Pharmacogenetics: genetic polymorphism in drug metabolism MCQs With Answer

Introduction

Pharmacogenetics: genetic polymorphism in drug metabolism MCQs With Answer is designed for M.Pharm students specializing in Clinical Pharmacokinetics and Therapeutic Drug Monitoring. This collection focuses on clinically relevant genetic variants that alter drug metabolism, transport, activation and clearance. Questions cover cytochrome P450 enzymes (CYP2D6, CYP2C9, CYP2C19, CYP3A5), phase II enzymes (TPMT, UGT1A1, NAT2), transporters (SLCO1B1, ABCB1), and clinically actionable gene–drug pairs. Emphasis is placed on phenotype implications (poor, intermediate, extensive, ultrarapid), dose adjustments, adverse effect risks, and integration of genotyping with therapeutic drug monitoring. These MCQs aim to deepen understanding for safe, individualized pharmacotherapy in clinical practice.

Q1. What best defines genetic polymorphism in drug metabolism?

• Random mutations that occur during drug therapy
• Common inherited genetic variations in drug-metabolizing enzymes that alter enzymatic activity
• Temporary changes in enzyme activity due to diet or disease
• Drug-induced enzyme inhibition caused by co-medications

Correct Answer: Common inherited genetic variations in drug-metabolizing enzymes that alter enzymatic activity

Q2. A patient is an ultrarapid CYP2D6 metabolizer. How is codeine analgesia most likely affected?

• Decreased analgesic effect due to reduced conversion to morphine
• Unchanged analgesic effect compared with normal metabolizers
• Increased risk of morphine toxicity due to excessive conversion from codeine
• Complete lack of response because codeine is not absorbed

Correct Answer: Increased risk of morphine toxicity due to excessive conversion from codeine

Q3. Which CYP2C19 phenotype is associated with reduced antiplatelet effect of clopidogrel?

• Ultrarapid metabolizer
• Extensive metabolizer
• Poor metabolizer
• Intermediate transporter

Correct Answer: Poor metabolizer

Q4. Low or absent TPMT activity predisposes patients to which adverse effect when given standard doses of azathioprine or mercaptopurine?

• Hypertension
• Severe myelosuppression (bone marrow toxicity)
• Increased drug clearance and treatment failure
• Hepatic enzyme induction

Correct Answer: Severe myelosuppression (bone marrow toxicity)

Q5. The UGT1A1*28 polymorphism most directly increases the risk of toxicity with which chemotherapeutic agent?

• Irinotecan due to reduced glucuronidation of SN-38

Correct Answer: Irinotecan due to reduced glucuronidation of SN-38

Q6. A SLCO1B1 reduced-function allele increases risk of simvastatin-associated myopathy by which mechanism?

• Increased hepatic uptake and lower plasma exposure
• Decreased hepatic uptake leading to higher systemic exposure
• Enhanced renal excretion of simvastatin
• Increased intestinal absorption reducing first-pass effect

Correct Answer: Decreased hepatic uptake leading to higher systemic exposure

Q7. For warfarin dosing, which pair of genetic variants most inform initial dose selection and bleeding risk?

• CYP3A4 and CES1
• CYP2C9 and VKORC1
• UGT1A1 and TPMT
• CYP2D6 and NAT2

Correct Answer: CYP2C9 and VKORC1

Q8. Dihydropyrimidine dehydrogenase (DPYD) deficiency is clinically important because it causes severe toxicity with which class of drugs?

• Aminoglycoside antibiotics
• Fluoropyrimidine chemotherapies (e.g., 5-FU, capecitabine)
• Statins
• Beta-lactam antibiotics

Correct Answer: Fluoropyrimidine chemotherapies (e.g., 5-FU, capecitabine)

Q9. Slow acetylator phenotype of NAT2 affects isoniazid therapy by increasing the risk of which adverse effect?

• Peripheral neuropathy and hepatotoxicity due to slower clearance
• Enhanced therapeutic effect with no toxicity
• Rapid drug inactivation and treatment failure
• Acute renal failure due to crystalluria

Correct Answer: Peripheral neuropathy and hepatotoxicity due to slower clearance

Q10. CYP3A5 expressors generally require what adjustment for tacrolimus dosing compared with non-expressors?

