Drug metabolism – principles MCQs With Answer

Drug metabolism – principles MCQs With Answer

Understanding drug metabolism is essential for B. Pharm students preparing for exams and real-world pharmacy practice. This concise, keyword-rich introduction covers core principles: phase I and phase II reactions, cytochrome P450 (CYP450) enzyme systems, first-pass metabolism, clearance, half-life, pharmacokinetics, drug interactions, induction and inhibition, genetic polymorphisms (e.g., CYP2D6, CYP2C19), and clinical implications for dosing and toxicity. Practicing targeted MCQs helps reinforce mechanisms, enzymes, kinetics, and factors affecting metabolism. Each question is designed to deepen concept mastery and improve exam readiness. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which enzyme family is primarily responsible for oxidative phase I drug metabolism in the liver?

• UDP-glucuronosyltransferases (UGTs)
• Sulfotransferases (SULTs)
• Cytochrome P450 (CYP450)
• Glutathione S-transferases (GSTs)

Correct Answer: Cytochrome P450 (CYP450)

Q2. Phase II metabolic reactions are best characterized by which process?

• Oxidation to form reactive metabolites
• Conjugation with endogenous substrates to increase water solubility
• Reduction of nitro groups only
• Hydrolysis exclusively by esterases

Correct Answer: Conjugation with endogenous substrates to increase water solubility

Q3. First-pass metabolism refers to drug metabolism occurring primarily in which organ before reaching systemic circulation?

• Kidney
• Liver
• Brain
• Lungs

Correct Answer: Liver

Q4. Which parameter defines the volume in which a drug would need to be uniformly distributed to produce the observed plasma concentration?

• Clearance
• Volume of distribution (Vd)
• Bioavailability (F)
• Extraction ratio

Correct Answer: Volume of distribution (Vd)

Q5. A drug shows saturation kinetics at therapeutic concentrations. Which kinetic model describes this behavior?

• First-order kinetics
• Zero-order kinetics / Michaelis-Menten at saturating concentrations
• Pseudo-first-order kinetics only
• Mixed-order kinetics that never saturates

Correct Answer: Zero-order kinetics / Michaelis-Menten at saturating concentrations

Q6. Which CYP450 isoform is most commonly implicated in metabolism of many drugs including statins and benzodiazepines?

• CYP1A2
• CYP2D6
• CYP3A4
• CYP2E1

Correct Answer: CYP3A4

Q7. Genetic polymorphism in which enzyme leads to variable metabolism of codeine to morphine?

• CYP3A4
• CYP2D6
• UGT1A1
• CYP1A2

Correct Answer: CYP2D6

Q8. Glucuronidation is catalyzed by which enzyme family?

• UDP-glucuronosyltransferases (UGTs)
• S-adenosylmethionine transferases
• Cytochrome P450 reductases
• N-acetyltransferases (NATs)

Correct Answer: UDP-glucuronosyltransferases (UGTs)

Q9. Which factor will NOT typically increase hepatic drug metabolism?

• Enzyme induction by rifampicin
• Chronic alcohol consumption inducing CYP2E1
• Severe hepatic cirrhosis
• Repeated drug exposure leading to upregulated enzymes

Correct Answer: Severe hepatic cirrhosis

Q10. Which conjugation pathway plays a major role in detoxifying electrophilic metabolites via glutathione?

• Sulfation
• Glucuronidation
• Glutathione conjugation mediated by GSTs
• N-acetylation

Correct Answer: Glutathione conjugation mediated by GSTs

Q11. Bioavailability (F) of an oral drug is defined as:

• The fraction of the dose absorbed unchanged into systemic circulation
• The time to reach maximum concentration
• The total clearance divided by Vd
• The fraction excreted unchanged in urine

Correct Answer: The fraction of the dose absorbed unchanged into systemic circulation

Q12. Which statement about hepatic extraction ratio (ER) is correct?

• High ER drugs are mainly clearance-limited by protein binding
• Low ER drugs are highly affected by hepatic blood flow
• High ER drugs have clearance approximating hepatic blood flow
• ER has no influence on first-pass metabolism

Correct Answer: High ER drugs have clearance approximating hepatic blood flow

Q13. Which drug is a classic CYP3A4 inhibitor that can cause significant drug interactions?

• Rifampicin
• Ketoconazole
• Carbamazepine
• Phenobarbital

Correct Answer: Ketoconazole

Q14. N-acetylation polymorphism affects metabolism of which of the following drugs?

• Isoniazid
• Warfarin
• Metoprolol
• Omeprazole

Correct Answer: Isoniazid

Q15. Enterohepatic recirculation of a drug prolongs which pharmacokinetic parameter?

• Volume of distribution
• Elimination half-life
• Bioavailability always decreases
• Protein binding percentage

Correct Answer: Elimination half-life

Q16. Which phase I reaction commonly introduces or unmasks a functional group such as –OH, –NH2, or –SH?

• Conjugation
• Oxidation
• Glucuronidation
• Sulfation

Correct Answer: Oxidation

Q17. Which clearance equation defines total body clearance?

