Quick Answer
Anti-tubercular therapy is a high-yield NEET PG pharmacology cluster.
- First-line ATT — Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E); India uses 2HRZE / 4HRE.
- Signature toxicities — H peripheral neuropathy (give pyridoxine); R orange fluids + CYP3A4 induction; Z hyperuricaemia + hepatotox; E optic neuritis + red-green colour loss.
- MDR-TB — resistance to H + R at minimum.
- XDR-TB (2021) — MDR/RR plus fluoroquinolone resistance plus resistance to bedaquiline OR linezolid.
- BPaL / BPaLM — 6-month all-oral regimen for MDR and pre-XDR TB (WHO 2022).
- India — NTEP (renamed from RNTCP in 2020), Nikshay portal, Ni-kshay Poshan Yojana (Rs 500/month DBT), 100 Day Intensified Campaign.
Tuberculosis remains India's biggest infectious-disease killer, with 27 lakh notified cases in 2023 alone — nearly a quarter of the global burden. That volume, combined with 2023-24 policy shifts (BPaL rollout, redefined XDR, dolutegravir compatibility) makes anti-tubercular therapy one of the densest NEET PG pharmacology topics.
This NEETPGAI deep dive walks through first-line and second-line ATT, the drug-by-drug toxicity flashcards examiners love, MDR/XDR treatment shifts under WHO 2022 guidance, TB-HIV interactions and the India-specific NTEP levers you need for AIIMS and INI-CET-style clinical scenarios. Pair this with the antibiotic pharmacology classification guide for the broader antimicrobial framework.
First-line anti-tubercular drugs
The India NTEP intensive phase is 2HRZE (2 months of isoniazid + rifampicin + pyrazinamide + ethambutol) and the continuation phase is 4HRE (4 months of isoniazid + rifampicin + ethambutol — ethambutol was retained in continuation from 2021 as fixed-dose combination policy).
| Drug | Mechanism | Signature toxicity | India / exam pearl |
|---|
| Isoniazid (INH, H) | Inhibits mycolic acid synthesis via KatG activation; blocks InhA | Peripheral neuropathy (pyridoxine depletion), hepatotoxicity, drug-induced SLE, sideroblastic anaemia | Give pyridoxine 10 mg/day to prevent neuropathy in adults; higher (50 mg) in pregnant, diabetic, alcoholic, HIV, malnourished, uraemic |
| Rifampicin (R) | Inhibits bacterial DNA-dependent RNA polymerase (β subunit — rpoB gene mutation → resistance) | Hepatotoxicity, orange discolouration of body fluids, flu-like syndrome, thrombocytopaenia, CYP3A4/P-gp induction | Warn about orange tears staining contact lenses; interacts with OCPs, warfarin, PIs, DOACs |
| Pyrazinamide (Z) | Prodrug — pyrazinamidase (pncA) converts to POA; disrupts membrane transport at acidic pH | Hyperuricaemia (arthralgia — sicca), hepatotoxicity, photosensitivity | Uric acid rise is dose-dependent; use with caution in gout |
| Ethambutol (E) | Inhibits arabinosyl transferase (embB) — mycobacterial cell wall | Dose-dependent optic neuritis, red-green colour blindness, hyperuricaemia | Baseline + monthly visual acuity + Ishihara; avoid in children less than 6 years who cannot report visual changes reliably |
Isoniazid deep dive
- Activated intracellularly by mycobacterial catalase-peroxidase (KatG). katG mutations → INH resistance.
- Peripheral neuropathy risk rises in slow acetylators (NAT2 polymorphism — common in Indians). Pyridoxine prophylaxis blunts this.
- Hepatotoxicity — check baseline LFTs; stop if ALT more than 5x upper limit of normal or symptomatic hepatitis.
Rifampicin deep dive
- CYP3A4 + P-gp induction is the reason DR-TB regimens often shift to rifabutin in HIV.
- Rifampicin reduces the efficacy of oral contraceptives, warfarin, ciclosporin, tacrolimus, most protease inhibitors, DOACs, itraconazole and voriconazole.
- Colours urine, tears, sweat, semen orange — reassure the patient and warn about lens staining.
