Anti-tubercular drugs: mechanisms and resistance MCQs With Answer

Introduction: This quiz collection focuses on anti-tubercular drugs, emphasizing mechanisms of action and molecular bases of resistance—key topics for M.Pharm students specializing in infectious disease pharmacology. Questions integrate detailed pharmacodynamic targets (e.g., mycolic acid synthesis, RNA polymerase, ATP synthase), drug activation pathways (katG, pyrazinamidase, ddn), and common resistance mutations (rpoB, katG, inhA, pncA, gyrA). Clinical implications such as cross-resistance, efflux-mediated resistance, and newer agents (bedaquiline, delamanid, pretomanid) are included to deepen understanding of treatment challenges and rational regimen design. These MCQs will test mechanistic knowledge, interpretation of resistance mechanisms, and implications for drug selection and therapeutic monitoring.

Q1. Which enzyme must activate isoniazid intracellularly for it to inhibit mycolic acid synthesis?

• KatG catalase-peroxidase
• InhA reductase
• PncA pyrazinamidase
• Ddn nitroreductase

Correct Answer: KatG catalase-peroxidase

Q2. The most common mechanism of high-level isoniazid resistance in Mycobacterium tuberculosis involves mutation in which gene?

• rpoB
• katG
• embB
• pncA

Correct Answer: katG

Q3. Rifampicin exerts its bactericidal action primarily by binding to which molecular target?

• DNA gyrase
• RNA polymerase β subunit
• ATP synthase c subunit
• 30S ribosomal subunit

Correct Answer: RNA polymerase β subunit

Q4. A common mutation conferring rifampicin resistance is located at which codon of rpoB and is frequently used as a molecular marker?

• S531L
• K65R
• A1401G
• GyrA D94G

Correct Answer: S531L

Q5. Pyrazinamide is most active under which condition and requires which enzyme for activation?

• Neutral pH; KatG
• Acidic pH; PncA pyrazinamidase
• Anaerobic conditions; Ddn nitroreductase
• High oxygen tension; InhA

Correct Answer: Acidic pH; PncA pyrazinamidase

Q6. Resistance to pyrazinamide is most commonly due to mutations in which gene?

• pncA
• katG
• rpoB
• embB

Correct Answer: pncA

Q7. Ethambutol inhibits which biosynthetic process in Mycobacterium tuberculosis?

• Synthesis of mycolic acids via InhA
• Arabinosyl transferase activity involved in arabinogalactan synthesis
• RNA synthesis by binding rpoB
• ATP synthesis in the bacterial membrane

Correct Answer: Arabinosyl transferase activity involved in arabinogalactan synthesis

Q8. Mutations in which gene are most frequently associated with ethambutol resistance?

• embB
• gyrA
• atpE
• rpsL

Correct Answer: embB

Q9. Streptomycin resistance typically arises from mutations in which targets?

• rpoB and embB
• rpsL (S12) and rrs (16S rRNA)
• atpE and Rv0678
• inhA promoter and katG

Correct Answer: rpsL (S12) and rrs (16S rRNA)

Q10. Fluoroquinolones act against M. tuberculosis by inhibiting which enzyme, and resistance often involves mutations in which gene?

• DNA gyrase; gyrA/gyrB
• RNA polymerase; rpoB
• ATP synthase; atpE
• Cell wall arabinosyltransferase; embB

Correct Answer: DNA gyrase; gyrA/gyrB

Q11. Bedaquiline’s primary mechanism is inhibition of:

• RNA polymerase
• DNA gyrase
• Mycobacterial ATP synthase
• Peptidoglycan cross-linking enzymes

Correct Answer: Mycobacterial ATP synthase

Q12. Major mechanisms of resistance to bedaquiline include mutations in which gene and upregulation of which efflux system regulator?

• gyrA; inhA
• atpE; Rv0678 (MmpL5 efflux pump regulator)
• rpoB; embB
• pncA; katG

Correct Answer: atpE; Rv0678 (MmpL5 efflux pump regulator)

Q13. Delamanid and pretomanid require activation by which type of enzyme and resistance commonly involves mutations in which gene?

• NADH-dependent dehydrogenase; katG
• Deazaflavin-dependent nitroreductase (ddn); ddn mutations
• Pyrazinamidase; pncA
• RNA polymerase; rpoB

Correct Answer: Deazaflavin-dependent nitroreductase (ddn); ddn mutations

Q14. Overexpression of inhA confers resistance to which drugs, and what is the biochemical basis?

• Isoniazid and ethambutol; decreased drug uptake
• Isoniazid and ethionamide; increased target enzyme levels reducing drug efficacy
• Rifampicin and rifapentine; mutation in RNA polymerase
• Fluoroquinolones; gyrase protection

Correct Answer: Isoniazid and ethionamide; increased target enzyme levels reducing drug efficacy

Q15. Para-aminosalicylic acid (PAS) acts primarily as which type of antibacterial agent and resistance often involves alterations in which pathway?

• Protein synthesis inhibitor; rpsL mutations
• Folate pathway antimetabolite; mutations affecting folate biosynthesis enzymes
• Cell wall inhibitor; embB mutations
• Membrane disruptor; atpE mutations

Correct Answer: Folate pathway antimetabolite; mutations affecting folate biosynthesis enzymes

Q16. Heteroresistance in tuberculosis refers to:

• Simultaneous presence of resistant and susceptible bacterial subpopulations within the same patient
• Resistance that only appears under laboratory conditions
• Resistance due to host immune suppression
• Resistance that is reversible with higher drug doses

Correct Answer: Simultaneous presence of resistant and susceptible bacterial subpopulations within the same patient

Q17. Which diagnostic technique detects specific mutations (e.g., rpoB, katG, inhA) and provides rapid genotypic resistance information?

• Phenotypic culture-based drug susceptibility testing (DST)
• Line probe assays / molecular PCR assays
• Acid-fast bacilli (AFB) smear microscopy
• Chest X-ray imaging

Correct Answer: Line probe assays / molecular PCR assays

Q18. Cross-resistance between isoniazid and ethionamide arises primarily because both target which enzyme?

• RNA polymerase
• InhA (enoyl-ACP reductase)
• DNA gyrase
• ATP synthase

Correct Answer: InhA (enoyl-ACP reductase)

Q19. Which pharmacodynamic characteristic is most associated with the sterilizing activity of rifampicin and pyrazinamide in TB therapy?

• Concentration-dependent killing at peak concentrations
• Time-dependent killing requiring sustained exposure above MIC
• Activity against dormant/non-replicating bacilli and intracellular organisms
• Selective binding to 30S ribosomal subunit

Correct Answer: Activity against dormant/non-replicating bacilli and intracellular organisms

Q20. Efflux pump–mediated resistance can reduce intracellular concentrations of several TB drugs. A common genetic mechanism causing efflux-mediated resistance is mutation or regulatory alteration in which type of gene?

• Structural enzyme genes like rpoB
• Regulatory transcriptional repressors/activators (e.g., Rv0678)
• Mitochondrial ribosomal proteins
• Host immune genes

Correct Answer: Regulatory transcriptional repressors/activators (e.g., Rv0678)

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