Paracetamol
Paracetamol is the international generic name for para-acetylaminophenol, also called acetaminophen, the generic name used in the United States. It is marketed under the brand names Tylenol, Panadol, Anacin-3 and many others. In scientific and pharmaceutical papers, it is often abbreviated as APAP, for N-Acetyl-Para-AminoPhenol.
For over 100 years, it has been widely known that paracetamol is an antipyretic (reduces fever) and an analgesic (reduces pain). Unlike COX-1-inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil) or naproxen (Aleve), paracetamol has no anti-inflammatory effects at clinical dosages and will not irritate the gastrointestinal tract.
Paracetamol is an excellent choice for adults, children and infants for alleviating the fever and pains associated with the flu (influenza) in both H1N1 or the seasonal flu.
Mechanism of Action
Even though paracetamol was discovered over 100 years ago and has been in wide use for over 50 years, the exact mechanism of its action is still debated.
Although mystery surrounds the specific cellular enzymes that are involved, it appears that paracetamol reduces pain by raising the pain threshold within the central nervous system.
As a fever-reducing agent, paracetamol inhibits the action of endogenous pyrogens (chemicals your body produces to raise your temperature during viral or bacterial infection) by blocking the production and release of prostaglandins in the brain.
As paracetamol has low protein-binding activity and a low molecular weight, it slips easily through the blood-brain barrier to act directly on the brain and spinal cord.
COX-3 and Other Enzymes
Cyclo-oxygenases are enzymes within the prostaglandin production pathway that your body produces upon infection or injury. Prostaglandins are important mediators of pain, fever and inflammation. During infection such as with the flu (influenza), the COX enzymes become active and convert arachidonic acid to prostaglandin H2, a precursor for many other inflammatory molecules.
Classic NSAIDs block both the COX-1 and COX-2 enzymes, thus reducing the amount of prostaglandins produced by the body. This reduces pain, fever and inflammation.
The central mystery in paracetamol's mechanism of action is this: how does paracetamol reduce fever and pain but not inflammation? All other COX inhibitors reduce all three symptoms.
Paracetamol has been shown in some studies to have little or no effect on COX-1 or COX-2 enzymes. Certainly, paracetamol is not associated with the gastrointestinal irritation that is common with all COX-1 inhibitors, meaning that paracetamol is kinder to your stomach than is aspirin or other NSAIDs.
Thus, it was hypothesized that paracetamol acts on another cyclo-oxygenase enzyme, called COX-3, a third COX enzyme. However, paracetamol itself may bind to arachidonic acid to form a complex that binds to and acts through the cannabinoid receptors in the brain, thus lowering the threshold of pain. Another possibility is that paracetamol blocks COX-1 enzymes (like aspirin) and is thus active in the CNS but is inactivated in an inflammatory environment by peroxides.
No matter how paracetamol works, it has been shown to be the safest alternative for the reduction of pain and fever associated with influenza. It causes no stomach irritation like other COX-1 inhibiting NSAIDs. Aspirin and other NSAIDs, when taken during influenza infection, have also been associated with Reyes Syndrome, an often fatal, devastating disease that attacks all the organs of the body, most seriously the liver and brain. Paracetamol has not been associated with Reyes Syndrome and is thus the safest option.
