Cytochrome P450 isoenzymes and polymorphisms MCQs With Answer

Introduction: Cytochrome P450 isoenzymes and polymorphisms MCQs With Answer is designed for M.Pharm students pursuing clinical pharmacokinetics and therapeutic drug monitoring. This quiz set focuses on the biochemical properties, major human CYP isoforms (CYP3A4, CYP2D6, CYP2C9, CYP2C19, etc.), genetic variants, and their clinical consequences—such as altered drug metabolism, drug–drug interactions, and personalized dosing strategies. Questions emphasize genotype–phenotype relationships, probe substrates, common inhibitors and inducers, population variability, and practical implications for dosing, adverse effects, and therapeutic drug monitoring. These MCQs aim to deepen understanding beyond basics and prepare students for applied clinical scenarios and exam-level questions.

Q1. What is the primary catalytic function of cytochrome P450 enzymes in drug metabolism?

• Conjugation (phase II) reactions like glucuronidation
• Oxidation via monooxygenase activity introducing oxygen into substrates
• Transport of drugs across hepatocyte membranes
• Hydrolysis of ester prodrugs in plasma

Correct Answer: Oxidation via monooxygenase activity introducing oxygen into substrates

Q2. Where are microsomal cytochrome P450 enzymes predominantly localized in hepatocytes?

• Mitochondrial matrix
• Ribosomes
• Endoplasmic reticulum (smooth ER / microsomes)
• Golgi apparatus

Correct Answer: Endoplasmic reticulum (smooth ER / microsomes)

Q3. Which CYP isoenzyme is responsible for metabolizing approximately one-third of clinically used drugs and is highly abundant in the liver?

• CYP1A2
• CYP2D6
• CYP3A4
• CYP2E1

Correct Answer: CYP3A4

Q4. Which statement best describes CYP2D6 properties?

• CYP2D6 is highly inducible by rifampin and barbiturates
• CYP2D6 shows extensive genetic polymorphism and metabolizes many psychotropics
• CYP2D6 primarily catalyzes glucuronidation reactions
• CYP2D6 is only expressed in extrahepatic tissues, not liver

Correct Answer: CYP2D6 shows extensive genetic polymorphism and metabolizes many psychotropics

Q5. Polymorphisms in which CYP enzyme most commonly affect warfarin metabolism and bleeding risk?

• CYP2C19
• CYP2C9
• CYP3A4
• CYP1A2

Correct Answer: CYP2C9

Q6. How does a CYP2D6 poor metabolizer phenotype typically affect codeine therapy?

• Increased conversion to morphine causing opioid toxicity
• Reduced conversion to morphine leading to decreased analgesic effect
• No effect because codeine is not metabolized by CYP2D6
• Greater formation of inactive metabolites causing drug accumulation

Correct Answer: Reduced conversion to morphine leading to decreased analgesic effect

Q7. Clopidogrel is a prodrug requiring bioactivation primarily by which CYP isoenzyme, and what is the clinical consequence of loss-of-function alleles?

• CYP3A4; increased bleeding risk
• CYP2C19; reduced antiplatelet efficacy and higher thrombotic risk
• CYP2D6; increased analgesia
• CYP1A2; enhanced drug clearance

Correct Answer: CYP2C19; reduced antiplatelet efficacy and higher thrombotic risk

Q8. A patient who is a CYP2C19 poor metabolizer receiving standard-dose omeprazole is most likely to experience which outcome?

• Reduced drug exposure and poor acid suppression
• Increased plasma omeprazole levels and enhanced acid suppression
• No change because omeprazole is renally excreted unchanged
• Faster clearance due to compensatory CYP induction

Correct Answer: Increased plasma omeprazole levels and enhanced acid suppression

Q9. Which CYP2D6 allele is a common loss-of-function variant in Caucasian populations?

• CYP2D6*1 (wild-type)
• CYP2D6*4
• CYP2D6*2 (increased function)
• CYP2D6*17 (gain of function)

Correct Answer: CYP2D6*4

Q10. The ultrarapid metabolizer phenotype for CYP2D6 is most commonly caused by which genetic mechanism?

• Point mutation creating premature stop codon
• Complete gene deletion on both alleles
• Gene duplication or multiplication (e.g., *1xN)
• Promoter methylation silencing the gene

Correct Answer: Gene duplication or multiplication (e.g., *1xN)

Q11. Which probe substrate is commonly used in phenotyping studies to assess CYP3A4 activity?

• Mephenytoin
• Midazolam
• S-paroxetine
• Warfarin

Correct Answer: Midazolam

Q12. Which of the following is a potent CYP3A4 inhibitor that can cause clinically significant drug interactions?

• Rifampin
• Ketanserin
• Ketoconazole
• Carbamazepine

Correct Answer: Ketoconazole

Q13. Which drug is a strong inducer of multiple CYP enzymes, notably CYP3A4, and can markedly reduce concentrations of coadministered substrates?

• Fluconazole
• Ritonavir
• Rifampin (rifampicin)
• Grapefruit juice

Correct Answer: Rifampin (rifampicin)

Q14. What is the fundamental difference between genotyping and phenotyping approaches for CYP enzymes?

• Genotyping measures enzyme activity in vivo; phenotyping detects DNA variants
• Genotyping detects specific alleles; phenotyping measures actual metabolic activity using probe drugs
• Genotyping is more expensive and always more informative than phenotyping
• Phenotyping identifies gene copy number exclusively

Correct Answer: Genotyping detects specific alleles; phenotyping measures actual metabolic activity using probe drugs

Q15. The catalytic cycle of cytochrome P450 requires which essential components/cofactors?

• NADPH-cytochrome P450 reductase and molecular oxygen
• ATP and glutathione
• FMN exclusively without oxygen
• UDP-glucuronic acid for phase II conjugation

Correct Answer: NADPH-cytochrome P450 reductase and molecular oxygen

Q16. A loss-of-function CYP allele is most likely to alter enzyme kinetics by which change?

• Increased Vmax with unchanged Km
• Decreased Vmax and reduced intrinsic clearance
• Decreased Km and increased clearance
• No change in Vmax or Km but altered drug absorption

Correct Answer: Decreased Vmax and reduced intrinsic clearance

Q17. Which population group has a relatively high prevalence of CYP2C19 poor metabolizers compared with Caucasians and Africans?

• East Asians (e.g., Chinese, Japanese)
• South Americans
• Sub-Saharan Africans
• Australians of European descent

Correct Answer: East Asians (e.g., Chinese, Japanese)

Q18. Genetic polymorphisms in P450 enzymes most directly alter which pharmacokinetic parameter?

• Volume of distribution (Vd)
• Absorption rate constant (Ka)
• Systemic clearance (CL)
• Protein binding percentage

Correct Answer: Systemic clearance (CL)

Q19. For which of the following drugs has regulatory guidance and clinical recommendations supporting CYP genotyping to guide therapy due to clear genotype–response relationships?

• Clopidogrel (CYP2C19)
• Acetaminophen
• Metformin
• Ibuprofen

Correct Answer: Clopidogrel (CYP2C19)

Q20. Combining CYP2C9 genotyping with therapeutic monitoring is most useful in optimizing initial dosing and safety for which anticoagulant?

• Heparin
• Warfarin
• Apixaban
• Enoxaparin

Correct Answer: Warfarin

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