Antimycobacterial Drugs

First-Line Anti-TB Drugs - TB Titans

📌 Mnemonic: RIPE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol).

• Isoniazid (H)

  • MOA: Inhibits mycolic acid synthesis (KatG activation).
  • ADRs: Peripheral neuropathy (give Pyridoxine B6 10-25mg), hepatotoxicity, drug-induced lupus.
  • Bactericidal. Monitor LFTs.

• Rifampicin (R)

  • MOA: Inhibits DNA-dependent RNA polymerase.
  • ADRs: Orange-red body fluids, hepatotoxicity, flu-like syndrome, potent CYP450 inducer.
  • Bactericidal.

• Pyrazinamide (Z)

  • MOA: Disrupts cell membrane (pncA activation); active in acidic pH (macrophages).
  • ADRs: Hepatotoxicity (most hepatotoxic, dose-dependent), hyperuricemia (gout), arthralgia.
  • Bactericidal. Monitor LFTs, uric acid.

• Ethambutol (E)

  • MOA: Inhibits arabinosyl transferase (cell wall).
  • ADRs: Optic neuritis (↓visual acuity, red-green color blindness), hyperuricemia.
  • Bacteriostatic. Monitor vision. Renal dose adjustment.

⭐ Ethambutol causes dose-dependent optic neuritis (retrobulbar); monitor visual acuity and color vision regularly.

Second-Line Anti-TB Drugs - Backup Brigade

For MDR/XDR-TB or first-line intolerance. Less effective, more toxic.

• Injectables (Aminoglycosides/Polypeptides):
  • Amikacin (Amk), Kanamycin (Km), Capreomycin (Cm)
  • ADRs: Ototoxic, Nephrotoxic ⚠️ Monitor.
• Fluoroquinolones (FQs):
  • Levofloxacin (Lfx), Moxifloxacin (Mfx)
  • ADRs: Tendinopathy, CNS effects, QT prolongation (Mfx).
• Oral Bacteriostatic Agents:
  • Cycloserine (Cs):
    • ADRs: CNS toxicity (psychosis, seizures 📌 Psycho-serine), neuropathy. Give Pyridoxine.
  • Ethionamide (Eto):
    • ADRs: GI upset, hepatotoxic, hypothyroidism.
  • PAS (Para-aminosalicylic acid):
    • ADRs: GI upset, hypersensitivity, goitrogenic.
• Newer/Repurposed Drugs:
  • Bedaquiline (Bdq):
    • ADRs: QT prolongation (⚠️ BBW), hepatotoxic.
  • Delamanid (Dlm):
    • ADRs: QT prolongation.
  • Linezolid (Lzd):
    • ADRs: Myelosuppression, neuropathy (long use > 28 days).

⭐ Bedaquiline & Delamanid are vital for MDR-TB, but watch for QT prolongation.

Anti-Leprosy Drugs - Hansen's Helpers

• Key Drugs (📌 RDC: Rifampicin, Dapsone, Clofazimine):
  • Dapsone: Folate antagonist. SE: Hemolysis (G6PD def.), agranulocytosis.
  • Rifampicin: RNA pol inhibitor. SE: Hepatotoxicity, orange-red urine.
  • Clofazimine: Phenazine dye; DNA binding. SE: Skin pigmentation (red-brown), GI upset.
• Multidrug Therapy (MDT) - WHO Regimens:
  • Paucibacillary (PB): 2 drugs (Rifampicin + Dapsone) for 6 months.
  • Multibacillary (MB): 3 drugs (Rifampicin + Dapsone + Clofazimine) for 12 months.
• Lepra Reactions & Management:
  • Type 1 (Reversal Reaction): Corticosteroids.
  • Type 2 (Erythema Nodosum Leprosum - ENL): Thalidomide (⚠️ teratogenic), Corticosteroids, Clofazimine.

⭐ Dapsone hypersensitivity syndrome (DHS): severe reaction (2-8 weeks post-start), fever, rash, systemic involvement.

TB Drug Regimens & Special Populations - TB Treatment Tactics

• Standard Regimen (New, Drug-Sensitive):
  • Intensive Phase (IP): 2 months HRZE.
  • Continuation Phase (CP): 4 months HRE (or HR).
• Special Populations - Key Adjustments:
  • Pregnancy: Avoid Streptomycin (fetal ototoxicity). HRZE safe. Add Pyridoxine (B6).
  • HIV Co-infection: Rifabutin preferred with PIs/NNRTIs to ↓interactions.
  • Renal Impairment: Modify Ethambutol, Pyrazinamide, Streptomycin doses.
• Drug-Resistant TB (DR-TB): Requires specialized, longer regimens (e.g., Bedaquiline, Linezolid, Pretomanid).

⭐ In pregnancy, Streptomycin is contraindicated (fetal ototoxicity). Standard HRZE is safe; always supplement Isoniazid with Pyridoxine (B6) to prevent neuropathy.

High‑Yield Points - ⚡ Biggest Takeaways

• Rifampicin: RNA polymerase inhibitor; orange-red body fluids; potent CYP450 inducer.
• Isoniazid (INH): Mycolic acid synthesis inhibitor; peripheral neuropathy (prevent with B6), hepatotoxicity.
• Pyrazinamide (PZA): Active in acidic pH (macrophages); hyperuricemia, hepatotoxicity.
• Ethambutol: Optic neuritis (red-green color blindness); check visual acuity.
• Streptomycin: Aminoglycoside; ototoxicity, nephrotoxicity; contraindicated in pregnancy.
• MDR-TB: Resistance to at least Isoniazid and Rifampicin.
• Leprosy drugs: Dapsone (G6PD hemolysis), Clofazimine (pigmentation), Rifampicin.