MCQ Quiz: Drug Metabolizing Enzymes

Welcome, PharmD students, to this MCQ quiz on Drug Metabolizing Enzymes (DMEs)! These remarkable biological catalysts are central to how the body processes and eliminates medications and other foreign compounds. Understanding the different phases of drug metabolism, key enzyme systems like Cytochrome P450s, and the multitude of factors influencing their activity—including genetics (pharmacogenomics), drug interactions, and patient characteristics—is fundamental to predicting drug efficacy and minimizing adverse events. This quiz will test your knowledge of these critical enzymes and their impact on pharmacotherapy. Let’s explore the world of biotransformation!

1. The primary purpose of drug metabolism (biotransformation) is generally to convert drugs into compounds that are:

• a) More lipid-soluble for better tissue distribution.
• b) More pharmacologically active.
• c) More water-soluble (polar) to facilitate their excretion from the body.
• d) Less susceptible to plasma protein binding.

Answer: c) More water-soluble (polar) to facilitate their excretion from the body.

2. Phase I drug metabolism reactions typically involve:

• a) Conjugation of the drug with an endogenous substrate.
• b) Reactions such as oxidation, reduction, or hydrolysis, which often introduce or unmask a functional group.
• c) Methylation or acetylation only.
• d) Directly excreting the unchanged drug.

Answer: b) Reactions such as oxidation, reduction, or hydrolysis, which often introduce or unmask a functional group.

3. The Cytochrome P450 (CYP450) enzyme system is a major group of enzymes primarily involved in which phase of drug metabolism?

• a) Phase II reactions
• b) Phase I reactions
• c) Drug absorption
• d) Drug distribution

Answer: b) Phase I reactions

4. CYP450 enzymes are predominantly located in which subcellular organelle, particularly in hepatocytes?

• a) Nucleus
• b) Mitochondria
• c) Endoplasmic reticulum (microsomes)
• d) Golgi apparatus

Answer: c) Endoplasmic reticulum (microsomes)

5. Phase II drug metabolism reactions involve:

• a) Breaking down large drug molecules into smaller ones.
• b) Unmasking functional groups on the drug molecule.
• c) Conjugation of the drug or its Phase I metabolite with an endogenous substrate (e.g., glucuronic acid, sulfate, glutathione).
• d) Activating prodrugs through hydrolysis.

Answer: c) Conjugation of the drug or its Phase I metabolite with an endogenous substrate (e.g., glucuronic acid, sulfate, glutathione).

6. Which of the following is an example of a Phase II conjugation reaction?

• a) Oxidation by CYP3A4
• b) Hydrolysis by an esterase
• c) Glucuronidation by UDP-glucuronosyltransferases (UGTs)
• d) Reduction by alcohol dehydrogenase

Answer: c) Glucuronidation by UDP-glucuronosyltransferases (UGTs)

7. The term “enzyme induction” refers to a process where exposure to a substance (e.g., a drug, environmental chemical) leads to:

• a) A decrease in the activity or amount of drug-metabolizing enzymes.
• b) An increase in the synthesis or activity of drug-metabolizing enzymes.
• c) Irreversible binding of the substance to the enzyme.
• d) A change in the drug’s pKa.

Answer: b) An increase in the synthesis or activity of drug-metabolizing enzymes.

8. Enzyme induction can lead to which of the following effects on a drug that is a substrate for the induced enzyme?

• a) Increased plasma concentrations and prolonged half-life of the substrate drug.
• b) Decreased plasma concentrations and shortened half-life of the substrate drug (if it’s metabolized to inactive products).
• c) No change in the substrate drug’s pharmacokinetics.
• d) Increased absorption of the substrate drug.

Answer: b) Decreased plasma concentrations and shortened half-life of the substrate drug (if it’s metabolized to inactive products).

9. “Enzyme inhibition” occurs when a substance:

• a) Increases the synthesis of metabolizing enzymes.
• b) Decreases the activity of metabolizing enzymes, often by binding to them.
• c) Enhances the renal excretion of enzymes.
• d) Stabilizes the enzyme structure.

