targets for schizophrenia are clearly identified and the genetic variation is understood
e. All of the antipsychotics are metabolized by CYP2D6
f. all of the above
g. a and b
h. a, b, and c
i. a, b, c, and d

Back 36

h. a, b, and c

Front 37

Which of the following is an example of a tumor genome‐related mechanism of cancer treatment failure? A polymorphism in:
a. Carboxylase (CE) which prevents irinotecan from being activated to SN‐38.
b. Thiopurine S‐methyltransferase (TPMT) which prevents metabolism of thioguanine analogs.
c. P‐glycoprotein (P‐gp or MDR1) causing increased drug efflux from a solid organ tumor.
d. Thymidylate synthase (TS, site of action for 5‐FU) leading to decreased TS activity in tumor.

Back 37

c. P‐glycoprotein (P‐gp or MDR1) causing increased drug efflux from a solid organ tumor.

Front 38

Based on the pharmacogenetic‐driven 6‐mercaptopurine dosing scheme presented in class, which dosing scheme would MOST LIKELY be seen in a TPMT pharmacogenetic‐derived dosing scheme for Azathioprine? [Homozygous wildtype = WT, homozygous mutant = mut, heterozygous = het, standard dose = sd]
a. WT: 100% sd; het: 50%; mut: 50%
b. WT: 100% sd; het: 50%; mut: 10%
c. WT: 90% sd; het: 50%; mut: 10%
d. WT: 50% sd; het: 50%; mut: 10%
e. WT: 10% sd; het: 50%; mut: 100%

Back 38

b. WT: 100% sd; het: 50%; mut: 10%

Front 39

Which of the following statements is FALSE regarding thiopurine S‐methyltransferase (TPMT)?
a. TPMT is a major metabolic enzyme for mercaptopurine, thioguanine, and azathioprine.
b. TPMT genetic variants are associated with both efficacy and toxicity in response to thioguanine analogs.
c. Patients with the *3/*3 genotype (homozygous variant) require an empirical reduction in 6‐MP dose.
d. Mutant homozygotes have less TPMT activity than heterozygotes.
e. All of the above are false
f. None of the above are false

Back 39

f. None of the above are false

Front 40

Which of the following BEST summarizes what is known about CYP3A5 and P‐glycoprotein pharmacogenetic associations with calcineurin/ mammalian target of rapamycin inhibitors?
a. Tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors but the dose of cyclosporine is not affected. P‐glycoprotein genotype influences cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

b. Tacrolimus and sirolimus dose requirements are smaller in CYP3A5 expressors but the dose of cyclosporine is not affected. P‐glycoprotein genotype influences sirolimus dose requirements, affects the tacrolimus dose requirements only in CYP3A5 expressors, and is not associated with cyclosporine dose requirements.

c. Cyclosporine dose requirements are larger in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences sirolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with tacrolimus dose requirements.

d. Cyclosporine dose requirements are smaller in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences tacrolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

Back 40

a. Tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors but the dose of cyclosporine is not affected. P‐glycoprotein genotype influences cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

Front 41

he ABCB1 genotype is associated with the risk of nephrotoxicity for which of the following immunosuppressants?
a. Cyclosporine
b. Mycophenolic acid
c. Sirolimus
d. all of the above
e. a and b
f. a and c
g. b and c
h. none of the above

Back 41

a. Cyclosporine

Front 42

Genetic variation in which of the following targets has been shown to affect the in vitro and/or in vivo
pharmacodynamics of an immunosuppressant?
a. Calcineurin
b. Mammalian target of rapamycin
c. Inosine monophosphate dehydrogenase
d. all of the above
e. a and b
f. a and c
g. b and c
h. none of the above

Back 42

c. Inosine monophosphate dehydrogenase

Front 43

The landmark studies by Materson et al., published 1993‐1995, showed which of the following?
a. Response to lipid lowering therapy is variable based upon race
b. Response to anticoagulation therapy is variable based upon VCORC1 status
c. Response to antihypertensive therapy across commonly used classes of drugs is variable across
races regardless of age
d. Response to anti‐arrhythmic therapy is variable based upon electrolyte channels

Back 43

c. Response to antihypertensive therapy across commonly used classes of drugs is variable across races regardless of age

