Lecture on Isoniazid

Jul 23, 2024

Lecture on Isoniazid

Key Points

  • Isoniazid: Most important drug for tuberculosis (TB).
  • Properties: Small molecule; freely soluble in water; passively diffused in mycobacterium.
  • Efficacy: Effective against both intra- and extracellular organisms.
    • Bacteriostatic against resting bacteria.
    • Bactericidal against rapidly dividing organisms.

Mechanism of Action

  • Prodrug: Activated by mycobacterial catalase-peroxidase (CADG).
  • Inhibits Enzymes:
    • Acyl protein carrier reductase (INHA).
    • Acyl protein carrier kinase (KSA).
  • Effect: Disrupts mycolic acid (essential for mycobacterial cell wall) synthesis; bactericidal effect.

Resistance Mechanism

  • Common Mechanisms:
    • Mutation of CADG gene (most common; severe resistance).
    • Associated with ethambutal resistance.
  • Low-Level Resistance:
    • Overexpression of INHA gene.
    • Mutation in KSA gene.

Metabolism and Excretion

  • Metabolized: By liver.
  • Excreted: By kidney.

Uses

  • First-Line Drug: For tuberculosis.
  • Drug of Choice: For latent tubercular infection.
  • Prophylaxis: Of TB.
  • Note: Not effective against Mycobacterium avium complex.
  • Dose:
    • Typical: 5 mg/kg/day or 300 mg once daily.
    • Serious/Malabsorption: Up to 10 mg/kg/day.

Side Effects

  • Neuropsychiatric Symptoms: Memory loss, hallucination, euphoria, epilepsy.
  • Peripheral Neuropathy: Due to inhibition of pyridoxine phosphokinase.
    • More common in slow acetylators.
  • Hepatotoxicity: More common in fast acetylators; exacerbated by rifampicin.
  • Sideroblastic Anemia: Inhibition of delta-ALA synthase; treatable with pyridoxine.
  • Other:
    • Shoulder Hand Syndrome: Arthritis.
    • Refractory Seizures: Treated with intravenous pyridoxine.
    • Hepatotoxicity, gynecomastia.

Treatment of Side Effects

  • Pyridoxine: 10-20 mg/day for adults; 5 mg/day for infants.
    • Improves symptoms of peripheral neuropathy, neuropsychiatric side effects, and anemia.
  • For Seizures: Benzodiazepines and barbiturates are effective; phenytoin is not.

Memorizing Tips

  • Use visuals and mnemonic devices to remember key points and mechanisms.
  • Group related information together for better recall.

Remember: The balance between efficacy against bacteria and side effect management is crucial for optimal use of isoniazid in TB treatment.