Basic Profile / Key Facts
Drug Category
- Antitubercular Agents
- Leprostatic Agents
Dosage Forms
Indications
For use in the treatment of pulmonary and extrapulmonary tuberculosis when other antitubercular drugs have failed.
Pharmacology
Ethinamate is bacteriostatic against M. tuberculosis. In a study examining ethionamide resistance, ethionamide administered orally initially decreased the number of culturable Mycobacterium tuberculosis organisms from the lungs of H37Rv infected mice. Drug resistance developed with continued ethionamide monotherapy, but did not occur when mice received ethionamide in combination with streptomycin or isoniazid.
Mechanism of Action
Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Ethionamide, like prothionamide and pyrazinamide, is a nicotinic acid derivative related to isoniazid. It is thought that ethionamide undergoes intracellular modification and acts in a similar fashion to isoniazid. Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
Absorption
Essentially completely absorbed following oral administration and not subjected to any appreciable first pass metabolism. Bioavailability approximately 100%.
Toxicity
Symptoms of overdose include convulsions, nausea, and vomiting.
Biotrnasformation / Drug Metabolism
Hepatic and extensive. Metabolized to the active metabolite sulfoxide, and several inactive metabolites. The sulphoxide metabolite has been demonstrated to have antimicrobial activity against Mycobacterium tuberculosis.
Contraindications
Ethionamide is contraindicated in patients with severe hepatic impairment and in patients who are hypersensitive
to the drug.
Drug Interactions
Trecator has been found to temporarily raise serum concentrations of isoniazid. Trecator may potentiate the
adverse effects of other antituberculous drugs administered concomitantly. In particular, convulsions have been
reported when ethionamide is administered with cycloserine and special care should be taken when the treatment
regimen includes both of these drugs. Excessive ethanol ingestion should be avoided because a psychotic reaction has
been reported.
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