Pyrazinamide is a first‑line antitubercular prodrug (pyrazinecarboxamide) with unique chemistry and metabolism important for B. Pharm students. Converted by mycobacterial pyrazinamidase (pncA) to pyrazinoic acid (POA), it exerts sterilizing activity against semi‑dormant Mycobacterium tuberculosis at acidic pH and helps shorten therapy. Key topics include structure, activation, mechanism (membrane energetics and FAS‑I inhibition), resistance (pncA mutations), human metabolism (POA → 5‑hydroxy‑POA via xanthine oxidase), pharmacokinetics, dose adjustments, hepatotoxicity and hyperuricemia. Understanding these principles aids safe dispensing, monitoring and interpretation of susceptibility tests. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which chemical name correctly describes pyrazinamide?
- Pyrazinecarboxamide
- Nicotinamide adenine dinucleotide
- Pyrazinoic acid
- Pyrazole sulfate
Correct Answer: Pyrazinecarboxamide
Q2. Pyrazinamide is a prodrug activated into its active form by which enzyme in Mycobacterium tuberculosis?
- Pyrazinamidase (pncA)
- β‑lactamase
- Mycobacterial catalase‑peroxidase (katG)
- DNA gyrase
Correct Answer: Pyrazinamidase (pncA)
Q3. The active metabolite of pyrazinamide that accumulates in mycobacteria is called:
- Pyrazinoic acid
- 5‑Hydroxypyrazinamide
- Nicotinic acid
- Pyrazole‑2‑carboxylic acid
Correct Answer: Pyrazinoic acid
Q4. Pyrazinamide shows optimal antimicrobial activity under which condition?
- Acidic pH (low pH)
- Neutral pH (7.4)
- Alkaline pH (high pH)
- Anaerobic conditions only
Correct Answer: Acidic pH (low pH)
Q5. The primary mechanism of action of pyrazinamide/pyrazinoic acid is best described as:
- Disruption of mycobacterial membrane energetics and inhibition of fatty acid synthase I
- Inhibition of peptidoglycan cross‑linking
- Inhibition of folate synthesis
- Blocking DNA replication by targeting topoisomerase
Correct Answer: Disruption of mycobacterial membrane energetics and inhibition of fatty acid synthase I
Q6. In human metabolism, pyrazinoic acid is further oxidized to which major urinary metabolite?
- 5‑Hydroxypyrazinoic acid
- Pyrazine sulfate
- Nicotinamide riboside
- Pyrazinamide glucuronide
Correct Answer: 5‑Hydroxypyrazinoic acid
Q7. Which mammalian enzyme primarily catalyzes the conversion of pyrazinoic acid to 5‑hydroxy‑pyrazinoic acid?
- Xanthine oxidase
- CYP3A4
- Alcohol dehydrogenase
- N‑acetyltransferase
Correct Answer: Xanthine oxidase
Q8. The most common genetic mechanism of pyrazinamide resistance in M. tuberculosis involves mutations in:
- pncA gene encoding pyrazinamidase
- rpoB gene encoding RNA polymerase
- katG gene encoding catalase‑peroxidase
- inhA promoter region only
Correct Answer: pncA gene encoding pyrazinamidase
Q9. Pyrazinamide is classified in TB regimens primarily because of its ability to:
- Kill semi‑dormant bacilli in acidic environments and shorten therapy
- Act as the main bacteriostatic agent in latent TB only
- Replace rifampicin in intensive phase
- Prevent transmission by rapid sputum sterilization within 24 hours
Correct Answer: Kill semi‑dormant bacilli in acidic environments and shorten therapy
Q10. The most serious adverse effect associated with pyrazinamide requiring monitoring is:
- Hepatotoxicity (elevated liver enzymes)
- Ototoxicity
- Bone marrow suppression
- Cardiotoxicity
Correct Answer: Hepatotoxicity (elevated liver enzymes)
Q11. Pyrazinamide commonly causes which metabolic disturbance that can precipitate gout?
- Hyperuricemia
- Hypokalemia
- Hyponatremia
- Hypercalcemia
Correct Answer: Hyperuricemia
Q12. Typical adult dosing of pyrazinamide in first‑line TB therapy is closest to which range?
- 20–25 mg/kg once daily
- 5–10 mg/kg once daily
- 50–60 mg/kg once daily
- 100 mg fixed dose only
Correct Answer: 20–25 mg/kg once daily
Q13. After oral administration, the approximate time to peak plasma concentration (Tmax) for pyrazinamide is:
- 1–2 hours
- 6–8 hours
- 24 hours
- 30 minutes
Correct Answer: 1–2 hours
Q14. The elimination half‑life of pyrazinamide in patients with normal renal function is approximately:
- 9–10 hours
- 1–2 hours
- 48 hours
- 30 minutes
Correct Answer: 9–10 hours
Q15. The primary route of excretion for pyrazinamide metabolites is:
- Renal excretion
- Biliary excretion into feces
- Exhalation as CO2
- Secretion in sweat
Correct Answer: Renal excretion
Q16. Pyrazinamide shows negligible activity against M. tuberculosis in vitro at neutral pH; this implies that standard susceptibility testing must be performed at:
- Acidic pH (approx. 5.5)
- Neutral pH (7.0–7.4)
- Alkaline pH (8.5)
- Any pH yields equivalent results
Correct Answer: Acidic pH (approx. 5.5)
Q17. Concurrent use of which antitubercular drug increases the risk of hepatotoxicity when combined with pyrazinamide?