Front 44

The presence β1‐49 and β1‐389 codon polymorphisms were grouped to form diplotypes in the paper published by Johnson et al., mentioned in lecture 1 of the CV pharmacogenetics series. Which of the following best describes the results presented?
a. β1‐49 and β1‐389 diplotypes were equally distributed among blacks and whites enrolled in the study
b. β1‐389 codon polymorphisms were associated with variable pharmacokinetic properties of metoprolol
c. Patients with wild type copies of both alleles (SR/SR) experienced a greater blood pressure response compared to variant carriers
d. β1‐49 and β1‐389 diplotypes were not predictive of blood pressure response or pharmacokinetic properties of metoprolol

Back 44

c. Patients with wild type copies of both alleles (SR/SR) experienced a greater blood pressure response compared to variant carriers

Front 45

Based upon the findings from the paper presented entitled “The APOE ε4 allele determines prognosis and the effect on Prognosis of Simvastatin in Survivors of MI” it can be generalized that:
a. ε2 allele carriers have a poorer prognosis compared to other APOE allele carriers and are likely to benefit from statins post–MI
b. ε4 allele carriers have a better prognosis and are less likely to benefit from statins post–MI
c. ε4 allele carrier status was not a significant predictor for survival pre or post statin therapy
d. ε4 allele carriers have a poorer prognosis when untreated compared to other APOE allele
carriers and are likely to benefit from statins post–MI

Back 45

d. ε4 allele carriers have a poorer prognosis when untreated compared to other APOE allele
carriers and are likely to benefit from statins post–MI

Front 46

VKORC1 polymorphisms have been associated with which of the following?
a. S‐warfarin plasma concentrations
b. R‐warfarin plasma concentrations
c. Warfarin weekly dose requirements
d. all of the above
e. a and b
f. a and c
g. b and c

Back 46

c. Warfarin weekly dose requirements

Front 47

The assigned reading by Frere et al., was a large clopidogrel pharmacogenetic study that suggested which of the following results?
a. CYP3A4*1B polymorphisms associate with clopidogrel response
b. CYP2C19*2 allele carriers have higher platelet reactivity (lower platelet response) after a loading dose of clopidogrel
c. Homozygous carriers of CYP2C19*2 had higher platelet reactivity compared to heterozygous carriers (Gene dose effect)
d. all of the above
e. a and b
f. a and c
g. b and c

Back 47

g. b and c

Front 48

Which of the following statements regarding safety biomarkers is TRUE?
a. Safety biomarkers predict drug toxicity and susceptibility to drug-related injuries.
b. Safety biomarkers predict therapeutic response to drugs.
c. Safety biomarkers can be used to screen out non-responder patients.
d. None of the above

Back 48

a. Safety biomarkers predict drug toxicity and susceptibility to drug-related injuries.

Front 49

The ratio of debrisoquine to the metabolite 4-hydroxydebrisoquine (DB/4OH-DB) has
frequently been used as an index of CYP2D6 activity. The ratio is calculated from the amount
of drug and metabolite recovered in urine over a defined time period. Which of the following
statements regarding this index is TRUE?

a. The DB/4OH-DB ratio will be higher in individuals with the *1/*1 CYP2D6 genotype than in individuals with the *4/*4 CYP2D6 genotype.
b. Ultrarapid metabolizers have higher values of the DB/4OH-DB ratio than Intermediate metabolizers.
c. The DB/4OH-DB ratio is largest in CYP2D6 Poor Metabolizers.
d. All of the above
e. A and B
f. A and C
g. B and C

Back 49

c. The DB/4OH-DB ratio is largest in CYP2D6 Poor Metabolizers.

Front 50

Which of the following statements regarding CYP2C pharmacogenetics is TRUE?
a. The CYP2C9*3 allele is a “loss-of-function” or non-functional allele.
b. The CYP2C9*2 allele is more common in Caucasians than African-Americans.
c. Voriconazole pharmacokinetics does not differ by CYP2C19 genotype.
d. H. pylori cure rate with triple therapy (antibiotics with omeprazole) is higher in
CYP2C19 poor metabolizers.
e. Two of the above are true.
f. Three of the above are true.
g. All of the above are true.

Back 50

e. Two of the above are true.

