Drug metabolism is a core topic for B. Pharm students covering phase I and phase II metabolic pathways, key enzymes (CYP450, UGT, SULT, NAT, GST), cofactors (NADPH, UDPGA, PAPS, SAM, GSH) and mechanisms of biotransformation. Understanding oxidation, reduction, hydrolysis, glucuronidation, sulfation, acetylation, methylation and glutathione conjugation helps predict drug interactions, bioactivation, toxicity and variability from genetic polymorphisms, age or disease. Clinical examples such as acetaminophen bioactivation to NAPQI, codeine conversion by CYP2D6, and isoniazid acetylation illustrate pharmacokinetic and safety implications. This concise review prepares you to apply metabolic concepts to dosing, drug design and therapeutics. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which of the following are typical Phase I metabolic reactions?
- Oxidation, reduction and hydrolysis
- Glucuronidation and sulfation
- Methylation and acetylation
- Conjugation with glutathione
Correct Answer: Oxidation, reduction and hydrolysis
Q2. The major superfamily of enzymes responsible for many Phase I oxidation reactions is:
- UDP-glucuronosyltransferases (UGTs)
- Glutathione S-transferases (GSTs)
- Cytochrome P450 monooxygenases (CYP450)
- Sulfotransferases (SULTs)
Correct Answer: Cytochrome P450 monooxygenases (CYP450)
Q3. Which cofactor is essential for most cytochrome P450 catalytic cycles?
- NADH
- NADPH
- ATP
- UDP-glucuronic acid (UDPGA)
Correct Answer: NADPH
Q4. UDP-glucuronosyltransferases (UGTs) catalyze which Phase II reaction?
- Sulfation
- Glucuronidation
- Acetylation
- Methylation
Correct Answer: Glucuronidation
Q5. Which cofactor is used by sulfotransferases (SULT) for sulfation reactions?
- UDPGA (UDP-glucuronic acid)
- PAPS (3′-phosphoadenosine-5′-phosphosulfate)
- SAM (S-adenosylmethionine)
- GSH (glutathione)
Correct Answer: PAPS (3′-phosphoadenosine-5′-phosphosulfate)
Q6. N-acetyltransferase (NAT) enzymes are primarily responsible for which conjugation?
- Glucuronidation
- Sulfation
- Acetylation
- Methylation
Correct Answer: Acetylation
Q7. Which enzyme family catalyzes glutathione conjugation to detoxify electrophiles?
- Cytochrome P450s (CYPs)
- UDP-glucuronosyltransferases (UGTs)
- Glutathione S-transferases (GSTs)
- Sulfotransferases (SULTs)
Correct Answer: Glutathione S-transferases (GSTs)
Q8. The toxic metabolite NAPQI, responsible for acetaminophen hepatotoxicity, is generated by which pathway?
- Direct Phase II glucuronidation
- Phase I oxidation by CYP enzymes (bioactivation)
- Renal tubular secretion
- Sulfation followed by acetylation
Correct Answer: Phase I oxidation by CYP enzymes (bioactivation)
Q9. Conversion of codeine to morphine is primarily mediated by which enzyme?
- CYP3A4
- CYP2C9
- CYP2D6
- UGT1A1
Correct Answer: CYP2D6
Q10. “First‑pass metabolism” mainly occurs in which locations?
- Kidney glomerulus only
- Liver and intestine (presystemic metabolism)
- Lung alveoli only
- Skin and muscle only
Correct Answer: Liver and intestine (presystemic metabolism)
Q11. In Michaelis-Menten kinetics, Vmax represents:
- The drug concentration at half‑maximal rate
- The maximal metabolic rate when enzyme is saturated
- The slope of the line at low substrate concentrations
- The elimination half‑life
Correct Answer: The maximal metabolic rate when enzyme is saturated
Q12. Which elimination kinetics is characterized by a constant amount of drug eliminated per unit time, independent of concentration?
- First-order kinetics
- Zero-order kinetics
- Mixed-order kinetics
- Second-order kinetics
Correct Answer: Zero-order kinetics
Q13. Which of the following drugs is a potent inducer of CYP3A4 and can decrease plasma levels of co-administered CYP3A4 substrates?
- Rifampicin
- Ketoconazole
- Cimetidine
- Fluconazole
Correct Answer: Rifampicin
Q14. Which drug is a CYP inhibitor known to increase plasma concentrations of other drugs metabolized by CYPs?
