Antimetabolites – Mercaptopurine MCQs With Answer

Antimetabolites – Mercaptopurine MCQs With Answer

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Antimetabolites – Mercaptopurine MCQs With Answer provides B.Pharm students a focused, clinical and mechanistic review of mercaptopurine (6‑MP), a key purine antimetabolite used in chemotherapy and immunosuppression. This introduction covers its mechanism of action as a purine analogue, activation by HGPRT to thio‑IMP and formation of thioguanine nucleotides, metabolism via xanthine oxidase and TPMT, major adverse effects (myelosuppression, hepatotoxicity), important drug interactions (allopurinol), pharmacokinetics, and monitoring requirements (CBC, LFTs, TPMT testing). Clear, exam‑oriented points emphasize therapeutics, dosing considerations, and safety to help you master core pharmacy concepts. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which enzyme is primarily responsible for converting mercaptopurine (6‑MP) into its active nucleotide form?

  • Thiopurine methyltransferase (TPMT)
  • Xanthine oxidase (XO)
  • Hypoxanthine‑guanine phosphoribosyltransferase (HGPRT)
  • Adenosine deaminase (ADA)

Correct Answer: Hypoxanthine‑guanine phosphoribosyltransferase (HGPRT)

Q2. Mercaptopurine is classified pharmacologically as which type of antimetabolite?

  • Pyrimidine analogue
  • Folate antagonist
  • Purine analogue
  • Ribonucleotide reductase inhibitor

Correct Answer: Purine analogue

Q3. The major cytotoxic mechanism of 6‑MP active metabolites involves:

  • Inhibition of microtubule polymerization
  • Inhibition of de novo purine nucleotide synthesis and incorporation into nucleic acids
  • Direct DNA alkylation causing cross‑links
  • Topoisomerase II inhibition leading to DNA strand breaks

Correct Answer: Inhibition of de novo purine nucleotide synthesis and incorporation into nucleic acids

Q4. A patient on 6‑MP is prescribed allopurinol. What is the most important clinical consequence of this co‑prescription?

  • Decreased 6‑MP efficacy due to enhanced clearance
  • Increased 6‑MP toxicity due to reduced xanthine oxidase metabolism
  • Protection against hepatotoxicity by enhancing methylation
  • No interaction; both drugs act on different pathways

Correct Answer: Increased 6‑MP toxicity due to reduced xanthine oxidase metabolism

Q5. Thiopurine methyltransferase (TPMT) polymorphism is clinically important because persons with deficient TPMT activity are at increased risk of:

  • Renal failure
  • Severe myelosuppression
  • Cardiotoxicity
  • Peripheral neuropathy

Correct Answer: Severe myelosuppression

Q6. Which laboratory tests are most critical to monitor routinely in a patient receiving 6‑MP?

  • Serum creatinine and electrolytes
  • Complete blood count (CBC) and liver function tests (LFTs)
  • Thyroid function tests and fasting glucose
  • Serum amylase and lipase

Correct Answer: Complete blood count (CBC) and liver function tests (LFTs)

Q7. 6‑MP is commonly used in the maintenance therapy of which malignancy?

  • Chronic myeloid leukemia (CML)
  • Acute lymphoblastic leukemia (ALL)
  • Hodgkin lymphoma
  • Non‑small cell lung cancer

Correct Answer: Acute lymphoblastic leukemia (ALL)

Q8. Which metabolite class formed from 6‑MP is primarily responsible for cytotoxicity through incorporation into DNA?

  • Thioguanine nucleotides (TGNs)
  • Thiouric acids
  • Methylated 6‑MP derivatives
  • 6‑MP glucuronides

Correct Answer: Thioguanine nucleotides (TGNs)

Q9. The inactivation of 6‑MP by xanthine oxidase results in which product?

  • Thioguanine nucleotides
  • 6‑Thiouric acid
  • Methyl‑6‑MP
  • 6‑MP phosphate

Correct Answer: 6‑Thiouric acid

Q10. A pharmacist advising on 6‑MP therapy should tell the prescriber to consider TPMT testing to:

  • Predict gastrointestinal tolerance
  • Adjust dose to reduce risk of severe myelotoxicity
  • Determine need for concurrent antivirals
  • Predict long‑term cardiotoxicity

Correct Answer: Adjust dose to reduce risk of severe myelotoxicity

Q11. Azathioprine’s relationship to 6‑MP is best described as:

  • An active metabolite unrelated to 6‑MP
  • A prodrug that is converted to 6‑MP
  • A competitive inhibitor of 6‑MP activation
  • An antidote to 6‑MP toxicity

Correct Answer: A prodrug that is converted to 6‑MP

Q12. Which adverse effect is most commonly dose‑limiting for mercaptopurine therapy?

  • Neurotoxicity
  • Myelosuppression
  • Ototoxicity
  • Pulmonary fibrosis

Correct Answer: Myelosuppression

Q13. Which pharmacokinetic property is true for oral mercaptopurine?

  • High oral bioavailability (>90%) with no first‑pass metabolism
  • Significant first‑pass metabolism resulting in variable bioavailability
  • Exclusively renal excretion of unchanged drug
  • Not absorbed orally and requires IV administration

Correct Answer: Significant first‑pass metabolism resulting in variable bioavailability

Q14. Which drug interaction can increase 6‑MP hematologic toxicity besides allopurinol?

  • Warfarin via CYP induction
  • Trimethoprim‑sulfamethoxazole due to marrow suppression
  • Metformin via increased renal clearance
  • Omeprazole via reduced gastric absorption

Correct Answer: Trimethoprim‑sulfamethoxazole due to marrow suppression

Q15. In the metabolic pathway of 6‑MP, methylation by TPMT primarily produces which outcome?

