10. ANTI-TUBERCULAR AGENTS

Anti-tubercular agents are drugs used to treat tuberculosis (TB), a serious infectious disease caused by Mycobacterium tuberculosis. These bacteria grow slowly and have a thick, lipid-rich cell wall, making them naturally resistant to many antibiotics. Therefore, TB treatment requires multiple drugs taken for long durations.

Introduction

Tuberculosis mainly affects the lungs but can also involve the kidneys, bones, meninges, and lymph nodes. Because of its ability to develop resistance quickly, TB must be treated with drug combinations to achieve cure and prevent relapse or drug-resistant strains.

Classification of Anti-Tubercular Agents

1. First-Line Drugs (Primary Drugs)

  • Isoniazid (INH)
  • Rifampicin
  • Pyrazinamide
  • Ethambutol
  • Streptomycin

These drugs form the backbone of standard TB therapy due to high efficacy and acceptable safety.

2. Second-Line Drugs

  • Ethionamide
  • Cycloserine
  • Capreomycin
  • Kanamycin / Amikacin
  • Para-aminosalicylic acid (PAS)

3. Newer Drugs

  • Bedaquiline
  • Delamanid
  • Pretomanid

Drug Profiles

Isoniazid (INH)

  • Mechanism: Inhibits mycolic acid synthesis, an essential component of TB cell wall.
  • Use: Most potent first-line drug; used for active TB and prophylaxis.
  • Adverse effects: Hepatitis, peripheral neuropathy (prevented with pyridoxine).

Ethionamide

  • Structural analog of INH.
  • Mechanism: Inhibits mycolic acid synthesis.
  • Use: Second-line agent for drug-resistant TB.
  • Side effects: GI upset, hepatotoxicity.

Ethambutol

  • Mechanism: Inhibits arabinosyl transferase, blocking cell wall synthesis.
  • Use: Given in combination to prevent resistance.
  • Adverse effect: Optic neuritis (loss of red-green color vision).

Pyrazinamide

  • Mechanism: Converted to pyrazinoic acid; works best in acidic environments inside macrophages.
  • Use: Very effective in early treatment phases.
  • Side effects: Hepatotoxicity, hyperuricemia.

Para-Amino Salicylic Acid (PAS)

  • Mechanism: Folate synthesis inhibitor (similar to sulfonamides).
  • Use: Second-line drug for multidrug-resistant TB.

Anti-Tubercular Antibiotics

Rifampicin

  • Mechanism: Inhibits DNA-dependent RNA polymerase, blocking mRNA synthesis.
  • Spectrum: Mycobacteria, Gram-positive bacteria, some Gram-negative organisms.
  • Side effects: Hepatitis, red-orange discoloration of body fluids, drug interactions (enzyme inducer).

Rifabutin

  • Similar to rifampicin but longer half-life.
  • Preferred in HIV patients due to fewer drug interactions.

Cycloserine

  • Mechanism: Inhibits cell wall synthesis by blocking alanine incorporation.
  • Use: MDR-TB cases.
  • Side effects: CNS toxicity (seizures, psychosis).

Streptomycin

  • Mechanism: Aminoglycoside antibiotic; inhibits protein synthesis.
  • Use: Severe TB cases and resistant infections.
  • Side effects: Ototoxicity and nephrotoxicity.

Capreomycin

  • Peptide antibiotic used in drug-resistant TB.
  • Side effects: Similar to aminoglycosides (ototoxicity).

Mechanism of Action Summary

  • Cell wall inhibition: Isoniazid, Ethionamide, Ethambutol
  • RNA synthesis inhibition: Rifampicin, Rifabutin
  • Protein synthesis inhibition: Streptomycin, Capreomycin, Cycloserine
  • Intracellular action in acidic environment: Pyrazinamide
  • Folate pathway inhibition: PAS

Standard Treatment Strategy

1. Intensive Phase (First 2 Months)

  • INH + Rifampicin + Pyrazinamide + Ethambutol

2. Continuation Phase (Next 4 Months)

  • INH + Rifampicin

This 6-month regimen is widely used and highly effective for drug-sensitive TB.

Adverse Effects of Anti-TB Drugs

  • Hepatotoxicity: INH, Rifampicin, Pyrazinamide
  • Peripheral neuropathy: INH
  • Optic neuritis: Ethambutol
  • Ototoxicity: Streptomycin, Capreomycin

Detailed Notes:

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