In 1948, Brodie and Axelrod determined that the analgesic effect of acetanilide was due to its active metabolite paracetamol--also known as acetaminophen



Yüklə 465 b.
tarix13.12.2017
ölçüsü465 b.
#15296





In 1948, Brodie and Axelrod determined that the analgesic effect of acetanilide was due to its active metabolite paracetamol--also known as acetaminophen.

  • In 1948, Brodie and Axelrod determined that the analgesic effect of acetanilide was due to its active metabolite paracetamol--also known as acetaminophen.

  • The product went on sale in the United States in 1955 under the brand name "Tylenol."



Paracetamol causes three times as many cases of liver failure as all other drugs combined, and is the most common cause of acute liver failure in the United States, accounting for 39% of cases.

  • Paracetamol causes three times as many cases of liver failure as all other drugs combined, and is the most common cause of acute liver failure in the United States, accounting for 39% of cases.

  • While this occurs through overdosing, even recommended doses, especially combined with small amounts of alcohol consumption, have caused irreversible liver failure.



Paracetamol is metabolized in the liver, resulting in a by-product, N-acetyl-p-benzoquinone imine (NAPQI), that can damage liver cells, but is typically converted into a harmless substance by glutathione.

  • Paracetamol is metabolized in the liver, resulting in a by-product, N-acetyl-p-benzoquinone imine (NAPQI), that can damage liver cells, but is typically converted into a harmless substance by glutathione.

  • However, large doses of paracetamol overwhelms the body's supply of glutathione, resulting in destruction of the liver cells.



Paracetamol toxicity can also cause kidney failure.

  • Paracetamol toxicity can also cause kidney failure.

  • People who have the highest risk for paracetamol related kidney failure include: heavy drinkers, elderly men, and persons with pre-existing liver or kidney damage.



Paracetamol acts as a pro-drug, with the active metabolite (AM404) being formed in the brain through conjugation of the deacetylated derivative of paracetamol (p-aminophenol) with arachidonic acid, by the action of fatty acid amide hydrolase (FAAH).

  • Paracetamol acts as a pro-drug, with the active metabolite (AM404) being formed in the brain through conjugation of the deacetylated derivative of paracetamol (p-aminophenol) with arachidonic acid, by the action of fatty acid amide hydrolase (FAAH).

  • At analgesic doses of paracetamol, AM404 which is formed in rat brain regions expressing high levels of FAAH, can indirectly activate CB1 receptors.















The purpose of this report was to explore a possible correlation between paracetamol and autism which acts through activation of the cannabinoid system. If this hypothesis is correct, it opens new avenues of investigation for possible autism treatment including agonists and antagonists of the CB1 and CB2 receptors.

  • The purpose of this report was to explore a possible correlation between paracetamol and autism which acts through activation of the cannabinoid system. If this hypothesis is correct, it opens new avenues of investigation for possible autism treatment including agonists and antagonists of the CB1 and CB2 receptors.







Prog Neuropsychopharmacol Biol Psychiatry 2012 Aug 7;38(2):260-9.

  • Prog Neuropsychopharmacol Biol Psychiatry 2012 Aug 7;38(2):260-9.



The purpose of this study was to determine if treatment with paracetamol or its metabolite, p-aminophenol, may cause developing neuronal cell death in vitro using embryonic mouse cortical neuronal cultures.

  • The purpose of this study was to determine if treatment with paracetamol or its metabolite, p-aminophenol, may cause developing neuronal cell death in vitro using embryonic mouse cortical neuronal cultures.

  • Our hypothesis was that the paracetamol metabolite p-aminophenol acting as an indirect agonist of cannabinoid receptors would cause apoptosis similarly to the naturally occurring cannabinoid anandamide.

  • Basic Clin Pharmacol Toxicol 2012 Feb;110(2):141-4





















Discussion

  • Discussion

  • Paracetamol is a commonly administered analgesic drug, and the results of my research have indicated that its use in children can increase the risk for autism. This risk may be due to a decrease in endocannabinoid tone in the brain. It may be possible to increase this tone through an FAAH inhibitor which increases endocannabinoid activity in the brain or through agmatine which augments endocannabinoid activity.





Acetanilide was discontinued due to unacceptable toxic effects, the most alarming being cyanosis due to methemoglobinemia.

  • Acetanilide was discontinued due to unacceptable toxic effects, the most alarming being cyanosis due to methemoglobinemia.



The U.S. Food and Drug Administration ordered the withdrawal of drugs containing phenacetin in 1983, owing to its carcinogenic and kidney-damaging properties (Federal Register of October 5, 1983).

  • The U.S. Food and Drug Administration ordered the withdrawal of drugs containing phenacetin in 1983, owing to its carcinogenic and kidney-damaging properties (Federal Register of October 5, 1983).



Yüklə 465 b.

Dostları ilə paylaş:




Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur ©www.genderi.org 2024
rəhbərliyinə müraciət

    Ana səhifə