Folate reductase inhibitors – Trimethoprim, Cotrimoxazole MCQs With Answer

Folate reductase inhibitors – Trimethoprim, Cotrimoxazole MCQs With Answer

Folate reductase inhibitors, especially trimethoprim and the combination cotrimoxazole (trimethoprim‑sulfamethoxazole), are vital for B.Pharm students learning antimicrobial pharmacology. This concise overview explains mechanisms — trimethoprim inhibits bacterial dihydrofolate reductase while sulfamethoxazole blocks dihydropteroate synthase — producing sequential folate synthesis blockade and synergy. Key topics covered include antimicrobial spectrum, clinical indications (UTIs, PCP, Nocardia, Stenotrophomonas), pharmacokinetics, dosing strategies, resistance mechanisms, adverse effects (megaloblastic anemia, hyperkalemia, hypersensitivity, crystalluria), drug interactions and monitoring. Emphasis is on rational use, dosing calculations, toxicity prevention and stewardship relevant to pharmacy practice. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary mechanism of action of trimethoprim?

• Inhibition of dihydrofolate reductase
• Inhibition of dihydropteroate synthase
• Inhibition of DNA gyrase
• Disruption of cell wall synthesis

Correct Answer: (Inhibition of dihydrofolate reductase)

Q2. Cotrimoxazole refers to which combination?

• Trimethoprim + Sulfamethoxazole
• Trimethoprim + Pyrimethamine
• Sulfadiazine + Pyrimethamine
• Sulfamethoxazole + Amoxicillin

Correct Answer: (Trimethoprim + Sulfamethoxazole)

Q3. The synergy between trimethoprim and sulfamethoxazole is due to:

• Independent inhibition of protein synthesis
• Sequential blockade of folate synthesis pathway
• Blocking DNA replication and RNA transcription simultaneously
• Inhibition of cell membrane function

Correct Answer: (Sequential blockade of folate synthesis pathway)

Q4. What is the usual fixed ratio of trimethoprim to sulfamethoxazole in cotrimoxazole?

• 1:20 (TMP:SMX)
• 1:1 (TMP:SMX)
• 1:5 (TMP:SMX)
• 5:1 (TMP:SMX)

Correct Answer: (1:5 (TMP:SMX))

Q5. Which of the following pathogens is a classic indication for high-dose TMP‑SMX therapy?

• Pneumocystis jirovecii (PCP)
• Streptococcus pyogenes
• Clostridioides difficile
• Vibrio cholerae

Correct Answer: (Pneumocystis jirovecii (PCP))

Q6. Trimethoprim can cause hyperkalemia by which renal mechanism?

• Enhancing aldosterone secretion
• Blocking epithelial sodium channels (ENaC) in the distal nephron
• Increasing potassium reabsorption in the proximal tubule
• Stimulating renin release

Correct Answer: (Blocking epithelial sodium channels (ENaC) in the distal nephron)

Q7. Which adverse effect is most directly related to folate antagonism by trimethoprim?

• Nephrotic syndrome
• Megaloblastic anemia
• Peripheral neuropathy
• Ototoxicity

Correct Answer: (Megaloblastic anemia)

Q8. Sulfonamides exert antibacterial effect by competitively antagonizing which substrate?

• Folate
• PABA (para-aminobenzoic acid)
• Thymidine
• Glucose-6-phosphate

Correct Answer: (PABA (para-aminobenzoic acid))

Q9. Which laboratory tests should be monitored during prolonged cotrimoxazole therapy?

• Liver enzymes only
• CBC and renal function
• Fasting glucose and lipids
• EEG and ECG

Correct Answer: (CBC and renal function)

Q10. Trimethoprim may cause a rise in serum creatinine due to:

• Acute tubular necrosis
• Inhibition of creatinine secretion without changing GFR
• Increased muscle breakdown
• Enhanced creatinine production in the liver

Correct Answer: (Inhibition of creatinine secretion without changing GFR)

Q11. Cotrimoxazole is contraindicated in neonates primarily because of:

• Risk of kernicterus from displacement of bilirubin
• Risk of respiratory depression
• Risk of congenital cardiac defects
• Risk of neonatal hypoglycemia

Correct Answer: (Risk of kernicterus from displacement of bilirubin)

Q12. Which resistance mechanism specifically reduces bacterial susceptibility to trimethoprim?

• Plasmid-mediated altered dihydrofolate reductase
• Overexpression of dihydropteroate synthase
• Production of beta-lactamase
• Efflux pumps for aminoglycosides

Correct Answer: (Plasmid-mediated altered dihydrofolate reductase)

Q13. Which clinical condition is an established indication for cotrimoxazole prophylaxis?

• Prevention of opportunistic infections in HIV with CD4 <200 cells/µL
• Routine surgical prophylaxis for clean procedures
• Prophylaxis of aspiration pneumonia
• Prevention of influenza transmission

Correct Answer: (Prevention of opportunistic infections in HIV with CD4 <200 cells/µL)

Q14. Cotrimoxazole shows reliable activity against which opportunistic bacterium?

