Why over the counter medication may kill you

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). 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. 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.

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