Medicinal uses of pyrimidine MCQs With Answer

Medicinal uses of pyrimidine MCQs With Answer are essential for B. Pharm students preparing for pharmacology and medicinal chemistry exams. Pyrimidine derivatives form the backbone of many antiviral, anticancer, and antineoplastic agents such as 5‑fluorouracil, zidovudine, lamivudine and trifluridine. This short, focused set of MCQs covers mechanisms (e.g., thymidylate synthase inhibition, nucleoside chain termination), metabolic activation, SAR, clinical indications and toxicity issues like DPD deficiency and hand‑foot syndrome. Each question reinforces drug actions, metabolic pathways and clinical uses to build exam confidence and practical understanding. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which of the following best defines a pyrimidine nucleus commonly found in medicinal chemistry?

• A six-membered aromatic heterocycle with two nitrogen atoms at positions 1 and 3
• A five-membered ring with two sulfurs
• An aliphatic chain of six carbons
• A bicyclic purine structure

Correct Answer: A six-membered aromatic heterocycle with two nitrogen atoms at positions 1 and 3

Q2. Which anticancer drug is a pyrimidine analogue that inhibits thymidylate synthase after conversion to FdUMP?

• Cisplatin
• 5‑Fluorouracil (5‑FU)
• Doxorubicin
• Paclitaxel

Correct Answer: 5‑Fluorouracil (5‑FU)

Q3. Capecitabine is clinically used as a prodrug of which pyrimidine antimetabolite?

• Trifluridine
• 5‑Fluorouracil (5‑FU)
• Azathioprine
• Cytarabine

Correct Answer: 5‑Fluorouracil (5‑FU)

Q4. Which enzyme deficiency significantly increases the risk of severe toxicity with 5‑fluorouracil therapy?

• Thymidine kinase
• Dihydropyrimidine dehydrogenase (DPD)
• Orotate phosphoribosyltransferase
• Ribonucleotide reductase

Correct Answer: Dihydropyrimidine dehydrogenase (DPD)

Q5. Which pyrimidine analogue is primarily used as a topical antiviral for herpes keratitis?

• Trifluridine
• 5‑Azacytidine
• Edoxudine
• Zidovudine

Correct Answer: Trifluridine

Q6. Zidovudine (AZT) is a thymidine analogue used against HIV. Its primary antiviral mechanism is:

• Inhibition of neuraminidase
• Incorporation into viral DNA causing chain termination via reverse transcriptase inhibition
• Inhibition of protease
• Blocking viral entry at GP120

Correct Answer: Incorporation into viral DNA causing chain termination via reverse transcriptase inhibition

Q7. Lamivudine (3TC) is a cytidine analogue used in HIV and HBV. Which of the following is true about its activation?

• Activated by viral thymidine kinase only
• Requires phosphorylation by cellular kinases to the triphosphate form
• Does not require phosphorylation to be active
• Activated by deoxyribonuclease

Correct Answer: Requires phosphorylation by cellular kinases to the triphosphate form

Q8. 5‑Azacytidine and decitabine are pyrimidine analogues used to treat myelodysplastic syndromes. Their main epigenetic action is:

• Inhibition of histone deacetylases
• Inhibition of DNA methyltransferases leading to hypomethylation
• Direct DNA intercalation without enzyme binding
• Activation of topoisomerase II

Correct Answer: Inhibition of DNA methyltransferases leading to hypomethylation

Q9. Which enzyme in de novo pyrimidine biosynthesis is targeted by leflunomide?

• Carbamoyl phosphate synthetase I (CPS I)
• Dihydroorotate dehydrogenase (DHODH)
• Thymidylate synthase
• Orotate phosphoribosyltransferase

Correct Answer: Dihydroorotate dehydrogenase (DHODH)

Q10. Which toxic effect is most characteristically associated with 5‑fluorouracil and capecitabine therapy?

• Ototoxicity
• Hand‑foot syndrome and mucositis
• Pulmonary fibrosis
• Hyperglycemia

Correct Answer: Hand‑foot syndrome and mucositis

Q11. The anticancer activity of 5‑FU is mediated primarily through which metabolite?

