CYP-1A2

Acetaminophen

CYP-2E1

Alcohol

CYP-2C9

Warfarin

CYP-2D6

Cardiovascular drugs

CRAP GPS induces my rage

CYP inducers

The study of genetic factors that underlie variation in drug response is called:

A) Pharmacodynamics

B) Pharmacogenomics

C) Toxicokinetics

D) Pharmaceutics

B. Pharmacogenomics

A linked series of alleles found at a locus on a chromosome is best described as a:

A) Haplotype

B) Genotype

C) Phenotype

D) Isoform

A. Haplotype

Phase I enzymes are involved in biotransformation of over what percentage of prescription drugs?

A) 25%

B) 50%

C) 75%

D) 95%

C. 75%

In pharmacogenetic nomenclature, each star-allele variation is defined by a specific sequence variation within the gene:

A) Promoter

B) Locus

C) Intron

D) Codon

B. Locus

Which CYP enzyme metabolizes beta blockers, antidepressants, antipsychotics, and opioid analgesics?

CYP2D6

The gene encoding CYP2D6 has over 100 defined alleles, making it highly:

A) Conserved

B) Polymorphic

C) Silent

D) Recessive

B. Polymorphic

Patients who are CYP2D6 poor or intermediate metabolizers are more likely to experience insufficient:

A) Pain relief

B) Bile secretion

C) Renal filtration

D) Platelet inhibition

A. Pain relief

CYP2D6 ultrarapid metabolizers are at increased risk for which opioid-related outcome?

A) Treatment failure

B) Side effects

C) Delayed absorption

D) Reduced activation

B. Side effects

What CYP enzyme preferentially metabolizes acidic drugs, including proton pump inhibitors, antidepressants, antiepileptics, and antiplatelet drugs?

CYP2C19

The rate-limiting enzyme in pyrimidine catabolism is:

A) CYP2D6

B) UGT1A1

C) DPD

D) TPMT

C. DPD

Partial deficiency of dihydropyrimidine dehydrogenase can dramatically reduce clearance of which chemotherapy drug?

A) Irinotecan

B) 5-fluorouracil

C) Methotrexate

D) Flucloxacillin

B) 5-fluorouracil

UDP glucuronosyltransferase 1A1 helps excrete drugs by conjugating glucuronic acid onto small:

A) Protein molecules

B) Lipophilic molecules

C) Inorganic ions

D) Nucleic acids

B. Lipophilic molecules

About 10% of Europeans are homozygous for UGT1A1*28, which is clinically recognized as:

A) Gilbert syndrome

B) Crigler-Najjar II

C) Rotor syndrome

D) Dubin-Johnson syndrome

A. Gilbert syndrome

Gilbert syndrome can cause 60–70% increased unconjugated bilirubin because UGT1A1 activity is reduced by about:

A) 10%

B) 30%

C) 60%

D) 90%

B. 30%

Which topoisomerase I inhibitor prodrug is first-line with 5-FU and leucovorin for colon or rectal cancer?

A) Azathioprine

B) Simvastatin

C) Irinotecan

D) Rasburicase

C. Irinotecan

Irinotecan causes cancer cell death primarily by inhibiting topoisomerase I, leading to termination of:

A) DNA replication

B) Protein translation

C) RNA splicing

D) Bilirubin conjugation

A. DNA replication

Which enzyme methylates aromatic and heterocyclic sulfhydryl compounds and deactivates thiopurine drugs?

A) G6PD

B) TPMT

C) DPD

D) BCRP

B. TPMT

About 10% of Europeans and Africans inherit one functional TPMT allele and therefore have:

A) Absent TPMT activity

B) Intermediate TPMT activity

C) Excessive TPMT activity

D) Normal TPMT activity

B. Intermediate TPMT activity

Azathioprine and 6-mercaptopurine are thiopurine drugs used to treat:

A) Immunologic disorders

B) Hyperlipidemia

C) Opioid toxicity

D) Acid reflux

A. Immunologic disorders

The first and rate-limiting enzyme of the pentose phosphate pathway that supplies significant NADPH is:

A) CYP2C19

B) OATP1B1

C) G6PD

D) UGT1A1

C. G6PD

G6PD deficiency is defined as enzyme activity below:

A) 10%

B) 30%

C) 60%

D) 90%

C. 60%

Most G6PD-deficient genotypes are associated with which severity range?

