Antimycobacterial Drugs

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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.

First-line Anti-TB Drugs: Features & Side Effects

⭐ 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.

WHO-recommended leprosy treatment and resistance timeline

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.

Practice Questions: Antimycobacterial Drugs

Test your understanding with these related questions

A patient with HIV who is currently on antiretroviral therapy consisting of zidovudine, lamivudine, and nevirapine is diagnosed with tuberculosis. Considering potential drug interactions, which of the following TB drugs should be changed in this patient?

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Flashcards: Antimycobacterial Drugs

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Rifampicin _____ once a month + dapsone 100mg daily + clofazimine 300mg once a month and 50 mg daily is used to treat leprosy in adults and children older than 14 years

TAP TO REVEAL ANSWER

Rifampicin _____ once a month + dapsone 100mg daily + clofazimine 300mg once a month and 50 mg daily is used to treat leprosy in adults and children older than 14 years

600mg

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