Paraminophenols and Paracetamol

Among the drugs belonging to the Paramminophenol family, the best known is paracetamol (TACHIPIRINA ®) or acetaminophen (term most used in the USA).

This drug binds negligibly to COX1 and COX2, while it has a much greater affinity for COX3, to which it complexes by inhibiting them.

For this reason it cannot be considered an NSAID (it is in fact devoid of significant anti-inflammatory activity and has only analgesic and antipyretic activity). Its mechanism of action, however, has yet to be fully clarified; in fact, it seems that in humans - as opposed to what happens in dogs - the inhibitory effect on COX-3 is insufficient to explain the antipyretic effects of acetaminophen. .

Paracetamol is the most used drug for pain ranging from mild to moderate (eg headache, menstrual pain), thanks also to the reduced side effects.
The dosage is 300/500 mg every 4/6 hours; it can become dangerous at doses over four grams per day. Although the therapeutic dose is below this limit, being an OTC drug (therefore available without a prescription), unintentional abuse or poisoning is not uncommon.

The most serious side effect linked to the abuse of paracetamol is linked to its hepatotoxicity, which can result in hepatic necrosis, sometimes fatal. Responsible for this side effect is a metabolite that is formed in the liver by the cytochromes. called N-acetyl iminoquinone, it gives rise to compounds of sum with glutathione, a powerful antioxidant that in the liver can detoxify foreign substances administered from the outside. When the production of this paracetamol metabolite depletes glutathione, the antioxidant action of the latter being lost, there is a loss of function of the liver enzymes which leads to lysis of the hepatocyte with the formation of necrotic areas that are often fatal.
The limit of 4 grams of paracetamol per day is actually lower than the maximum dose tolerated by a healthy person (6 grams / day), but it also serves to protect people suffering from liver diseases.
In case of paracetamol intoxication, glutathione is not suitable as an antivenin drug because it can only be injected intramuscularly and is therefore absorbed slowly. For this reason, its derivative is used, called acetylcysteine ​​(FLUIMUCIL ®) which in itself is a mucolytic drug, therefore suitable for facilitating the elimination of mucus from the airways. The task of drugs belonging to the category of mucolytics is to break the bonds. of sulphide so that the proteins that compose it "unwind" becoming more susceptible to proteases (enzymes dedicated to their degradation).
In case of paracetamol intoxication, acetylcysteine ​​is administered very slowly intravenously. Therapy continues until blood tests show the reestablishment of liver enzymes.