Front 51

Tacrolimus dose requirements have been associated with the genotype for which of the following CYP enzymes?
a. CYP1A2
b. CYP2A6
c. CYP2C8
d. CYP2C9
e. CYP2C19
f. CYP2D6
g. CYP3A4
h. CYP3A5

Back 51

h. CYP3A5

Front 52

Which of the following statements regarding UGT1A1*28 is/are TRUE?

a. UGT1A1*28 is a variant allele associated with increased gene expression and increased
glucuronidation.
b. A majority of the population is homozygous for UGT1A1*28.
c. Individuals with a homozygous UGT1A1*28 genotype are at greater risk for neutropenia with irinotecan (Camptosar).
d. A and B
e. A and C
f. B and C

Back 52

c. Individuals with a homozygous UGT1A1*28 genotype are at greater risk for neutropenia with irinotecan (Camptosar).

Front 53

A polymorphism that results in reduced activity (i.e., reduced transporter function) was discovered in the ABCG2 gene, which encodes for the transporter Breast Cancer Resistance
Protein (BCRP). Similar to P-glycoprotein, BCRP is expressed in the intestine and blood brain barrier. Which of the following could be a potential consequence of variation in the ABCG2 gene?
a. Decreased oral absorption of mitoxantrone and methotrexate.
b. Increased oral absorption of mitoxantrone and methotrexate.
c. Decreased brain penetration of BCRP substrate drugs (e.g., imatinib).
d. Increased brain penetration of BCRP substrate drugs (e.g., imatinib).
e. A and C
f. A and D
g. B and C
h. B and D

Back 53

h. B and D

Front 54

Drug-drug interactions with digoxin are typically mediated through which of the following transporters?
a. Breast cancer resistance protein (ABCG2)
b. Dipeptide transporter (hPepT1)
c. P-glycoprotein (ABCB1)
d. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP-C)
e. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP-8)
f. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP-B)
g. Multidrug resistance-associated protein 2 (MRP2; ABCC2)

Back 54

c. P-glycoprotein (ABCB1)

Front 55

Abacavir hypersensitivity has been associated with genetic variation in which of the following genes?
a. ALOX5
b. CRHR1
c. HLA subtype B
d. Prothrombin
e. VKORC1
f. None of the above

Back 55

c. HLA subtype B

Front 56

A polymorphism in the SCN1A gene (sodium channel) was the first polymorphism in a drug
target associated with differential dosage requirements in clinical use of which of the following drug classes?
a. Analgesics
b. Antidepressants
c. Antiepileptics
d. Antipsychotics
e. All of the above
f. None of the above

Back 56

c. Antiepileptics

Front 57

A variant allele of the MC1R gene (Melanocortin-1 receptor), usually associated with hair and skin pigmentation, is also associated with which of the following?
a. Antipsychotic effects
b. Analgesic effects
c. Antiepileptic effects
d. Antidepressant effects
e. All of the above
f. None of the above

Back 57

b. Analgesic effects

Front 58

Which of the following genes may affect feeding behavior and weight gain with use of
antipsychotics?

a. 5-HT2A
b. 5-HT2C
c. ABCB1
d. DRD2
e. a&b
f. b&c
g. All of the above
h. None of the above

Back 58

b. 5-HT2C

Front 59

Which of the following is an example of a commercially available American Society of Clinical Oncology (ASCO) recommended pharmacogenetic test?
a. Luminex 100
b. Oncotype DX
c. Genotype DX
d. Applied Biosystems 7300 RT
e. None of the above

Back 59

b. Oncotype DX

Front 60

Based on the pharmacogenetic-driven 6-mercaptopurine dosing scheme presented in class,
which dosing scheme would MOST LIKELY be seen in a TPMT pharmacogenetic-derived
dosing scheme for Azathioprine? [Homozygous wildtype = WT, homozygous mutant = mut,
heterozygous = het, standard dose = sd]
a. WT: 100% sd; het: 50%; mut: 50%
b. WT: 90% sd; het: 50%; mut: 10%
c. WT: 50% sd; het: 50%; mut: 10%
d. WT: 10% sd; het: 50%; mut: 100%
e. WT: 100% sd; het: 50%; mut: 10%

