Acetaminophen, toxicity

The nurse immediately reportsany signs of acetaminophen toxicity, such as nausea, vomiting, anorexia, malaise, diaphoresis abdominal pain, confusion, liver tenderness hypotension, arrhythmias jaundice, and acute hepatic and renal failure. Early diagnoss is important because liver failure may be reversible. Toxicity is treated with gastric lavage, preferably within 4 hours of ingestion of the acetaminophen. Liver function studiesare perform ed frequently. Acetylcysteine (Mucomyst) is an antidote to acetaminophen toxicity and acts by protect-... 

The answer is c. (Hardman, pp 632-633.) Nausea, vomiting, abdominal pain, and diarrhea are early signs of the severe liver toxicity caused by high levels of acetaminophen other symptoms of acetaminophen toxicity include dizziness, excitement, and disorientation. N-acetyl-L-cysteine is the appropriate treatment for acetaminophen overdose. 

Figure 5.11 Gene expression changes associated with acetaminophen toxicity in liver. (From Reilly, T.R etal., Biochem. Biophys. Res. Commun., 282, 321-328, 2001. With permission.)...

Early signs and symptoms of acetaminophen toxicity include anorexia, nausea, diaphoresis, and generalized weakness within the first 12-24 hr. 

Later signs of acetaminophen toxicity include vomiting, right upper quadrant tenderness, and elevated liver function tests within 48 to 72 hr after ingestion. 

Lane JE, Belson MG, Brown DK, Scheetz A. Chronic acetaminophen toxicity a case report and review of the literature. J Emerg Med. 2002 23 253-256. 

Coen M, Lenz EM, Nicholson JK, Wilson ID, Pognan F, Lindon JC. An integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy. Chem Res Toxicol 2003 16 295-303. 

Ruepp SU, Tonge RP, Shaw J, Wallis N, Pognan F. Genomics and proteomic analysis of acetaminophen toxicity in mouse liver. Toxicol Sci 2002 65 135-150. 

Murphy R, Scartz R, Watkins PB. Severe acetaminophen toxicity in a patient receiving isoniazid. Ann Intern Med 1990 113 799-800. 

The mechanism of acetaminophen toxicity has been studied extensively in experimental animals. Oxidation of acetaminophen in the liver via cytochrome P450 results in the formation of a cytotoxic electrophile, N-acetyl-p-benzoquinoneimine (NAPQI), that binds to hepatic protein. In the kidney, the formation of a one-electron oxidation product, namely N-acetyl-benzosemiquinoneimine radical, occurs via prostaglandin H synthase. This free radical binds to renal proteins and damages the renal medulla. 

Figure 18.9. Proposed scheme for acetaminophen toxicity and the role of mitochondria and peroxnitrite. [Adapted from Jaeschke and Bajt (2006).]...

Zhu, J.-H., and Lei, X. G. Double null of selenium-glutathione peroxidase-1 and copper,zinc-superoxide dismutase enhances resistance of mouse primary hepatocytes to acetaminophen toxicity. Exp. Biol. Med. 231 545-552, 2006. 

FIGURE 37.2. Metabolism and mechanism of acetaminophen toxicity. Bioactivation of acetaminophen by P450 enzymes results in the formation of the reactive intermediate (NAPQI) which forms covalent protein adducts with glutathione which is then converted to mercapturic acid. When the amount of the reactive metabolite formed exceeds the glutathione available for binding, the excess metabolite binds to tissue molecules resulting in centrilobular hepatic necrosis. 

Large doses of acetaminophen can cause renal and hepatic toxicity in rats and mice. Toxicity is characterized by renal tubular necrosis in the proximal tubules (Schnellmann, 2001). Acetaminophen toxicity has also been reported in humans. Generally, toxicosis is a result of large overdoses which result in proximal tubular necrosis. Aspirin, ibuprofen, and acetaminophen are the important analgesics, which are reported to cause toxicosis in veterinary medicine. Renal lesions including renal tubular necrosis and papillary necrosis have been reported in dogs. 

Guo GL, Moffit JS, Nicol CJ, Ward JM, Aleksunes LA, Slitt AL, Kliewer SA, Manautou JE, Gonzalez FJ. Enhanced acetaminophen toxicity by activation of the pregnane X receptor. Toxicol Sci 2004 82 374-80. 

Goldfinger R, Ahmed KS, Pitchumoni CS, Weseley SA. Concomitant alcohol and drug abuse enhancing acetaminophen toxicity. Report of a case. Am J Gastroenterol 1978 70(4) 385-8. 

Masutani J. Oxidative stress and redox imbalance in acetaminophen toxicity. Pharmocogenom. 2001 1(3) 165-166. 

A large body of evidence is available examining the acute toxicity of acetaminophen in animal models. Mice and rats have been widely used to study the toxic effects of acetaminophen. Since the rat is relatively resistant, the mouse has been the most widely used species to study both the mechanisms of acetaminophen toxicity and to examine chemicals that potentiate or protect from the toxicity. Hepatotoxic-ity and nephrotoxicity are the two main effects associated with acute overdose of acetaminophen. Of these, death in most species is due to acute hepatic failure. LD50 values range from 350 to 4500mgkg depending on the species and the route of acetaminophen administration, mice (LD50 350-... 

Bartlett D (2004) Acetaminophen toxicity. Journal of Emergency Nursing 30 281-283. 

Zaher H, Buters JT, Ward JM, et al. (1998) Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 douhle-null mice. Toxicology and Applied Pharmacology 152 193-199. 

Chemical-induced liver injury is differentially modified by diabetes in murine type 1 diabetic models. Contrary to the enhanced hepatotoxicity in diabetic rats, diabetes in mice tends to protect animals from severe hepatotoxicity. It has been reported that the induction of diabetes in Swiss mice did not increase the susceptibility of mice to CCI4 hepatotoxicity as occurs in rats. Development of diabetes also protected mice from acetaminophen toxicity. Further studies also showed that streptozotocin-induced diabetic mice were substantially resistant to lethal doses... 

The packaging of the kava products was unavailable for identification purposes. Liver biopsy revealed active fulminant hepatitis with extensive necrosis and tests for viral hepatitis were negative. She underwent a successful liver transplantation and was able to return to normal activity upon recovery (34). Unfortunately, no information was provided indicating that acetaminophen toxicity had been ruled out, and the observed toxic effect could also have been associated with a large, undiagnosed acetaminophen ingestion. 

Early signs of acetaminophen toxicity anorexia, nausea, diaphoresis, generalized weakness within first 12-24 h. Later signs of toxicity vomiting, right upper quadrant tenderness, elevated liver function tests within 48-72 hours after ingestion. Antidote Acetylcysteine (N-acetylcysteine) Mucomyst. 

Indications Emphysema, bronchitis, tuberculosis, bronchiectasis, tracheostomy care, antidote for acetaminophen toxicity... 

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