• FUTP incorporation into DNA
• FdUMP inhibition of thymidylate synthase
• Fluorodeoxyuridine inhibition of topoisomerase I
• 5‑Fluorouridine blocking RNA polymerase directly

Correct Answer: FdUMP inhibition of thymidylate synthase

Q12. Which pyrimidine analogue is combined with tipiracil for metastatic colorectal cancer treatment?

• Trifluridine
• 5‑Fluorouracil
• Cytarabine
• 5‑Azacytidine

Correct Answer: Trifluridine

Q13. Which structural modification at the 5‑position of the pyrimidine ring often enhances anticancer activity?

• Methylation at N1
• Halogenation or fluorination at C5
• Replacing nitrogen with oxygen at position 3
• Adding a long alkyl chain to C2

Correct Answer: Halogenation or fluorination at C5

Q14. Which pyrimidine nucleoside analogue is used primarily in acute myeloid leukemia (AML) and is known as cytosine arabinoside?

• Cytarabine (Ara‑C)
• Gemcitabine
• Capecitabine
• Azacitidine

Correct Answer: Cytarabine (Ara‑C)

Q15. Resistance to 5‑FU in tumor cells is commonly due to:

• Overexpression of thymidylate synthase
• Increased DPD activity leading to accumulation of 5‑FU
• Enhanced uptake of 5‑FU into mitochondria
• Mutation in viral reverse transcriptase

Correct Answer: Overexpression of thymidylate synthase

Q16. Which salvage pathway enzyme phosphorylates thymidine to thymidine monophosphate?

• Thymidine kinase
• Ribonucleotide reductase
• Thymidylate synthase
• Orotate decarboxylase

Correct Answer: Thymidine kinase

Q17. Emtricitabine is structurally related to which pyrimidine base?

• Uracil
• Cytosine
• Thymine
• Adenine

Correct Answer: Cytosine

Q18. Which pyrimidine drug’s mechanism involves incorporation into RNA leading to faulty RNA processing as part of its cytotoxicity?

• 5‑Fluorouracil (via FUTP)
• Zidovudine
• Leflunomide
• Trifluridine (when used alone)

Correct Answer: 5‑Fluorouracil (via FUTP)

Q19. Which enzyme converts 5‑FU to FdUMP, the active inhibitor of thymidylate synthase?

• Thymidylate synthase
• Thymidine phosphorylase and subsequent kinases
• DNA polymerase
• UDP‑glucuronosyltransferase

Correct Answer: Thymidine phosphorylase and subsequent kinases

Q20. In the context of antiviral pyrimidine analogues, chain termination typically occurs because:

• The analogue lacks a 3’‑OH required for phosphodiester bond formation
• The analogue binds irreversibly to protease
• The analogue increases membrane rigidity preventing viral release
• The analogue enhances host RNA synthesis

Correct Answer: The analogue lacks a 3’‑OH required for phosphodiester bond formation

Q21. Which pyrimidine antimetabolite is specifically activated preferentially in tumor tissues by thymidine phosphorylase when given as an oral prodrug?

• Capecitabine
• Cytarabine
• Azacitidine
• Lamivudine

Correct Answer: Capecitabine

Q22. Which statement about trifluridine pharmacology is true?

• It is given orally as a monotherapy with long systemic half‑life
• It is phosphorylated and incorporated into DNA, causing dysfunction
• It acts by inhibiting proteasome function
• It is an antifolate that inhibits dihydrofolate reductase

Correct Answer: It is phosphorylated and incorporated into DNA, causing dysfunction

Q23. Which pyrimidine derivative is commonly used as an immunosuppressant antimetabolite in organ transplantation?

• Azathioprine (a purine analogue mainly)
• Flucytosine
• 5‑Azacytidine
• None of the above are pyrimidine antimetabolites primarily used as immunosuppressants

Correct Answer: None of the above are pyrimidine antimetabolites primarily used as immunosuppressants

Q24. Which test or monitoring is important before starting high‑dose 5‑FU therapy?

• Measurement of serum creatine kinase
• Screening for DPD deficiency or genotyping of DPYD gene
• Thyroid function tests exclusively
• Hepatitis serology only

Correct Answer: Screening for DPD deficiency or genotyping of DPYD gene

Q25. Which adverse effect is more characteristic of thymidine analogue antiretrovirals like zidovudine?

