Fluorouracil MCQs With Answer

Introduction: Fluorouracil (5‑FU) MCQs With Answer is a focused review designed for B.Pharm students covering pharmacology, mechanism, metabolism, clinical uses, toxicities, and therapeutic monitoring of 5‑FU. This antimetabolite and pyrimidine analog inhibits thymidylate synthase via FdUMP, forming a key part of colorectal, breast, gastric and head‑and‑neck cancer regimens (eg, FOLFOX, FOLFIRI). Important topics include DPD‑mediated catabolism and pharmacogenetic DPYD testing, differences between bolus and infusion toxicities, oral prodrugs like capecitabine, and antidote uridine triacetate. Clear understanding of these concepts supports safe dosing, toxicity prevention and rational combination therapy. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which mechanism best describes how fluorouracil (5‑FU) exerts its cytotoxic effect?

  • Inhibition of thymidylate synthase by formation of a stable ternary complex with FdUMP and folate
  • Direct intercalation into DNA causing strand breaks
  • Alkylation of guanine residues leading to cross‑linking
  • Inhibition of topoisomerase II preventing DNA religation

Correct Answer: Inhibition of thymidylate synthase by formation of a stable ternary complex with FdUMP and folate

Q2. Which intracellular metabolites are directly responsible for 5‑FU’s inhibition of DNA synthesis and incorporation into RNA?

  • FdUMP and FUTP
  • 5‑FU glucuronide and 5‑FU sulfate
  • 5‑FU monophosphate only
  • 5‑FU unchanged

Correct Answer: FdUMP and FUTP

Q3. During which phase of the cell cycle is 5‑FU most active?

  • S phase
  • M phase
  • G0 phase
  • G2 phase

Correct Answer: S phase

Q4. Capecitabine relates to 5‑FU in what way?

  • Capecitabine is an oral prodrug that is enzymatically converted to 5‑FU in tumor tissue
  • Capecitabine is an inactive metabolite excreted unchanged
  • Capecitabine is an intravenous salt form of 5‑FU
  • Capecitabine is an antidote that reverses 5‑FU toxicity

Correct Answer: Capecitabine is an oral prodrug that is enzymatically converted to 5‑FU in tumor tissue

Q5. Which enzyme is primarily responsible for systemic catabolism of 5‑FU and influences patient susceptibility to severe toxicity?

  • Dihydropyrimidine dehydrogenase (DPD)
  • Cytochrome P450 3A4
  • Thiopurine methyltransferase (TPMT)
  • N‑acetyltransferase 2 (NAT2)

Correct Answer: Dihydropyrimidine dehydrogenase (DPD)

Q6. What is the recommended antidote for life‑threatening 5‑FU overdose or severe early toxicity?

  • Uridine triacetate
  • Leucovorin
  • Activated charcoal
  • Flumazenil

Correct Answer: Uridine triacetate

Q7. How does leucovorin (folinic acid) influence 5‑FU activity when given concurrently?

  • Leucovorin stabilizes the FdUMP–thymidylate synthase complex, enhancing 5‑FU cytotoxicity
  • Leucovorin inactivates 5‑FU by competitive inhibition
  • Leucovorin reduces 5‑FU renal excretion, increasing toxicity
  • Leucovorin prevents 5‑FU uptake into tumor cells

Correct Answer: Leucovorin stabilizes the FdUMP–thymidylate synthase complex, enhancing 5‑FU cytotoxicity

Q8. Which toxicity pattern is classically associated with bolus intravenous 5‑FU compared with prolonged infusion?

  • Bolus administration causes more myelosuppression while continuous infusion causes more mucositis and diarrhea
  • Bolus causes more hand‑foot syndrome while infusion causes alopecia only
  • Bolus causes cardiotoxicity exclusively while infusion causes neurotoxicity
  • Bolus causes renal toxicity while infusion causes pulmonary fibrosis

Correct Answer: Bolus administration causes more myelosuppression while continuous infusion causes more mucositis and diarrhea

Q9. Which cardiac adverse event has been reported with 5‑FU therapy?

  • Coronary vasospasm leading to chest pain and ischemia
  • Progressive dilated cardiomyopathy within hours
  • Complete heart block in all patients
  • Pulmonary embolism due to procoagulant effect

Correct Answer: Coronary vasospasm leading to chest pain and ischemia

Q10. Where does the majority of 5‑FU metabolism occur in the body?

  • Liver by dihydropyrimidine dehydrogenase
  • Kidney by glomerular filtration
  • Lungs by alveolar enzymes
  • Intestinal flora only

Correct Answer: Liver by dihydropyrimidine dehydrogenase

Q11. Which laboratory test is essential to monitor during 5‑FU chemotherapy?

  • Complete blood count with differential
  • Fasting blood glucose only
  • Thyroid function tests weekly
  • Serum creatine kinase only

Correct Answer: Complete blood count with differential

Q12. FOLFOX regimen contains which combination of agents?

  • 5‑FU, leucovorin (folinic acid) and oxaliplatin
  • 5‑FU, doxorubicin and cyclophosphamide
  • Capecitabine, paclitaxel and cisplatin
  • 5‑FU, methotrexate and vincristine

Correct Answer: 5‑FU, leucovorin (folinic acid) and oxaliplatin

Q13. Which topical use is associated with 5‑FU cream formulations?