  • Activation to cytotoxic TGNs
  • Detoxification leading to less active methylated metabolites
  • Conversion to a prodrug form for better absorption
  • Formation of nephrotoxic compounds

Correct Answer: Detoxification leading to less active methylated metabolites

Q16. Which clinical condition is an established non‑oncologic indication for thiopurines derived from 6‑MP?

  • Rheumatoid arthritis only
  • Inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
  • Type 1 diabetes mellitus
  • Alzheimer disease

Correct Answer: Inflammatory bowel disease (Crohn’s disease and ulcerative colitis)

Q17. Which symptom should a patient on 6‑MP promptly report as a sign of severe myelosuppression?

  • Dry mouth
  • Fever or signs of infection
  • Mild headache
  • Skin hyperpigmentation

Correct Answer: Fever or signs of infection

Q18. Genetic testing for TPMT before starting 6‑MP helps primarily to:

  • Predict long‑term liver fibrosis risk
  • Identify patients at risk for severe hematologic toxicity who may need dose reduction
  • Determine renal dosing adjustments
  • Decide if antiemetics are required

Correct Answer: Identify patients at risk for severe hematologic toxicity who may need dose reduction

Q19. Which formulation or route of administration is most common for mercaptopurine in maintenance therapy?

  • Oral tablets
  • Intravenous infusion
  • Intramuscular injection
  • Topical ointment

Correct Answer: Oral tablets

Q20. A mechanistic reason why 6‑MP can cause hepatotoxicity includes:

  • Formation of methylated metabolites that accumulate in the liver
  • Direct binding to hepatic ribosomes causing necrosis
  • Primary excretion as unchanged drug into bile ducts
  • Activation by renal enzymes producing toxic intermediates

Correct Answer: Formation of methylated metabolites that accumulate in the liver

Q21. Which statement about dosing adjustments for 6‑MP is correct?

  • Doses are increased in TPMT‑deficient patients to overcome reduced metabolism
  • Doses are often reduced in patients with low TPMT activity to avoid toxicity
  • No dose adjustments are needed for drug interactions
  • Renal impairment exclusively determines dose adjustments

Correct Answer: Doses are often reduced in patients with low TPMT activity to avoid toxicity

Q22. Which laboratory abnormality is an early indicator of 6‑MP-induced bone marrow suppression?

  • Elevated serum potassium
  • Progressive decline in absolute neutrophil count
  • Isolated hypercalcemia
  • Persistently elevated amylase

Correct Answer: Progressive decline in absolute neutrophil count

Q23. Which of the following best describes mercaptopurine’s effect on nucleic acid metabolism?

  • Stimulates ribonucleotide reductase to increase DNA synthesis
  • Competes with purine bases and causes faulty DNA/RNA synthesis
  • Acts as a pyrimidine analogue to block thymidylate synthase
  • Enhances folate uptake to support nucleotide production

Correct Answer: Competes with purine bases and causes faulty DNA/RNA synthesis

Q24. If a patient exhibits severe hepatotoxicity on 6‑MP, the most appropriate immediate action is:

  • Continue therapy and add hepatoprotective supplements
  • Discontinue 6‑MP and evaluate liver function and alternatives
  • Double the dose to induce auto‑tolerance
  • Switch to another purine analogue without evaluation

Correct Answer: Discontinue 6‑MP and evaluate liver function and alternatives

Q25. Which of the following is a correct statement about 6‑MP metabolites and measurement?

  • Thioguanine nucleotide levels can be measured to assess therapeutic exposure
  • Methylated metabolites are not clinically relevant and are never measured
  • 6‑Thiouric acid levels predict TPMT genotype accurately
  • Plasma 6‑MP concentration correlates directly with efficacy and toxicity

Correct Answer: Thioguanine nucleotide levels can be measured to assess therapeutic exposure

Q26. Which patient factor increases risk of severe toxicity from standard doses of 6‑MP?

  • High TPMT activity
  • Concurrent allopurinol therapy
  • Young age without comorbidities
  • Concurrent vitamin D supplementation

Correct Answer: Concurrent allopurinol therapy

Q27. From a medicinal chemistry perspective, 6‑MP mimics which endogenous molecules?

  • Pyrimidine nucleotides like thymidine
  • Purine bases such as hypoxanthine and guanine
  • Amino acids like methionine
  • Folate cofactors

Correct Answer: Purine bases such as hypoxanthine and guanine

Q28. Which clinical monitoring schedule is most appropriate after initiating 6‑MP?

  • No monitoring is required after baseline labs
  • Frequent CBC monitoring initially, then periodically; LFTs regularly
  • Only yearly CBC and LFT testing
  • Cardiac monitoring weekly is essential

Correct Answer: Frequent CBC monitoring initially, then periodically; LFTs regularly

Q29. Resistance to mercaptopurine in tumor cells may develop through which mechanism?

  • Overexpression of xanthine oxidase increasing activation
  • Loss or decreased activity of HGPRT reducing activation to nucleotides
  • Increased TPMT leading to more TGNs formation
  • Enhanced drug uptake into cells

Correct Answer: Loss or decreased activity of HGPRT reducing activation to nucleotides

Q30. For safe clinical use, patient counselling for 6‑MP should include which of the following points?

  • No need to report infections or unusual bruising
  • Avoid live vaccines and report signs of infection or bleeding; comply with lab monitoring
  • Stop lab monitoring after three months of treatment
  • Take high‑dose vitamin C to prevent toxicity

Correct Answer: Avoid live vaccines and report signs of infection or bleeding; comply with lab monitoring

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