• Peripheral neuropathy only
• Bone marrow suppression and macrocytic anemia
• Severe renal failure in most patients
• Cough and bronchospasm

Correct Answer: Bone marrow suppression and macrocytic anemia

Q26. Which enzyme catalyzes the conversion of orotate to orotidine monophosphate in pyrimidine biosynthesis?

• Orotate phosphoribosyltransferase (OPRT)
• Ribonuclease
• Thymidylate synthase
• Uracil N‑glycosylase

Correct Answer: Orotate phosphoribosyltransferase (OPRT)

Q27. Which pyrimidine analogue is associated with photosensitivity and should be used cautiously in sun‑exposed patients?

• 5‑Fluorouracil
• Trifluridine
• Azacitidine
• Capecitabine (can cause photosensitivity/hand‑foot reactions)

Correct Answer: Capecitabine (can cause photosensitivity/hand‑foot reactions)

Q28. The incorporation of fluorinated pyrimidine metabolites into RNA primarily disrupts which cellular process?

• Protein glycosylation
• RNA processing and function leading to defective protein synthesis
• Mitochondrial DNA replication exclusively
• Lipid membrane synthesis

Correct Answer: RNA processing and function leading to defective protein synthesis

Q29. Which pyrimidine drug is known to cause pancreatitis in rare cases?

• Lamivudine
• Cytarabine
• Didanosine (a purine analogue, not pyrimidine)
• None of the above

Correct Answer: None of the above

Q30. Which of the following is a mechanism by which tumor cells reduce clinical efficacy of nucleoside pyrimidine drugs?

• Increased drug uptake via nucleoside transporters
• Decreased activity of kinases required for phosphorylation of the prodrug
• Loss of DNA methylation globally
• Increased sensitivity to apoptosis

Correct Answer: Decreased activity of kinases required for phosphorylation of the prodrug

Q31. Which pyrimidine analogue is most frequently used in hepatitis B management?

• Lamivudine (3TC)
• 5‑Fluorouracil
• Trifluridine
• Cytarabine

Correct Answer: Lamivudine (3TC)

Q32. Gemcitabine is a difluorinated cytidine analogue used in several cancers. Its primary cytotoxic action includes:

• RNA polymerase activation
• Inhibition of ribonucleotide reductase and DNA chain termination after incorporation
• Selective inhibition of thymidylate synthase only
• Activation of DHODH

Correct Answer: Inhibition of ribonucleotide reductase and DNA chain termination after incorporation

Q33. Which metabolite of 5‑FU forms a stable ternary complex with thymidylate synthase and folate cofactors?

• FUTP
• FdUMP
• 5‑Fluorouridine
• Uridine diphosphate

Correct Answer: FdUMP

Q34. For a pyrimidine nucleoside analogue to act as a chain terminator, which property is essential?

• Retention of a 3’‑OH group
• Lack of a 3’‑OH group or presence of a modified 3′ moiety preventing chain elongation
• Ability to bind to membrane receptors
• High lipophilicity for intracellular accumulation

Correct Answer: Lack of a 3’‑OH group or presence of a modified 3′ moiety preventing chain elongation

Q35. Which laboratory parameter is most important to monitor during therapy with cytotoxic pyrimidine antimetabolites?

• Complete blood count (CBC) for myelosuppression
• Serum cholesterol
• Fasting blood glucose
• Serum sodium only

Correct Answer: Complete blood count (CBC) for myelosuppression

Q36. Which pyrimidine analogue is used intrathecally or systemically for leukemias and requires careful CNS toxicity monitoring?

• Cytarabine (Ara‑C)
• Lamivudine
• Capecitabine
• Fluorouracil

Correct Answer: Cytarabine (Ara‑C)

Q37. Which oral pyrimidine antimetabolite is selectively activated in tumor rather than normal tissues, improving therapeutic index?

• Capecitabine
• Cytarabine
• 5‑Azacytidine
• Zidovudine

Correct Answer: Capecitabine

Q38. Which of the following agents is used as an antifungal pyrimidine derivative interfering with fungal RNA synthesis?

• Flucytosine (5‑FC)
• Fluconazole
• Amphotericin B
• Voriconazole

Correct Answer: Flucytosine (5‑FC)

Q39. Structure–activity relationship (SAR) for nucleoside analogues often focuses on sugar moiety modification. Which sugar change commonly confers resistance to degradation by nucleosidases?

