Pharmacogenomics and genetics of adverse drug reactions MCQs With Answer

Pharmacogenomics and pharmacogenetics explore how genetic variation influences drug response and the risk of adverse drug reactions. For B.Pharm students, mastering concepts such as CYP450 polymorphisms, TPMT, NAT2, UGT1A1, HLA alleles, drug metabolism, pharmacokinetics, pharmacodynamics, genotype–phenotype correlations, and pharmacovigilance is essential for safe, personalized therapy. This focused, high-yield collection links molecular mechanisms to clinical consequences, testing methods (PCR, sequencing, microarrays), interpretation, and management strategies to prevent immunologic and dose-related toxicities. Questions emphasize practical application for therapeutics, dosing, and patient counseling to prepare you for exams and clinical practice. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What best defines pharmacogenomics?

• Study of how single genes affect drug response in individuals
• Study of how environmental factors alter drug pharmacokinetics
• Study of how the entire genome influences drug response and adverse drug reactions
• Clinical monitoring of adverse drug events without genetic testing

Correct Answer: Study of how the entire genome influences drug response and adverse drug reactions

Q2. A patient who is a CYP2D6 poor metabolizer takes codeine for pain. What is the most likely clinical outcome?

• Increased conversion of codeine to morphine with opioid toxicity
• Reduced analgesic effect due to impaired conversion to morphine
• No change; codeine metabolism is not affected by CYP2D6
• Increased risk of allergic reaction to codeine

Correct Answer: Reduced analgesic effect due to impaired conversion to morphine

Q3. Which HLA allele is strongly associated with abacavir hypersensitivity and should be screened before therapy?

• HLA-B*15:02
• HLA-B*57:01
• HLA-A*02:01
• HLA-DRB1*04:01

Correct Answer: HLA-B*57:01

Q4. Which genetic marker is linked with carbamazepine-induced Stevens-Johnson syndrome in certain Asian populations?

• CYP2C9*3
• HLA-B*15:02
• TPMT*3A
• UGT1A1*28

Correct Answer: HLA-B*15:02

Q5. TPMT (thiopurine S-methyltransferase) deficiency predisposes patients to which adverse effect when treated with azathioprine or 6-mercaptopurine?

• Severe myelosuppression (bone marrow toxicity)
• Immune-mediated skin rash only
• Renal tubular necrosis
• Hyperglycemia

Correct Answer: Severe myelosuppression (bone marrow toxicity)

Q6. A patient with UGT1A1*28 homozygosity receives irinotecan. Which toxicity risk is increased?

• Severe neutropenia and diarrhea
• Hypoglycemia
• QT prolongation
• Ototoxicity

Correct Answer: Severe neutropenia and diarrhea

Q7. Which gene variant is most commonly associated with increased risk of statin-induced myopathy (especially simvastatin)?

• SLCO1B1 c.521T>C (rs4149056)
• CYP3A4*1B
• VKORC1 -1639G>A
• HLA-B*57:01

Correct Answer: SLCO1B1 c.521T>C (rs4149056)

Q8. Which two genetic factors most directly influence warfarin dose requirements?

• CYP2D6 and HLA-B alleles
• CYP2C9 and VKORC1 genotypes
• TPMT and NAT2 genotypes
• UGT1A1 and SLCO1B1 variants

Correct Answer: CYP2C9 and VKORC1 genotypes

Q9. What does the phenotype “poor metabolizer” typically indicate?

• High enzyme activity leading to rapid drug clearance
• Low or absent enzyme activity resulting in reduced metabolism of a substrate drug
• Unchanged drug metabolism compared to the general population
• Increased production of active metabolites only

Correct Answer: Low or absent enzyme activity resulting in reduced metabolism of a substrate drug

Q10. Which laboratory method is commonly used for rapid genotyping of known single-nucleotide polymorphisms in clinical pharmacogenetic testing?

• Real-time PCR (TaqMan SNP genotyping)
• Urine drug screen
• ELISA for protein expression
• Mass spectrometry of metabolites

Correct Answer: Real-time PCR (TaqMan SNP genotyping)

Q11. A patient is a CYP2C19 poor metabolizer prescribed clopidogrel after stent placement. What is the expected clinical implication?

• Increased activation of clopidogrel and bleeding risk
• Reduced activation of clopidogrel and higher risk of thrombotic events
• No effect, clopidogrel activation is CYP3A4 dependent only
• Immediate allergic reaction to clopidogrel

Correct Answer: Reduced activation of clopidogrel and higher risk of thrombotic events

Q12. Which condition predisposes patients to hemolytic anemia after exposure to primaquine or dapsone?

• TPMT deficiency
• G6PD deficiency
• CYP2D6 ultrarapid metabolism
• HLA-B*15:02 positive status

Correct Answer: G6PD deficiency

Q13. Slow acetylator phenotype of NAT2 increases risk of toxicity with which drug?

• Isoniazid (INH) causing hepatotoxicity and peripheral neuropathy
• Metformin causing lactic acidosis
• Warfarin causing bleeding
• Abacavir causing hypersensitivity

Correct Answer: Isoniazid (INH) causing hepatotoxicity and peripheral neuropathy

Q14. Which genomic testing approach provides the most comprehensive assessment of genetic variants across the entire genome?

• Targeted single-gene PCR
• Whole-genome sequencing (WGS)
• Serum biochemical assay
• Drug concentration therapeutic monitoring

Correct Answer: Whole-genome sequencing (WGS)

Q15. What is “phenoconversion” in pharmacogenomics?

• A change in genotype due to drug exposure
• An observed drug-drug interaction that alters the metabolic phenotype compared with the underlying genotype
• Conversion of prodrug to active drug by enzymes
• Laboratory error in genotyping assays

Correct Answer: An observed drug-drug interaction that alters the metabolic phenotype compared with the underlying genotype

Q16. Which is an evidence-based clinical utility of pharmacogenomic testing?