Ethambutol deep dive
- Optic neuritis presents as bilateral decreased visual acuity with red-green (Ishihara) dyschromatopsia; central or centro-caecal scotoma.
- Reversible if stopped early — permanent if continued.
- Renally excreted — reduce dose in creatinine clearance below 50 mL/min.
Second-line anti-tubercular drugs
Used in drug-resistant TB or when first-line is contraindicated.
| Class | Drug | Toxicity |
|---|
| Fluoroquinolones | Levofloxacin, moxifloxacin | QT prolongation, tendinitis, dysglycaemia; moxifloxacin more QT-prone |
| Second-line injectables | Amikacin, capreomycin, kanamycin | Nephrotoxicity, ototoxicity, hypokalaemia (capreomycin) |
| Oxazolidinones | Linezolid | Myelosuppression, peripheral + optic neuropathy, lactic acidosis, serotonin syndrome |
| Diarylquinoline | Bedaquiline | QT prolongation (monitor ECG); hepatotoxicity |
| Nitroimidazoles | Delamanid, pretomanid | QT prolongation, hepatotoxicity; pretomanid teratogenic in animals |
| Cycloserine / terizidone | | Psychosis, seizures, depression — give pyridoxine |
| Ethionamide / prothionamide | | GI intolerance, hepatotoxicity, hypothyroidism |
| Para-aminosalicylic acid (PAS) | | GI intolerance, hypothyroidism |
| Clofazimine | | Reddish-brown skin discolouration, ichthyosis, QT prolongation |
High-yield exam pattern: three drugs simultaneously prolong QT — bedaquiline, delamanid and moxifloxacin/levofloxacin. When combined, ECG monitoring is mandatory.
MDR-TB and XDR-TB — definitions and treatment
2021 WHO redefinition (critical for NEET PG 2027)
| Category | Definition |
|---|
| Mono-resistant TB | Resistance to one first-line drug only |
| Poly-resistant TB | Resistance to more than one first-line drug, but not both H and R |
| MDR-TB | Resistance to at least H + R |
| Pre-XDR-TB | MDR/RR-TB + resistance to any fluoroquinolone |
| XDR-TB (updated 2021) | MDR/RR-TB + fluoroquinolone resistance + resistance to bedaquiline OR linezolid |
| RR-TB | Rifampicin resistance (with or without other drug resistance) |
The 2021 XDR redefinition dropped injectable second-line resistance from the definition because injectables are no longer the backbone of DR-TB therapy — bedaquiline and linezolid are.
BPaL and BPaLM — the 2022 shift
WHO 2022 endorsed a 6-month, all-oral regimen for MDR-TB and pre-XDR-TB:
- BPaL — Bedaquiline + Pretomanid + Linezolid × 6 months (with the option to extend to 9 months).
- BPaLM — BPaL + Moxifloxacin, preferred when fluoroquinolone susceptibility is retained.
Backed by the TB-PRACTECAL and ZeNix trials — cure rates over 89 percent, replacing 18-24 month injectable-based regimens.
India's NTEP is scaling BPaL through Programmatic Management of Drug-Resistant TB (PMDT) sites, with active drug safety monitoring for linezolid neuropathy and bedaquiline QT.
Long conventional MDR regimen (still used when BPaL contraindicated)
Individualised 18-20 month regimen built around bedaquiline, linezolid, levofloxacin/moxifloxacin, clofazimine and cycloserine.
Special situations
Pediatric TB
- Weight-band dosing per WHO 2022 tables; India NTEP uses paediatric dispersible FDCs.
- Ethambutol contraindicated below 6 years (some guidelines allow with careful monitoring).
- Streptomycin avoided as ototoxicity is silent in infants.
Extrapulmonary TB
| Site | Notes |
|---|
| TB lymphadenitis | Most common EPTB in India; FNAC + Xpert MTB/RIF; 6 months ATT |
| TB meningitis (TBM) | 12 months ATT + adjunctive steroids (dexamethasone tapering over 6-8 weeks) |
| Spinal TB (Pott disease) | Thoracic > lumbar; gibbus deformity; 12 months ATT; surgery only for cord compression or instability |
| Genitourinary TB | Sterile pyuria; painless haematuria; classic on IVP with cortical scars |
| Abdominal TB | Wet, dry and fibrotic forms; ascites with high protein and low SAAG |
TB-HIV co-infection
- Rifampicin induces CYP3A4 — reduces PIs and NNRTIs.
