|MadSci Network: Medicine|
Velma, You have asked a good question that brings up some interesting science. Aspirin, or acetyl salicylic acid, acts as an inhibitor of an enzyme called cyclooxygenase, often abbreviated as COX. COX mediates the conversion of arachidonic acid to prostaglandin H2. Prostaglandins in general are involved in the processes that cause pain and inflammation. By inhibiting the COX enzymes, aspirin prevents the synthesis of prostaglandins, and thereby reduces both pain and inflammation. (If you want to know the chemical structures of arachidonic acid and prostaglandins, or want to know more about how they are synthesized biochemically, any good college-level biochemistry textbook should have plenty of information for you, so I won't go into detail here.) About ten years ago, scientists discovered that there are actually two forms of the cyclooxygenase enzyme, termed COX-1 and COX-2. It was determined that COX-1 is found throughout the body and performs many “housekeeping” functions. COX-2 is found mainly in inflamed tissues, and is more specifically associated with causing inflammation. Aspirin inhibits both COX-1 and COX-2. Since COX-1 is found throughout the body, especially in the gastrointestinal tract, kidneys, and platelets, it is believed that inhibition of this enzyme leads to the unwanted side effects such as gastrointestinal damage (ulcers), renal dysfunction, and platelet abnormalities. Newer anti-inflammatory drugs, such as rofecoxib (Vioxx) and celecoxib (Celebrex) were designed by pharmaceutical researchers to specifically inhibit COX-2 and not COX-1, so they have fewer side effects. The mechanism of action of acetaminophen, the active ingredient in the Tylenol brand, however is not fully understood. It also inhibits the COX- 1 and COX-2 enzymes just like aspirin does, but not very strongly, so there must be something more important going on. Since it only weakly inhibits COX-2, there is little anti-inflammatory effects. Acetaminophen seems to exert its pain-reducing effect more directly on the central nervous system by reducing the threshold of pain. This effect is believed to be due inhibition of the actions of chemical mediators that sensitize the pain receptors to mechanical or chemical stimulation. The antipyretic (fever-reducing) activity is exerted by blocking the effects of the chemical pyrogen on the hypothalamic heat-regulating center. Additional mechanisms of action have also been suggested for acetaminophen, including inhibition of nitric oxide formation that results from activation of substance P and N-methyl-D-aspartate (NMDA) receptor stimulation. Active research is underway now in many laboratories to more specifically determine the mode of action of acetaminophen.
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