Effect of Acetaminophen (Paracetamol) on the Liver



What causes an acetaminophen overdose?

The most paracetamol (APAP) that is safe for most people to take is 4,000 milligrams (4 grams) in a 24-hour period. An overdose means you have taken more than 4,000 milligrams (4 grams) in a 24-hour period.
Planned overdose: Sometimes people take too much APAP on purpose to harm themselves.
Unplanned overdose: An accidental overdose may occur because of any of the following:
Taking more APAP than recommended:
Sometimes people take too much APAP if their pain or fever did not go away after taking the recommended dose. Sometimes people take APAP for too many days in row.
There are many medicines that contain APAP along with other drugs. These include medicines for colds, the flu, allergies, or trouble sleeping. You may have taken more than one medicine that contains APAP, and the total was too much.
Cases of severe liver injury have been reported in patients who took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period, took two or more acetaminophen-containing products simultaneously, or combined alcohol with acetaminophen products.
It is recommended that pharmacists contact prescribers to discuss an alternative when they receive a prescription for a combination product with more than 325 mg of acetaminophen per dosage unit.
Signs and symptoms:

Most patients who have taken an overdose of acetaminophen will initially be asymptomatic, as clinical evidence of end-organ toxicity often does not manifest until 24-48 hours after an acute ingestion. To identify whether a patient is at risk, the clinician should determine the time(s) of ingestion, the quantity, and the formulation of acetaminophen ingested.
Minimum toxic doses of acetaminophen for a single ingestion, posing significant risk of severe hepatotoxicity, are as follows:
Adults: 7.5-10 g
Children: 150 mg/kg; 200 mg/kg in healthy children aged 1-6 years
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). 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 :

Activated charcoal can be used to decrease absorption of paracetamol if the patient presents for treatment soon after the overdose. It soaks up the APAP remaining in the stomach and acts as an emetic.
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.
Liver Transplant:
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.
read more