Answer: b) Decreases the activity of metabolizing enzymes, often by binding to them.

10. Competitive enzyme inhibition typically involves an inhibitor that:

• a) Binds irreversibly to the enzyme’s active site.
• b) Binds to a site different from the substrate binding site.
• c) Binds reversibly to the same active site as the substrate, competing with it.
• d) Increases the Vmax of the enzyme.

Answer: c) Binds reversibly to the same active site as the substrate, competing with it.

11. Pharmacogenomics of drug-metabolizing enzymes studies how:

• a) Diet affects enzyme activity.
• b) Genetic variations (polymorphisms) in genes encoding these enzymes influence drug metabolism and response.
• c) Age affects enzyme levels.
• d) All drugs are metabolized by the same enzyme.

Answer: b) Genetic variations (polymorphisms) in genes encoding these enzymes influence drug metabolism and response.

12. A patient who is a “poor metabolizer” (PM) for a specific CYP450 enzyme due to genetic polymorphisms will likely experience what when given a standard dose of a drug primarily inactivated by that enzyme?

• a) Subtherapeutic drug levels and reduced efficacy.
• b) Higher plasma concentrations of the parent drug and increased risk of toxicity.
• c) Faster drug clearance.
• d) No difference in drug response compared to extensive metabolizers.

Answer: b) Higher plasma concentrations of the parent drug and increased risk of toxicity.

13. CYP2D6 is a highly polymorphic enzyme responsible for metabolizing many drugs, including certain beta-blockers, antidepressants, and opioids. An individual with multiple functional copies of the CYP2D6 gene might be classified as a(n):

• a) Poor metabolizer (PM)
• b) Intermediate metabolizer (IM)
• c) Extensive metabolizer (EM)
• d) Ultrarapid metabolizer (UM)

Answer: d) Ultrarapid metabolizer (UM)

14. Grapefruit juice is a well-known inhibitor of which major drug-metabolizing enzyme, primarily in the gut wall?

• a) CYP2D6
• b) CYP2C19
• c) CYP3A4
• d) CYP1A2

Answer: c) CYP3A4

15. Thiopurine S-methyltransferase (TPMT) is a Phase II enzyme involved in the metabolism of thiopurine drugs (e.g., azathioprine). Patients with deficient TPMT activity are at high risk of:

• a) Reduced efficacy of thiopurines.
• b) Severe, life-threatening myelosuppression if given standard doses of thiopurines.
• c) Rapid metabolism of thiopurines.
• d) Hepatotoxicity unrelated to myelosuppression.

Answer: b) Severe, life-threatening myelosuppression if given standard doses of thiopurines.

16. A prodrug is a medication that is administered in an inactive or less active form and is then converted to its active form in the body, often through the action of:

• a) Excretory transporters.
• b) Drug-metabolizing enzymes.
• c) Plasma protein binding.
• d) Renal filtration.

Answer: b) Drug-metabolizing enzymes.

17. If a patient is an ultrarapid metabolizer of an enzyme that converts a prodrug to its active form, they might experience:

• a) Reduced formation of the active drug and therapeutic failure.
• b) Slower onset of action.
• c) Increased and faster formation of the active drug, potentially leading to increased effects or toxicity.
• d) No conversion of the prodrug.

Answer: c) Increased and faster formation of the active drug, potentially leading to increased effects or toxicity.