A) Mild and silent

B) Moderate and severe

C) Severe and lethal

D) Mild and moderate

B. Moderate and severe

Patients with G6PD deficiency receiving rasburicase are at increased risk for hemolytic anemia and:

A) Methemoglobinemia

B) Aplastic anemia

C) Sideroblastic anemia

D) Megaloblastic anemia

A. Methemoglobinemia

Which transporter is on the hepatocyte sinusoidal membrane and takes up mainly weakly acidic drugs and endogenous compounds?

A) BCRP

B) OATP1B1

C) P-glycoprotein

D) CFTR

B. OATP1B1

HMG-CoA reductase inhibitors are highly effective lipid-lowering drugs better known as:

A) Statins

B) Fibrates

C) Resins

D) Niacins

A. Statins

Patients receiving simvastatin with reduced OATP1B1 function should receive which dose adjustment?

A) Higher dose

B) Lower dose

C) Loading dose

D) No dose

B. Lower dose

If OATP1B1 function is reduced:

less simvastatin enters liver
more simvastatin stays in blood
higher systemic statin exposure
higher risk of statin myopathy/rhabdomyolysis

BCRP is an ATP-binding cassette efflux transporter found on epithelial cells of the kidney, liver, intestine, and endothelial cells of the:

A) Blood-brain barrier

B) Splenic sinusoids

C) Bone marrow

D) Cardiac valves

A. Blood-brain barrier

Severe hypersensitivity drug reactions include toxic epidermal necrolysis, Stevens-Johnson syndrome, and which organ injury?

A) Kidney injury

B) Liver injury

C) Lung injury

D) Splenic injury

B. Liver injury

Which drug’s hypersensitivity reaction is probably mediated by cytotoxic CD8 T cells?

A) Abacavir

B) Simvastatin

C) Irinotecan

D) Digoxin

A. Abacavir

Which phase I drug-metabolizing enzyme acts primarily on acidic drugs, including S-warfarin, phenytoin, and NSAIDs?

A) CYP2D6

B) CYP2C9

C) CYP3A4

D) CYP1A2

B. CYP2C9

Rare genetic variants in the coding region of VKORC1 may cause bleeding disorders or:

A) Codeine toxicity

B) Warfarin resistance

C) Statin myopathy

D) Digoxin accumulation

B. Warfarin resistance

The VKORC1-1639G>A variant occurs most commonly in which population, helping explain ethnic differences in warfarin dosing?

A) Asian populations

B) African populations

C) Northern Europeans

D) Native Australians

A. Asian populations

Pharmacogenomics recognizes that drug-response variation may be caused by:

A) One vitamin deficiency

B) One renal transporter

C) Multiple genetic variants

D) Only CYP3A4

C. Multiple genetic variants

Using genetic information to guide drug and dose selection for subgroups or individual patients is called:

A) Empiric dosing

B) Precision medicine

C) Drug tolerance

D) First-pass metabolism

B. Precision medicine

Two or more alternative forms of a gene arising by mutation at the same genetic locus are called:

A) Alleles

B) Haplotypes

C) Isoforms

D) Promoters

A. Alleles

Allele frequency refers to the percentage of times a specific allele is observed relative to:

A) All possible alleles

B) All expressed proteins

C) All coding SNPs

D) All chromosomes

A. All possible alleles

A single base-pair substitution occurring in a coding region is called a:

A) Copy number variant

B) Coding SNP

C) Haplotype

D) Linked locus

B. Coding SNP

A DNA segment present in variable copy number between individuals is called a:

A) CNV

B) nsSNP

C) Haplotype

D) Locus

A. CNV

A nonsynonymous SNP is a single base-pair substitution that causes a change in:

A) Amino acid sequence

B) Copy number

C) Allele frequency

D) Chromosome number

A. Amino acid sequence

Linkage disequilibrium refers to nonrandom association of alleles at two or more loci descended from a single ancestral:

A) Drug substrate

B) Chromosome

C) Protein isoform

D) Coding region

B. Chromosome

P450 phase I biotransformation reactions typically modify which parts of endogenous or xenobiotic compounds?

