Hepatotoxic, definition

The human experience regarding exposure to dimethylhydrazines is limited to case reports describing severe but nonlethal effects following accidental acute exposures. There are limited data suggesting subclinical hepatotoxicity following subchronic occupational exposure to unspecified low levels of 1,1-dimethylhydrazine. No definite exposure concentrations or durations were available in these reports, and the data are not useful for quantitative derivation of AEGLs. 

Laboratory signs of hepatic damage were documented in 37 patients, including three cases of hepatitis (2) pirpro-fen can definitely be considered hepatotoxic. 

Azithromycin is efficacious in animal models of toxoplasmic encephalitis. In a Phase I/II dose-escalation stndy of pyrimethamine (50 mg/day) plus azithromycin (900,1200, or 1500 mg/day) for induction and maintenance treatment in 30 patients with AIDS and definite or snspected Toxoplasma encephalitis, the overall response rate was 67% after 6 weeks of induction therapy (1). However, maintenance therapy for 24 weeks with this combination was associated with a high relapse rate (47%) only six patients snccessfully completed induction and maintenance therapy. Adverse events were common (particn-larly in those taking azithromycin 1500 mg) and inclnded hepatotoxicity, bone marrow suppression, ototoxicity, and gastrointestinal disturbances, which led 20% of patients to withdraw. All adverse events resolved on withdrawal. 

The database incorporates information about 54 nosological entities pertaining to chemical-produced acute intoxications, which give rise to hepatotoxic effects of any type of severity, with manifestations presented by 455 signs. The differential diagnosis within a definite disease class is predominantly based on clinical features of an individual disease, i.e. etiopathogenesis. 

NO is freely diffusible in liver, how different isoforms affect hepatocytes differently remains to be determined. Although nitrotyrosine levels correlate with injury and reflect both oxidative and nitrosative stress, there is no definitive proof this is specifically involved in APAP-induced cell death. One interesting possibility that needs to be examined is whether mitochondrial NO is important in hepatotoxicity and if it is regulated by INK. 

On rare occasions, hepatotoxicity and toxic leukopenia have been observed during polymyxin-E (colistin) treatment, but a definite causal relationship has not been established. The most serious side effect of the polymyxins is their nephrotoxicity. Polymyxin-B is more nephrotoxic than polymyxin-E and the sulfate derivatives of both are more toxic than their corresponding methylsulfonates. The toxic effects are dose dependent and doses above the recommended range may be dangerous. The principal nephrotoxic effect of the polymyxins is on the epithelium of the renal... 

Wang JL, Chang CH, Young-Xu Y, Chan KA. Systematic review and metaanalysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection. Antimicrob Agents Chemother 2010 54(6) 2409-19. 

---