Back 60

e. WT: 100% sd; het: 50%; mut: 10%

Front 61

Choose the MOST LIKELY mechanism(s) of why cancer treatments can fail.
a. Tumor cell over-expresses metabolizing enzyme of drug
b. Tumor cell under-expresses co-factor to drug metabolizing enzyme.
c. Tumor cell over-expresses transport enzyme which pumps drug out of cell
d. a and b
e. a and c

Back 61

e. a and c

Front 62

Which of the following statements regarding CYP2D6 is/are TRUE?
a. Approximately 5% of drugs are metabolized by CYP2D6.
b. CYP2D6 poor metabolizers are more common in Caucasian populations than
Asian populations.
c. CYP2D6 poor metabolizers would have lower plasma concentrations of the
antidepressant nortriptyline compared to ultrarapid metabolizers.
d. None of the above.
e. All of the above.

Back 62

b. CYP2D6 poor metabolizers are more common in Caucasian populations than
Asian populations.

Front 63

Which of the following statements regarding CYP3A4 and CYP3A5 is/are TRUE?
a. SNPs in CYP3A5 have more functional relevance than SNPs in CYP3A4.
b. CYP3A5 is a minor contributor to drug metabolism, even in individuals who are
homozygous carriers of CYP3A5*1.
c. SNPs in CYP3A4 (e.g., CYP3A4*1B) have been shown to affect dose-normalized tacrolimus concentrations.
d. None of the above.
e. All of the above.

Back 63

a. SNPs in CYP3A5 have more functional relevance than SNPs in CYP3A4

Front 64

Which of the following transporters plays an important role in the pharmacokinetics of pravastatin and rosuvastatin?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MDR1 (ABCB1)
d. MRP2 (ABCC2)
e. MRP3 (ABCC3)
f. OATP-C (SLC21A6)
g. None of the above.

Back 64

f. OATP-C (SLC21A6)

Front 65

A polymorphism that results in reduced activity (i.e., reduced transporter function) was
discovered in the ABCB1 gene, which encodes for the transporter P-glycoprotein. Which of the following could be a potential consequence of this genetic variation?
a. Decreased oral absorption of drugs that are P-glycoprotein substrates.
b. Decreased exposure in the brain of drugs that are P-glycoprotein substrates.
c. Increased oral absorption of drugs that are P-glycoprotein substrates.
d. Increased exposure in the brain of drugs that are P-glycoprotein substrates.
e. A and B
f. A and D
g. B and C
h. C and D

Back 65

h. C and D

Front 66

Antipsychotic induced weight gain has been associated with polymorphisms in which of
the following receptors?
a. β1-adrenergic receptor (β1AR)
b. β2- adrenergic receptor (β2AR)
c. Histamine H1 receptor
d. Serotonin 5-HT2C receptor
e. None of the above.

Back 66

d. Serotonin 5-HT2C receptor

Front 67

hich of the following is most likely to be a mechanism of cancer treatment failure?
A polymorphism that results in:
a. Decreased carboxylase (CE) activity
b. Decreased thiopurine S-methyltransferase (TPMT) activity
c. Decreased P-glycoprotein (P-gp or MDR1) activity
d. Decreased UGT1A1 activity

Back 67

a. Decreased carboxylase (CE) activity

Front 68

Carbamazepine is primarily metabolized by which of the following CYP enyzme(s)?
a. CYP2C9
b. CYP2C19
c. CYP3A4
d. A and B
e. A, B and C

Back 68

c. CYP3A4

Front 69

Which of the following statements is/are TRUE?
a. The maximum dose of phenytoin is not different in patients who carry the
CYP2C9*3 allele.
b. The maximum dose of carbamazepine is reduced in patients who carry the CYP2C9*3 allele.
c. The ABCB1 3435C>T (P-glycoprotein) genotype is not associated with dosing
requirements for phenytoin.
d. The ABCB1 3435C>T (P-glycoprotein) genotype is associated with adverse effects to carbamazepine.
e. A and C
f. B and D
g. none of the above

Back 69

c. The ABCB1 3435C>T (P-glycoprotein) genotype is not associated with dosing
requirements for phenytoin.