A) Functional groups

B) Chromosome arms

C) Peptide bonds

D) Nuclear receptors

A. Functional groups

Which CYP is highly polymorphic, metabolizes about 25% of drugs, and converts codeine to morphine?

A) CYP2C9

B) CYP2D6

C) CYP2C19

D) CYP3A5

B. CYP2D6

CYP2D6 performs which reaction to convert codeine into morphine?

A) O-demethylation

B) Glucuronidation

C) S-methylation

D) Acetylation

A. O-demethylation

Morphine, the active metabolite of codeine, provides analgesia by binding which CNS receptor?

A) μ opioid receptor

B) GABA-A receptor

C) NMDA receptor

D) D2 receptor

A. μ opioid receptor

After equal codeine doses, CYP2D6 extensive metabolizers usually experience which outcome?

A) Desired analgesic effect

B) No drug activation

C) Severe bleeding

D) Statin toxicity

A. Desired analgesic effect

“Extensive metabolizer” basically means normal metabolizer.

After equal codeine doses, CYP2D6 poor and intermediate metabolizers are more likely to experience:

A) Insufficient analgesic effects

B) Severe warfarin resistance

C) Excess morphine toxicity

D) Rapid drug clearance

A. Insufficient analgesic effects

After equal codeine doses, CYP2D6 ultrarapid metabolizers have higher risk for side effects such as drowsiness and:

A) Respiratory depression

B) Bladder cancer

C) Mucositis

D) Hand-foot syndrome

A. Respiratory depression

Which CYP preferentially metabolizes acidic drugs, including PPIs, antidepressants, antiepileptics, and antiplatelet drugs?

A) CYP2D6

B) CYP2C19

C) CYP2B6

D) CYP1A2

B. CYP2C19

Clopidogrel is best described as which type of cardiovascular medication?

A) Direct thrombin inhibitor

B) Thienopyridine antiplatelet prodrug

C) Reversible P2Y12 antagonist

D) Cyclooxygenase-1 inhibitor

B. Thienopyridine antiplatelet prodrug

Clopidogrel is indicated for prevention of which clinical event category?

A) Atherothrombotic events

B) Ventricular arrhythmias

C) Pulmonary vasospasm

D) Biliary obstruction

A. Atherothrombotic events

The active metabolites of clopidogrel inhibit platelet aggregation by selectively and irreversibly blocking which stimulus pathway?

A) Thrombin-induced fibrin formation

B) ADP-induced platelet aggregation

C) Collagen-induced vasospasm

D) Prostacyclin-mediated dilation

B. ADP-induced platelet aggregation

About 85% of administered clopidogrel is rapidly converted by hepatic esterases into which products?

A) Active thiol metabolites

B) Toxic quinone intermediates

C) Inactive carboxylic acid derivatives

D) Glucuronidated biliary conjugates

C. Inactive carboxylic acid derivatives

About 15% of clopidogrel is converted to its active thiol metabolite through two sequential oxidation reactions mediated mostly by:

A) CYP2C19

B) CYP2D6

C) CYP1A2

D) CYP3A5

A. CYP2C19

A CYP2C19 *2/*17 patient is not an ultrarapid metabolizer because *17 cannot fully compensate for:

A) Increased CYP3A4 activity

B) Nonfunctional CYP2C19 alleles

C) Excess platelet ADP signaling

D) Rapid esterase hydrolysis

B. Nonfunctional CYP2C19 alleles

A patient taking clopidogrel carries CYP2C19 nonfunctional alleles. Which outcome becomes more likely?

A) Myelosuppression

B) Cardiovascular events

C) Gilbert syndrome

D) Methemoglobinemia

B. Cardiovascular events

Which phase I enzyme is encoded by the DPYD gene?

