Polymorphisms affecting drug metabolism and transport MCQs With Answer

Introduction

This quiz collection focuses on polymorphisms affecting drug metabolism and transport — a crucial area in cellular and molecular pharmacology for M.Pharm students. Genetic variants in drug-metabolizing enzymes (like CYPs, UGTs, TPMT) and transporters (such as OATP1B1, P‑glycoprotein) can markedly alter drug pharmacokinetics, efficacy and toxicity. Understanding common variant examples, phenotype categories (poor, intermediate, normal, ultrarapid), mechanisms (altered expression, splicing, catalytic activity), clinical consequences (dose adjustment, adverse reactions), and genotyping methods enables rational therapeutic decisions. These MCQs explore molecular mechanisms, clinically relevant examples (warfarin, clopidogrel, irinotecan, statins, thiopurines), population differences and lab approaches to prepare you for advanced pharmacogenomic applications in pharmacy practice.

Q1. Which genetic alteration is best described as a single nucleotide change occurring commonly in the population that can influence drug response?

• Copy number variation (CNV)
• Single nucleotide polymorphism (SNP)
• Chromosomal translocation
• De novo mutation

Correct Answer: Single nucleotide polymorphism (SNP)

Q2. A patient has an ultrarapid metabolizer phenotype of CYP2D6. Which clinical consequence is most likely when treating with codeine?

• Reduced analgesic effect due to decreased activation
• Increased risk of toxicity from rapid conversion to morphine
• No effect on codeine response because CYP2D6 is not involved
• Increased plasma codeine concentrations causing sedation

Correct Answer: Increased risk of toxicity from rapid conversion to morphine

Q3. Loss‑of‑function alleles of CYP2C19 (for example *2/*3) most directly affect the clinical efficacy of which drug?

• Warfarin
• Clopidogrel
• Metoprolol
• Atorvastatin

Correct Answer: Clopidogrel

Q4. Variants in CYP2C9 and VKORC1 together are most relevant to genotype‑guided dosing of which anticoagulant?

• Heparin
• Apixaban
• Warfarin
• Clopidogrel

Correct Answer: Warfarin

Q5. The UGT1A1*28 polymorphism (TA7 promoter repeat) predisposes patients to severe toxicity with which chemotherapeutic agent due to reduced glucuronidation?

• 5‑Fluorouracil
• Irinotecan
• Cisplatin
• Paclitaxel

Correct Answer: Irinotecan

Q6. A patient with low or absent TPMT activity is at high risk of myelosuppression when treated with which class of drugs?

• Beta‑lactam antibiotics
• Thiopurines (e.g., azathioprine, 6‑mercaptopurine)
• Statins
• SSRIs

Correct Answer: Thiopurines (e.g., azathioprine, 6‑mercaptopurine)

Q7. Deficiency in dihydropyrimidine dehydrogenase (DPYD) most increases the risk of severe toxicity with which drug?

• Imatinib
• Fluoropyrimidines (5‑fluorouracil, capecitabine)
• Vancomycin
• Metformin

Correct Answer: Fluoropyrimidines (5‑fluorouracil, capecitabine)

Q8. The SLCO1B1*5 allele reduces hepatic uptake of certain statins and is associated with an increased risk of which adverse event?

• Hepatotoxicity only
• Renal failure
• Statin‑associated myopathy/rhabdomyolysis
• QT prolongation

Correct Answer: Statin‑associated myopathy/rhabdomyolysis

Q9. Polymorphisms in ABCB1 (P‑glycoprotein) primarily affect drug disposition by altering which process?

• Phase II conjugation in the liver
• Active efflux of drugs across cell membranes
• Drug absorption by altering pH gradients
• Renal glomerular filtration rate

Correct Answer: Active efflux of drugs across cell membranes

Q10. Carboxylesterase 1 (CES1) polymorphisms can alter activation or clearance of ester prodrugs. A loss‑of‑function CES1 variant would most likely cause which outcome for a prodrug requiring CES1 activation?

