What is the toxic metabolite of paracetamol?

What is the toxic metabolite of paracetamol?

When taken in overdose the liver conjugation becomes inundated, causing paracetamol to be metabolised by an alternative pathway. This results in a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is itself inactivated by glutathione, rapidly preventing any harm.

What is the active metabolite of paracetamol?

Alternatively, paracetamol effects may be mediated by an active metabolite (p-aminophenol). p-Aminophenol is conjugated with arachidonic acid by fatty acid amide hydrolase to form AM404.

What are the toxic effects of paracetamol?

The toxic effects of paracetamol most often occur in the liver and kidneys. Phosphate and lactate turn-over can also be impaired. Paracetamol poisoning can induce temporary liver disfunction or even irreversible liver failure with liver transplantation as the only therapeutic possibility.

Which drug is given in paracetamol toxicity?

Oral N-Acetylcysteine The oral formulation of NAC (Mucomyst) is the drug of choice for the treatment of acetaminophen overdose.

How is paracetamol metabolized?

Paracetamol is metabolized primarily in the liver (Figure 1) by enzymes of phase I and II. Phase I reaction for paracetamol may occur by oxidation, reduction, and hydrolysis: It results in polar metabolites of the original chemicals and leads either to activation or inactivation of the drug.

What enzyme breaks down paracetamol?

At therapeutic doses, paracetamol is predominantly metabolized by hepatic sulfation and glucuronidation, with less than 5%–10% being metabolized by the hepatic CYP system (predominantly CYP2E1 and CYP3A4) to N-acetyl-p-benzoquinoneimine (NAPQI), a highly reactive intermediate metabolite responsible for paracetamol- …

How many mg of paracetamol is toxic?

In adults, an acute ingestion of more than 150 mg/kg or 12 g of acetaminophen is considered a toxic dose and poses a high risk of liver damage. In children, acute ingestion of 250 mg/kg or more poses significant risk for acetaminophen-induced hepatotoxicity.

Can paracetamol increase liver enzymes?

Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury.

How is paracetamol toxicity calculated?

Potential toxicity should be assessed and a toxicologist consulted when:

1. >200 mg/kg (or 10 g) ingested over a 24 hour period.
2. >150 mg/kg/day (or 6 g) ingested over a 48 hour period.
3. >100 mg/kg/day ingested over a 72 hour period.

What is the chemical name of paracetamol?

N-(4-hydroxyphenyl)acetamide
N-(4-hydroxyphenyl)ethanamide
Acetaminophen/IUPAC ID

Acetaminophen (paracetamol), also commonly known as Tylenol, is the most commonly taken analgesic worldwide and is recommended as first-line therapy in pain conditions by the World Health Organization (WHO). It is also used for its antipyretic effects, helping to reduce fever.

How paracetamol is metabolized?

What neutralizes paracetamol?

Intravenous acetylcysteine is the antidote to treat paracetamol overdose and is virtually 100% effective in preventing liver damage when given within 8 hours of the overdose.

How is paracetamol metabolized in the body?

Paracetamol is primarily metabolised in the liver by conjugation to glucuronide and sulphate. A small amount (about 3-10% of a therapeutic dose) is metabolised by oxidation and the reactive intermediate metabolite thus formed is bound preferentially to the liver glutathione and excreted as cystein and mercapturic acid conjugates.

What are paraserts/paracetamol suppositories?

Paraserts/Paracetamol Suppositories may be especially useful in patients unable to take oral forms of paracetamol, e.g. post-operatively or with nausea and vomiting. Dosages should be based on the child’s age and weight.

How much paracetamol is toxic to the liver?

Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below). It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested) become irreversibly bound to liver tissue. a.

What happens if you eat paracetamol?

Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below). It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested) become irreversibly bound to liver tissue.