Mechanism of action of sulfonamides MCQs With Answer

Introduction

Understanding the mechanism of action of sulfonamides is essential for B.Pharm students studying antimicrobial pharmacology. Sulfonamides are structural analogs of para-aminobenzoic acid (PABA) that competitively inhibit dihydropteroate synthase, blocking folic acid synthesis required for thymidine and purine production. This bacteriostatic effect, important pharmacodynamic interactions (notably synergy with trimethoprim inhibiting dihydrofolate reductase), resistance mechanisms, adverse effects and clinical uses form core concepts in therapeutics. Study of structure–activity relationships, pharmacokinetics (acetylation, renal excretion), and drug interactions (warfarin, methotrexate) deepens clinical understanding. Examples include sulfamethoxazole, sulfadiazine and sulfadoxine; clinical considerations include hypersensitivity, hemolysis in G6PD deficiency and crystalluria risk, which are important for safe prescribing. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary molecular target of sulfonamides in bacteria?

• Inhibition of DNA gyrase
• Inhibition of dihydropteroate synthase
• Inhibition of peptidoglycan cross-linking
• Inhibition of ribosomal 50S subunit

Correct Answer: Inhibition of dihydropteroate synthase

Q2. Sulfonamides are structural analogs of which endogenous bacterial substrate?

• Tetrahydrofolate
• Para-aminobenzoic acid (PABA)
• Dihydrofolic acid
• Folic acid

Correct Answer: Para-aminobenzoic acid (PABA)

Q3. The antibacterial effect of sulfonamides is best described as:

• Bactericidal when used alone
• Bacteriostatic when used alone
• Fungicidal
• Bactericidal against anaerobes only

Correct Answer: Bacteriostatic when used alone

Q4. Combining sulfonamides with trimethoprim results in:

• Antagonism due to overlapping toxicities
• No interaction—independent effects
• Synergistic bactericidal activity by sequential blockade of folate pathway
• Reduced absorption of both drugs

Correct Answer: Synergistic bactericidal activity by sequential blockade of folate pathway

Q5. Which enzyme is inhibited by trimethoprim, producing synergy with sulfonamides?

• Dihydropteroate synthase
• Dihydrofolate reductase
• Thymidylate synthase
• RNA polymerase

Correct Answer: Dihydrofolate reductase

Q6. A common resistance mechanism to sulfonamides is:

• Production of beta-lactamases
• Mutation or plasmid-encoded altered dihydropteroate synthase with reduced drug affinity
• Efflux of trimethoprim
• Inactivation by acetylation in the periplasm

Correct Answer: Mutation or plasmid-encoded altered dihydropteroate synthase with reduced drug affinity

Q7. Which pharmacokinetic process commonly affects sulfonamide elimination?

• Glomerular filtration only with no tubular handling
• Renal excretion including acetylation and tubular secretion
• Exclusively hepatic metabolism with biliary excretion
• Metabolic activation to prodrug in the gut

Correct Answer: Renal excretion including acetylation and tubular secretion

Q8. Sulfonamide-induced crystalluria can be minimized by:

• Alkalinization of urine
• Acidification of urine
• Co-administration of calcium supplements
• Avoiding hydration

Correct Answer: Alkalinization of urine

Q9. Which adverse effect is a serious immunologic reaction associated with sulfonamides?

• Stevens–Johnson syndrome
• Bronchospasm due to histamine release
• Peripheral neuropathy
• Aplastic crisis due to parvovirus

Correct Answer: Stevens–Johnson syndrome

Q10. Sulfamethoxazole is most frequently combined with which partner drug in clinical practice?

• Pyrimethamine
• Trimethoprim
• Amoxicillin
• Ciprofloxacin

Correct Answer: Trimethoprim

Q11. Which statement about human folate metabolism explains selective toxicity of sulfonamides?

• Humans synthesize folate de novo and are inhibited by sulfonamides
• Humans obtain folate from diet and do not use dihydropteroate synthase, so are less affected
• Bacterial folate metabolism is identical to human, causing major host toxicity
• Sulfonamides inhibit mammalian dihydrofolate reductase strongly

Correct Answer: Humans obtain folate from diet and do not use dihydropteroate synthase, so are less affected

Q12. Structural requirement essential for sulfonamide antibacterial activity is the presence of:

• A free para-amino group on an aniline ring and a sulfonamide moiety
• A beta-lactam ring
• A quaternary ammonium group
• A nitro group at ortho position

Correct Answer: A free para-amino group on an aniline ring and a sulfonamide moiety

Q13. Which clinical use is most appropriate for sulfonamide therapy?

• Treatment of viral influenza
• Uncomplicated urinary tract infections and Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole
• Systemic fungal infections as first-line
• Active tuberculosis as monotherapy

Correct Answer: Uncomplicated urinary tract infections and Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole

Q14. Which laboratory test is important to monitor in patients receiving long-term sulfonamides?

• Serum potassium only
• Complete blood count for agranulocytosis and hemolysis
• Arterial blood gases weekly
• Serum amylase for pancreatitis

Correct Answer: Complete blood count for agranulocytosis and hemolysis

Q15. In patients with G6PD deficiency, sulfonamides may cause:

• Pulmonary fibrosis
• Hemolytic anemia
• Hypertension
• Nephrotic syndrome

Correct Answer: Hemolytic anemia

Q16. Which of the following increases bacterial resistance to sulfonamides?

