Factors affecting drug metabolism MCQs With Answer

Introduction: For B. Pharm students, mastering Factors affecting drug metabolism MCQs With Answer is essential for understanding pharmacokinetics and safe pharmacotherapy. This concise, SEO-friendly guide covers key determinants of drug metabolism — phase I and II reactions, cytochrome P450 isoenzymes, genetic polymorphism, age, sex, organ disease, enzyme induction/inhibition, first-pass effect, and clinically important drug–drug and herb–drug interactions. Each MCQ emphasizes mechanism, clinical examples (CYP3A4, CYP2D6, UGT), and enzyme kinetics (Km, Vmax, clearance) to deepen conceptual and applied knowledge. Use these targeted questions to identify gaps and build confidence for exams and practice. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What primarily distinguishes Phase I from Phase II drug metabolism?

• Phase I introduces functional groups; Phase II conjugates to increase water solubility
• Phase I conjugates drugs; Phase II removes functional groups
• Phase I occurs only in the intestine; Phase II occurs only in the liver
• Phase I always increases water solubility more than Phase II

Correct Answer: Phase I introduces functional groups; Phase II conjugates to increase water solubility

Q2. Which organ is the major site for drug metabolism?

• Liver
• Kidney
• Bone marrow
• Adipose tissue

Correct Answer: Liver

Q3. Which enzyme family is responsible for the majority of Phase I oxidative drug metabolism?

• Cytochrome P450 (CYP450)
• UDP-glucuronosyltransferases (UGTs)
• Glutathione S-transferases (GSTs)
• Alcohol dehydrogenases

Correct Answer: Cytochrome P450 (CYP450)

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

• CYP3A4
• CYP2D6
• CYP1A2
• CYP2C9

Correct Answer: CYP3A4

Q5. A B. Pharm student studying genetic polymorphisms should recognize which CYP isoform commonly shows clinically significant polymorphism affecting drug response?

• CYP2D6
• CYP3A4
• CYP3A5
• CYP2E1

Correct Answer: CYP2D6

Q6. Which drug is a classic inducer of hepatic CYP enzymes leading to increased metabolism of co-administered drugs?

• Rifampin
• Ketoconazole
• Grapefruit juice
• Cimetidine

Correct Answer: Rifampin

Q7. Which common food/beverage inhibits intestinal and hepatic CYP3A4 and can increase bioavailability of some drugs?

• Grapefruit juice
• Green tea
• Milk
• Orange juice

Correct Answer: Grapefruit juice

Q8. In neonates, drug metabolism is generally:

• Reduced due to immature hepatic enzyme systems
• Increased because liver enzymes are hyperactive
• Unchanged compared with adults
• Primarily renal rather than hepatic

Correct Answer: Reduced due to immature hepatic enzyme systems

Q9. How does advanced age typically affect hepatic drug metabolism?

• Decreased clearance due to reduced hepatic blood flow and enzyme activity
• Marked increase in clearance due to compensatory enzyme induction
• No effect on metabolism but increases absorption
• Eliminates first-pass metabolism entirely

Correct Answer: Decreased clearance due to reduced hepatic blood flow and enzyme activity

Q10. What is the first-pass effect?

• Pre-systemic metabolism in the gut and liver that reduces oral drug bioavailability
• Drug metabolism that occurs only after systemic distribution
• Enzyme induction after chronic dosing
• Conjugation by kidney enzymes before excretion

Correct Answer: Pre-systemic metabolism in the gut and liver that reduces oral drug bioavailability

Q11. For a high extraction ratio drug, the hepatic clearance is most dependent on which factor?

• Hepatic blood flow
• Plasma protein binding
• Renal excretion
• Volume of distribution

Correct Answer: Hepatic blood flow

Q12. How does high plasma protein binding affect the rate of hepatic metabolism?

• Decreases metabolism because only free drug is available to enzymes
• Increases metabolism by carrying drug to the liver
• Has no effect on metabolism but affects absorption
• Converts drug into inactive metabolites directly in plasma

Correct Answer: Decreases metabolism because only free drug is available to enzymes

Q13. Enzyme induction most directly affects which kinetic parameter of drug metabolism?

• Increases Vmax (maximum metabolic rate)
• Increases Km (substrate affinity)
• Decreases Vmax
• Eliminates Km from kinetics

Correct Answer: Increases Vmax (maximum metabolic rate)

Q14. Enzyme inhibition generally results in which clinical effect?

• Decreased clearance and increased plasma concentration of the inhibited drug
• Faster elimination and reduced half-life of the substrate drug
• Increased production of active metabolites only
• No clinical effect unless combined with induction

Correct Answer: Decreased clearance and increased plasma concentration of the inhibited drug

Q15. Which Phase II conjugation pathway is most important for acetaminophen and many other drugs?

• Glucuronidation (UGT-mediated)
• Sulfation only
• Methylation exclusively
• Phosphorylation

Correct Answer: Glucuronidation (UGT-mediated)

Q16. Enterohepatic recirculation typically causes what effect on a drug’s pharmacokinetics?

