The principal toxic metabolite of acetaminophen , N -acetyl- p -benzoquinone imine NAPQI , is produced by the hepatic cytochrome P enzyme system; glutathione stores in the liver detoxify this metabolite. An acute overdose depletes glutathione stores in the liver.
As a result, NAPQI accumulates, causing hepatocellular necrosis and possibly damage to other organs eg, kidneys, pancreas. Theoretically, alcoholic liver disease Alcohol-Related Liver Disease Alcohol consumption is high in most Western countries.
However, therapeutic doses of acetaminophen in alcoholic patients are not associated with hepatic injury. Most of these adverse events were the result of dosing errors because the drug is dosed in milligrams but dispensed in milliliters. Because these overdoses are iatrogenic, reliable information regarding time and total dose is available. The Rumack-Matthew nomogram see Figure: Rumack-Matthew nomogram for single acute acetaminophen ingestions Rumack-Matthew nomogram for single acute acetaminophen ingestions Acetaminophen poisoning can cause gastroenteritis within hours and hepatotoxicity 1 to 3 days after ingestion.
Severity of hepatotoxicity after a single acute overdose is predicted by serum Overdoses acetaminophen overdose has not been determined, and consultation with a toxicologist or a poison control center is recommended. Symptoms, which occur in 4 stages see table Stages of Acute Acetaminophen Poisoning Stages of Acute Acetaminophen Poisoning Acetaminophen poisoning can cause gastroenteritis within hours and hepatotoxicity 1 to 3 days after ingestion.
Renal failure and pancreatitis may occur, occasionally without liver failure. Acetaminophen overdose should be considered in all patients with nonaccidental ingestions that may be suicide attempts and in children with ingestions because formulations containing acetaminophen are frequently ingested in such overdoses and are not reported.
Also, because acetaminophen often causes minimal symptoms during the early stages and is potentially lethal but treatable, ingestion should be considered in all patients with accidental ingestions as well. Consider occult acetaminophen toxicity in all patients who have ingestions. Likelihood and severity of hepatotoxicity caused by an acute ingestion can be predicted by the amount ingested or, more accurately, by the serum acetaminophen level. If the time of acute ingestion is known, the Rumack-Matthew nomogram Professional.
Rumack-Matthew nomogram for single acute acetaminophen ingestions Rumack-Matthew nomogram for single acute acetaminophen ingestions Acetaminophen poisoning can cause gastroenteritis within hours and hepatotoxicity 1 to 3 days after ingestion. Higher levels indicate possible hepatotoxicity. Semilogarithmic plot of plasma acetaminophen levels vs time. Cautions for use of this nomogram:. Pediatrics 55 6 : —, ; reproduced by permission of Pediatrics.
If poisoning is confirmed or strongly suspected or if the time of ingestion is unclear or unknown, additional testing is indicated. Liver tests are done and, in suspected severe poisoning, prothrombin time is measured. Aspartate aminotransferase AST and alanine aminotransferase ALT results correlate with the stage of poisoning see table Stages of Acute Acetaminophen Poisoning Stages of Acute Acetaminophen Poisoning Acetaminophen poisoning can cause gastroenteritis within hours and hepatotoxicity 1 to 3 days after ingestion.
Common causes include hepatitis B and C viruses, nonalcoholic steatohepatitis NASH , alcohol-related liver disease, and autoimmune liver If poisoning is severe, bilirubin and international normalized ratio may be elevated. Low-level transaminase elevations eg, up to 2 or 3 times the upper limit of normal may occur in adults taking therapeutic doses of acetaminophen for days or weeks.
These elevations appear to be transient, usually resolve or decrease even with continued acetaminophen use , are usually clinically asymptomatic, and are probably insignificant. Although the biomarkers may indicate exposure to acetaminophen , they do not conclusively indicate acetaminophen -induced hepatotoxicity. Other biomarkers such as microRNA are under investigation but are not standard diagnostic tools. Poor prognostic indicators at 24 to 48 hours postingestion include all of the following:.
Acute acetaminophen toxicity does not predispose patients to cirrhosis. Activated charcoal may be given if acetaminophen is likely to still remain in the gastrointestinal GI tract. N - Acetylcysteine is an antidote for acetaminophen poisoning. This drug is a glutathione precursor that decreases acetaminophen toxicity by increasing hepatic glutathione stores and possibly via other mechanisms.
It helps prevent hepatic toxicity by inactivating the toxic acetaminophen metabolite NAPQI N -acetyl- p -benzoquinone imine before it can injure liver cells. However, it does not reverse damage to liver cells that has already occurred.
For acute poisoning, N - acetylcysteine is given if hepatotoxicity is likely based on acetaminophen dose or serum level. The drug is most effective if given within 8 hours of acetaminophen ingestion. After 24 hours, the benefit of the antidote is questionable, but it should still be given. If degree of toxicity is uncertain, N - acetylcysteine should be given until toxicity is ruled out. N - Acetylcysteine is equally effective given IV or orally.
IV therapy is given as a continuous infusion. For children, dosing may need to be adjusted to decrease the total volume of fluid delivered; consultation with a poison control center is recommended. Oral acetylcysteine is unpalatable; it is given diluted in a carbonated beverage or fruit juice and may still cause vomiting.
If vomiting occurs, an antiemetic can be used; if vomiting occurs within 1 hour of a dose, the dose is repeated. However, vomiting may be protracted and may limit oral use. Allergic reactions are unusual but have occurred with oral and IV use. Liver failure is treated supportively. Patients with fulminant liver failure Acute Liver Failure Acute liver failure is caused most often by drugs and hepatitis viruses.
Cardinal manifestations are jaundice, coagulopathy, and encephalopathy. Diagnosis is clinical. Treatment is mainly supportive See also Overview of Transplantation. Doctors will determine if transplantation is necessary if the above tests are significantly abnormal and the patient has developed hepatic encephalopathy, a disorder of the brain caused by a dysfunctional liver. Learn about other Liver Disease States. Children's Hospital's main campus is located in the Lawrenceville neighborhood.
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Liver Transplant. Acetaminophen Toxicity Symptoms Initial symptoms of acetaminophen toxicity can take up to 12 hours to appear.
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