18. Which of the following is NOT a common factor that can influence the activity of drug-metabolizing enzymes?

• a) Genetic polymorphisms
• b) Concomitant medications (drug-drug interactions)
• c) Diet and environmental exposures (e.g., smoking, charbroiled meats)
• d) The drug’s color or shape

Answer: d) The drug’s color or shape

19. N-acetyltransferase 2 (NAT2) is a Phase II enzyme that exhibits polymorphisms leading to “slow acetylator” and “fast acetylator” phenotypes. This is clinically relevant for drugs like:

• a) Warfarin
• b) Isoniazid and hydralazine
• c) Digoxin
• d) Simvastatin

Answer: b) Isoniazid and hydralazine

20. The primary site of extensive first-pass metabolism for orally administered drugs is the:

• a) Kidney
• b) Lung
• c) Liver (and to some extent, the gut wall)
• d) Spleen

Answer: c) The liver (and to some extent, the gut wall)

21. Which of the following is a consequence of enzyme inhibition?

• a) Decreased plasma concentration of the substrate drug.
• b) Increased metabolism of the substrate drug.
• c) Increased plasma concentration and prolonged half-life of the substrate drug, potentially leading to toxicity.
• d) Shortened duration of action of the substrate drug.

Answer: c) Increased plasma concentration and prolonged half-life of the substrate drug, potentially leading to toxicity.

22. “Mechanism-based inhibition” (suicide inhibition) of a CYP450 enzyme occurs when:

• a) The inhibitor reversibly competes with the substrate.
• b) The inhibitor is metabolized by the enzyme to a reactive intermediate that irreversibly inactivates the enzyme.
• c) The inhibitor binds to an allosteric site.
• d) The inhibitor induces the synthesis of more enzyme.

Answer: b) The inhibitor is metabolized by the enzyme to a reactive intermediate that irreversibly inactivates the enzyme.

23. Smoking (tobacco) is known to induce which CYP450 enzyme, potentially affecting the metabolism of drugs like theophylline and olanzapine?

• a) CYP2D6
• b) CYP2C9
• c) CYP1A2
• d) CYP3A4

Answer: c) CYP1A2

24. Liver disease, such as cirrhosis, can significantly impair drug metabolism by:

• a) Increasing the number of functional hepatocytes.
• b) Reducing the number of functional hepatocytes, decreasing enzyme activity, and altering hepatic blood flow.
• c) Enhancing all Phase I and Phase II metabolic pathways.
• d) Only affecting renal excretion.

Answer: b) Reducing the number of functional hepatocytes, decreasing enzyme activity, and altering hepatic blood flow.

25. UDP-glucuronosyltransferases (UGTs) are a family of Phase II enzymes responsible for:

• a) Acetylation
• b) Sulfation
• c) Glucuronidation
• d) Methylation

Answer: c) Glucuronidation

26. Polymorphisms in UGT1A1 are associated with altered metabolism of irinotecan and bilirubin, potentially leading to increased risk of toxicity (e.g., Gilbert’s syndrome for bilirubin). Which condition is related to irinotecan?

• a) Severe neutropenia and diarrhea
• b) Hypersensitivity reactions
• c) Nephrotoxicity
• d) Cardiotoxicity

Answer: a) Severe neutropenia and diarrhea

27. A “drug-drug-gene interaction” implies that:

• a) A drug interaction is solely dependent on the dose.
• b) The effect of a drug interaction (e.g., inhibition or induction) is influenced or modified by an individual’s genetic makeup for a DME or transporter.
• c) Only genes, not drugs, are involved.
• d) The drug causes a gene mutation.

Answer: b) The effect of a drug interaction (e.g., inhibition or induction) is influenced or modified by an individual’s genetic makeup for a DME or transporter.

28. St. John’s Wort is a herbal product known to be a potent inducer of which major drug-metabolizing enzyme, leading to numerous drug interactions?

• a) CYP1A2
• b) CYP2C9
• c) CYP2D6
• d) CYP3A4

Answer: d) CYP3A4

29. The general outcome of Phase II metabolism is the formation of metabolites that are:

• a) More lipid-soluble and more active than the parent drug.
• b) More water-soluble, larger, and generally inactive, facilitating excretion.
• c) Identical in structure to the parent drug.
• d) Less susceptible to renal filtration.

Answer: b) More water-soluble, larger, and generally inactive, facilitating excretion.

30. For a drug primarily metabolized by a polymorphic enzyme, knowing a patient’s metabolizer phenotype can help in:

• a) Choosing the color of the tablet.
• b) Predicting the drug’s taste.
• c) Individualizing the drug dose to optimize efficacy and minimize adverse reactions.
• d) Determining the manufacturing cost.