• Lower starting dose because of reduced metabolism
• Higher starting dose because of increased metabolism
• No change; CYP3A5 does not affect tacrolimus
• A single loading dose only, then standard maintenance

Correct Answer: Higher starting dose because of increased metabolism

Q11. Polymorphism in the ABCB1 gene (P-glycoprotein) most commonly affects which pharmacokinetic parameter?

• Drug formulation stability
• Drug absorption and distribution via efflux transport at barriers
• Hepatic phase II conjugation rates
• Covalent binding to plasma proteins

Correct Answer: Drug absorption and distribution via efflux transport at barriers

Q12. Which statement correctly contrasts genotyping and phenotyping for enzyme activity?

• Genotyping measures current enzyme activity; phenotyping identifies genetic variants
• Phenotyping predicts future drug response based on DNA sequence
• Genotyping identifies inherited variants; phenotyping measures present functional activity influenced by environment
• They are identical tests with different names

Correct Answer: Genotyping identifies inherited variants; phenotyping measures present functional activity influenced by environment

Q13. Copy number variation (gene duplication) of CYP2D6 typically results in which phenotype?

• Poor metabolizer
• Ultrarapid metabolizer
• Intermediate transporter
• No effect on metabolism

Correct Answer: Ultrarapid metabolizer

Q14. A true “poor metabolizer” phenotype for a drug eliminated primarily by a single hepatic enzyme will most likely show which pharmacokinetic change?

• Decreased AUC and shorter half-life
• Unchanged clearance and AUC
• Increased AUC and prolonged half-life
• Increased renal clearance compensating for hepatic loss

Correct Answer: Increased AUC and prolonged half-life

Q15. Hepatic carboxylesterase 1 (CES1) loss-of-function polymorphism can reduce activation of which type of prodrug, lowering efficacy?

• Oseltamivir (neuraminidase prodrug activated by CES1)
• Warfarin (non-prodrug requiring VKORC1 interaction)
• Allopurinol (xanthine oxidase inhibitor)
• Vancomycin (glycopeptide antibiotic)

Correct Answer: Oseltamivir (neuraminidase prodrug activated by CES1)

Q16. Phenoconversion refers to which clinical phenomenon?

• Genotype changing spontaneously during therapy
• Environmental or drug interactions altering observed phenotype despite genotype
• Permanent loss of enzyme gene by deletion
• Switching from one metabolic pathway to another due to aging

Correct Answer: Environmental or drug interactions altering observed phenotype despite genotype

Q17. Combining genotyping with therapeutic drug monitoring (TDM) provides which main clinical advantage?

• Eliminates need for clinical assessment of response
• Allows static dosing tables for all patients
• Enables individualized initial dosing and dynamic adjustment based on measured drug concentrations
• Makes TDM redundant because genotype predicts exact concentration

Correct Answer: Enables individualized initial dosing and dynamic adjustment based on measured drug concentrations

Q18. Which population-level consideration is important when applying pharmacogenetic dosing guidelines?

• All populations have identical allele frequencies, so no adjustment is needed
• Allele frequencies vary by ethnicity, affecting prevalence of metabolizer phenotypes and guideline applicability
• Genetic testing is unnecessary in populations with high variability
• Dosing guidelines should ignore ethnicity to ensure equality

Correct Answer: Allele frequencies vary by ethnicity, affecting prevalence of metabolizer phenotypes and guideline applicability

Q19. The CYP2C19 *2 allele is best described as which type of variant?

• Gain-of-function allele causing ultrarapid metabolism
• Loss-of-function allele causing reduced or absent enzyme activity
• Promoter polymorphism that increases expression
• Synonymous SNP with no functional consequence

Correct Answer: Loss-of-function allele causing reduced or absent enzyme activity

Q20. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines primarily provide which service to clinicians?

• Free genetic testing kits mailed to clinics
• Dosing recommendations that translate genotype results into actionable prescribing advice
• Regulatory approval for new drugs based on genetics
• Standardized PCR protocols for laboratory genotyping

Correct Answer: Dosing recommendations that translate genotype results into actionable prescribing advice

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