Drug metabolism – principles and pathways MCQs With Answer

Drug metabolism – principles and pathways MCQs With Answer

This concise, student-focused introduction outlines core concepts of drug metabolism and biotransformation for B.Pharm candidates. You will review phase I (oxidation, reduction, hydrolysis) and phase II (conjugation) pathways, major enzyme systems such as CYP450, UGTs and transferases, and clinically important ideas like first-pass metabolism, prodrugs, enzyme induction/inhibition, pharmacogenetic polymorphisms, bioactivation and enterohepatic recirculation. Emphasis is placed on metabolic clearance, Michaelis–Menten kinetics, and drug–drug interactions that alter pharmacokinetics. This keyword-rich overview prepares you to apply principles in formulation, dosing and therapeutic monitoring. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which enzyme family is responsible for the majority of phase I oxidative metabolism of drugs?

• Flavin-containing monooxygenases (FMOs)
• Cytochrome P450 (CYP) enzymes
• Carboxylesterases
• UDP-glucuronosyltransferases (UGTs)

Correct Answer: Cytochrome P450 (CYP) enzymes

Q2. Which reaction is NOT typically classified as a phase I metabolic reaction?

• Oxidation
• Reduction
• Glucuronidation
• Hydrolysis

Correct Answer: Glucuronidation

Q3. Glucuronidation is an example of which type of metabolic process?

• Phase I functionalization
• Phase II conjugation
• Renal excretion
• Enterohepatic recirculation

Correct Answer: Phase II conjugation

Q4. Which CYP isoform metabolizes the largest proportion of marketed drugs?

• CYP1A2
• CYP2D6
• CYP2C9
• CYP3A4

Correct Answer: CYP3A4

Q5. A prodrug is best defined as:

• An inactive compound converted to an active drug by metabolic biotransformation
• A drug metabolite that is excreted unchanged
• A compound that inhibits metabolic enzymes
• A formulation designed for delayed release

Correct Answer: An inactive compound converted to an active drug by metabolic biotransformation

Q6. The primary toxic metabolite of paracetamol (acetaminophen) that causes hepatotoxicity is:

• Glucuronide conjugate
• Sulfate conjugate
• N-acetyl-p-benzoquinone imine (NAPQI)
• Glutathione-stable metabolite

Correct Answer: N-acetyl-p-benzoquinone imine (NAPQI)

Q7. Which phase II reaction commonly uses UDP-glucuronic acid as a cofactor?

• Sulfation
• Glucuronidation
• Acetylation
• Methylation

Correct Answer: Glucuronidation

Q8. First-pass metabolism refers to:

• Metabolism occurring after renal excretion
• Metabolism of a drug before it reaches systemic circulation, typically in gut wall and liver
• Metabolism exclusively in the lung
• Phase II reactions only

Correct Answer: Metabolism of a drug before it reaches systemic circulation, typically in gut wall and liver

Q9. Which factor does NOT directly affect hepatic clearance according to the well-stirred model?

• Hepatic blood flow (Q)
• Fraction unbound in plasma (fu)
• Intrinsic clearance (Clint)
• Gastric pH

Correct Answer: Gastric pH

Q10. CYP2D6 polymorphism can lead to which clinically relevant phenotype?

• Ultrafast, extensive, intermediate and poor metabolizers
• Only poor metabolizers
• Only ultrafast metabolizers
• No variation in metabolic capacity

Correct Answer: Ultrafast, extensive, intermediate and poor metabolizers

Q11. Which of the following is a common example of a mechanism-based (irreversible) CYP inhibitor?

• Ketoconazole
• Rifampin
• Grapefruit juice furanocoumarins
• Omeprazole

Correct Answer: Grapefruit juice furanocoumarins

Q12. Enzyme induction typically leads to:

• Decreased metabolic clearance of co-administered drugs
• Increased metabolic clearance of co-administered drugs
• Immediate inhibition of enzyme activity
• No change in drug metabolism

Correct Answer: Increased metabolic clearance of co-administered drugs

Q13. Which organelle is the primary site for many phase I CYP-mediated reactions in hepatocytes?

• Mitochondria
• Endoplasmic reticulum (microsomes)
• Golgi apparatus
• Peroxisomes

Correct Answer: Endoplasmic reticulum (microsomes)

Q14. Michaelis–Menten Km represents:

• The maximum metabolic rate
• The substrate concentration at which rate is half of Vmax
• The elimination half-life
• The bioavailability of a drug

Correct Answer: The substrate concentration at which rate is half of Vmax

Q15. Which conjugation pathway helps detoxify reactive electrophilic metabolites by forming a stable conjugate with a tripeptide?

