Paracetamol intoxication

Paracetamol' is one of the most widely used analgesic − antipyretic (Paralen&reg;).
 * The acetanilide derivative contained in paracetamol is biotransformed in the liver' by cytochrome P450 to the highly hepatotoxic N-acetyl-p-benzoquinonimine' which is in therapeutic doses immediately inactivated by glutathione. When glutathione is depleted, the hepatocytes are damaged and centrizonal necrosis occurs. A similar biotransformation takes place in the kidneys → also necrosis and kidney damage.

Toxicity

 * Already a dose higher than 140 mg/kg' (70 kg human − 20 tablets of Paralen 500&reg; = hepatotoxic dose),
 * children are less sensitive (they do not have functional cytochrome P450),
 * more sensitive are alcoholics, patients on antiepileptics.

Clinical picture

 * Early symptoms' − nausea, vomiting,
 * latency from ingestion (2−3 days) is typical,
 * hepatorenal stage - symptoms of liver failure and renal failure, encephalopathy, rise in prothrombin time, metabolic acidosis, death.

Treatment

 * Administer activated charcoal, suppress vomiting (metoclopramide),
 * 'antidote - N-acetylcysteine initial dose 140-150 mg/kg, continued dose 70 mg/kg, the dosage varies according to the time of intoxication and the method of administration.
 * indication is suspicion of ingestion or paracetamol value in plasma 200 mg/l or more in 2 h after ingestion,
 * hemoperfusion is also effective.

Related Articles

 * Antidepressant intoxication
 * Benzodiazepine intoxication