Front 70

The SCN1A polymorphism is of general importance because:
a. of its demonstrated role in pharmacoresistance to carbamazepine therapy
b. of the prominence of sodium channel blockade in treatment of epilepsy
c. of its relationship to the expression of p-glycoprotein
d. all of the above

Back 70

b. of the prominence of sodium channel blockade in treatment of epilepsy

Front 71

SNPs/Haplotypes in the VKORC1 gene have been associated with variable response to what drug?
a. Metoprolol
b. Hydrochlorothiazide
c. Simvastatin
d. Warfarin

Back 71

d. Warfarin

Front 72

he β1-389 and 49 polymorphisms have been associated with which of the choices below?
a. Variable pharmacokinetics with warfarin
b. Variable pharmacodynamic response to warfarin
c. Variable pharmacokinetics with metoprolol
d. Variable pharmacodynamic response to metoprolol

Back 72

d. Variable pharmacodynamic response to metoprolol

Front 73

In 1995, Materson et al. reported which of the following findings in the New England
Journal of Medicine?
a. APOE variant alleles are associated with increased risk for MI
b. Approximately 50% of patients achieve desired BP goals after initial treatment
with antihypertensive agents
c. Weekly dosage requirements for patients on warfarin therapy is associated with CYP2C9 genotypes
d. α-adducin genotype was associated with variable response to
hydrochlorothiazide

Back 73

b. Approximately 50% of patients achieve desired BP goals after initial treatment

Front 74

Which of the following would not be considered an ethical, legal or social concern with the use of genotype in medical practice?
a. the possibility of health and life insurance companies denying coverage to individuals with certain rare or more costly genotypes.
b. the uncertainty that arises if genetic disorders are diagnosed which are either
symptom less or where no effective interventions are yet available to improve their outcome.
c. the proper roles for the various health professionals dealing with
pharmacogenomics.
d. the social consequences of using racial or ethnic categories in research and clinical care.
e. the observation that racial characteristics correlate better with biological processes than genotype.

Back 74

e. the observation that racial characteristics correlate better with biological processes than genotype.

Front 75

True (A) or false (B). The ability to predict response to pharmacological treatment or to diagnose a genetic disorder from a single gene or gene mutation is only probabilistic and does not yield definitive predictions.

Back 75

True

Front 76

Gene duplication has been identified for which of the following CYP enzymes?
a. CYP1A2
b. CYP2C8
c. CYP2C19
d. CYP2D6
e. CYP3A5

Back 76

d. CYP2D6

Front 77

A polymorphism in which of the following CYP enzymes has been shown to affect dose-
normalized tacrolimus concentrations?
a. CYP2C8
b. CYP2C9
c. CYP2D6
d. CYP3A4
e. CYP3A5

Back 77

e. CYP3A5

Front 78

The cure rates for Helicobacter pylori infection and peptic ulcer achieved by using
standard dual therapy has been shown to be highest in individuals carrying two copies
of variant alleles for which of the following CYP enzymes?
a. CYP1A2
b. CYP2C9
c. CYP2C19
d. CYP2D6
e. CYP3A5

Back 78

c. CYP2C19

Front 79

A low activity genetic variant of which of the following UGT enzymes may be a risk factor for the development of prostate cancer?
a. UGT1A1
b. UGT1A6
c. UGT1A9
d. UGT2B7
e. UGT2B15

Back 79

e. UGT2B15

Front 80

Genetic variation in which of the following UGT enzymes has been associated with toxicity with irinotecan therapy?
a. UGT1A1
b. UGT1A6
c. UGT1A9
d. UGT2B7
e. UGT2B15

Back 80

a. UGT1A1

Front 81

Which of the following transporters plays an important role in the development of
resistance and also the intestinal absorption and hepatobiliary excretion of anticancer drugs such as topetecan and mitoxantrone?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MRP2 (ABCC2)
d. MRP3 (ABCC3)
e. None of the above.

Back 81

a. BCRP (ABCG2)

Front 82

Which one of the following transporters is associated with Dubin-Johnson syndrome, a hereditary defect in bilirubin glucuronide elimination that leads to conjugated
hyperbilirubinemia?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MRP2 (ABCC2)
d. MRP3 (ABCC3)
e. None of the above.