• CL = (0.693 × Vd) / t1/2
• CL = Vmax / Km
• CL = Dose / AUC
• CL = Vd × t1/2

Correct Answer: CL = Dose / AUC

Q18. Which process is least likely to be involved in renal elimination of drugs?

• Glomerular filtration
• Active tubular secretion
• Passive reabsorption influenced by urine pH
• Hepatic glucuronidation

Correct Answer: Hepatic glucuronidation

Q19. A competitive inhibitor of a CYP enzyme will typically cause which effect on Vmax and Km for a substrate?

• Vmax decreased, Km decreased
• Vmax unchanged, Km increased
• Vmax increased, Km unchanged
• Vmax decreased, Km increased

Correct Answer: Vmax unchanged, Km increased

Q20. Which enzyme catalyzes acetylation reactions in humans?

• Cytochrome P450 3A4
• N-acetyltransferases (NATs)
• Sulfotransferases (SULTs)
• UDP-glucuronosyltransferases (UGTs)

Correct Answer: N-acetyltransferases (NATs)

Q21. Which factor decreases the glomerular filtration of a drug that is highly protein-bound?

• Increased hepatic clearance
• Decreased plasma protein binding (more free drug)
• High degree of plasma protein binding
• Enhanced renal secretion

Correct Answer: High degree of plasma protein binding

Q22. Prodrugs are designed primarily to:

• Be active at the site of administration without metabolism
• Avoid metabolic conversion and excretion
• Improve bioavailability, stability, or targeting by requiring metabolic activation
• Inhibit metabolic enzymes

Correct Answer: Improve bioavailability, stability, or targeting by requiring metabolic activation

Q23. Which metabolic pathway is most important for paracetamol detoxification at therapeutic doses?

• CYP-mediated oxidation to NAPQI exclusively
• Glucuronidation and sulfation
• Direct renal excretion only
• N-acetylation to inactive metabolites

Correct Answer: Glucuronidation and sulfation

Q24. Which statement about enzyme induction is correct?

• Induction decreases the amount of enzyme expressed
• Induction usually occurs immediately after a single dose
• Induction can increase clearance and reduce drug plasma levels
• Induction always leads to toxicity

Correct Answer: Induction can increase clearance and reduce drug plasma levels

Q25. Which method is commonly used to assess in vivo drug metabolism and clearance?

• Mass spectrometry of tissues only
• Measurement of plasma concentration vs time and calculation of AUC
• Assessing mouth mucosa color changes
• Measuring urine pH only

Correct Answer: Measurement of plasma concentration vs time and calculation of AUC

Q26. Which is a Phase I reduction reaction commonly seen in drug metabolism?

• Glucuronidation
• Nitro reduction
• Sulfation
• Acetylation

Correct Answer: Nitro reduction

Q27. Which drug interaction scenario is most likely when a patient takes rifampicin with oral contraceptives?

• Rifampicin inhibits metabolism of contraceptives, increasing effect
• Rifampicin induces metabolism of contraceptives, decreasing efficacy
• No interaction expected
• Rifampicin displaces contraceptives from plasma proteins, increasing toxicity

Correct Answer: Rifampicin induces metabolism of contraceptives, decreasing efficacy

Q28. Hepatic clearance (CLh) can be approximated by which relationship?

• CLh = Qh × ER (hepatic blood flow × extraction ratio)
• CLh = Vd / t1/2 solely
• CLh = Km / Vmax
• CLh = bioavailability × dose

Correct Answer: CLh = Qh × ER (hepatic blood flow × extraction ratio)

Q29. Which enzyme polymorphism is clinically important for response to clopidogrel?

• CYP1A2 polymorphism
• CYP2C19 polymorphism
• CYP2E1 polymorphism
• UGT1A1 polymorphism

Correct Answer: CYP2C19 polymorphism

Q30. Which statement about sulfation is true?

• Sulfation is a major pathway only in adults
• Sulfation uses 3′-phosphoadenosine-5′-phosphosulfate (PAPS) as a sulfate donor
• Sulfation always produces toxic metabolites
• Sulfation is catalyzed by UGT enzymes

Correct Answer: Sulfation uses 3′-phosphoadenosine-5′-phosphosulfate (PAPS) as a sulfate donor

Q31. Which factor most strongly affects drug reabsorption in renal tubules?

• Urine flow rate only
• Drug lipophilicity and urine pH (ionization)
• Plasma protein binding only
• Hepatic extraction ratio

Correct Answer: Drug lipophilicity and urine pH (ionization)

Q32. Michaelis-Menten Km represents:

• The maximum rate of metabolism
• The substrate concentration at which the reaction rate is half Vmax
• The elimination half-life
• The volume of distribution

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

Q33. Which clinical consequence is expected when a patient with poor CYP2D6 metabolism receives standard doses of a CYP2D6-metabolized prodrug like codeine?

