Elucidating mechanism of drug induced toxicity

The exact mechanism of antituberculosis drug-induced hepatotoxicity is unknown, but toxic metabolites are suggested to play a crucial role in the development, at least in the case of isoniazid.

Priorities for future studies include basic studies to elucidate the mechanism of antituberculosis drug-induced hepatotoxicity, genetic risk factor studies and the development of shorter and safer tuberculosis drug regimens.

In this paper we review the incidence, pathology and clinical features of antituberculosis drug-induced hepatotoxicity, discuss the metabolism and mechanisms of toxicity of isoniazid, rifampicin and pyrazinamide, and describe risk factors and management of antituberculosis drug-induced hepatotoxicity.

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dating matrimonial muslim united arab emirates 2016 - Elucidating mechanism of drug induced toxicity

A higher dose of 60 mg/kg was tested for analyses but resulted in severe hemorrhaging.

The dose-response analyses for APAP resulted in no elevated liver enzyme levels for a 75 mg/kg and 150 mg/kg dose.

The PARP inhibition analysis for cocaine and APAP was conducted at 6 and 18 hours post initial dose, respectively, when the highest levels of PARP were observed.

Inhibition analyses determined that ALT declined significantly when DIQ was administered immediately following the initial toxicant dose for both toxicants.

A PARP inhibition analysis was conducted with cocaine and (APAP) to understand the impact of a PARP inhibitor, 1,5-dihydroxyisoquinoline (DIQ), on PARP activity in the liver.

A 50 mg/kg dose of cocaine or a 300 mg/kg dose of APAP was administered, followed by a 10 mg/kg dose of DIQ at 1) the time of initial toxicant dose (0 hour), or 2) 1 hour after initial toxicant dose (1hr).A dose of 50 mg/kg for cocaine, and a dose of 300 mg/kg for APAP were used to analyze temporal trends for both toxicants.Both cocaine and APAP produced incremental increases in ALT at the 2 hour, 6 hour, 18 hour, and 24 hour time points, respectively.Median duration of symptoms was 18.5 days and time from admission to treatment initiation was 11 days.Fifteen of 100 children died, 4 were lost to follow-up, and 27/81 (33 %) of survivors had intermediate or severe disability upon treatment completion.Drug toxicity may cause liver injury, resulting in damage to cells and tissues.

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