• Stenotrophomonas maltophilia
• Pseudomonas aeruginosa
• Enterococcus faecalis
• Clostridium perfringens

Correct Answer: (Stenotrophomonas maltophilia)

Q15. Which of the following is a common dermatologic adverse reaction to sulfonamides?

• Stevens‑Johnson syndrome
• Alopecia areata
• Psoriasis exacerbation
• Vitiligo

Correct Answer: (Stevens‑Johnson syndrome)

Q16. In uncomplicated urinary tract infection, cotrimoxazole is primarily active against which common pathogen?

• Escherichia coli
• Neisseria gonorrhoeae
• Streptococcus pneumoniae
• Bacteroides fragilis

Correct Answer: (Escherichia coli)

Q17. The bactericidal effect of TMP‑SMX combination is due to:

• Concentration‑dependent membrane disruption
• Combined sequential blockade leading to inhibition of DNA precursor synthesis
• Inhibition of ribosomal 50S subunit alone
• Chelation of essential metal ions

Correct Answer: (Combined sequential blockade leading to inhibition of DNA precursor synthesis)

Q18. Which drug interaction is clinically significant with cotrimoxazole?

• Increased warfarin anticoagulant effect
• Reduced effect of metformin
• Inactivation of benzodiazepines
• Decreased levels of digoxin

Correct Answer: (Increased warfarin anticoagulant effect)

Q19. Which measure helps prevent sulfonamide‑induced crystalluria?

• Maintain good hydration and urine alkalinization
• Administer with high‑fat meals
• Avoid coadministration with antacids
• Shorten infusion time

Correct Answer: (Maintain good hydration and urine alkalinization)

Q20. A common hematologic adverse effect of prolonged TMP‑SMX therapy is:

• Hemolytic anemia in G6PD deficiency
• Polycythemia vera
• Lymphocytosis
• Thrombocytosis

Correct Answer: (Hemolytic anemia in G6PD deficiency)

Q21. Trimethoprim shows selectivity for bacterial DHFR over human DHFR because:

• Human DHFR is absent in cells
• Bacterial DHFR has higher affinity for trimethoprim
• Trimethoprim is actively transported only into bacteria
• Human cells metabolize trimethoprim immediately

Correct Answer: (Bacterial DHFR has higher affinity for trimethoprim)

Q22. High‑dose TMP‑SMX for Pneumocystis jirovecii pneumonia is typically calculated based on which component?

• Sulfamethoxazole dose
• Total combined weight-based dose without specifying component
• Trimethoprim dose (mg/kg/day)
• Renal function only

Correct Answer: (Trimethoprim dose (mg/kg/day))

Q23. Which patient group should generally avoid cotrimoxazole due to increased risk?

• Patients with documented sulfa allergy
• Adults with controlled hypertension
• Patients on long‑term statin therapy
• Patients with seasonal allergies

Correct Answer: (Patients with documented sulfa allergy)

Q24. Which of the following organisms is intrinsically resistant to sulfonamides due to lack of PABA pathway dependence?

• Pseudomonas aeruginosa
• Enterococcus faecalis
• Mycoplasma pneumoniae
• Staphylococcus aureus

Correct Answer: (Mycoplasma pneumoniae)

Q25. Which statement about pharmacokinetics of trimethoprim is true?

• Trimethoprim is poorly absorbed orally
• Trimethoprim achieves good tissue penetration, including the prostate
• Trimethoprim is only available as a topical agent
• Trimethoprim has negligible renal excretion

Correct Answer: (Trimethoprim achieves good tissue penetration, including the prostate)

Q26. Which monitoring parameter is most important when initiating cotrimoxazole in an elderly patient on ACE inhibitors?

• Serum potassium
• Thyroid function tests
• Fasting blood glucose
• Serum magnesium

Correct Answer: (Serum potassium)

Q27. Which adverse reaction is more attributable to the sulfonamide component than to trimethoprim?

• Hyperkalemia
• Crystalluria and hypersensitivity rash
• Inhibition of creatinine secretion
• Agranulocytosis uniquely caused by trimethoprim

Correct Answer: (Crystalluria and hypersensitivity rash)

Q28. Which clinical use of cotrimoxazole is supported by evidence?

• Treatment of uncomplicated viral pharyngitis
• Therapy for nocardiosis
• First‑line treatment for tuberculosis
• Routine use for Candida oral thrush

Correct Answer: (Therapy for nocardiosis)

Q29. Which drug when coadministered with cotrimoxazole can markedly increase risk of myelosuppression?

• Methotrexate
• Metformin
• Amlodipine
• Atorvastatin

Correct Answer: (Methotrexate)

Q30. For safe dispensing counseling, which instruction is appropriate for patients prescribed oral cotrimoxazole?

• Take with plenty of fluids and report rash or jaundice promptly
• Avoid all dairy products while on therapy
• Stop antihypertensives while taking cotrimoxazole
• Double the dose if you miss a dose

Correct Answer: (Take with plenty of fluids and report rash or jaundice promptly)

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