Ethionamide adverse effects

Ethionamide This structural analog of isoniazid is believed not to act by the same mechanism. It is effective after oral administration, and is widely distributed throughout the body, including the CSF. Metabolism is extensive. Ethionamide [e thye on AM ide] can inhibit acetylation of isoniazid (Figure 33.7). The urine is the main route of excretion. Adverse effects that limit its use include gastric irritation, hepatotoxicity, peripheral neuropathies, and optic neuritis. Isoniazid... 

Severe allergic skin reactions, alopecia, acne, and purpura can occur in patients taking ethionamide (1,12). Other adverse effects include acneiform eruptions, photodermatitis, and hair loss (13). 

Neurotoxic adverse effects may be potentiated by the concurrent use of cycioserine and ethionamide. 

Two cases of alopecia due to ethionamide administration were reported from India (44 ). In both cases gradual recovery followed withdrawal of the compound. Two reports from Germany (45, 46 ) referred to the use of isoprodian, a combination of isoniazid, prothionamide and dapsone, in the treatment of pulmonary tuberculosis. In both cases the adverse effects were stated to be minimal, and although in one series a transient faU in haemoglobin level and erythrocyte count was noted, values returned to normal with continued therapy. If this work is substantiated it seems likely that this particular combination wiU be more widely used, especially as, in combination with... 

An interesting and unusual adverse effect attributed to pyrazinamide was described in a paper from the United States (54 ). A patient was described who suffered several attacks of acute intermittent porphyria whilst under treatment for tuberculosis. The first attack occurred after 18 months therapy with isoniazid and ethambutol. The second episode occurred after 14 days treatment with rifampicin, 7 days treatment with pyrazinamide and 3 days treatment with streptomycin. The patient was subsequently treated successfully with a combination of rifampicin, ethambutol and capreomycin. The compounds were investigated for their capacity to induce hepatic delta-aminolaev-ulinic acid synthesis in an in vitro preparation of rat Uver. The results showed that pyrazinamide had a greater potential for inducing the enzyme activity than any of the other compounds. It is worthy of note, however, that in this in vitro system para-aminosalicylic acid, rifampicin, cycloserine and ethionamide all induced increased delta-aminolaevulinic acid synthesis. 

Finally, some drugs widely used including lithium, ethionamide, sulfonamides carbutamide, p-aminobenzoic acid, p-aminosalycilic acid, ketoconazole, or phenylbutazone have adverse side effects on the thyroid [26]. 

Ethionamide is a congener of INH, but cross-resistance does not occur. The major disadvantage of ethionamide is severe gastrointestinal irritation and adverse neurologic effects at doses needed to achieve effective plasma levels. 

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