Pharmacology of Antitubercular Agents

Pharmacology of Antitubercular Agents explains mechanisms and actions of drugs used to kill or inhibit Mycobacterium tuberculosis.

Pharmacology of Antitubercular Agents

• Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis.
• Effective treatment requires a prolonged, multi-drug regimen to achieve the following goals:
• Prevent resistance
• Ensure complete eradication of the bacteria
• Treat both active and latent bacilli (intracellular and extracellular)

First-Line Antitubercular Drugs (HRZE)

• These are the standard drugs used for the treatment of tuberculosis and form the cornerstone of therapy.
• They are effective against both active and latent tuberculosis.

1. Isoniazid (INH)

   • Mechanism of Action: Inhibits mycolic acid synthesis in the bacterial cell wall.
   • Adverse Effects: Hepatotoxicity, peripheral neuropathy, hemolysis in G6PD deficiency.

2. Rifampicin

   • Mechanism of Action: Inhibits DNA-dependent RNA polymerase, blocking RNA synthesis.
   • Adverse Effects: Hepatotoxicity, orange discoloration of body fluids, enzyme induction.

3. Pyrazinamide

   • Mechanism of Action: Disrupts mycobacterial membrane metabolism (exact mechanism unclear).
   • Adverse Effects: Hepatotoxicity, hyperuricemia (may cause gout).

4. Ethambutol

   • Mechanism of Action: Inhibits arabinosyl transferase, reducing cell wall synthesis.
   • Adverse Effects: Optic neuritis, reduced visual acuity, red-green color blindness.

Second-Line Antitubercular Drugs

• These drugs are typically used when first-line drugs are ineffective, such as in multidrug-resistant (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB).

1. Streptomycin

   • Mechanism of Action: Aminoglycoside antibiotic that inhibits protein synthesis by binding to bacterial ribosomes.

2. Ethionamide

   • Mechanism of Action: Inhibits mycolic acid synthesis by interfering with the fatty acid synthase II complex.

3. Cycloserine

   • Mechanism of Action: Inhibits cell wall synthesis by blocking the incorporation of D-alanine into peptidoglycan.

4. Para-aminosalicylic acid (PAS)

   • Mechanism of Action: Interferes with folic acid metabolism, inhibiting bacterial growth.

5. Fluoroquinolones (e.g., levofloxacin)

   • Mechanism of Action: Inhibits bacterial DNA gyrase and topoisomerase IV, interfering with DNA replication and transcription.

Fixed-Dose Combination (FDC) Therapy

• Purpose: FDC therapy is used to improve patient adherence to treatment and reduce the risk of drug resistance
• Example: HRZE in a single tablet (commonly used in the DOTS – Directly Observed Treatment, Short-course program)

Click Here to Watch the Best Pharma Videos