First-line Drugs Act on Different Targets of Mycobacterium

🟢 Lite — Quick Review (1h–1d)

Rapid summary for last-minute revision before your INI CET exam.

Chemotherapy of microbial infections is the largest Pharmacology block in INI CET, dominated by anti-tuberculosis therapy under RNTCP guidelines. The Category I regimen is 2 HRZE / 4 HR (2 months isoniazid + rifampicin + pyrazinamide + ethambutol, then 4 months HR), while Category II (relapse/failure) adds streptomycin: 2 HRZES / 1 HRZE / 5 HRE.

INH inhibits mycolic acid synthesis via a KatG-activated INH-NAD adduct; co-prescribe pyridoxine (B6) to prevent peripheral neuropathy.
Rifampicin inhibits DNA-dependent RNA polymerase and is a potent CYP3A4 inducer — it lowers OCP, warfarin, and protease-inhibitor levels.
P. vivax/ovale radical cure needs chloroquine + primaquine 14 days; screen for G6PD deficiency before primaquine.
Severe malaria: IV artesunate; chloroquine-resistant P. falciparum uses ACT (artesunate-based combination therapy).

Drug	Key toxicity
Isoniazid	Hepatotoxicity, peripheral neuropathy, sideroblastic anaemia
Rifampicin	Orange body fluids, CYP induction, hepatotoxicity
Pyrazinamide	Hyperuricaemia (gout), hepatotoxicity
Ethambutol	Optic neuritis, red-green colour blindness
Streptomycin	Ototoxicity, nephrotoxicity

🟡 Standard — Regular Study (2d–2mo)

Standard content for students with a few days to months.

Anti-tuberculosis regimens (RNTCP)

First-line drugs act on different targets of Mycobacterium tuberculosis. INH is a prodrug activated by KatG to form an adduct with NAD that blocks InhA (enoyl-ACP reductase), halting mycolic acid synthesis. Rifampicin binds the β-subunit of DNA-dependent RNA polymerase, blocking transcription. Pyrazinamide requires PncA-mediated conversion to pyrazinoic acid, which acidifies and disrupts membrane energetics in acidic phagolysosomes — explaining its unique activity against semi-dormant bacilli. Ethambutol inhibits arabinosyl transferase, blocking arabinogalactan cell-wall assembly.

RNTCP Category	Intensive phase	Continuation phase	Indication
Cat I (new)	2 HRZE	4 HR	New sputum-positive PTB
Cat II (retreatment)	2 HRZES + 1 HRZE	5 HRE	Relapse, failure, or default
Cat IV (MDR-TB)	6–9 months (kanamycin, levofloxacin, ethionamide, cycloserine, PAS)	18 months	MDR-TB

Antimalarial agents

Chloroquine-sensitive P. vivax/ovale: chloroquine for acute attack + primaquine 14 days for radical cure of hepatic hypnozoites.
Chloroquine-resistant P. falciparum: ACT — artesunate + sulfadoxine-pyrimethamine (AS+SP) or artemether-lumefantrine.
Severe/complicated malaria: IV artesunate 2.4 mg/kg at 0, 12, 24 h, then daily.
Primaquine contraindication: G6PD deficiency (screening mandatory) — causes oxidative haemolysis.

HIV / HAART

INI CET frequently tests first-line regimens. NNRTI-based zidovudine + lamivudine + nevirapine is standard; ritonavir-boosted lopinavir is the PI alternative. Zidovudine causes anaemia and myopathy; stavudine causes peripheral neuropathy and lipodystrophy; abacavir risks hypersensitivity in HLA-B*57:01 carriers.

Common interaction traps

Rifampicin induces CYP3A4 → OCP failure, warfarin resistance, subtherapeutic protease inhibitors.
INH inhibits CYP2C19/CYP3A4 and is synergistic with carbamazepine hepatotoxicity.
Pyrazinamide + allopurinol: antagonism; PZA raises uric acid but is not treated.

🔴 Extended — Deep Study (3mo+)

Comprehensive coverage for students on a longer study timeline.

Leprosy (MDT) and antileprotic drugs

WHO multidrug therapy prevents dapsone resistance. Multibacillary leprosy (≥6 lesions, BI positive): rifampicin 600 mg monthly + dapsone 100 mg daily + clofazimine 300 mg monthly + clofazimine 50 mg daily for 12 months. Paucibacillary (single-lesion PB): single-dose ROM (rifampicin + ofloxacin + minocycline) is an alternative. Clofazimine is only added in multibacillary regimens — a classic MCQ trap. Dapsone causes methaemoglobinaemia, sulfone syndrome (fever, exfoliative dermatitis, lymphadenopathy), and G6PD-mediated haemolysis.

MDR-TB and XDR-TB

MDR-TB = resistance to at least INH + rifampicin. XDR-TB adds fluoroquinolone and one inject-able (amikacin/kanamycin/capreomycin). Cat IV uses 6–8 drugs including bedaquiline (ATP synthase inhibitor — QT prolongation), delamanid, linezolid, and carbapenems with clavulanate. INI CET has asked about bedaquiline’s MOA (mycobacterial F-ATP synthase) and its black-box QT warning.

Dosing calculations frequently tested

CrCl (Cockcroft-Gault) for aminoglycoside dosing: CrCl = [(140 − age) × weight] / (72 × SCr) × 0.85 (females). Aminoglycosides and vancomycin require renal adjustment.
Loading dose when Vd is large or urgent effect needed: LD = Vd × target Cp × weight.
Anion gap metabolic acidosis (AG = Na⁺ + K⁺ − Cl⁻ − HCO₃⁻, normal 8–12) — seen in INH overdose due to lactic acidosis and seizures; treat with pyridoxine and haemodialysis.

Common mistakes and clinical pearls

Confusing primaquine’s role — it has no schizonticidal action against P. falciparum; it is solely for hypnozoite eradication in vivax/ovale.
Believing ethambutol causes peripheral neuropathy (it causes optic neuritis).
Forgetting pyridoxine 10 mg daily with INH in pregnancy, diabetes, alcoholism, and chronic kidney disease.
Assuming rifampicin is bacteriostatic — it is bactericidal and given as intermittent supervised doses (DOTS) to ensure compliance.

Practice prompts:

A 32-year-old pregnant woman on Category I DOTS develops tingling in her feet. Which prophylactic vitamin was omitted, and at what dose?
A G6PD-deficient man returns with relapsing P. vivax. Why is primaquine contraindicated, and what alternative prevents relapse?

Continue your study

View this topic in your INI CET (AIIMS PG) roadmap — see where “Topic 5” fits in your personalised plan
Build a quick revision plan — 1-day sprint covering highest-weight topics
INI CET (AIIMS PG) exam overview — pattern, eligibility, and syllabus
All Pharmacology notes — browse sibling topics in this subject

Content adapted based on your selected roadmap duration. Switch tiers using the selector above.

First-line Drugs Act on Different Targets of Mycobacterium