Back 82

c. MRP2 (ABCC2)

Front 83

polymorphism that results in reduced activity (i.e., reduced transporter function) was
discovered in the ABCB1 gene, which encodes for the transporter P-glycoprotein.
Which of the following could be a potential consequence of this genetic variation?
a. Decreased oral absorption of drugs that are P-glycoprotein substrates.
b. Decreased exposure in the brain of drugs that are P-glycoprotein substrates.
c. Increased oral absorption of drugs that are P-glycoprotein substrates.
d. Increased exposure in the brain of drugs that are P-glycoprotein substrates.
e. A and B
f. A and D
g. B and C
h. C and D

Back 83

h. C and D

Front 84

Which of the following is an example of a novel molecularly-based “targeted” therapy for cancer?
a. Imatinib (Gleevec)
b. Irinotecan (Camptosar)
c. Mercaptopurine (Purinethol)
d. Methotrexate (Trexall)

Back 84

a. Imatinib (Gleevec)

Front 85

Which of the following statements is TRUE regarding thiopurine S- methyltransferase (TPMT)?
a. The TPMT pathway is not a major metabolic pathway for mercaptopurine,
thioguanine, and azathioprine.
b. TPMT genetic variants are associated with both efficacy and toxicity in response to thioguanine analogs.
c. Patients with the *1/*1 genotype (homozygous wild-type) require an empirical 65% reduction in 6-MP.
d. Mutant homozygotes have more TPMT activity than heterozygotes.

Back 85

b. TPMT genetic variants are associated with both efficacy and toxicity in response to thioguanine analogs.

Front 86

Which of the following groups had the BEST response to treatment with metoprolol as measured by the 24-hour blood pressure response?
a. Subjects with a homozygous haplotype in the β1-389 and β1-49.
b. Subjects with a variant allele in GNβ3.
c. Subjects with the B1B1 genotype of CETP.
d. Subjects who were α-adducin variant carriers.

Back 86

a. Subjects with a homozygous haplotype in the β1-389 and β1-49.

Front 87

The polymorphism in GNβ3 that has been associated with increased blood pressure
response to diuretics is which of the following?
a. A SNP.
b. A deletion.
c. A repeat of a variable number of 12 bases.
d. A polymorphism identified by the presence or absence of a restriction enzyme cutting site.

Back 87

b. A deletion.

Front 88

What response should be measured in a study evaluating the clinical relevance of haplotypes in the VKORC1 gene?
a. Occurrence of bleeding events in subjects taking warfarin.
b. Response to diuretic therapy with HCTZ in terms of blood pressure.
c. Prevention of secondary cardiovascular events in terms of treatment with simvastatin.
d. Mean warfarin dose required to acquire target anticoagulation intensity.

Back 88

d. Mean warfarin dose required to acquire target anticoagulation intensity.

Front 89

Which one of the following transporters is most likely to limit bioavailability of valacyclovir?
a. Breast cancer resistance protein (ABCG2)
b. Dipeptide transporter (hPepT1)
c. P-glycoprotein (ABCB1)
d. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP-C)
e. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP-8)
f. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP-B)
g. Multidrug resistance-associated protein 2 (MRP2; ABCC2)

Back 89

b. Dipeptide transporter (hPepT1)

Front 90

Which one of the following transporters is associated with Dubin‐Johnson syndrome, a hereditary
defect in bilirubin glucuronide elimination that leads to conjugated hyperbilirubinemia?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MDR1 (ABCB1)
d. MRP2 (ABCC2)
e. MRP3 (ABCC3)
f. OATP1B1 (SLCO1B1)
g. OATP1B3 (SLCO1B3)
h. OATP2B1 (SLCO2B1)
i. OCTN1 (SLC22A4)
j. None of the above.

Back 90

d. MRP2 (ABCC2)

Front 91

Abacavir is an antiretroviral drug used for the treatment of HIV. The prescribing information includes a black box
warning regarding treatment in patients who carry a particular variant allele. Which of the following best
describes the genetic association found with abacavir?
a. Polymorphism(s) in a UGT enzyme with abacavir metabolism.
b. Polymorphism(s) in alcohol dehydrogenase and abacavir metabolism.
c. Polymorphism(s) in Apolipoprotein E4 and abacavir adherence.
d. Polymorphism(s) in the major histocompatibility complex and abacavir hypersensitivity.
e. None of the above.

Back 91

d. Polymorphism(s) in the major histocompatibility complex and abacavir hypersensitivity.