Paracetamol, Tylenol (p-Aminophenol Derivatives.)

Acetaminophen = paracetamol= Tylenol= para-Aminophenol derivative:

Acetaminophen (Tylenol) has fewer toxic effects than either precursor. Phenacetin and acetanilide are no longer used therapeutically because they have been linked to methemoglobinemia.

Acetaminophen is less plasma protein bound than the salicylates.A minor toxic metabolite
is generated by the metabolism of acetaminophen. This toxic metabolite is normally conjugated to glutathione (small protein) in the liver and excreted via the kidney. However, with the depletion of glutathione in certain disease states, such as liver cirrhosis and necrosis, and following chronic use of high doses of acetaminophen, this toxic reactive metabolite can accumulate and induce liver damage.


Mechanism of Action

Acetaminophen is a weak inhibitor of peripheral COX (so it is not anti inflammatory). Its analgesic effects may arise from inhibition of prostanoid synthesis in the CNS. The antipyretic effects of acetaminophen are similar to those of aspirin in that it acts at the level of the hypothalamus to reduce pyrogen-initiated alterations in body temperature by inhibiting
prostaglandin synthesis.

Pharmacological Effects and Clinical Uses Acetaminophen is similar to salicylates in that it is a
useful analgesic for mild to moderate pain, with equal efficacy to aspirin, and like aspirin, it is antipyretic. However, acetaminophen not effective in platelet aggregation and is not antiinflammatory. Thus, it is not useful for patients with arthritis or other inflammatory
diseases. It is also not useful as an antithrombotic agent in the prevention of myocardial infarction or transient ischemic attacks.

Acetaminophen does not produce the gastric ulceration that can occur with aspirin and is
useful in patients who are salicylate sensitive or who have a history of ulcers or other gastric ulcerations.

Adverse Effects, Contraindications, and Drug Interactions:

The onset (time till the symptoms occur) of toxicity may not occur for several days, and the predominant damage is to the liver.The initial signs of toxicity occur within 12 to 24 hours and include nausea and vomiting. Signs of hepatotoxicity occur within 72 hours. In addition to hepatotoxic effects, renal necrosis and myocardial damage may occur.

Acetaminophen is contraindicated in late-stage alcoholism, In addition, barbiturates and phenytoin induce the metabolism so decrease the effectiveness of acetaminophen. Acetaminophen crosses the placenta but is nonetheless used in pregnant women with few side
effects for the mother or the fetus.