- Use rifabutin (weaker CYP3A4 inducer) with PI-based ART.
- Dolutegravir + rifampicin → double DTG to 50 mg BD; TLD (tenofovir + lamivudine + dolutegravir) is India NACO's 2020 first-line ART and is compatible using this adjustment.
- IRIS (immune reconstitution inflammatory syndrome) may worsen TB signs after ART start; do not stop ART unless life-threatening.
- Start ATT first, then ART within 2 weeks if CD4 less than 50 and by 8 weeks otherwise; for TBM, delay ART by 8 weeks to reduce IRIS mortality.
Review the HIV/AIDS management guide for full ART sequencing.
Latent TB infection (LTBI)
- Screen high-risk (HIV, contacts of pulmonary TB, dialysis, anti-TNF candidates) with Mantoux (TST) or IGRA.
- Preferred regimens — 3HP (rifapentine + isoniazid weekly × 12 doses) or 4R (rifampicin daily × 4 months) or 6H / 9H (isoniazid alone).
- India NTEP prioritises household contacts of a pulmonary TB index and PLHIV.
TB in pregnancy
- HRZE is safe. Streptomycin is contraindicated (VIII cranial nerve fetal ototoxicity).
- Second-line drugs — bedaquiline and delamanid have limited data; use only when benefit clear.
NEET PG MCQ traps
- Isoniazid + pyridoxine — always given together; ask why in slow acetylators, DM, HIV, alcoholics, uraemia, pregnancy.
- Rifampicin orange body fluids — reassure, not toxicity.
- Rifampicin + OCP failure — CYP3A4 induction; counsel alternative contraception.
- Ethambutol — red-green colour vision loss; avoid under 6 years.
- Pyrazinamide + hyperuricaemia — asymptomatic urate rise common; frank gout uncommon.
- Streptomycin — CN VIII toxicity, contraindicated in pregnancy.
- Bedaquiline — QT prolongation; monitor ECG at baseline, 2, 12 and 24 weeks.
- Linezolid — myelosuppression and peripheral neuropathy; mitochondrial toxicity mechanism.
- Cycloserine — psychosis, seizures; give pyridoxine.
- Ethionamide — hypothyroidism; check TSH.
- MDR-TB — H + R resistance minimum.
- XDR-TB (2021) — add fluoroquinolone resistance + bedaquiline OR linezolid resistance.
- BPaL / BPaLM — 6 months oral; WHO 2022 endorsement.
- Rifabutin — replaces rifampicin in HIV with PI-based ART.
- Dolutegravir + rifampicin — double DTG dose.
- TBM — 12 months ATT + dexamethasone.
- Ni-kshay Poshan Yojana — Rs 500/month DBT for notified TB patients.
- 3HP — rifapentine + INH weekly × 12; preferred LTBI regimen in adults.
- RNTCP → NTEP — renamed in 2020, "elimination" target 2025 (from SDG 2030).
- 99DOTS — missed-call verification adherence tool.
Recent updates and India context
- NTEP (National TB Elimination Programme) — renamed from RNTCP in 2020 with the goal of eliminating TB by 2025, five years ahead of the SDG target. FY 2023 recorded 27 lakh notifications, the highest ever.
- Nikshay portal — mandatory case notification for public and private sector; drives Ni-kshay Poshan Yojana Rs 500/month DBT (nutritional support), Ni-kshay 2.0 for community engagement, and the Ni-kshay Mitra donor programme.
- BPaL rollout — being scaled across PMDT centres in India from 2023; replaces the older Bangladesh regimen and shorter injectable-containing MDR regimens.
- 100 Day Intensified TB Elimination Campaign — launched December 2024 in 347 high-burden districts using door-to-door screening, CY-TB and Xpert Ultra rapid molecular diagnostics.
- Universal DST — every notified case is now offered rapid molecular DST (Xpert MTB/RIF or Truenat) at NTEP labs.