  • Treatment of actinic keratosis and superficial basal cell carcinoma
  • Topical analgesia for neuropathic pain
  • Antifungal therapy for dermatophytes
  • Local steroid‑sparing anti‑inflammatory

Correct Answer: Treatment of actinic keratosis and superficial basal cell carcinoma

Q14. A common mechanism by which tumor cells develop resistance to 5‑FU is:

  • Upregulation or increased expression of thymidylate synthase
  • Mutation of estrogen receptor alpha
  • Increased glutathione conjugation
  • Deletion of topoisomerase I gene

Correct Answer: Upregulation or increased expression of thymidylate synthase

Q15. What is the most important dose‑limiting toxicity for bolus 5‑FU therapy?

  • Myelosuppression, particularly neutropenia
  • Peripheral neuropathy
  • Ototoxicity
  • Vision loss

Correct Answer: Myelosuppression, particularly neutropenia

Q16. Which statement about 5‑FU and pregnancy is correct?

  • 5‑FU is teratogenic and generally contraindicated during pregnancy
  • 5‑FU is safe and recommended in the first trimester
  • 5‑FU has no effect on fetal development
  • 5‑FU is only contraindicated during labor, not pregnancy

Correct Answer: 5‑FU is teratogenic and generally contraindicated during pregnancy

Q17. Which adverse effect is particularly associated with oral capecitabine compared with intravenous 5‑FU?

  • Hand‑foot syndrome (palmar‑plantar erythrodysesthesia)
  • Immediate anaphylactic shock in all patients
  • Severe ototoxicity in low doses
  • Profound hyperglycemia in every case

Correct Answer: Hand‑foot syndrome (palmar‑plantar erythrodysesthesia)

Q18. Which enzyme catalyzes the initial conversion of 5‑FU to FUMP in the anabolic pathway?

  • Orotate phosphoribosyltransferase (OPRT)
  • Thymidine kinase
  • UDP‑glucuronosyltransferase
  • Cytidine deaminase

Correct Answer: Orotate phosphoribosyltransferase (OPRT)

Q19. Which 5‑FU metabolite is primarily incorporated into RNA causing dysfunctional RNA processing?

  • FUTP
  • FdUMP
  • 5‑FU glucuronide
  • FdUTP only involved in DNA

Correct Answer: FUTP

Q20. Which pre‑treatment test helps predict risk of severe 5‑FU toxicity?

  • DPYD genotyping or measurement of DPD enzyme activity
  • HLA‑B*57:01 screening
  • Serum amylase only
  • Baseline urine culture

Correct Answer: DPYD genotyping or measurement of DPD enzyme activity

Q21. How should clinicians manage patients with complete DPD deficiency regarding 5‑FU?

  • Avoid 5‑FU and capecitabine due to risk of life‑threatening toxicity
  • Use standard dose with close monitoring only
  • Double the dose to overcome resistance
  • Switch to topical 5‑FU only

Correct Answer: Avoid 5‑FU and capecitabine due to risk of life‑threatening toxicity

Q22. Within what time window is uridine triacetate most effective after 5‑FU overdose or early severe toxicity?

  • Within 96 hours of exposure
  • Only after 7 days
  • Any time up to 6 months
  • It is not time‑dependent

Correct Answer: Within 96 hours of exposure

Q23. What is the approximate plasma half‑life of 5‑FU following IV administration?

  • Very short, around 10–20 minutes
  • Approximately 24 hours
  • Several weeks due to tissue binding
  • Half‑life is negligible and not measurable

Correct Answer: Very short, around 10–20 minutes

Q24. Which cancer type is a primary indication for 5‑FU–based chemotherapy?

  • Colorectal cancer
  • Chronic myeloid leukemia only
  • Multiple myeloma exclusively
  • Benign prostatic hyperplasia

Correct Answer: Colorectal cancer

Q25. How does continuous infusion of 5‑FU affect its toxicity profile compared to bolus dosing?

  • Continuous infusion reduces myelosuppression but increases mucosal toxicity
  • Continuous infusion eliminates all toxicities
  • Continuous infusion causes more immediate hypersensitivity reactions
  • Continuous infusion leads only to renal toxicity

Correct Answer: Continuous infusion reduces myelosuppression but increases mucosal toxicity

Q26. Leucovorin is chemically identified as which of the following?

  • Folinic acid (calcium folinate)
  • Folic acid (pteroylglutamic acid)
  • Ascorbic acid (vitamin C)
  • Fumaric acid

Correct Answer: Folinic acid (calcium folinate)

Q27. The primary biochemical consequence of thymidylate synthase inhibition by 5‑FU is:

  • Depletion of dTMP leading to impaired DNA synthesis and repair
  • Accumulation of purines enhancing DNA replication
  • Increased synthesis of ribonucleotides
  • Direct cleavage of peptide bonds in proteins

Correct Answer: Depletion of dTMP leading to impaired DNA synthesis and repair

Q28. Which local adverse reaction is commonly seen with topical 5‑FU therapy?

  • Erythema, irritation and ulceration at application site
  • Generalized systemic rash in all users
  • Permanent hair loss on intact skin
  • Immediate systemic hypotension

Correct Answer: Erythema, irritation and ulceration at application site

Q29. How is 5‑FU classified pharmacologically?

  • Pyrimidine antimetabolite
  • Purine analog
  • Alkylating agent
  • Monoclonal antibody

Correct Answer: Pyrimidine antimetabolite

Q30. Which regimen is an oral alternative to IV 5‑FU in combination with oxaliplatin for colorectal cancer?

  • CAPOX (capecitabine plus oxaliplatin), also called XELOX
  • ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
  • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
  • R‑CHOP with rituximab only

Correct Answer: CAPOX (capecitabine plus oxaliplatin), also called XELOX

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