Drugs Used In Tuberculosis

First-Line Antimycobacterial Drugs

Members: Isoniazid (INH), rifampin, pyrazinamide, ethambutol, and streptomycin are the five first-line agents for treatment of tuberculosis. INH and rifampin are the two most active drugs.

Isoniazid (INH)

INH is the most active drug for the treatment of tuberculosis caused by susceptible strains. It is structurally similar to pyridoxine. It is bactericidal for actively growing tubercle bacilli. INH is able to penetrate into phagocytic cells and thus is active against both extracellular and intracellular organisms.

INH inhibits synthesis of mycolic acids, which are essential components of mycobacterial cell walls.

INH is readily absorbed from the gastrointestinal tract, and it diffuses readily into all body fluids and tissues. Metabolism of INH, especially acetylation by liver N-acetyltransferase, is genetically determined. INH metabolites and a small amount of unchanged drug are excreted mainly in the urine. The dose need be adjusted in severe hepatic insufficiency.

Clinical Uses: Used in the treatment and prevention of tuberculosis.

Adverse Reactions: The incidence and severity of untoward reactions to INH are related to dosage and duration of administration. INH-induced hepatitis is the most frequent major toxic effect and the risk of hepatitis greater in old age, alcoholics and possibly during pregnancy and the post-partum period.

Peripheral neuropathy is more likely to occur in slow acetylators and patients with predisposing conditions such as malnutrition, alcoholism, diabetes, AIDS, and uremia. Neuropathy is due to a relative pyridoxine deficiency. INH promotes excretion of pyridoxine, and this toxicity is readily reversed or can be prevented by administration of pyridoxine. CNS system toxicity, which is less common, includes memory loss, psychosis, and seizures, and may also respond to pyridoxine.