ethionamide

Action and Spectrum

Actions and spectrum: 

Ethionamide disrupts the production of mycolic acids in Mycobacterium tuberculosis which are essential for the bacterial cell wall structural integrity. This disrupt the synthesis of acids, leading to bacterial cell death, hindering the growth and survival of the bacteria. It is used to treat drug resistant strains of Mycobacterium tuberculosis, responsible for tuberculosis and is typically wont work for other bacterial infections. 

Drug Interaction

Adverse Reaction

Frequency Defined 

>10% 

Disorder of GIT 

Frequency Not Defined 

Peripheral neuropathy 

Depression 

Postural hypotension 

Dizziness 

Headache 

Drowsiness 

Psychosis 

Gynecomastia 

Excessive salivation 

Impotence 

Photosensitivity 

Hypoglycemia 

Rash 

Black Box Warning

Black Box Warning 

None

Contraindication / Caution

Contraindication/caution: 

It is contraindicated for individuals with hypersensitivity, severe liver disease, pregnancy, severe mental health disorders, diabetes, and peripheral neuropathy. 

 It can cause liver toxicity thus it is usually avoided in those with severe liver impairment or liver disease. 

Pregnant women should avoid ethionamide unless the benefits outweigh the risks. Ethionamide can also interfere with blood sugar levels and worsen glycemic control in diabetes patients also cause peripheral neuropathy, so close monitoring is necessary. 

Pregnancy / Lactation

Pregnancy warnings: 

US FDA pregnancy category: C 

Lactation: 

Excreted into human milk is unknown 

Pregnancy Categories: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women. 

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology:    

Ethionamide (ETH) is a crucial second line medication for tuberculosis especially for multidrug resistant Mycobacterium infections. Unlike isoniazid (INH) ETH operates on a different mechanism by activating an EthA enzyme. This leads to the creation of a Soxide metabolite with enhanced antimicrobial efficacy. 

Pharmacodynamics: 

Ethionamide is well-absorbed orally reaching peak plasma concentrations of 20 µg/mL. It penetrates in normal and inflamed meninges and producing equivalent CSF concentrations. It is metabolized by the liver and interferes with INH acetylation. 

Pharmacokinetics: 

Absorption 

It is effectively absorbed from the gastrointestinal tract after oral administration. 

Distribution 

It distributes widely throughout the body including the lungs. 

Metabolism 

Ethionamide is primarily metabolized by the liver through the enzyme CYP450 2C19 to its active metabolite 2-ethyl-4-amidopyridine (EAP). 

Excretion and Elimination 

It is primarily excreted in urine with the half-life of 2-3 hours and its active metabolite EAP 8 to 12 hours. 

Adminstartion

Administration: 

Ethionamide is orally administered with meals to minimize gastrointestinal side effects. Treatment duration varies based on the severity of TB infection. 

Patient Information Leaflet

Patient information leaflet: 

Generic Name: ethionamide 

Why do we use ethionamide? 

Ethionamide is an antibiotic helps in treating tuberculosis, belongs to thioamide class inhibits the protein synthesis which are responsible for growth and reproduction of bacteria. Mostly, used in combination with other antibiotics to give more effectiveness in treating TB resistant cases or drug resistant cases.