Answer: c) Individualizing the drug dose to optimize efficacy and minimize adverse reactions.

31. Which of these is NOT a primary characteristic of Phase I metabolic reactions?

• a) Often involve CYP450 enzymes.
• b) Introduce or expose a functional group.
• c) Always result in detoxification and inactivation of the drug.
• d) Can sometimes lead to the formation of active or even toxic metabolites.

Answer: c) Always result in detoxification and inactivation of the drug.

32. The nomenclature CYP3A4 indicates:

• a) Cytochrome P450 family 3, subfamily A, polypeptide 4.
• b) Cytochrome Protein type 3, activity level A, form 4.
• c) A Phase II enzyme.
• d) A drug transporter.

Answer: a) Cytochrome P450 family 3, subfamily A, polypeptide 4.

33. If a drug is a known substrate of CYP2C19 and a patient is a CYP2C19 poor metabolizer, co-administration of a potent CYP2C19 inhibitor would likely:

• a) Have a minimal additional effect on the drug’s clearance.
• b) Significantly increase the drug’s clearance.
• c) Convert the patient to an ultrarapid metabolizer.
• d) Cause a paradoxical decrease in drug levels.

Answer: a) Have a minimal additional effect on the drug’s clearance. (The enzyme is already poorly functional).

34. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are enzymes involved in the metabolism of:

• a) Acetaminophen
• b) Ethanol (alcohol)
• c) Caffeine
• d) Warfarin

Answer: b) Ethanol (alcohol)

35. A drug interaction mediated by DMEs that results in increased formation of a toxic metabolite would lead to:

• a) Reduced therapeutic effect.
• b) Enhanced therapeutic effect.
• c) Increased risk of dose-dependent toxicity.
• d) Faster elimination of the parent drug without consequence.

Answer: c) Increased risk of dose-dependent toxicity. (e.g., acetaminophen toxicity)

36. Genetic polymorphisms in drug-metabolizing enzymes are a major cause of:

• a) Uniform drug response in all patients.
• b) Interindividual variability in drug efficacy and toxicity.
• c) Only changes in drug absorption.
• d) The color differences in medications.

Answer: b) Interindividual variability in drug efficacy and toxicity.

37. Flavin-containing monooxygenases (FMOs) are another class of Phase I enzymes that primarily metabolize drugs containing which heteroatoms?

• a) Carbon and hydrogen
• b) Nitrogen, sulfur, and phosphorus
• c) Oxygen only
• d) Halogens (fluorine, chlorine)

Answer: b) Nitrogen, sulfur, and phosphorus

38. Understanding drug-food interactions mediated by DMEs is important. For example, consumption of charbroiled meats can induce CYP1A2, potentially _______ the levels of drugs metabolized by this enzyme.

• a) increasing
• b) decreasing
• c) not affecting
• d) reversing

Answer: b) decreasing

39. Hydrolysis reactions, a type of Phase I metabolism, are carried out by enzymes such as:

• a) CYP450s
• b) Esterases and amidases
• c) UGTs
• d) SULTs

Answer: b) Esterases and amidases

40. The clinical consequence of inhibiting a DME that is responsible for converting an inactive prodrug to its active form would be:

• a) Increased levels of the active drug and potential toxicity.
• b) Decreased levels of the active drug and potential therapeutic failure.
• c) Faster conversion to the active drug.
• d) No effect on drug activity.

Answer: b) Decreased levels of the active drug and potential therapeutic failure.

41. Which factor is least likely to directly alter the intrinsic activity of a specific drug-metabolizing enzyme per molecule of enzyme?

• a) A competitive inhibitor drug.
• b) A genetic polymorphism affecting the enzyme’s active site.
• c) The patient’s gender.
• d) A mechanism-based inhibitor.

Answer: c) The patient’s gender. (Gender can influence enzyme levels or expression, but less directly the intrinsic activity per molecule compared to direct inhibitors or genetic structural changes).

