A concise pharmacology guide for medical students and exam preparation
Tuberculosis (TB) remains one of the most studied and tested topics in pharmacology. Whether you’re preparing for medical exams or brushing up on clinical knowledge, understanding how anti-TB drugs work and where they fail is essential. This guide breaks it all down clearly, from drug classification to treatment protocols.
Watch this video for a visual explanation:
First-Line Anti-TB Drugs (HRZES)
The classic first-line drugs are remembered by the acronym HRZES: Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E), and Streptomycin (S). However, Streptomycin is no longer considered a true first-line agent in current guidelines, it has been moved to the second-line category. It is still included here for comparative and exam purposes.
| Property | Isoniazid (H) | Rifampicin (R) | Pyrazinamide (Z) | Ethambutol (E) | Streptomycin (S) |
| Action | Bactericidal | Bactericidal | Bactericidal | Bacteriostatic | Bactericidal |
| Targets | Both | Both | Intracellular only | Both | Extracellular only |
| Hepatotoxic? | Yes | Yes | Yes (maximum) | No | No |
| Safe in pregnancy? | Yes | Yes | Avoided | Yes | Contraindicated |
| Key side effect | Peripheral neuropathy | Orange urine | Hyperuricemia / Gout | Optic neuritis / Red-green color blindness | Nephrotoxic, Ototoxic, Neuromuscular blockade |
A few key points worth memorizing:
- Ethambutol is the only bacteriostatic drug among the first-line agents. All others are bactericidal.
- Pyrazinamide is uniquely effective only against intracellular bacteria, while Streptomycin works only extracellularly. The remaining three target both.
- Isoniazid, Rifampicin, and Pyrazinamide are all hepatotoxic. Pyrazinamide carries the highest risk of liver damage.
- Streptomycin is an aminoglycoside and is absolutely contraindicated in pregnancy — it causes irreversible hearing loss in the baby.
- Ethambutol causes optic neuritis, leading to visual disturbances and specifically red-green color blindness.
- Pyrazinamide can precipitate gout by raising uric acid levels (hyperuricemia).
Isoniazid (INH) — In Depth
Mechanism: Isoniazid is a prodrug, it is inactive on its own. It gets activated by a bacterial enzyme called catalase-peroxidase, after which it inhibits mycolic acid synthesis, a critical component of the mycobacterial cell wall.
Side effects: The name INH is a helpful mnemonic, it Injures Nerves and Hepatic tissue. This means peripheral neuropathy and hepatotoxicity are the two main concerns.
The peripheral neuropathy arises from Vitamin B6 (pyridoxine) deficiency caused by isoniazid. B6 supplementation is often given alongside it to prevent this. Isoniazid is also metabolized via acetylation, classifying it as a SHIP drug (Sulfonamides, Hydralazine, Isoniazid, Procainamide), drugs associated with drug-induced lupus (SLE) as a rare side effect.
Rifampicin (R) — In Depth
Mechanism: Rifampicin inhibits bacterial RNA polymerase by binding to its beta subunit, blocking transcription, the process by which DNA is read to form RNA.
Side effects: The most recognizable is orange discoloration of body secretions, especially urine (also affects sweat, tears, and saliva). More importantly, Rifampicin is a potent enzyme inducer. It speeds up the metabolism of many other drugs, making them less effective, classic examples include warfarin (may need to be switched to heparin) and oral contraceptive pills, where increased estrogen metabolism can lead to contraceptive failure.
Two more exam-worthy points: Rifampicin is safe in renal failure and requires no dose adjustment (R for Rifampicin, R for Renal safe). It must also always be taken on an empty stomach, since food significantly interferes with absorption.
Second-Line Anti-TB Drugs
Second-line drugs fall into four main groups:
1. Bactericidal — Fluoroquinolones Ofloxacin, Levofloxacin, Moxifloxacin, and Gatifloxacin. Mnemonic: “Oh My God”, Ofloxacin, Moxifloxacin, Gatifloxacin.
2. Bactericidal — Injectables Capreomycin, Kanamycin, Amikacin, and Streptomycin (reclassified here). Being aminoglycosides, they share the same class side effects: nephrotoxicity, ototoxicity, and neuromuscular blockade.
3. Bacteriostatic — Oral Agents Ethionamide, Cycloserine, PAS (para-aminosalicylic acid), and Thioacetazone. Key points to remember: Ethionamide causes hypothyroidism and is also hepatotoxic. Cycloserine, “cyclo = psycho” can cause psychosis. PAS can also cause hypothyroidism. Thioacetazone is contraindicated in HIV patients and is largely no longer in routine use.
4. Repurposed Drugs Now Approved for TB Two drugs originally used for other conditions are now formally approved for TB: Linezolid (originally for MRSA) main side effect is peripheral neuropathy. Clofazimine (originally for leprosy) causes skin dryness and pigmentation.
New Drugs Specifically Approved for TB
Three newer agents have been developed for drug-resistant TB:
Bedaquiline inhibits mycobacterial ATP synthase, cutting off the bacteria’s energy supply. Mnemonic: the bacteria is so exhausted it has to lie in bed bedaquiline.
Delamanid and Pteromalid both contain “manid” in their names. They are mycolic acid synthesis inhibitors, binding to a different site than isoniazid but achieving the same outcome disrupting the mycobacterial cell wall.
TB Treatment Regimens
Drug-Sensitive TB — Standard 6-Month Regimen
All patients regardless of age, disease severity, or site (pulmonary or extrapulmonary), follow the same regimen: 2 months of HRZE (4 drugs) followed by 4 months of HR (2 drugs). This 2+4 structure is the global standard for drug-sensitive TB.
Drug-Resistant TB — Classification
| Classification | Definition |
| MDR-TB | Resistant to both Isoniazid (H) and Rifampicin (R) |
| Pre-XDR-TB | MDR-TB + resistance to any Fluoroquinolone |
| XDR-TB | Pre-XDR-TB + resistance to Bedaquiline or Linezolid |
XDR stands for Extensively Drug-Resistant (not “extreme”). Knowing this distinction, and the stepwise definition of each tier, is frequently tested.
Conclusion
Understanding anti-tubercular drugs, first-line, second-line, and newer agents is key for safe treatment and exam preparation. Grasping mechanisms, major side effects, and resistance patterns like MDR and XDR TB ensures rational therapy and better clinical outcomes.