- Rifampicin
- Carbamazepine
- Fluconazole
- St John’s wort
Correct Answer: Fluconazole
Q15. Enterohepatic recirculation affects drug disposition by:
- Preventing biliary excretion entirely
- Enhancing renal clearance only
- Causing biliary excretion followed by intestinal deconjugation and reabsorption, prolonging half-life
- Directly inactivating drugs in plasma
Correct Answer: Causing biliary excretion followed by intestinal deconjugation and reabsorption, prolonging half-life
Q16. Neonates are particularly vulnerable to toxicity from drugs requiring which pathway due to immature enzyme activity?
- Glucuronidation (UGT-dependent)
- Sulfation (SULT-dependent)
- Methylation (SAM-dependent)
- Glutathione conjugation (GST-dependent)
Correct Answer: Glucuronidation (UGT-dependent)
Q17. Genetic polymorphism of which enzyme commonly causes poor and ultra‑rapid metabolizer phenotypes affecting many drugs?
- CYP3A4
- CYP2D6
- UGT2B7
- GSTP1
Correct Answer: CYP2D6
Q18. Which enzyme converts reactive epoxide intermediates into less reactive diols?
- Epoxide hydrolase
- Carbonyl reductase
- UDP-glucuronosyltransferase
- Sulfotransferase
Correct Answer: Epoxide hydrolase
Q19. Which cofactor provides methyl groups in methylation reactions during Phase II metabolism?
- PAPS (3′-phosphoadenosine-5′-phosphosulfate)
- UDPGA (UDP-glucuronic acid)
- SAM (S-adenosylmethionine)
- GSH (glutathione)
Correct Answer: SAM (S-adenosylmethionine)
Q20. Which Phase II conjugation generally produces the largest increase in water solubility and renal elimination?
- Methylation
- Glucuronidation
- Acetylation
- Reduction
Correct Answer: Glucuronidation
Q21. Aspirin is rapidly converted in the body primarily by which metabolic reaction?
- Hydrolysis to salicylic acid followed by conjugation
- Direct methylation
- Glutathione conjugation only
- Oxidative deamination
Correct Answer: Hydrolysis to salicylic acid followed by conjugation
Q22. Which extra‑hepatic tissue contributes significantly to first-pass metabolism of some orally administered drugs?
- Pancreas
- Small intestine (enterocytes)
- Bone marrow
- Adipose tissue
Correct Answer: Small intestine (enterocytes)
Q23. Intrinsic clearance (Clint) of a drug refers to:
- The clearance determined solely by renal blood flow
- Hepatic metabolic capacity independent of blood flow limitations
- The volume of distribution at steady state
- Clearance due to biliary excretion only
Correct Answer: Hepatic metabolic capacity independent of blood flow limitations
Q24. Which of the following is a classic example of a prodrug activated by hepatic esterases to its active form?
- Enalapril (converted to enalaprilat)
- Paracetamol (acetaminophen)
- Ibuprofen
- Warfarin
Correct Answer: Enalapril (converted to enalaprilat)
Q25. A common Phase I reaction that introduces a hydroxyl group into a drug molecule is called:
- Hydroxylation
- Glucuronidation
- Acetylation
- Sulfation
Correct Answer: Hydroxylation
Q26. Which intestinal bacterial enzyme can deconjugate glucuronides, contributing to enterohepatic recycling?
- Beta-glucuronidase
- Urease
- Alpha-amylase
- Cholesterol esterase
Correct Answer: Beta-glucuronidase
Q27. Slow acetylator phenotype for isoniazid metabolism is associated with:
- Decreased risk of toxicity
- Increased risk of isoniazid-induced peripheral neuropathy and hepatotoxicity
- Ultra‑rapid clearance of isoniazid
- No clinical consequences
Correct Answer: Increased risk of isoniazid-induced peripheral neuropathy and hepatotoxicity
Q28. Which enzyme class primarily catalyzes reduction of ketones and aldehydes in drug metabolism?
- Carbonyl reductases
- Cytochrome P450s
- UDP-glucuronosyltransferases
- Sulfotransferases
Correct Answer: Carbonyl reductases
Q29. Conjugation with which molecule is critical to detoxify the reactive metabolite NAPQI from acetaminophen?
- UDP-glucuronic acid
- PAPS
- Glutathione (GSH)
- S-adenosylmethionine (SAM)
Correct Answer: Glutathione (GSH)
Q30. How does moderate to severe liver disease commonly affect hepatic drug metabolism?
- Increases hepatic clearance and shortens half‑life
- Decreases hepatic clearance leading to prolonged half‑life and higher exposure
- No change in drug metabolism
- Only affects renal excretion without altering hepatic metabolism
Correct Answer: Decreases hepatic clearance leading to prolonged half‑life and higher exposure
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.
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