• Increased formation of active metabolite and overdose risk
• Decreased conversion to active metabolite and reduced analgesia
• No change in response
• Enhanced renal excretion of codeine

Correct Answer: Decreased conversion to active metabolite and reduced analgesia

Q34. Which of the following is an example of a drug activated by hepatic metabolism (prodrug)?

• Loratadine
• Enalapril
• Warfarin
• Diazepam

Correct Answer: Enalapril

Q35. Which substance is a major cofactor required for glucuronidation?

• Glutathione
• UDP-glucuronic acid (UDPGA)
• PAPS
• Acetyl-CoA

Correct Answer: UDP-glucuronic acid (UDPGA)

Q36. Which clinical factor tends to decrease hepatic clearance of high extraction ratio drugs?

• Increased hepatic blood flow
• Cardiac failure reducing hepatic blood flow
• Enzyme induction increasing intrinsic clearance
• Co-administration of enzyme inducers

Correct Answer: Cardiac failure reducing hepatic blood flow

Q37. Which pathway is most important in the detoxification of acetaminophen overdose?

• Inhibition of CYP3A4
• Administration of N-acetylcysteine to replenish glutathione
• Administration of rifampicin to induce metabolism
• Alkalinization of urine

Correct Answer: Administration of N-acetylcysteine to replenish glutathione

Q38. Which drug is known to be a strong inducer of many CYP enzymes, especially CYP3A4?

• Ketoconazole
• Rifampicin
• Fluoxetine
• Cimetidine

Correct Answer: Rifampicin

Q39. Protein binding affects drug metabolism mainly by altering which parameter?

• Intrinsic hepatic enzyme activity
• Free (unbound) fraction available for metabolism and elimination
• Phase II enzyme expression
• The molecular structure of the drug

Correct Answer: Free (unbound) fraction available for metabolism and elimination

Q40. Which of the following is TRUE about biliary excretion of drugs?

• Only lipophilic drugs undergo biliary excretion
• Large molecular weight and polar conjugates are often excreted in bile
• Biliary excretion does not contribute to enterohepatic recirculation
• All drugs secreted in bile are immediately inactive

Correct Answer: Large molecular weight and polar conjugates are often excreted in bile

Q41. Which analytical parameter indicates the extent of drug removal from the body per unit time?

• Half-life
• Clearance
• Volume of distribution
• Bioavailability

Correct Answer: Clearance

Q42. Which clinical scenario would most likely reduce first-pass metabolism and increase oral bioavailability?

• Co-administration of a potent CYP inducer
• Hepatic impairment reducing enzyme activity
• Increased intestinal CYP3A4 activity
• Concurrent administration of activated charcoal

Correct Answer: Hepatic impairment reducing enzyme activity

Q43. Which metabolic pathway is primarily involved in the formation of sulfate conjugates?

• SULT enzymes using PAPS as cofactor
• UGTs using UDPGA as cofactor
• GSTs using glutathione
• NATs using acetyl-CoA

Correct Answer: SULT enzymes using PAPS as cofactor

Q44. Which pharmacokinetic term describes the time required for the plasma concentration to decrease by half?

• Clearance
• Elimination half-life (t1/2)
• Bioavailability
• Extraction ratio

Correct Answer: Elimination half-life (t1/2)

Q45. Which of the following drugs is primarily metabolized by CYP2C9 and requires dose adjustments with genetic variants?

• Warfarin
• Metformin
• Gentamicin
• Insulin

Correct Answer: Warfarin

Q46. In a one-compartment model with first-order elimination, steady state during continuous dosing is achieved after approximately how many half-lives?

• About 1 half-life
• About 3–5 half-lives
• About 10 half-lives
• Steady state is instantaneous

Correct Answer: About 3–5 half-lives

Q47. Which laboratory approach helps identify specific CYP enzyme involvement in drug metabolism in vitro?

• Use of selective chemical inhibitors or recombinant CYP enzymes
• Measurement of blood pressure after dosing
• Assessment of urine color changes
• Clinical observation only

Correct Answer: Use of selective chemical inhibitors or recombinant CYP enzymes

Q48. Which statement best describes intrinsic clearance (CLint)?

• CLint is the clearance determined solely by hepatic blood flow
• CLint reflects the liver’s inherent ability to metabolize a drug independent of blood flow and binding
• CLint equals volume of distribution times half-life
• CLint is the fraction of drug excreted unchanged in urine

Correct Answer: CLint reflects the liver’s inherent ability to metabolize a drug independent of blood flow and binding

Q49. Which reaction type typically decreases lipid solubility and increases renal excretion of a drug?

• Conjugation (phase II) reactions
• Hydrophobic methylation
• Active tubular reabsorption
• Membrane transport into adipose tissue

Correct Answer: Conjugation (phase II) reactions

Q50. Which factor is LEAST likely to cause a clinically significant drug–drug interaction via altered metabolism?

• Co-administration of a strong CYP inhibitor
• Genetic polymorphism in a major drug-metabolizing enzyme
• Timing of administration separated by several hours with no enzyme modulation
• Chronic use of an enzyme inducer

Correct Answer: Timing of administration separated by several hours with no enzyme modulation

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