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Paracetamol toxicity is caused by excessive use or overdose of the analgesic drug paracetamol (called acetaminophen in North America). Mainly causing liver injury, paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States and the United Kingdom it is the most common cause of acute liver failure.〔〔 Many individuals with paracetamol toxicity may have no symptoms at all in the first 24 hours following overdose. Others may initially have nonspecific complaints such as vague abdominal pain and nausea. With progressive disease, signs of liver failure may develop; these include low blood sugar, low blood pH, easy bleeding, and hepatic encephalopathy. Some will spontaneously resolve, although untreated cases may result in death. Damage to the liver, or hepatotoxicity, results not from paracetamol itself, but from one of its metabolites, ''N''-acetyl-''p''-benzoquinoneimine (NAPQI)(also known as N-acetylimidoquinone).〔(Metabolism of acetaminophen (paracetamol), acetanilide and phenacetin )〕 NAPQI depletes the liver's natural antioxidant glutathione and directly damages cells in the liver, leading to liver failure.〔 Risk factors for toxicity include excessive chronic alcohol intake, fasting or anorexia nervosa, and the use of certain drugs such as isoniazid. Treatment is aimed at removing the paracetamol from the body and replacing glutathione. Activated charcoal can be used to decrease absorption of paracetamol if the patient presents for treatment soon after the overdose; the antidote acetylcysteine acts as a precursor for glutathione, helping the body regenerate enough to prevent damage to the liver.〔 N-acetylcysteine can neutralize NAPQI by itself as well.〔 A liver transplant is often required if damage to the liver becomes severe. Patients treated early have a good prognosis, whereas patients that develop major liver abnormalities typically have a poor outcome. Efforts to prevent paracetamol overdose include limiting individual sales of the drug and combining paracetamol with methionine, which is converted into glutathione in the liver. ==Signs and symptoms== The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, pallor, and sweating.〔 However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. Rarely, after massive overdoses, patients may develop symptoms of metabolic acidosis and coma early in the course of poisoning. The second phase occurs between 24 and 72 hours following overdose and consists of signs of increasing liver damage. In general, damage occurs in hepatocytes as they metabolize the paracetamol. The individual may experience right upper quadrant pain. The increasing liver damage also alters biochemical markers of liver function; International normalized ratio (INR) and the hepatic transaminases alanine transaminase and aspartate transaminase rise to abnormal levels. Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome or multiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver. The third phase follows at 3 to 5 days, and is marked by complications of massive hepatic necrosis leading to fulminant hepatic failure with complications of coagulation defects, hypoglycemia, kidney failure, hepatic encephalopathy, cerebral edema, sepsis, multiple organ failure, and death.〔 If the third phase is survived, the hepatic necrosis runs its course, and liver and kidney function typically return to normal in a few weeks. The severity of paracetamol toxicity varies depending on the dose and whether appropriate treatment is received. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Paracetamol toxicity」の詳細全文を読む スポンサード リンク
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