Ethionamide – chemistry and mechanism MCQs With Answer

Ethionamide – Chemistry and Mechanism MCQs With Answer

Ethionamide is a second-line anti-tubercular thioamide whose chemistry and mechanism are essential for B.Pharm students studying drug action and resistance. This introduction covers ethionamide’s chemical class, prodrug activation by EthA monooxygenase, and inhibition of mycolic acid synthesis via InhA (enoyl-ACP reductase) NAD-adduct formation. Key topics include structure–activity relationships, molecular targets, common resistance mechanisms (EthA or inhA mutations), pharmacokinetics, hepatic metabolism, and major adverse effects such as hepatotoxicity and peripheral neuropathy. Understanding these concepts helps in rational therapy, therapeutic monitoring, and anticipating drug interactions. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which chemical class does ethionamide belong to?

• Thioamides
• Hydrazides
• Macrolides
• Fluoroquinolones

Correct Answer: Thioamides

Q2. Ethionamide is primarily used as which type of anti-tubercular agent?

• First-line bactericidal agent
• Second-line agent for drug-resistant TB
• Prophylactic vaccine component
• Topical anti-mycobacterial

Correct Answer: Second-line agent for drug-resistant TB

Q3. Ethionamide requires activation to exert its antibacterial effect. Which enzyme activates it in Mycobacterium tuberculosis?

• EthA monooxygenase
• CYP3A4 in human liver
• KatG catalase-peroxidase
• DNA gyrase

Correct Answer: EthA monooxygenase

Q4. What is the primary molecular target of the activated ethionamide metabolite?

• RNA polymerase
• Enoyl-ACP reductase (InhA)
• Dihydrofolate reductase
• Peptidoglycan transpeptidase

Correct Answer: Enoyl-ACP reductase (InhA)

Q5. The mechanism of inhibition of InhA by ethionamide involves which of the following?

• Direct covalent alkylation of the enzyme active site cysteine
• Formation of an NAD adduct that inhibits InhA
• Intercalation into DNA to prevent transcription
• Competitive inhibition of folate synthesis

Correct Answer: Formation of an NAD adduct that inhibits InhA

Q6. Which functional group is essential in ethionamide for its anti-mycobacterial activity?

• Thioamide (–CSNH2) group
• Hydroxyl (–OH) group
• Carboxyl (–COOH) group
• Fluoro substituent

Correct Answer: Thioamide (–CSNH2) group

Q7. Cross-resistance between ethionamide and isoniazid most commonly arises due to mutations in which gene?

• rpoB
• inhA or its promoter
• gyrA
• embB

Correct Answer: inhA or its promoter

Q8. A common resistance mechanism to ethionamide is loss of function in EthA. What is the consequence of EthA mutation?

• Increased drug uptake into bacteria
• Failure to activate the prodrug, causing resistance
• Enhanced conversion to toxic metabolites
• Increased binding of ethionamide to InhA

Correct Answer: Failure to activate the prodrug, causing resistance

Q9. Which clinical adverse effect is most characteristically associated with ethionamide and often requires pyridoxine supplementation?

• Peripheral neuropathy
• Renal tubular acidosis
• Cardiac arrhythmia
• Ototoxicity

Correct Answer: Peripheral neuropathy

Q10. Routine monitoring is recommended for ethionamide therapy primarily because of risk to which organ?

• Lungs
• Liver
• Pancreas
• Thyroid only

Correct Answer: Liver

Q11. Structurally, ethionamide shows pharmacological similarity to which first-line TB drug?

• Rifampicin
• Isoniazid
• Pyrazinamide
• Streptomycin

Correct Answer: Isoniazid

Q12. Which statement about ethionamide pharmacokinetics is correct?

• It is an inactive prodrug activated within the host liver only
• It is activated within mycobacterial cells by EthA enzyme
• It bypasses hepatic metabolism and is excreted unchanged
• It is primarily eliminated via biliary excretion without metabolism

Correct Answer: It is activated within mycobacterial cells by EthA enzyme

Q13. Structure–activity relationship (SAR) studies indicate which modification decreases ethionamide activity?

• Retention of thioamide moiety
• Substitution that removes the thioamide sulfur
• Small alkyl substitution at the 2-position
• Maintaining the pyridine ring

Correct Answer: Substitution that removes the thioamide sulfur

Q14. Which laboratory test is most appropriate to monitor ethionamide toxicity during therapy?

• Serum creatinine only
• Liver function tests (LFTs)
• Serum amylase
• Pulmonary function tests

Correct Answer: Liver function tests (LFTs)

Q15. Co-administration of which vitamin is recommended with ethionamide to reduce neuropathy risk?