42. What does it mean if a drug is described as an “autoinducer” of its own metabolism?

• a) The drug inhibits its own metabolism.
• b) The drug induces the enzymes responsible for its own metabolism, leading to decreased concentrations over time with chronic dosing.
• c) The drug is not metabolized.
• d) The drug’s metabolism is independent of enzyme activity.

Answer: b) The drug induces the enzymes responsible for its own metabolism, leading to decreased concentrations over time with chronic dosing. (e.g., carbamazepine)

43. Glutathione S-transferases (GSTs) are Phase II enzymes that conjugate drugs or their metabolites with glutathione, primarily to:

• a) Increase their lipophilicity.
• b) Detoxify electrophilic compounds and facilitate their excretion.
• c) Activate prodrugs.
• d) Hydrolyze ester bonds.

Answer: b) Detoxify electrophilic compounds and facilitate their excretion.

44. Understanding the contribution of different DMEs to a drug’s overall clearance is important for predicting:

• a) The drug’s color.
• b) The most likely pathways for drug interactions and the impact of specific enzyme polymorphisms.
• c) The drug’s solubility.
• d) The drug’s pKa.

Answer: b) The most likely pathways for drug interactions and the impact of specific enzyme polymorphisms.

45. If a drug is metabolized by multiple CYP enzymes (e.g., CYP3A4 and CYP2D6), inhibition of only one of these enzymes might lead to:

• a) Complete cessation of metabolism.
• b) A less pronounced increase in drug levels compared to inhibition of a sole metabolic pathway.
• c) A paradoxical increase in metabolism via the other pathway.
• d) No effect on drug levels.

Answer: b) A less pronounced increase in drug levels compared to inhibition of a sole metabolic pathway.

46. The therapeutic index of a drug can be effectively narrowed if:

• a) Its metabolizing enzyme is induced in a poor metabolizer.
• b) Its metabolizing enzyme is inhibited, leading to higher-than-expected concentrations.
• c) The patient is an ultrarapid metabolizer of a prodrug that converts it to an inactive form.
• d) The drug is administered with food.

Answer: b) Its metabolizing enzyme is inhibited, leading to higher-than-expected concentrations.

47. Age-related changes in drug metabolism are particularly significant in neonates due to immature enzyme systems and in the elderly due to:

• a) Increased hepatic blood flow and enzyme activity.
• b) Decreased hepatic blood flow, potentially reduced enzyme mass/activity, and polypharmacy.
• c) Uniformly faster metabolism of all drugs.
• d) Enhanced Phase I and Phase II reactions.

Answer: b) Decreased hepatic blood flow, potentially reduced enzyme mass/activity, and polypharmacy.

48. A key role for pharmacists regarding DMEs is to:

• a) Perform genetic sequencing in the pharmacy.
• b) Identify potential drug-drug, drug-food, and drug-gene interactions involving DMEs and counsel patients/providers accordingly.
• c) Only dispense drugs that are not metabolized.
• d) Ignore the metabolic pathways of drugs.

Answer: b) Identify potential drug-drug, drug-food, and drug-gene interactions involving DMEs and counsel patients/providers accordingly.

49. The process of drug metabolism can sometimes lead to the formation of pharmacologically active metabolites. These active metabolites can:

• a) Only contribute to the drug’s toxicity.
• b) Contribute to the drug’s therapeutic effect and/or its toxicity.
• c) Always have a shorter half-life than the parent drug.
• d) Never be further metabolized.

Answer: b) Contribute to the drug’s therapeutic effect and/or its toxicity.

50. Understanding the background and pharmacogenomics of Drug Metabolizing Enzymes is crucial for pharmacists to:

• a) Predict exact drug concentrations in every patient.
• b) Optimize drug therapy by anticipating variability in response and minimizing adverse effects.
• c) Determine the cost of medications.
• d) Only manage inventory of prodrugs.

Answer: b) Optimize drug therapy by anticipating variability in response and minimizing adverse effects.