• Prolonged half-life and possible secondary peaks in plasma concentration
• Rapid elimination without reabsorption
• Decreased oral bioavailability
• Immediate conversion to inactive metabolites

Correct Answer: Prolonged half-life and possible secondary peaks in plasma concentration

Q17. Which route of administration bypasses the hepatic first-pass effect?

• Intravenous
• Oral
• Rectal (entirely bypasses first-pass)
• Oral transmucosal

Correct Answer: Intravenous

Q18. Chronic smoking affects drug metabolism by primarily inducing which enzyme?

• CYP1A2
• UGT1A1
• CYP2C19
• Alcohol dehydrogenase

Correct Answer: CYP1A2

Q19. Chronic alcohol consumption commonly induces which CYP enzyme involved in metabolism of acetaminophen and other substrates?

• CYP2E1
• CYP3A4
• CYP2D6
• CYP1A2

Correct Answer: CYP2E1

Q20. Pregnancy often alters drug metabolism; which general trend is frequently observed?

• Increased metabolism of some drugs due to induction of certain CYPs such as CYP3A4
• Complete cessation of hepatic metabolism
• Uniform reduction in all drug metabolic pathways
• Inability to conjugate drugs

Correct Answer: Increased metabolism of some drugs due to induction of certain CYPs such as CYP3A4

Q21. How does severe liver disease affect drug metabolism?

• Reduces hepatic metabolism leading to decreased clearance and higher plasma levels
• Enhances metabolism through compensatory enzyme synthesis
• Shifts metabolism exclusively to Phase II reactions
• Only affects renal excretion not hepatic metabolism

Correct Answer: Reduces hepatic metabolism leading to decreased clearance and higher plasma levels

Q22. The most common type of genetic variation causing altered drug-metabolizing enzyme activity is:

• Single nucleotide polymorphism (SNP)
• Chromosomal translocation
• Large chromosomal deletion only
• Complete gene absence in all populations

Correct Answer: Single nucleotide polymorphism (SNP)

Q23. In Michaelis-Menten kinetics, which parameter reflects the affinity of the enzyme for substrate?

• Km
• Vmax
• CLint (intrinsic clearance)
• t1/2 (half-life)

Correct Answer: Km

Q24. When hepatic enzymes are saturated at therapeutic concentrations, the drug elimination follows which kinetic order?

• Zero-order kinetics
• First-order kinetics
• Mixed-order kinetics never occurs
• Second-order kinetics

Correct Answer: Zero-order kinetics

Q25. Which of the following drugs commonly demonstrates zero-order elimination at therapeutic/toxic concentrations?

• Phenytoin
• Amoxicillin
• Metformin
• Ranitidine

Correct Answer: Phenytoin

Q26. Activation of a prodrug is dependent on which process?

• Metabolic conversion by enzymes to the active moiety
• Passive diffusion into tissues only
• Renal filtration only
• Mechanical breakdown in the stomach

Correct Answer: Metabolic conversion by enzymes to the active moiety

Q27. Gilbert’s syndrome affects which conjugation enzyme and can alter drug handling?

• UGT1A1 (glucuronidation)
• CYP3A4 (oxidation)
• GST (glutathione conjugation)
• NAT2 (acetylation)

Correct Answer: UGT1A1 (glucuronidation)

Q28. Which CYP enzyme is primarily responsible for metabolizing warfarin (S- and R- enantiomers are differentially metabolized)?

• CYP2C9
• CYP2D6
• CYP3A4
• CYP1A2

Correct Answer: CYP2C9

Q29. In CYP2D6 poor metabolizers administered codeine, what is the expected clinical effect?

• Reduced analgesic effect due to decreased conversion to morphine
• Increased toxicity from excessive morphine formation
• No change since codeine is not metabolized
• Immediate allergic reaction

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

Q30. How can severe renal failure indirectly affect hepatic drug metabolism?

• Uremic toxins can downregulate hepatic enzymes and reduce metabolism
• Renal failure always increases hepatic enzyme activity
• Renal failure has no influence on hepatic drug metabolism
• It converts Phase I reactions to Phase II exclusively

Correct Answer: Uremic toxins can downregulate hepatic enzymes and reduce metabolism

Q31. Which herbal supplement is a known inducer of CYP3A4 and can reduce plasma levels of many drugs?

• St. John’s Wort
• Ginkgo biloba
• Echinacea
• Turmeric

Correct Answer: St. John’s Wort

Q32. If Drug A is a CYP3A4 inhibitor and Drug B is a CYP3A4 substrate, co-administration most likely causes which outcome?

• Increased plasma concentration of Drug B and potential toxicity
• Decreased plasma concentration of Drug B and therapeutic failure
• No change in Drug B levels
• Immediate precipitation of Drug B in plasma

Correct Answer: Increased plasma concentration of Drug B and potential toxicity

Q33. Which of the following is a Phase I reaction?