• Vitamin C
• Vitamin B6 (pyridoxine)
• Vitamin D
• Vitamin K

Correct Answer: Vitamin B6 (pyridoxine)

Q16. Ethionamide’s antibacterial effect on mycobacteria is mainly due to inhibition of:

• Protein synthesis at the 30S ribosomal subunit
• Mycolic acid synthesis in the cell wall
• DNA gyrase activity
• ATP synthase

Correct Answer: Mycolic acid synthesis in the cell wall

Q17. Which resistance mechanism would most likely NOT confer ethionamide resistance?

• Mutations in ethA gene impairing activation
• Mutations in inhA decreasing drug binding
• Increased expression of efflux pumps extruding drug
• Mutations in rpoB leading to rifampicin resistance only

Correct Answer: Mutations in rpoB leading to rifampicin resistance only

Q18. In medicinal chemistry terms, ethionamide’s thioamide moiety is important because it:

• Promotes rapid renal clearance
• Is required for prodrug activation and target interaction
• Increases aqueous solubility dramatically
• Prevents penetration into mycobacterial cells

Correct Answer: Is required for prodrug activation and target interaction

Q19. Which clinical scenario favors use of ethionamide?

• Latent TB without resistance
• MDR-TB with resistance to isoniazid and rifampicin
• UTI caused by E. coli
• Allergic reaction to pyridoxine

Correct Answer: MDR-TB with resistance to isoniazid and rifampicin

Q20. Ethionamide activation leads to reactive intermediates. These intermediates most directly interfere with:

• Ribosomal RNA methylation
• NAD-dependent fatty acid synthesis enzymes
• Cell membrane ion channels
• Topoisomerase IV

Correct Answer: NAD-dependent fatty acid synthesis enzymes

Q21. Which adverse effect requires prompt evaluation and possible discontinuation of ethionamide?

• Transient mild nausea
• Marked elevation of transaminases indicating hepatotoxicity
• Mild metallic taste in mouth
• Temporary hair thinning

Correct Answer: Marked elevation of transaminases indicating hepatotoxicity

Q22. Which laboratory method is commonly used in research to detect ethionamide resistance mutations?

• Whole-genome sequencing or targeted gene sequencing of ethA/inhA
• Gram staining
• ELISA for circulating drug levels
• Serum glucose monitoring

Correct Answer: Whole-genome sequencing or targeted gene sequencing of ethA/inhA

Q23. Which structural feature of ethionamide promotes its penetration into mycobacterial cells?

• Highly polar charged groups
• Moderate lipophilicity from aromatic/pyridine ring
• Large bulky peptide chains
• Attached oligosaccharide residues

Correct Answer: Moderate lipophilicity from aromatic/pyridine ring

Q24. Combining ethionamide with which of the following requires caution because of overlapping hepatotoxicity?

• Pyridoxine alone
• Isoniazid or pyrazinamide
• Oral antacids
• Topical antifungals

Correct Answer: Isoniazid or pyrazinamide

Q25. Which statement about ethionamide and isoniazid cross-resistance is TRUE?

• Cross-resistance never occurs because targets are different
• Cross-resistance can occur due to shared InhA target or promoter mutations
• Cross-resistance is complete for all clinical isolates
• Cross-resistance depends only on human metabolism

Correct Answer: Cross-resistance can occur due to shared InhA target or promoter mutations

Q26. In drug design, improving ethionamide potency often focuses on which approach?

• Removing the thioamide to reduce toxicity
• Modifying the pyridine ring to enhance binding to InhA
• Increasing molecular weight beyond 1000 Da
• Adding charged polysaccharide chains

Correct Answer: Modifying the pyridine ring to enhance binding to InhA

Q27. Which clinical management step is recommended when a patient on ethionamide develops neuropathic symptoms?

• Ignore symptoms as they resolve spontaneously
• Start or increase pyridoxine and assess need for dose adjustment
• Switch immediately to high-dose isoniazid
• Stop monitoring liver function tests

Correct Answer: Start or increase pyridoxine and assess need for dose adjustment

Q28. Which property describes ethionamide’s activity against Mycobacterium tuberculosis?

• Targets extracellular gram-negative bacteria primarily
• Interferes with mycolic acid synthesis specific to mycobacteria
• Is primarily an antifungal agent
• Acts exclusively as an immune stimulant

Correct Answer: Interferes with mycolic acid synthesis specific to mycobacteria

Q29. Which molecular diagnostic finding would most strongly suggest ethionamide resistance?

• Point mutation in inhA promoter region
• Increased serum albumin
• Deletion of human CYP2E1 gene
• Elevated urinary sodium

Correct Answer: Point mutation in inhA promoter region

Q30. For B.Pharm students, which learning objective best summarizes the importance of ethionamide study?

• Understanding formulation excipients only
• Linking chemical structure, prodrug activation, molecular mechanism, resistance, and safety monitoring
• Memorizing brand names without mechanism knowledge
• Studying pharmacoeconomics exclusively

Correct Answer: Linking chemical structure, prodrug activation, molecular mechanism, resistance, and safety monitoring

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