Metabolism of drugs MCQs With Answer

Introduction: Drug metabolism is a core topic in pharmacokinetics that examines how the body chemically modifies drugs through biotransformation. B. Pharm students must understand hepatic and extrahepatic metabolism, Phase I (oxidation, reduction, hydrolysis) and Phase II (conjugation) reactions, roles of CYP450 enzymes, factors affecting clearance and half-life, first-pass effect, prodrugs and bioactivation, and clinically important drug–drug interactions. Key concepts include intrinsic clearance, extraction ratio, enzyme induction and inhibition, genetic polymorphisms (e.g., CYP2D6, NAT2), and transporter influence (P-gp). Mastery of these mechanisms supports rational dosing, safety, and therapeutic optimization. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary purpose of Phase I metabolic reactions in drug biotransformation?

  • Increase molecular polarity directly for excretion
  • Introduce or expose functional groups to facilitate Phase II conjugation
  • Attach glucuronic acid to the drug molecule
  • Transport drug across cell membranes

Correct Answer: Introduce or expose functional groups to facilitate Phase II conjugation

Q2. Which cytochrome P450 isoform is most commonly implicated in the metabolism of a wide range of clinically used drugs?

  • CYP1A2
  • CYP2D6
  • CYP3A4
  • CYP2C19

Correct Answer: CYP3A4

Q3. Glucuronidation is catalyzed by which enzyme family?

  • Sulfotransferases (SULTs)
  • N-acetyltransferases (NATs)
  • UDP-glucuronosyltransferases (UGTs)
  • Glutathione S-transferases (GSTs)

Correct Answer: UDP-glucuronosyltransferases (UGTs)

Q4. First-pass metabolism primarily affects which route of drug administration?

  • Intravenous
  • Intramuscular
  • Oral
  • Subcutaneous

Correct Answer: Oral

Q5. Which of the following is an example of a Phase II conjugation that increases water solubility?

  • Oxidation by CYP450
  • Hydrolysis by esterases
  • Glucuronidation
  • Reduction by nitroreductases

Correct Answer: Glucuronidation

Q6. A drug exhibiting zero-order kinetics means:

  • Rate of elimination is proportional to drug concentration
  • Rate of elimination is constant regardless of concentration
  • Drug is eliminated only by renal filtration
  • Drug follows Michaelis-Menten kinetics with high Km

Correct Answer: Rate of elimination is constant regardless of concentration

Q7. Which phase I reaction is primarily responsible for oxidative metabolism of many lipophilic drugs?

  • Conjugation with sulfate
  • CYP450-mediated hydroxylation
  • Acetylation
  • Glutathione conjugation

Correct Answer: CYP450-mediated hydroxylation

Q8. Which statement best defines intrinsic clearance (Clint)?

  • Clearance limited only by renal blood flow
  • Ability of the liver to remove drug in absence of flow limitations and binding constraints
  • Volume of plasma completely cleared per unit time in the whole body
  • Clearance after oral dosing only

Correct Answer: Ability of the liver to remove drug in absence of flow limitations and binding constraints

Q9. Which enzyme group is responsible for acetylation of drugs such as isoniazid and sulfonamides?

  • UDP-glucuronosyltransferases
  • N-acetyltransferases (NATs)
  • Sulfotransferases (SULTs)
  • Monoamine oxidases (MAOs)

Correct Answer: N-acetyltransferases (NATs)

Q10. Which process can lead to drug bioactivation producing a toxic metabolite?

  • Conjugation to glucuronic acid
  • Hydrolysis to inactive polar metabolites
  • CYP-mediated oxidation producing a reactive intermediate
  • Sulfation that always increases excretion

Correct Answer: CYP-mediated oxidation producing a reactive intermediate

Q11. Which transport protein is most associated with efflux of drugs from intestinal epithelium affecting oral bioavailability?

  • Albumin
  • P-glycoprotein (P-gp)
  • OATP1B1
  • Renal organic anion transporter (OAT)

Correct Answer: P-glycoprotein (P-gp)

Q12. Competitive inhibition of a drug-metabolizing enzyme typically results in:

  • Permanent enzyme inactivation requiring new enzyme synthesis
  • No change in Km and decreased Vmax
  • Increase in apparent Km with unchanged Vmax
  • Decrease in both Km and Vmax

Correct Answer: Increase in apparent Km with unchanged Vmax

Q13. Enterohepatic recirculation affects drug pharmacokinetics by:

  • Decreasing drug half-life by rapid renal excretion
  • Causing secondary peaks and prolonging half-life
  • Preventing conjugation reactions in the liver
  • Increasing protein binding in plasma

Correct Answer: Causing secondary peaks and prolonging half-life

Q14. Which conjugation pathway becomes saturated at high substrate concentrations and is important for endogenous and xenobiotic metabolism?