A) Dihydropyrimidine dehydrogenase

B) Thiopurine S-methyltransferase

C) UDP glucuronosyltransferase

D) Hepatic carboxylesterase

A. Dihydropyrimidine dehydrogenase

DPD is a major elimination route for which chemotherapy drug class?

A) Fluoropyrimidine chemotherapy agents

B) Platinum alkylating agents

C) Antifolate chemotherapy agents

D) Anthracycline chemotherapy agents

A. Fluoropyrimidine chemotherapy agents

5-fluorouracil targets rapidly dividing cancer cells primarily by inhibiting:

A) DNA synthesis

B) Bile secretion

C) Platelet activation

D) Vitamin K recycling

A. DNA synthesis

Most 5-fluorouracil is catabolized and excreted through which enzyme pathway?

A) UGT1A1 glucuronidation

B) DPD pyrimidine catabolism

C) CYP2D6 O-demethylation

D) TPMT S-methylation

B. DPD pyrimidine catabolism

A patient with DPYD *2A/*13 receives 5-fluorouracil. What is the expected pharmacokinetic consequence?

A) Increased 5-FU clearance

B) Reduced 5-FU clearance

C) Complete clopidogrel failure

D) Increased bilirubin conjugation

B. Reduced 5-FU clearance

DPD deficiency increases 5-FU toxicity partly by increasing which toxic metabolites?

A) SN-38 and bilirubin

B) Morphine and thioguanine

C) 5-FUMP and 5-FdUMP

D) PAPS and acetyl-CoA

C. 5-FUMP and 5-FdUMP

UGT1A1 is a phase II enzyme that conjugates glucuronic acid onto small lipophilic molecules such as:

A) Bilirubin

B) Codeine

C) Warfarin

D) Digoxin

A. Bilirubin

UGT1A1-mediated glucuronidation helps small lipophilic molecules become excretable into:

A) Urine only

B) Bile

C) Sweat

D) Saliva

B. Bile

Patients with UGT1A1 *28/*28 are at increased risk for adverse drug reactions because of reduced:

A) Renal filtration

B) Biliary formation

C) Platelet aggregation

D) P450 induction

B. Biliary formation

Irinotecan is hydrolyzed by hepatic carboxylesterases into which cytotoxic metabolite?

A) 5-FdUMP

B) SN-38

C) Morphine

D) Thioguanine

B. SN-38

SN-38 causes chemotherapy effects by inhibiting topoisomerase I, which terminates:

A) DNA replication

B) Protein folding

C) Platelet aggregation

D) Pyrimidine catabolism

A. DNA replication

UGT1A1 *28 increases irinotecan toxicity because SN-38 inactivation depends on which enzyme?

A) CYP2C19

B) DPD

C) UGT1A1

D) TPMT

C. UGT1A1

Phase I reactions mediated by hepatic P450 enzymes commonly modify functional groups such as OH, SH, NH2, and:

A) OCH3

B) PAPS

C) HGPRTase

D) HLA

A. OCH3

CYP2D6 is involved in metabolism of about 25% of drugs and generally handles which type of compounds?

A) Neutral compounds

B) Basic compounds

C) Steroid compounds

D) Sulfated compounds

B. Basic compounds

CYP2C19 is known to preferentially metabolize which type of drugs?

A) Basic drugs

B) Neutral drugs

C) Acidic drugs

D) Protein drugs

C. Acidic drugs

Which drug class is among the acidic drug classes preferentially metabolized by CYP2C19?

A) Proton-pump inhibitors

B) Thiopurine drugs

C) Statin drugs

D) Opioid analgesics

A. Proton-pump inhibitors

Which cytochrome P450 enzyme is used to metabolize HIV drugs?

A) CYP2C9

B) CYP2D6

C) CYP2B6

D) CYP1A2

C. CYP2B6

Dihydropyrimidine dehydrogenase is encoded by which gene?

