Acetaminophen and Ibuprofen overdosage.

An Update of N-acetylcysteine Treatment for Acute Acetaminophen Toxicity in Children. Marzullo L. Curr Opin Pediatr. 2005;17(2):239–245 Acetaminophen Toxicity in Children. American Academy of Pediatrics. Committee on Drugs. Pediatrics. 2001; 108(4):1020–1024 Clinical Report—Fever and Antipyretic Use in Children. Section on Clinical Pharmacology and Therapeutics; Committee on Drugs, Sullivan JE, Farrar HC . Pediatrics. 2011;127(3): 580–587 Efficacy and Safety of Ibuprofen and Acetaminophen in Children and Adults: A Meta-Analysis and Qualitative Review. Pierce CA, Voss B. Ann Pharmacother. 2010;44(3): 489–506 Nonsteroidal Antiinflammatory Drugs. Holubek W. In: Nelson LS, Lewin NA, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. New York, NY: McGraw-Hill Companies; 2011:528–536 Acetylcysteine for Acetaminophen Poisoning. Heard KJ. N Engl J Med. 2008;359(3):285–292 Fever is one of the most common symptoms managed by pediatricians. Many parents fear that fever is harmful to their children, leading to an estimated 30% of illness visits. Acetaminophen and ibuprofen remain the most common antipyretic medications, with numerous over-the-counter and prescription preparations available in the United States. Studies have reported that as many as one-half of parents administer the incorrect dose of acetaminophen and ibuprofen. Acetaminophen is metabolized mainly in the liver by conjugation with sulfate and glucuronide. When an excessive amount of acetaminophen is present, it overwhelms the normal conjugation pathway, and metabolism is channeled to the cytochrome P-450 pathway, which produces the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is detoxified by glutathione; however, when gluthathione becomes depleted, NAPQI binds directly to hepatocytes, causing cellular necrosis. A therapeutic dosage of acetaminophen is 75 mg/kg per 24-hour period, not to exceed 4 g in 24 hours. Single dosages of 10 to 15 mg/kg given every 4 to 6 hours orally generally are regarded as safe and effective. Liver toxicity in children has been reported after one dose of 120 to 150 mg/kg, with a higher risk of toxicity associated with fasting, liver disease, a history of excessive alcohol use, or the coadministration of medications that induce the cytochrome P-450 pathway. Clinical manifestations of acetaminophen overdose can be gradual and nonspecific. Four clinical stages of acetaminophen toxicity have been described. The first stage occurs during the initial 12 to 24 hours after ingestion, during which time the patient may experience anorexia, malaise, diaphoresis, nausea, and vomiting. The second stage, or latent phase, begins during the subsequent 12 to 24 hours. During this phase, the clinical presentation may vary and include elevation of liver enzyme levels, liver enlargement, or right upper quadrant abdominal pain. Patients also may be asymptomatic. The third stage occurs 3 to 5 days after ingestion and is characterized by recurrence of anorexia, nausea, vomiting, and malaise. Liver enzyme levels may worsen and be accompanied by signs of liver failure, including jaundice, hypoglycemia, coagulopathy, and encephalopathy. The fourth stage is associated with either complete recovery or progression to liver failure. If acetaminophen toxicity is suspected, a serum acetaminophen level should be obtained and plotted on the Rumack-Matthew nomogram, which can be found in standard references as well as the New England Journal of Medicine citation provided here. Given the acetaminophen level and the number of hours postingestion, the nomogram stratifies the patient’s risk into one of three categories: no risk, possible risk, or probable risk of hepatotoxicity. If the serum acetaminophen level plots above the possible risk threshold for the time postingestion, treatment should be initiated. In addition, liver enzyme levels, coagulation profile, serum electrolytes, and complete blood count should be obtained before therapy as well as after treatment is completed. The main therapy for acetaminophen toxicity is administration ofN-acetylcysteine (NAC). The therapeutic effect of NAC occurs via multiple mechanisms within the liver, including increasing gluthathione and directly detoxifying NAPQI. in brief