• Increased active drug exposure and toxicity
• Decreased generation of active metabolite and reduced efficacy
• No change because CES1 only affects transporters
• Increased renal elimination of the prodrug

Correct Answer: Decreased generation of active metabolite and reduced efficacy

Q11. A missense polymorphism that lowers the catalytic efficiency (kcat) of an enzyme would most directly change which kinetic parameter?

• Km only
• Vmax (and therefore kcat)
• Protein molecular weight
• Half‑life of the mRNA

Correct Answer: Vmax (and therefore kcat)

Q12. Which laboratory method provides base‑level resolution and is considered the gold standard for identifying known and novel single nucleotide variants in pharmacogenes?

• PCR‑RFLP
• Sanger or next‑generation DNA sequencing
• Western blotting
• Immunohistochemistry

Correct Answer: Sanger or next‑generation DNA sequencing

Q13. Gene duplication of CYP2D6 typically produces which metabolizer phenotype?

• Poor metabolizer
• Intermediate metabolizer
• Normal (extensive) metabolizer
• Ultrarapid metabolizer

Correct Answer: Ultrarapid metabolizer

Q14. A genetic variant that decreases hepatic clearance of a drug will most commonly produce which change in pharmacokinetic parameters?

• Decreased half‑life
• Increased clearance
• Increased half‑life and increased AUC
• Decreased volume of distribution

Correct Answer: Increased half‑life and increased AUC

Q15. The CYP3A5*3 allele causes aberrant splicing and markedly reduced CYP3A5 expression. This is an example of what class of polymorphism?

• Promoter repeat polymorphism
• Splice site or intronic polymorphism affecting mRNA processing
• Copy number amplification resulting in overexpression
• Synonymous coding SNP with no functional consequence

Correct Answer: Splice site or intronic polymorphism affecting mRNA processing

Q16. How can inherited loss‑of‑function variants in a metabolizing enzyme influence the risk of drug–drug interactions?

• They eliminate the possibility of any interactions
• They can increase interaction risk because compensatory pathways may be saturated
• They always protect against interactions by decreasing metabolism
• They convert pharmacokinetic interactions into purely pharmacodynamic ones

Correct Answer: They can increase interaction risk because compensatory pathways may be saturated

Q17. Which statement about population differences in pharmacogene allele frequencies is correct?

• CYP2C19 loss‑of‑function alleles are more frequent in East Asian populations than in Europeans
• All pharmacogene allele frequencies are identical across ethnic groups
• CYP2C19 loss‑of‑function alleles are exclusive to European populations
• Ethnic variation is irrelevant for clinical pharmacogenetics

Correct Answer: CYP2C19 loss‑of‑function alleles are more frequent in East Asian populations than in Europeans

Q18. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend considering SLCO1B1 genotype when prescribing which statin because of myopathy risk?

• Pravastatin
• Simvastatin
• Fluvastatin
• Rosuvastatin only

Correct Answer: Simvastatin

Q19. Which best distinguishes pharmacogenetics from pharmacogenomics?

• Pharmacogenetics studies food–drug interactions while pharmacogenomics studies drug–drug interactions
• Pharmacogenetics focuses on single‑gene effects; pharmacogenomics examines genome‑wide influences on drug response
• They are identical terms with no distinction
• Pharmacogenetics uses proteomics while pharmacogenomics uses transcriptomics

Correct Answer: Pharmacogenetics focuses on single‑gene effects; pharmacogenomics examines genome‑wide influences on drug response

Q20. For warfarin, which approach combines genotype information (CYP2C9 and VKORC1) to improve initial dosing compared with empirical dosing?

• Therapeutic drug monitoring without genotype
• Genotype‑guided dosing algorithms
• Fixed standard dosing for all patients
• Randomized dose escalation

Correct Answer: Genotype‑guided dosing algorithms

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