• Decreased PABA synthesis by bacteria
• Increased intracellular concentration of sulfonamide
• Overproduction of PABA by bacteria
• Enhanced penetration of drug into bacterial cell

Correct Answer: Overproduction of PABA by bacteria

Q17. Sulfonamides are contraindicated in late pregnancy primarily because of:

• Risk of neonatal kernicterus due to displacement of bilirubin
• High risk of teratogenic skeletal defects
• Severe maternal hypertension
• Induction of labor

Correct Answer: Risk of neonatal kernicterus due to displacement of bilirubin

Q18. Which pharmacodynamic parameter best describes sulfonamide activity against bacteria?

• Peak/MIC ratio-dependent killing
• Time above MIC is most critical for action
• Concentration-independent bacteriostatic effect determined by degree of folate blockade
• Post-antibiotic effect of several days

Correct Answer: Concentration-independent bacteriostatic effect determined by degree of folate blockade

Q19. A plasmid-mediated resistance mechanism that alters the target enzyme results in:

• Increased susceptibility to sulfonamides
• No change in resistance phenotype
• Reduced binding of sulfonamides to dihydropteroate synthase and clinical resistance
• Enhanced drug activation inside bacteria

Correct Answer: Reduced binding of sulfonamides to dihydropteroate synthase and clinical resistance

Q20. Which sulfonamide is long-acting and often used in prophylactic antimalarial combinations?

• Sulfisoxazole
• Sulfadoxine
• Sulfacetamide
• Sulfamethizole

Correct Answer: Sulfadoxine

Q21. Which statement about sulfonamide absorption and distribution is correct?

• They are poorly absorbed orally and never reach systemic circulation
• They are well absorbed orally and distribute widely, including into CSF when meninges are inflamed
• They are only effective topically and have no systemic use
• They require IV formulation to be active

Correct Answer: They are well absorbed orally and distribute widely, including into CSF when meninges are inflamed

Q22. Which drug interaction is a major concern with sulfonamides?

• Inhibition of warfarin metabolism leading to increased anticoagulant effect
• Induction of CYP450 causing decreased phenytoin levels
• Blocking of digoxin absorption reducing efficacy
• Chelation with tetracyclines leading to decreased sulfonamide levels

Correct Answer: Inhibition of warfarin metabolism leading to increased anticoagulant effect

Q23. In the folate synthesis pathway, dihydropteroate synthase catalyzes the condensation of PABA with:

• Para-aminophenol
• 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (pteridine derivative)
• Folic acid directly
• Thymidine monophosphate

Correct Answer: 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (pteridine derivative)

Q24. Which sulfonamide is commonly used topically for ocular infections?

• Sulfamethoxazole
• Sulfacetamide
• Sulfadoxine
• Sulfisoxazole

Correct Answer: Sulfacetamide

Q25. The structure–activity relationship important for sulfonamide potency includes which substitution pattern?

• Ortho substitution on the aniline ring enhances activity
• Para-amino group is essential; N1 heterocyclic substitutions modulate potency and solubility
• Removal of the sulfonyl group increases potency
• Adding bulky groups at para position increases water solubility and potency

Correct Answer: Para-amino group is essential; N1 heterocyclic substitutions modulate potency and solubility

Q26. Which organism is typically resistant to sulfonamides due to intrinsic lack of folate synthesis pathway?

• Streptococcus pyogenes
• Enterococcus faecalis
• Chlamydia trachomatis
• Plasmodium falciparum

Correct Answer: Chlamydia trachomatis

Q27. Which monitoring parameter is relevant when sulfonamides are co-prescribed with methotrexate?

• Liver function tests only
• Complete blood count and signs of bone marrow suppression
• Serum potassium exclusively
• Pulmonary function tests

Correct Answer: Complete blood count and signs of bone marrow suppression

Q28. What effect does bacterial overexpression of efflux pumps have on sulfonamide activity?

• Increases susceptibility to sulfonamides
• Decreases intracellular drug concentrations and contributes to resistance
• Has no effect because sulfonamides act extracellularly
• Converts sulfonamides into inactive metabolites

Correct Answer: Decreases intracellular drug concentrations and contributes to resistance

Q29. In laboratory susceptibility testing, a high inoculum of bacteria can falsely suggest resistance to sulfonamides because:

• Sulfonamides are concentration-dependent killers
• Excess PABA produced by large bacterial populations can outcompete drug binding
• Sulfonamides degrade quickly in agar
• High inoculum increases pH making drug inactive

Correct Answer: Excess PABA produced by large bacterial populations can outcompete drug binding

Q30. Which therapeutic scenario justifies use of sulfonamide–trimethoprim as first-line therapy?

• Uncomplicated community-acquired MRSA skin abscess in all cases
• Prophylaxis and treatment of Pneumocystis jirovecii in immunocompromised patients
• First-line monotherapy for bacterial endocarditis
• Empiric therapy for viral upper respiratory infection

Correct Answer: Prophylaxis and treatment of Pneumocystis jirovecii in immunocompromised patients

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