• Oxidation by CYP450 enzymes
• Glucuronidation by UGT
• Glutathione conjugation
• Acetylation only

Correct Answer: Oxidation by CYP450 enzymes

Q34. The principal purpose of Phase II conjugation reactions is to:

• Increase water solubility to facilitate renal excretion
• Make drugs more lipophilic for tissue uptake
• Convert drugs to prodrugs
• Only deactivate drugs irreversibly

Correct Answer: Increase water solubility to facilitate renal excretion

Q35. What is the relationship between half-life (t1/2), volume of distribution (Vd), and clearance (Cl)?

• t1/2 = (0.693 × Vd) / Cl
• t1/2 = Cl / Vd
• t1/2 = Vd × Cl
• t1/2 is independent of Vd and Cl

Correct Answer: t1/2 = (0.693 × Vd) / Cl

Q36. For a drug with a high hepatic extraction ratio, which strategy will most effectively reduce its clearance?

• Reducing hepatic blood flow
• Altering plasma protein binding only
• Decreasing oral dose
• Increasing renal perfusion

Correct Answer: Reducing hepatic blood flow

Q37. Which class of drugs or circumstances most commonly requires therapeutic drug monitoring because of variable metabolism?

• Drugs with narrow therapeutic index and variable metabolism such as warfarin and phenytoin
• Over-the-counter analgesics only
• All topical drugs
• Inhaled anesthetics exclusively

Correct Answer: Drugs with narrow therapeutic index and variable metabolism such as warfarin and phenytoin

Q38. A CYP2D6 ultra-rapid metabolizer taking codeine is at risk for which outcome?

• Increased conversion to morphine and potential opioid toxicity
• Reduced analgesia due to impaired conversion
• Complete resistance to opioids
• Severe renal failure immediately

Correct Answer: Increased conversion to morphine and potential opioid toxicity

Q39. How long does it typically take for enzyme induction to develop after starting an inducing drug?

• Days to weeks because new enzyme synthesis is required
• Within minutes after the first dose
• Never, induction is instantaneous
• Only after months of continuous therapy

Correct Answer: Days to weeks because new enzyme synthesis is required

Q40. Enzyme inhibition by a co-administered drug typically appears:

• Rapidly, often within hours of co-administration
• Only after weeks of therapy
• Only after drug withdrawal
• After enzyme synthesis completes in days

Correct Answer: Rapidly, often within hours of co-administration

Q41. Stereoselective metabolism refers to which phenomenon?

• Different metabolic rates or pathways for drug enantiomers
• Equal metabolism of all stereoisomers
• Metabolism only of racemic mixtures
• Metabolism that depends solely on pH

Correct Answer: Different metabolic rates or pathways for drug enantiomers

Q42. An increase in plasma albumin binding will most likely do what to the unbound fraction and hepatic clearance of a highly protein-bound drug?

• Decrease the unbound fraction and decrease hepatic metabolism of the drug
• Increase unbound fraction and increase hepatic clearance
• Not affect unbound fraction but increase Vd
• Convert drug to active metabolite in plasma

Correct Answer: Decrease the unbound fraction and decrease hepatic metabolism of the drug

Q43. Pharmacogenetic testing for CYP variants is useful because it can:

• Help individualize drug dosing and reduce adverse effects
• Completely prevent all drug–drug interactions
• Replace therapeutic drug monitoring for all drugs
• Ensure once-daily dosing for everyone

Correct Answer: Help individualize drug dosing and reduce adverse effects

Q44. Which site of CYP3A4 expression contributes importantly to the intestinal first-pass metabolism of orally administered drugs?

• Enterocytes of the small intestine
• Colon lumen only
• Pancreatic acinar cells
• Red blood cells

Correct Answer: Enterocytes of the small intestine

Q45. Which inducer has caused contraceptive failure due to increased metabolism of oral contraceptives?

• Rifampin
• Ketoconazole
• Fluoxetine
• Amiodarone

Correct Answer: Rifampin

Q46. The metabolic ratio used in phenotyping typically represents which calculation?

• Parent drug concentration divided by metabolite concentration
• Metabolite concentration multiplied by dose
• Clearance divided by volume of distribution
• Half-life multiplied by dose frequency

Correct Answer: Parent drug concentration divided by metabolite concentration

Q47. Microsomal P450-catalyzed oxidations generally require which cofactors?

• NADPH and molecular oxygen
• ATP and GTP only
• UDP-glucuronic acid exclusively
• Glutathione and sulfate

Correct Answer: NADPH and molecular oxygen

Q48. Glucuronidation reactions require which cofactor?

• UDP-glucuronic acid (UDPGA)
• NADH only
• ATP and CoA
• FAD and FMN

Correct Answer: UDP-glucuronic acid (UDPGA)

Q49. Formation of reactive metabolites that covalently bind hepatic proteins can lead to which clinical consequence?

• Drug-induced liver injury (hepatotoxicity)
• Guaranteed therapeutic success
• Reduced absorption from the gut
• Enhanced renal clearance only

Correct Answer: Drug-induced liver injury (hepatotoxicity)

Q50. Consumption of cruciferous vegetables (e.g., broccoli) can affect drug metabolism by inducing which enzyme?

• CYP1A2
• UGT2B7 exclusively
• CYP2C9 only
• CYP3A7 in adults

Correct Answer: CYP1A2

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