- CY-TB (Cy-Tb) — the new IGRA-alternative TST antigen introduced in 2023 for LTBI screening.
- Digital adherence — 99DOTS (missed-call verification), MERM (medication event reminder monitors), and video-observed therapy replacing thrice-weekly community DOTS for select cohorts.
- Private sector engagement — Joint Effort for Elimination of TB (JEET) and STEPS provide free NTEP drugs and diagnostics to patients in private care, addressing India's 50 percent private-sector diagnostic burden.
- TB Preventive Therapy (TPT) expansion — WHO 2020 guidance expanded LTBI treatment to household contacts of any age; India NTEP rolled 3HP out in 2022.
Frequently asked questions
What is the difference between MDR-TB, pre-XDR-TB and XDR-TB?
MDR-TB is resistance to at least isoniazid plus rifampicin — the two most powerful first-line drugs. Pre-XDR-TB is MDR-TB with additional resistance to any fluoroquinolone (levofloxacin or moxifloxacin). XDR-TB, per the updated 2021 WHO definition, is MDR or rifampicin-resistant TB with additional resistance to any fluoroquinolone AND at least one of bedaquiline or linezolid — reflecting the shift from injectables to newer oral agents. Recognising the distinction is critical because BPaL-based regimens now cover MDR and pre-XDR, while true XDR needs individualised salvage therapy.
What is the BPaL regimen and why is it a game-changer for MDR-TB?
BPaL is a 6-month, all-oral, three-drug regimen of Bedaquiline plus Pretomanid plus Linezolid endorsed by the WHO in 2022 for MDR-TB, pre-XDR-TB and treatment-intolerant rifampicin-resistant TB. It replaces the older 18-24 month injectable-containing regimens with cure rates over 89 percent in trials (ZeNix, TB-PRACTECAL). The BPaLM variant adds moxifloxacin. India's NTEP is rolling out BPaL through PMDT sites, transforming DR-TB from a two-year ordeal into a 6-month oral course.
Which first-line ATT drug causes optic neuritis and how do you monitor?
Ethambutol causes dose-dependent optic neuritis presenting as decreased visual acuity and red-green colour blindness (Ishihara plate defects). It is contraindicated in children younger than 6 years because they cannot reliably report visual changes. Baseline visual acuity plus red-green colour vision testing must be documented before starting ethambutol in any age group, with monthly monitoring. The toxicity is usually reversible if the drug is stopped promptly. Dose adjustment is essential in renal impairment because ethambutol is renally excreted.
Why does rifampicin cause drug interactions in HIV co-infection?
Rifampicin is a potent inducer of CYP3A4 and P-glycoprotein, dramatically reducing serum levels of protease inhibitors and non-nucleoside reverse transcriptase inhibitors — the backbones of many older ART regimens. This can cause virological failure. In TB-HIV co-infection, rifabutin is preferred over rifampicin with PI-based ART because it is a weaker CYP3A4 inducer. Dolutegravir tolerates concomitant rifampicin if the dolutegravir dose is doubled to 50 mg twice daily. India's NACO TLD regimen (tenofovir + lamivudine + dolutegravir) is broadly compatible with rifampicin using this dose adjustment.
What is the Nikshay portal and how does India digitally track TB patients?
Nikshay is India's web-based case notification and monitoring system for TB, mandatory for both public and private-sector providers under the Notification of TB rules. It tracks diagnosis, treatment initiation, drug regimen, adherence, follow-up sputum results and outcome. The Ni-kshay Poshan Yojana provides Rs 500 per month direct benefit transfer for nutritional support to every notified TB patient during treatment. Digital adherence tools like 99DOTS (missed-call verification), MERM (medication event reminder monitors), and video-observed therapy have replaced the older thrice-weekly DOTS model at Anganwadi centres for many patient cohorts.
This content is for educational purposes for NEET PG exam preparation. It is not a substitute for professional medical advice, diagnosis, or treatment. Clinical information has been reviewed by qualified medical professionals.
Written by: NEETPGAI Editorial Team
Reviewed by: Pending SME Review
Last reviewed: July 2026
