Sulfonamides hepatotoxicity

A more recent report shows clear sulfonamide-induced idiosyncratic responses in dogs (mostly Dobermans) that encompasses fever, arthropathy, blood dyscrasias (neutropenia, thrombocytopenia, or hemolytic anemia) hepatotoxicity, skin eruptions, uveitis, and keratoconjunctivitis sicca [65], These symptoms became apparent as soon... 

Serious adverse effects are rare except in AIDS patients. TMP-SMX can cause the same adverse effects as those associated with sulfonamide administration, including skin rashes, central nervous system (CNS) disturbances, and blood dyscrasias. Blood dyscrasias, hepatotoxicity, and skin rashes are particularly common in patients with AIDS. Most of the adverse effects of this combination are due to the sulfamethoxazole component. Trimethoprim may increase the hematological toxicity of sulfamethoxazole. Long-term use of trimethoprim in persons with borderline foUc acid deficiency, such as alcoholics and the malnourished, may result in megaloblastic anemia, thrombocytopenia, and granulocytopenia. 

The same types of liver disease occur with co-trimox-azole as with sulfonamides alone (109-111). Mild rises in serum transaminases and cholestatic hepatotoxicity are well reported, usually starting after a latent period of several weeks, and associated with a rash. There have been very few case reports of fulminant hepatic failure associated with co-trimoxazole. 

Although the horse appears to be refractory to the hepatic effects of most NSAIDs, their hepato-toxic potential should be considered, especially when they are concomitantly administered with other potentially hepatotoxic agents, such as fluoroquinolones, potentiated sulfonamides or anabolic steroids. In addition, many herbal preparations are potential hepatotoxic agents and clients may administer these compounds concurrently with prescribed NSAIDs without consulting their veterinarian. Echinacea and kava kava products, for example, are reported to be potential hepatotoxins and both are used in herbal remedy products that claim to produce calming or sedating effects in horses (Abebe 2002). 

Adverse effects that are not dose related most commonly include rash, fever, or hepatotoxicity, as well as relatively uncommon but serious reactions such as bone marrow suppression, thrombocytopenia, pancreatitis, and hepatitis. For most patients with idiosyncratic reactions, sulfasalazine must be discontinued. In some patients who have experienced allergic reactions to sulfasalazine, a desensitization procedure can be instituted. By gradually increasing sulfasalazine dosage over weeks to months, patient tolerance has been improved. Most of the idiosyncratic reactions observed with sulfasalazine are similar to those with the class of sulfonamides in general. 

Methenamine (Hiprex) At low urinary pH, is hydrolyzed to formaldehyde which is bactericidal. Formaldehyde kills Gram-negatives, Gram-positives, and funai. Precipitates in presence of sulfonamides. Ammonia produced is somewhat toxic, particularly to the liver. Decrease dose if hepatotoxicity develODS. PO. Conversion to formaldehyde in urine is enhanced by low pH. The acid salts, hippurate or mandelate, help maintain acidic urine. Is not converted to formaldehvde in serum. 

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