Liver acetaminophen overdose induced

Mechanism of Action An intratracheal respiratory inhalant that splits the linkage of mucoproteins, reducingtheviscosityof pulmonary secretions.Tiierapeutic Effect Facilitates the removal of pulmonary secretions by coughing, postural drainage, mechanical means. Protects against acetaminophen overdose-induced hepatotoxicity. Pharmacokinetics Protein binding 83% (injection). Rapidly and extensively metabolized in liver. Deacetylated by the liver to cysteine and subsequently metabolized. Excreted in urine. Half-life 5.6 hr (injection). 

Figure 5. Acetaminophen overdose induces liver necrosis by formation of more hepatotoxin (metabolite A) than can be deactivated by glutathione conjugation (metabolite B). ...

Lawson JA, Farhood A, Hopper RD, Bajt ML, Jaeschke H (2000) The hepatic mflammatoTy response after acetaminophen overdose role of neutrophils. Toxicol Sci 54 509-516 Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients a meta-analysis of prospective studies. JAMA 279 1200-1205 Lazerow SK, Abdi MS, Lewis JH (2005) Drug-induced liver disease 2004. Curr Opin Gastroenterol 21 283-292... 

Grewal KK, Racz WJ (1993) Intracellular calcium disruption as a secondary event in acetaminophen-induced hepatotoxicity. Can J Physiol Pharmacol 71 26-33 Gujral JS, Knight TR, Earhood A, Bajt ML, Jaeschke H (2002) Mode of cell death after acetaminophen overdose in mice apoptosis or oncotic necrosis Toxicol Sci 67 322-328 Gujral JS, Hinson JA, Earhood A, Jaeschke H (2004) NADPH oxidase-derived oxidant stress is critical for neutrophil cytotoxicity during endotoxemia. Am J Physiol Gastrointest Liver Physiol 287 G243-252... 

Rumack BH, Peterson RC, Koch GG, Amara lA (1981) Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med 141 380-385 Sakaida I, Kayano K, Wasaki S, Nagatomi A, Matsumura Y, Okila K (1995) Protection against acetaminophen-induced liver injury in vivo by an iron chelator, deferoxamine. Scand J Gastroenterol 30 61-67... 

Acute overdose with acetaminophen (>300 mg kg ) results in hepatotoxicity and/or nephrotoxicity. Although hepatotoxicity is frequently the predominant toxicity, acetaminophen nephrotoxicity can occur in the absence of marked hepatic toxicity. In these cases, liver function returns to normal or near normal levels before the onset of nephrotoxicity. Acute acetaminophen nephrotoxicity is generally characterized as oliguric acute renal failure with acute tubular necrosis. Acetaminophen can also induce acute nephrotoxicity in therapeutic doses, but chronic alcohol intake usually accompanies renal toxicity in these patients. 

The chronic abuse of alcohol predisposes to hepatic damage following overdose of acetaminophen because ethanol (A) Blocks acetaminophen metabolism Causes thiamine deficiency Displaces acetaminophen from plasma proteins Induces liver drug-metabolizing enzymes Inhibits renal clearance of acetaminophen... 

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