  • Glucuronidation
  • Sulfation
  • Acetylation
  • Glutathione conjugation

Correct Answer: Sulfation

Q15. A potent CYP3A4 inducer like rifampin is expected to:

  • Decrease metabolism of CYP3A4 substrates leading to toxicity
  • Increase metabolism of CYP3A4 substrates leading to reduced plasma levels
  • Block P-gp efflux and increase absorption
  • Directly inhibit renal clearance mechanisms

Correct Answer: Increase metabolism of CYP3A4 substrates leading to reduced plasma levels

Q16. Genetic polymorphism in CYP2D6 can result in which clinical phenotypes?

  • Only normal metabolizers for all drugs
  • Poor, intermediate, extensive, and ultra-rapid metabolizers
  • Universal protection against drug toxicity
  • Elimination of phase II reactions

Correct Answer: Poor, intermediate, extensive, and ultra-rapid metabolizers

Q17. Which type of metabolic reaction is primarily catalyzed by esterases?

  • Oxidation
  • Reduction
  • Hydrolysis of ester or amide bonds
  • Glutathione conjugation

Correct Answer: Hydrolysis of ester or amide bonds

Q18. Hepatic extraction ratio is defined as:

  • Fraction of drug removed by kidney per pass through liver
  • Fraction of drug removed by liver during one pass through hepatic circulation
  • Ratio of bile excretion to urine excretion
  • Fraction of drug bound to plasma proteins

Correct Answer: Fraction of drug removed by liver during one pass through hepatic circulation

Q19. Which conjugation reaction uses glutathione to detoxify reactive metabolites?

  • Glucuronidation
  • Sulfation
  • Glutathione S-transferase-mediated conjugation
  • Acetylation by NAT

Correct Answer: Glutathione S-transferase-mediated conjugation

Q20. In Michaelis-Menten kinetics, Vmax represents:

  • The substrate concentration at which velocity is half maximal
  • The maximum reaction velocity when the enzyme is saturated with substrate
  • The enzyme affinity for substrate
  • The clearance of the drug from plasma

Correct Answer: The maximum reaction velocity when the enzyme is saturated with substrate

Q21. Which factor decreases hepatic clearance of a drug with low extraction ratio?

  • Decreased plasma protein binding
  • Reduced hepatic enzyme activity
  • Increased hepatic blood flow
  • Enhanced first-pass effect

Correct Answer: Reduced hepatic enzyme activity

Q22. Prodrugs are designed to:

  • Be pharmacologically active without metabolism
  • Enhance absorption or targeting by undergoing metabolic activation
  • Always avoid hepatic metabolism entirely
  • Reduce the need for phase II reactions

Correct Answer: Enhance absorption or targeting by undergoing metabolic activation

Q23. Which of the following is a non-microsomal metabolic pathway?

  • CYP450-mediated oxidation in the endoplasmic reticulum
  • Monoamine oxidase activity in mitochondria
  • UGT-mediated glucuronidation in microsomes
  • Sulfotransferase activity in the cytosol

Correct Answer: Monoamine oxidase activity in mitochondria

Q24. A drug with high protein binding is likely to have which characteristic regarding hepatic clearance?

  • High free fraction and high clearance
  • Low free fraction and potentially reduced clearance for low extraction drugs
  • No change in clearance with enzyme inhibition
  • Always rapid renal elimination

Correct Answer: Low free fraction and potentially reduced clearance for low extraction drugs

Q25. Which agent is a known CYP450 inhibitor that can increase plasma levels of coadministered substrates?

  • Rifampin
  • Phenobarbital
  • Ketoconazole
  • Carbamazepine

Correct Answer: Ketoconazole

Q26. Sulfation uses which cofactor for conjugation reactions?

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

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

Q27. Which metabolic pathway is particularly important for detoxification of electrophilic intermediates and protection against hepatotoxicity?

  • Acetylation by NAT
  • Glutathione conjugation
  • Phase I reduction only
  • Sulfation at high capacity

Correct Answer: Glutathione conjugation

Q28. Renal excretion of a metabolite is increased when:

  • Metabolite is more lipophilic than parent drug
  • Metabolite is highly protein bound
  • Metabolite is more hydrophilic and polar than parent drug
  • Metabolite undergoes enterohepatic recycling

Correct Answer: Metabolite is more hydrophilic and polar than parent drug

Q29. Which process can reduce first-pass metabolism and increase oral bioavailability?

  • Co-administration with a CYP inducer
  • Use of a prodrug activated in the liver
  • Formulation for sublingual or buccal absorption
  • Increasing hepatic blood flow

Correct Answer: Formulation for sublingual or buccal absorption

Q30. Which parameter describes the time required for plasma drug concentration to decrease by 50%?

  • Clearance
  • Volume of distribution
  • Half-life (t1/2)
  • Bioavailability

Correct Answer: Half-life (t1/2)

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