Methotrexate MCQs With Answer

Methotrexate MCQs With Answer offers B. Pharm students a focused review of methotrexate pharmacology, clinical uses, dosing principles, adverse effects, monitoring and drug interactions. These MCQs explore mechanism of action as a dihydrofolate reductase inhibitor, antifolate properties, intracellular polyglutamation, pharmacokinetics, renal excretion, and considerations for high-dose therapy with leucovorin rescue. Questions emphasize toxicity management, teratogenicity, laboratory monitoring (CBC, LFTs, renal function), and common interactions (NSAIDs, penicillins, trimethoprim), and practical dosing scenarios in oncology and rheumatology. This concise, exam-oriented set will reinforce conceptual understanding and clinical application for pharmacy practice. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which enzyme is the primary pharmacological target of methotrexate?

• Dihydrofolate reductase
• Thymidylate synthase
• DNA polymerase
• Adenosine deaminase

Correct Answer: Dihydrofolate reductase

Q2. Methotrexate exerts anti-inflammatory effects partly by increasing which extracellular mediator?

• Histamine
• Adenosine
• Prostaglandin E2
• Bradykinin

Correct Answer: Adenosine

Q3. Intracellular retention and prolonged action of methotrexate is mainly due to:

• Glucuronidation
• Polyglutamation
• Albumin binding
• Renal tubular secretion

Correct Answer: Polyglutamation

Q4. Which route of administration is preferred for high-dose methotrexate in oncology requiring controlled plasma levels?

• Oral
• Intramuscular
• Intravenous
• Topical

Correct Answer: Intravenous

Q5. The major route of elimination for methotrexate is:

• Hepatic metabolism to inactive metabolites
• Renal excretion by glomerular filtration and tubular secretion
• Exhalation as CO2
• Biliary excretion unchanged only

Correct Answer: Renal excretion by glomerular filtration and tubular secretion

Q6. Which clinical use is NOT an approved indication for methotrexate?

• Acute lymphoblastic leukemia treatment
• Rheumatoid arthritis management
• Psoriasis therapy
• Uncomplicated bacterial skin infections

Correct Answer: Uncomplicated bacterial skin infections

Q7. The most important folinic acid (leucovorin) rescue principle after high-dose methotrexate is to:

• Give leucovorin before methotrexate infusion
• Start leucovorin rescue at an appropriate interval after methotrexate to mitigate toxicity without blocking antitumor effect
• Avoid leucovorin because it potentiates toxicity
• Use folic acid instead of leucovorin for rescue

Correct Answer: Start leucovorin rescue at an appropriate interval after methotrexate to mitigate toxicity without blocking antitumor effect

Q8. A key laboratory test to monitor during methotrexate therapy is:

• Serum amylase only
• Complete blood count (CBC)
• Fasting blood glucose only
• Thyroid stimulating hormone

Correct Answer: Complete blood count (CBC)

Q9. Which adverse effect is MOST characteristic of methotrexate therapy?

• Myelosuppression with pancytopenia
• Hyperglycemia
• Permanent alopecia only
• Chronic cough as the main toxicity

Correct Answer: Myelosuppression with pancytopenia

Q10. Methotrexate is contraindicated in pregnancy because it is:

• Neuroprotective
• Teratogenic and abortifacient
• Completely inactivated by placental enzymes
• A safe supplement during pregnancy

Correct Answer: Teratogenic and abortifacient

Q11. Which drug interaction increases methotrexate toxicity by reducing its renal clearance?

• Proton pump inhibitors
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Metformin
• Insulin

Correct Answer: Nonsteroidal anti-inflammatory drugs (NSAIDs)

Q12. In low-dose weekly regimens for rheumatoid arthritis, the common adjunct to reduce side effects is:

• Daily high-dose folic acid
• Weekly folic or folinic acid supplementation
• High-dose aspirin
• Continuous IV hydration

Correct Answer: Weekly folic or folinic acid supplementation

Q13. Acute pulmonary toxicity from methotrexate typically presents as:

• Interstitial pneumonitis with cough and dyspnea
• Immediate anaphylaxis only
• Isolated hemoptysis without dyspnea
• Pulmonary embolism exclusively

Correct Answer: Interstitial pneumonitis with cough and dyspnea

Q14. A pharmacist counseling a patient on oral methotrexate should emphasize which dosing schedule for rheumatoid arthritis?

• Daily administration
• Once weekly administration
• Twice daily administration
• Continuous infusion

Correct Answer: Once weekly administration

Q15. High-dose methotrexate therapy requires which supportive measure to prevent renal precipitation?

