Novel acetylcysteine regimens for treatment of paracetamol overdose

Abstract

Pathophysiology of paracetamol-induced liver injuryAcute paracetamol administration is associated with significant depletion of glutathione (GSH), attributed to covalent binding of an intermediate paracetamol metabolite, N-acetyl-p-benzoquinone imine (NAPQI) to critical proteins and enzymes within hepatocytes. Restoration of intrahepatic glutathione concentrations in animals minimized the extent of NAPQI covalent binding to Novel acetylcysteine regimens for treatment of paracetamol overdose W. Stephen Waring Abstract: Paracetamol (acetaminophen) overdose remains the leading cause of death or transplantation due to acute liver failure in many parts of the world. Acetylcysteine has long been recognized as an effective antidote, via oral or intravenous administration, minimizing the risk and severity of acute liver injury if administered sufficiently early after a paracetamol overdose. Despite this, its mechanisms of action remain obscure, and there is uncertainty regarding the optimal dose and duration of treatment. The intravenous infusion protocol was originally developed as a three-step loading regimen; it causes very high early peak plasma concentrations of acetylcysteine whereas the later maintenance infusion is associated with much lower concentrations. This pharmacokinetic profile is associated with two particular concerns: a high rate of occurrence of adverse effects that occur after the initial loading infusion, and the possibility that the maintenance phase of treatment might deliver too low a dose of acetylcysteine for optimum protection against liver injury. Recently described novel administration regimens offer different rates of intravenous acetylcysteine administration in both the loading and maintenance phases. These alternative regimens appear to be well tolerated in small patient groups, but too few clinical data are available to evaluate their comparative efficacy in preventing paracetamol-induced liver injury.

Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role ofNigella sativa

“…NAPQI is detoxified by intracellular glutathione (GSH) in therapeutic doses (Dahlin et al 1984). Accordingly, NAPQI has been implicated as responsible metabolite of paracetamol toxicity (Waring 2012). In paracetamoloverdosing cases, glutathione stores are depleted, and a rapid increase in the concentration of NAPQI causes necrosis (Bessems & Vermeulen 2001).…”

Delays during the administration of acetylcysteine for the treatment of paracetamol overdose

“…Recently, a number of alternative two‐infusion acetylcysteine regimens have been trialled, and these are associated with a lower incidence of adverse effects . Reducing the number of infusions required is also likely to reduce infusion delays.…”

Comparative Study of the Possible Hepatoprotective Effect of Each of N-acetylcysteine, Coenzyme Q10 and Aloe Vera Gel in Acute Acetaminophen Induced Hepatotoxicity in Albino Rats. (Histological and Biochemical Study)

“…Decrease in the serum activity of SOD is a sensitive index in hepatocellular damage and is the most sensitive enzymatic index in hepatic injury (Ferah et al, 2013). GSH contains sulfhydryl donor groups and can act as a powerful intracellular reducing agent and antioxidant (Waring 2012).…”

“…It is one of the most common causes of poisoning due to pharmaceutical agent (Wexler et al 2005). APAP overdose is the primary cause of acute liver failure throughout the world (Antoine et al 2012 andMcGill 2012).…”