A) DPYD

B) G6PD

C) UGT1A1

D) CYP2C9

A. DPYD

Phase II biotransformation reactions generally do what to drugs or metabolites

A) Oxidize heme iron

B) Remove introns

C) Reduce oxygen

D) Conjugate endogenous molecules

D. Conjugate endogenous molecules

Which gene is involved in pharmacologic deactivation of thiopurines?

A) CYP2D6

B) DPYD

C) OATP1B1

D) TPMT

D. TPMT

TPMT is most directly involved in deactivation of which drug class?

A) Antiplatelets

B) Thiopurines

C) Statins

D) Opioids

B. Thiopurines

The gene encoding G6PD is located on which chromosome?

A) Chromosome 7

B) Chromosome 12

C) X chromosome

D) Y chromosome

C. X chromosome

Because G6PD is encoded on the X chromosome, G6PD deficiency classically follows which inheritance pattern?

A) X-linked pattern

B) Autosomal dominant pattern

C) Autosomal recessive pattern

D) Mitochondrial pattern

A. X-linked pattern

Transport of statins into hepatocytes is mediated by which transporter?

A) BCRP

B) P-glycoprotein

C) CFTR

D) OATP1B1

D. OATP1B1

Warfarin is metabolized primarily by which phase I enzyme?

A) CYP3A4

B) CYP2D6

C) CYP2C9

D) CYP2B6

C. CYP2C9

Epigenomics refers to heritable patterns of gene expression not attributable to changes in what?

A) Primary DNA sequence

B) Drug dose

C) Protein folding

D) Hepatic blood flow

A. Primary DNA sequence

Which pair represents classic examples of epigenomic regulation?

A) SNPs and CNVs

B) DNA methylation and histone modifications

C) Haplotypes and alleles

D) Oxidation and reduction

B. DNA methylation and histone modifications

A patient has VKORC1 -1639G>A plus CYP2C9 *2 or *3 and receives a normal warfarin dose. What risk increases?

A) Clopidogrel failure

B) Codeine toxicity

C) Gilbert syndrome

D) Bleeding

D. Bleeding

Abacavir hypersensitivity reactions are associated with which HLA allele variant?

A) HLA-B*57:01

B) HLA-B*27:05

C) HLA-DQ2

D) HLA-DR4

A. HLA-B*57:01

Flucloxacillin-induced liver toxicity is associated with which HLA polymorphism?

A) HLA-DQ8

B) HLA-DR3

C) HLA-B*57:01

D) HLA-A*31:01

C. HLA-B*57:01

A 62-year-old woman with advanced colon cancer is treated
with intravenous 5-fluorouracil. Within a few days, she
develops severe diarrhea, and within a week, she shows severe
neutropenia. Which of the following polymorphisms is most
likely to be responsible?
(A) CYP2D6*1x3
(B) CYP2C19*2
(C) CYP2C9*3
(D) DPYD*2A
(E) UGT1A1*28

(D) DPYD*2A

A 38-year-old man is being treated for HIV-induced acquired
immunodeficiency syndrome (AIDS). When abacavir ther￾apy is begun, he develops a severe skin rash. Which of the
following pharmacogenomic diagnoses might explain this
skin rash?
(A) CYP2D6*3 (PM)
(B) CYP3A5*3 (PM)
(C) HLA-B*57:01 (EM)
(D) SLCO1B1*5 (PM)

(C) HLA-B*57:01 (EM)

Which of the following polymorphisms is associated with risk of hemolysis and increased resistance to malaria?
(A) CYP2D6*3
(B) CYP2D19*2
(C) TPMT*2
(D) UGT1A1*28
(E) G6PD-(A)–Canton

(E) G6PD-(A)–Canton

A 7-year-old child is brought to the emergency department in
coma with cyanosis. Her mother states that the girl was given
codeine with acetaminophen because of severe bruising after
a fall. Shortly after the first dose, the child became unrespon￾sive and “turned blue.” Which of the following alleles might
be responsible for this presentation?
(A) CYP2D6*1x3
(B) CYP2C19*2
(C) CYP2C9*3
(D) DPYD*2A
(E) UGT1A1*28

(A) CYP2D6*1x3