• Alkalinization of urine and aggressive hydration
• Administration of sodium bicarbonate orally only
• Complete fluid restriction
• Use of diuretics to concentrate urine

Correct Answer: Alkalinization of urine and aggressive hydration

Q16. Methotrexate inhibits DNA synthesis primarily by depleting which cofactor?

• Tetrahydrofolate
• Vitamin B12
• Coenzyme A
• NADPH

Correct Answer: Tetrahydrofolate

Q17. Which monitoring parameter is essential before each dose of methotrexate in chronic therapy?

• Serum sodium
• Complete blood count and liver function tests
• ECG
• Serum magnesium

Correct Answer: Complete blood count and liver function tests

Q18. Trimethoprim-sulfamethoxazole coadministration may increase methotrexate toxicity because trimethoprim:

• Enhances hepatic metabolism of methotrexate
• Competes for renal excretion and inhibits folate pathways
• Induces methotrexate polyglutamation
• Acts as a leucovorin substitute

Correct Answer: Competes for renal excretion and inhibits folate pathways

Q19. In intrathecal methotrexate therapy, one must take special care to avoid which complication?

• Neurotoxicity including chemical arachnoiditis
• Hepatic steatosis only
• Peripheral neuropathy exclusively
• Cardiac arrhythmia primarily

Correct Answer: Neurotoxicity including chemical arachnoiditis

Q20. Which statement about methotrexate protein binding and distribution is TRUE?

• Methotrexate is highly lipid soluble and accumulates in adipose tissue
• Methotrexate is moderately protein bound and distributes to body fluids and cells
• Methotrexate remains only in the vascular compartment
• Methotrexate does not enter synovial fluid

Correct Answer: Methotrexate is moderately protein bound and distributes to body fluids and cells

Q21. Which of the following increases the risk of methotrexate-induced hepatotoxicity?

• Alcohol consumption
• Daily vitamin C intake
• Regular physical exercise
• Low-protein diet

Correct Answer: Alcohol consumption

Q22. Folic acid supplementation during low-dose methotrexate therapy is intended to:

• Completely negate methotrexate efficacy
• Reduce hematologic and gastrointestinal toxicity while preserving efficacy
• Increase methotrexate serum levels
• Replace leucovorin in high-dose rescue

Correct Answer: Reduce hematologic and gastrointestinal toxicity while preserving efficacy

Q23. Which clinical sign should prompt immediate evaluation for methotrexate toxicity?

• New onset mucositis and fever
• Mild transient headache
• Intermittent muscle cramps after exercise
• Stable mild arthralgia

Correct Answer: New onset mucositis and fever

Q24. Methotrexate is classified pharmacologically as which type of agent?

• Antimetabolite (antifolate)
• Alkylating agent
• Anthracycline antibiotic
• Topoisomerase inhibitor

Correct Answer: Antimetabolite (antifolate)

Q25. Which pediatric consideration is important for methotrexate dosing in leukemia?

• Renal function and body surface area–based dosing
• No need to adjust for renal function
• Use a fixed adult dose for all children
• Avoid leucovorin rescue in children

Correct Answer: Renal function and body surface area–based dosing

Q26. If a patient has rising serum creatinine during methotrexate therapy, the pharmacist should recognize that this may lead to:

• Decreased methotrexate toxicity due to redistribution
• Increased methotrexate levels and risk of severe toxicity
• No change in methotrexate elimination
• Increased hepatic clearance compensating fully

Correct Answer: Increased methotrexate levels and risk of severe toxicity

Q27. Which of the following best describes the timing of leucovorin rescue after high-dose methotrexate?

• Begin immediately during methotrexate infusion
• Begin at a specified interval after infusion once levels are declining, commonly around 24 hours
• Administer only if symptoms develop
• Leucovorin is never used with high-dose methotrexate

Correct Answer: Begin at a specified interval after infusion once levels are declining, commonly around 24 hours

Q28. Which laboratory assay is used to guide leucovorin rescue after high-dose methotrexate?

• Serum methotrexate concentration
• Serum potassium
• Serum bilirubin only
• Prothrombin time only

Correct Answer: Serum methotrexate concentration

Q29. Chronic low-dose methotrexate for rheumatoid arthritis typically requires monitoring of which frequency for LFTs initially?

• Monthly for the first few months, then periodically
• Never monitor LFTs
• Once every five years
• Hourly during therapy

Correct Answer: Monthly for the first few months, then periodically

Q30. Which statement about methotrexate and vaccines is correct?

• Live vaccines should generally be avoided or timed carefully during immunosuppressive methotrexate therapy
• All vaccines are safe and unchanged by methotrexate
• Methotrexate enhances live vaccine responses
• Vaccination status is irrelevant before starting methotrexate

Correct Answer: Live vaccines should generally be avoided or timed carefully during immunosuppressive methotrexate therapy

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