• Replacement of ribose with arabinose (as in Ara‑C)
• Removing all hydroxyl groups completely
• Adding a large charged group at 5′ position only
• Replacing sugar with benzene

Correct Answer: Replacement of ribose with arabinose (as in Ara‑C)

Q40. Which pyrimidine antimetabolite directly targets DNA methylation and can reactivate silenced tumor suppressor genes?

• Decitabine
• Cytarabine
• Capecitabine
• Trifluridine

Correct Answer: Decitabine

Q41. Which pharmacokinetic feature is crucial for prodrugs like capecitabine to achieve tumor selectivity?

• High plasma protein binding only
• Sequential enzymatic conversion with high tumor expression of activating enzymes
• Complete renal excretion unchanged
• Poor oral bioavailability

Correct Answer: Sequential enzymatic conversion with high tumor expression of activating enzymes

Q42. In pyrimidine analogue chemotherapy, leucovorin is sometimes given with 5‑FU. Its role is to:

• Detoxify 5‑FU in the liver
• Stabilize the FdUMP‑TS‑methylene tetrahydrofolate ternary complex increasing 5‑FU efficacy
• Act as an antiemetic
• Inhibit thymidine phosphorylase

Correct Answer: Stabilize the FdUMP‑TS‑methylene tetrahydrofolate ternary complex increasing 5‑FU efficacy

Q43. Which pyrimidine drug is contraindicated or used with extreme caution in pregnancy due to teratogenicity?

• 5‑Fluorouracil
• Lamivudine
• Trifluridine eye drops (topical) only
• All pyrimidine antimetabolites with cytotoxic action

Correct Answer: All pyrimidine antimetabolites with cytotoxic action

Q44. Which pyrimidine derivative is used as an oral immunomodulatory agent that inhibits pyrimidine synthesis and reduces lymphocyte proliferation?

• Leflunomide
• Decitabine
• Zidovudine
• Cytarabine

Correct Answer: Leflunomide

Q45. Hand‑foot syndrome associated with capecitabine or 5‑FU is best managed initially by:

• Immediate chemotherapy discontinuation permanently
• Dose modification, topical emollients and symptomatic care
• High‑dose systemic steroids only
• Switching to anthracycline therapy

Correct Answer: Dose modification, topical emollients and symptomatic care

Q46. Which laboratory abnormality may indicate bone marrow toxicity from zidovudine therapy?

• Elevated alanine transaminase only
• Macrocytic anemia and neutropenia
• Hyperkalemia
• Hypoglycemia

Correct Answer: Macrocytic anemia and neutropenia

Q47. Combining pyrimidine analogues with agents that inhibit DNA repair (e.g., PARP inhibitors) is thought to:

• Decrease cytotoxicity of pyrimidines
• Potentiate DNA damage and increase anticancer efficacy
• Only affect antiviral activity not cancer therapy
• Prevent phosphorylation of the analogue

Correct Answer: Potentiate DNA damage and increase anticancer efficacy

Q48. Which clinical scenario most strongly suggests DPD deficiency leading to severe 5‑FU toxicity?

• Severe mucositis, diarrhea and neutropenia after first low‑dose 5‑FU administration
• Gradual onset mild nausea after weeks of therapy
• Hair loss only without systemic symptoms
• Isolated cough after treatment

Correct Answer: Severe mucositis, diarrhea and neutropenia after first low‑dose 5‑FU administration

Q49. A pyrimidine analogue used as an oral antimetabolite for metastatic colorectal cancer includes which combination?

• Trifluridine and tipiracil
• Lamivudine and zidovudine
• Cytarabine and daunorubicin
• 5‑Azacytidine and decitabine

Correct Answer: Trifluridine and tipiracil

Q50. For B. Pharm students, understanding medicinal pyrimidines requires integration of several disciplines. Which combination best represents the core areas to study?

• Pharmacology, medicinal chemistry, pharmacokinetics and clinical therapeutics
• Only organic chemistry and biochemistry
• Microbiology and botany exclusively
• Mathematics and statistics only

Correct Answer: Pharmacology, medicinal chemistry, pharmacokinetics and clinical therapeutics

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