• Routine elimination of therapeutic drug monitoring
• Guiding initial drug selection or dose to reduce toxicity and improve efficacy
• Predicting non-genetic drug interactions only
• Replacing all clinical judgement in prescribing

Correct Answer: Guiding initial drug selection or dose to reduce toxicity and improve efficacy

Q17. In allele nomenclature such as CYP2D6*4, what does the “*4” indicate?

• The chromosomal location of the gene
• A specific variant or allele number with defined sequence differences
• The enzyme activity level expressed as a percentage
• The number of copies of the CYP2D6 gene

Correct Answer: A specific variant or allele number with defined sequence differences

Q18. Which adverse drug reaction is most likely immune-mediated and unpredictable from dose alone?

• Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)
• Acetaminophen dose-dependent hepatotoxicity
• Gentamicin ototoxicity related to cumulative dose
• Warfarin-induced bleeding from overdose

Correct Answer: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Q19. Which example best represents pharmacodynamic pharmacogenomics?

• CYP2C9 variants altering warfarin clearance
• VKORC1 polymorphism affecting warfarin sensitivity at the drug target
• UGT1A1 variants affecting irinotecan glucuronidation
• SLCO1B1 variant altering statin hepatic uptake

Correct Answer: VKORC1 polymorphism affecting warfarin sensitivity at the drug target

Q20. Which is a classic pharmacokinetic pharmacogenetic example?

• HLA-B*57:01 and abacavir hypersensitivity
• CYP2D6 ultrarapid metabolism converting codeine to morphine rapidly
• VKORC1 variation altering warfarin target sensitivity
• HLA-B*15:02 and carbamazepine SJS

Correct Answer: CYP2D6 ultrarapid metabolism converting codeine to morphine rapidly

Q21. Why is allele frequency across different populations important in pharmacogenomics?

• It determines the half-life of all drugs globally
• It influences population-specific risk of gene-related adverse drug reactions and guides screening strategies
• It replaces the need for individual genotyping
• It only affects laboratory assay design, not clinical care

Correct Answer: It influences population-specific risk of gene-related adverse drug reactions and guides screening strategies

Q22. Which international resource produces peer-reviewed clinical prescribing guidelines for actionable gene-drug pairs?

• WHO Essential Medicines Committee
• CPIC (Clinical Pharmacogenetics Implementation Consortium)
• FDA Adverse Event Reporting System only
• CDC Immunization Schedule

Correct Answer: CPIC (Clinical Pharmacogenetics Implementation Consortium)

Q23. A patient has a known actionable genotype predicting poor metabolism of Drug X. What is the recommended management approach?

• Ignore genotype and proceed with standard dosing
• Adjust dose or choose an alternative drug based on pharmacogenomic guidance
• Stop all medications indefinitely
• Wait for therapeutic failure before changing therapy

Correct Answer: Adjust dose or choose an alternative drug based on pharmacogenomic guidance

Q24. Which clinical specimen is most commonly used for DNA-based pharmacogenetic testing?

• Serum
• Plasma
• Peripheral blood leukocytes (whole blood) or buccal swab for DNA
• Urine

Correct Answer: Peripheral blood leukocytes (whole blood) or buccal swab for DNA

Q25. What genetic change is typically responsible for CYP2D6 ultrarapid metabolizer status that can lead to codeine toxicity?

• Loss-of-function point mutation (null allele)
• Gene duplication or multiplication of active CYP2D6 alleles
• Promoter hypermethylation reducing expression
• HLA-B allele substitution

Correct Answer: Gene duplication or multiplication of active CYP2D6 alleles

Q26. Which commonly prescribed drug can cause phenoconversion by inhibiting CYP2C19 and reducing clopidogrel activation?

• Omeprazole (a proton pump inhibitor)
• Amoxicillin
• Vitamin C
• Insulin

Correct Answer: Omeprazole (a proton pump inhibitor)

Q27. How does pharmacovigilance integrate with pharmacogenomics to improve drug safety?

• By ignoring genetic data and focusing only on spontaneous reports
• By collecting genotype-phenotype adverse event data to identify gene-drug safety signals
• By replacing clinical trials with genetic tests
• By limiting drug access to genetically tested individuals only

Correct Answer: By collecting genotype-phenotype adverse event data to identify gene-drug safety signals

Q28. In which situation is preemptive multi-gene pharmacogenomic panel testing most likely to be cost-effective?

• Young healthy individuals unlikely to take medications
• Patients expected to receive multiple medications over time or those with polypharmacy
• When only a single, low-impact drug is being considered
• To replace routine lab monitoring for all patients

Correct Answer: Patients expected to receive multiple medications over time or those with polypharmacy

Q29. Which adverse drug reaction type is generally predictable and related to dose and pharmacokinetics?

• Idiosyncratic immune-mediated reaction
• Type A (dose-dependent) toxicity such as aminoglycoside nephrotoxicity
• Allergic rash unrelated to dose
• Genetic hypersensitivity that occurs at very low doses only

Correct Answer: Type A (dose-dependent) toxicity such as aminoglycoside nephrotoxicity

Q30. Regarding HLA-B*57:01 testing before abacavir therapy, which statement is correct?

• Testing is unnecessary because abacavir hypersensitivity cannot be predicted
• Positive HLA-B*57:01 predicts a high risk of abacavir hypersensitivity and testing is recommended before starting abacavir
• HLA testing predicts only cardiovascular side effects of abacavir
• HLA-B*57:01 status determines dosing frequency but not hypersensitivity risk

Correct Answer: Positive HLA-B*57:01 predicts a high risk of abacavir hypersensitivity and testing is recommended before starting abacavir

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