How is paracetamol converted to paracetamol glucuronide?

How is paracetamol converted to paracetamol glucuronide?

UDP-Glucuronyl transferases conjugate 52%–57% paracetamol become paracetamol glucuronide and hepatic sulfotransferases conjugate 30%–44% paracetamol become paracetamol sulfate, a nontoxic conjugate, and are then excreted through urine.

Which drugs are metabolized by glucuronide conjugation?

Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.

Does paracetamol undergo glucuronidation?

Paracetamol has two main pathways of metabolism in humans: sulfation and glucuronidation, to increase hydrophilicity prior to excretion.

What is the mechanism of toxicity in paracetamol overdose?

Toxic Mechanism: The main toxicity following paracetamol poisoning is acute liver injury which results from the formation of a toxic metabolite of paracetamol, N-acetyl-p-benzoquinone imine (NAPQI).

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.

Why is Napqi toxic?

Paracetamol (acetaminophen) is toxic because its breakdown products form a compound that reacts with the glutathione. The breakdown product, N-acetyl-p-benzo-quinone imine; NAPQI) reacts with the sulphydryl groups of glutathione, which are used up by the excessive amount of breakdown product.

How is paracetamol metabolised?

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver (90-95%) and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol.

What is the toxic metabolite of acetaminophen?

All of the harmful effects of acetaminophen have been attributed to the production of its toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI).

Why is NAPQI toxic?

How does the liver metabolise paracetamol?

It is metabolised in the liver (90-95%) and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours.

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.

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.

Which is the glucuronide of paracetamol acetaminophen?

Acetaminophen O-beta-D-glucosiduronic acid is a beta-D-glucosiduronic acid that is the O-glucuronide of paracetamol ( acetaminophen ). It has a role as a drug metabolite.

How does paracetamol become glucuronide in urine?

UDP-Glucuronyl transferases conjugate 52%–57% paracetamol become paracetamol glucuronide and hepatic sulfotransferases conjugate 30%–44% paracetamol become paracetamol sulfate, a nontoxic conjugate, and are then excreted through urine.

How is acetaminophen glucuronide related to beta thalassemia?

Acetaminophen glucuronide is found to be associated with beta-thalassemia, which is an inborn error of metabolism. Acetaminophen O-beta-D-glucosiduronic acid is a beta-D-glucosiduronic acid that is the O-glucuronide of paracetamol ( acetaminophen ). It has a role as a drug metabolite. It derives from a paracetamol and a beta-D-glucuronic acid.

How is paracetamol found to be toxic to the liver?

In the original studies of the mechanisms of toxicity, paracetamol was found to cause liver damage through conversion by hepatic cytochrome P450 enzymes to a minor but toxic intermediate metabolite [65–68] and this was subsequently identified as N-acetyl-p-benzoquinoneimine [69, 70].