• Glucuronidation
• Sulfation
• Glutathione conjugation
• Acetylation

Correct Answer: Glutathione conjugation

Q16. Which drug is bioactivated to morphine by CYP2D6?

• Codeine
• Fentanyl
• Hydrocodone
• Aspirin

Correct Answer: Codeine

Q17. Which statement best describes enterohepatic recirculation?

• Permanent renal elimination of a drug
• Biliary excretion of conjugates followed by intestinal deconjugation and reabsorption
• Metabolism limited to the intestinal mucosa only
• Complete hepatic detoxification without reabsorption

Correct Answer: Biliary excretion of conjugates followed by intestinal deconjugation and reabsorption

Q18. Isoniazid metabolism exhibits polymorphism due to variation in which enzyme class?

• UDP-glucuronosyltransferases (UGTs)
• N-acetyltransferase (NAT)
• CYP3A4
• Sulfotransferases (SULTs)

Correct Answer: N-acetyltransferase (NAT)

Q19. Which clinical consequence is expected when a potent CYP3A4 inhibitor is co-administered with a drug primarily metabolized by CYP3A4?

• Decreased plasma concentration of the victim drug
• Increased plasma concentration and risk of toxicity of the victim drug
• No change in pharmacokinetics
• Accelerated elimination via kidneys

Correct Answer: Increased plasma concentration and risk of toxicity of the victim drug

Q20. Which process typically reduces lipophilicity and enhances renal elimination of drugs?

• Phase I oxidation only
• Conjugation (phase II) reactions
• Passive diffusion into tissues
• Protein binding

Correct Answer: Conjugation (phase II) reactions

Q21. Which is a correct example of a phase I hydrolytic enzyme important for ester prodrugs?

• Carboxylesterase
• Glutathione S-transferase
• UDP-glucuronosyltransferase
• Sulfotransferase

Correct Answer: Carboxylesterase

Q22. Chronic cigarette smoking most commonly induces which CYP isoform?

• CYP1A2
• CYP2E1
• CYP2D6
• CYP3A4

Correct Answer: CYP1A2

Q23. A drug that follows zero-order kinetics is characterized by:

• Elimination rate proportional to concentration
• Constant amount eliminated per unit time regardless of concentration
• First-order elimination with variable half-life
• Instantaneous elimination

Correct Answer: Constant amount eliminated per unit time regardless of concentration

Q24. Which assay preparation is commonly used to study hepatic microsomal metabolism in vitro?

• Plasma ultrafiltrate
• Liver microsomes
• Whole blood
• Isolated mitochondria

Correct Answer: Liver microsomes

Q25. Which cofactor is essential for cytochrome P450 monooxygenase catalysis?

• ATP
• NADPH
• Coenzyme A
• Glutathione

Correct Answer: NADPH

Q26. Sulfation predominantly uses which donor molecule?

• UDP-glucuronic acid
• 3′-phosphoadenosine-5′-phosphosulfate (PAPS)
• Acetyl-CoA
• Glutathione

Correct Answer: 3′-phosphoadenosine-5′-phosphosulfate (PAPS)

Q27. Which of the following increases drug clearance by inducing metabolic enzymes and transporters?

• Rifampin
• Ketoconazole
• Cimetidine
• Grapefruit juice

Correct Answer: Rifampin

Q28. Which is a common clinical measure to adjust dosing when metabolism is significantly reduced?

• Increase dose frequency without monitoring
• Reduce dose or increase dosing interval and consider therapeutic drug monitoring
• Always switch to a prodrug
• Ignore metabolism changes as they are clinically insignificant

Correct Answer: Reduce dose or increase dosing interval and consider therapeutic drug monitoring

Q29. Which metabolic reaction is catalyzed by N-acetyltransferase (NAT)?

• Methylation of catechols
• Acetylation of aromatic amines and hydrazines
• Glucuronidation of phenols
• Sulfation of alcohols

Correct Answer: Acetylation of aromatic amines and hydrazines

Q30. Which statement best describes pharmacogenetic impact on drug metabolism?

• Genetic variation cannot alter drug response
• Polymorphisms in metabolic enzymes can change drug levels, efficacy and risk of adverse effects
• Only transporters affect interindividual variability
• Pharmacogenetics is irrelevant to dose selection

Correct Answer: Polymorphisms in metabolic enzymes can change drug levels, efficacy and risk of adverse effects

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com