- Isoniazid
- Ethambutol
- Streptomycin
- Amikacin
Correct Answer: Isoniazid
Q18. Which laboratory tests are most important to monitor during pyrazinamide therapy?
- Liver function tests (ALT/AST) and serum uric acid
- Complete blood count only
- Serum amylase and lipase only
- Thyroid function tests
Correct Answer: Liver function tests (ALT/AST) and serum uric acid
Q19. A mutation that abolishes pyrazinamidase activity will most likely result in which phenotype?
- Pyrazinamide resistance
- Increased pyrazinamide susceptibility
- Cross‑resistance to rifampicin
- Loss of virulence but retained drug susceptibility
Correct Answer: Pyrazinamide resistance
Q20. The gene commonly sequenced to detect pyrazinamide resistance in clinical isolates is:
- pncA
- rpoB
- katG
- embB
Correct Answer: pncA
Q21. Pyrazinamide is structurally most closely related to which compound?
- Nicotinamide (a nicotinamide analog)
- Sulfanilamide
- Aminoglycoside backbone
- Fluoroquinolone scaffold
Correct Answer: Nicotinamide (a nicotinamide analog)
Q22. Dose adjustment of pyrazinamide is necessary in which condition due to impaired metabolite excretion?
- Renal impairment
- Mild seasonal allergies
- Uncomplicated hypertension
- Hyperthyroidism
Correct Answer: Renal impairment
Q23. Which diagnostic approach most directly detects the molecular basis of pyrazinamide resistance?
- Sequencing of the pncA gene
- Acid‑fast stain of sputum
- Serum pyrazinamide levels only
- Chest X‑ray
Correct Answer: Sequencing of the pncA gene
Q24. Inhibition of xanthine oxidase (for example by allopurinol) would be expected to have what effect on pyrazinamide metabolites?
- Decrease formation of 5‑hydroxy‑pyrazinoic acid, potentially raising POA levels
- Increase conversion of PZA to POA in bacteria
- Directly inactivate pyrazinamide
- No effect on pyrazinamide metabolism
Correct Answer: Decrease formation of 5‑hydroxy‑pyrazinoic acid, potentially raising POA levels
Q25. Which clinical statement about pyrazinamide use in pregnancy is most accurate according to current WHO recommendations?
- It is included in standard first‑line TB regimens and may be used in pregnancy
- It is absolutely contraindicated in all trimesters
- It must be replaced by streptomycin in pregnancy
- It is only used after delivery
Correct Answer: It is included in standard first‑line TB regimens and may be used in pregnancy
Q26. Which of the following best explains why pyrazinamide contributes to shortening TB treatment?
- It kills persistent bacilli in acidic lesions that other drugs spare
- It rapidly sterilizes sputum within hours
- It prevents reinfection by boosting immunity
- It acts synergistically with streptomycin only
Correct Answer: It kills persistent bacilli in acidic lesions that other drugs spare
Q27. A patient on pyrazinamide develops asymptomatic hyperuricemia. What is the appropriate management?
- Continue pyrazinamide and monitor; treat only if symptomatic gout occurs
- Immediately stop pyrazinamide permanently
- Start high‑dose corticosteroids
- Replace pyrazinamide with ethambutol without further evaluation
Correct Answer: Continue pyrazinamide and monitor; treat only if symptomatic gout occurs
Q28. Which laboratory susceptibility test condition gives the most reliable pyrazinamide result?
- Low pH medium (e.g., pH 5.5) for pyrazinamide testing
- High salt concentration medium
- Standard neutral pH agar used for other TB drugs
- Liquid culture with pH >7.0 only
Correct Answer: Low pH medium (e.g., pH 5.5) for pyrazinamide testing
Q29. Which adverse effect is an indication to stop pyrazinamide immediately?
- Marked hepatotoxicity with significant ALT/AST elevation and symptoms
- Mild asymptomatic elevation of uric acid only
- Transient mild nausea without liver enzyme rise
- Minor rash without systemic signs
Correct Answer: Marked hepatotoxicity with significant ALT/AST elevation and symptoms
Q30. The presence of a pncA promoter mutation in an M. tuberculosis isolate most likely results in:
- Reduced expression of pyrazinamidase and pyrazinamide resistance
- Increased susceptibility to pyrazinamide
- Rifampicin resistance due to cross‑talk between genes
- No change in drug susceptibility
Correct Answer: Reduced expression of pyrazinamidase and pyrazinamide resistance
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