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Aina Meducci 2012


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Panadol @ Paracetamol

Down with slight fever and running nose last night, my mum suggested panadol to prevent the fever becoming worse. During the pharmacology class, the panadol is used as pain relieve and also to promote body inflammation but also there are some side effect including gastric. Lets review!


Panadol (brand name), paracetamol (International non-proprietary name), acetaminophen (united state adopted name) is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer). It is commonly used for the relief of headaches, other minor aches and pains, and is a major ingredient in numerous cold and flu remedies. In combination with opioid analgesics, paracetamol can also be used in the management of more severe pain such as post surgical pain and providing palliative care in advanced cancer patients.The onset of analgesia is approximately 11 minutes after oral administration of paracetamol, and its half-life is 1–4 hours.

Paracetamol chemical structure

Paracetamol is used for the relief of and pains associated with many parts of the body. It has analgesic properties comparable to those of aspirin, while its anti-inflammatory effects are weaker. It is better tolerated than aspirin in patients in whom excessive gastric acid secretion or prolongation of bleeding time may be a concern. Paracetamol can relieve pain in mild arthritis but has no effect on the underlying inflammation, redness, and swelling of the joint. It is as effective as the nonsteroidal anti-inflammatory drug ibuprofen in relieving the pain of osteoarthritis of the knee.Paracetamol has relatively little anti-inflammatory activity, unlike other common analgesics such as the NSAIDs aspirin and ibuprofen.

Mechanism of action

The main mechanism of action of paracetamol is considered to be the inhibition of cyclooxygenase (COX), and recent findings suggest that it is highly selective for COX-2.

While it has analgesic and antipyretic properties comparable to those of aspirin or other NSAIDs, its peripheral anti-inflammatory activity is usually limited by several factors, one of which is high level of peroxides present in inflammatory lesions. However, in some circumstances, even peripheral anti-inflammatory activity comparable to other NSAIDs can be observed.Because of its selectivity for COX-2 it does not significantly inhibit the production of the pro-clotting thromboxanes.

The COX family of enzymes are responsible for the metabolism of arachidonic acid to prostaglandin H2, an unstable molecule that is, in turn, converted to numerous other pro-inflammatory compounds. Classical anti-inflammatories such as the NSAIDs block this step. Only when appropriately oxidized is the COX enzyme highly active.

Paracetamol reduces the oxidized form of the COX enzyme, preventing it from forming pro-inflammatory chemicals.This leads to a reduced amount of Prostaglandin E2 in the CNS, thus lowering the hypothalamic set-point in the thermoregulatory centre.

The production of prostaglandins is part of the body's inflammatory response to injury, and inhibition of prostaglandin production around the body by blocking the cyclooxygenase enzymes known as COX-1 and COX-2 has long been known to be the mechanism of action of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. However, their action in blocking COX-1 is known to be responsible for also causing the unwanted gastrointestinal side effects associated with these drugs.

***The mechanism by which paracetamol reduces fever and pain is still a source of debate.The reason for this confusion has largely been due to the fact that paracetamol reduces the production of prostaglandins—pro-inflammatory chemicals.Aspirin also inhibits the production of prostaglandins, but, unlike aspirin, paracetamol does not have much anti-inflammatory action. Likewise, whereas aspirin inhibits the production of the pro-clotting chemicals thromboxanes, paracetamol does not. Aspirin is known to inhibit the cyclooxygenase (COX) family of enzymes, and, because of paracetamol's partial similarity of aspirin's action, much research has focused on whether paracetamol also inhibits COX. It is now clear, however, that paracetamol acts via (at least) two pathways.


Paracetamol is metabolised primarily in the liver, into non-toxic products. Three metabolic pathways are notable:
  • Glucuronidation is believed to account for 40% to two-thirds of the metabolism of paracetamol.Sulfation
  • (sulfate conjugation) may account for 20–40%.
  • N-hydroxylation and rearrangement, then GSH conjugation, accounts for less than 15%. The hepatic cytochrome P450 enzyme system metabolizes paracetamol, forming a minor yet significant alkylating metabolite known as NAPQI (N-acetyl-p-benzo-quinone imine).NAPQI is then irreversibly conjugated with the sulfhydryl groups of glutathione.

  • All three pathways yield final products that are inactive, non-toxic, and eventually excreted by the kidneys. In the third pathway, however, the intermediate product NAPQI is toxic. NAPQI is primarily responsible for the toxic effects of paracetamol; this constitutes an example of toxication.

At usual doses, NAPQI is quickly detoxified by conjugation. Following overdose, and possibly also in extensive and ultrarapid metabolizers, this detoxification pathway becomes saturated, and, as a consequence, NAPQI accumulates (toxicity) and cause liver damage.

Veterinary use

Paracetamol is extremely toxic to cats. Cats lack the necessary glucuronyl transferase enzymes to safely break paracetamol down, and minute portions of a tablet may prove fatal. Initial symptoms include vomiting, salivation, and discolouration of the tongue and gums.

Unlike an overdose in humans, liver damage is rarely the cause of death; instead,methemoglobin formation and the production of Heinz bodies in red blood cells inhibit oxygen transport by the blood, causing asphyxiation (methemoglobemia and hemolytic anemia).

Treatment with N-acetylcysteine, methylene blue or both is sometimes effective after the ingestion of small doses of paracetamol.Although paracetamol is believed to have no significant anti-inflammatory activity, it has been reported to be as effective as aspirin in the treatment of musculoskeletal pain in dogs.

sources; Paracetamol-wikipedia, mechanism of action of paracetamol www.pharmweb.net

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