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Cox-II Inhibitors

Launched in 1998, COX II inhibitors are a recent addition to the nonsteroidal anti-inflammatory drugs (NSAIDS) family.  Though not necessarily more effective at reducing inflammation and pain than older, traditional nonsteroidal anti-inflammatory drugs such as aspirin and naproxen, they represented an advance over the older drugs because they were believed to cause less stomach irritation.  However, COX-2 inhibitors are still classified as NSAIDS.  Some doctors recommended that you not take them on an empty stomach. 

They are called COX-2 inhibitors because they block an enzyme called "Cyclooxygenase".  "Cyclooxygenase" is believed to trigger pain and inflammation in the body.  If you block the COX-2, you block the inflammation.

There was disagreement surrounding the use of COX II inhibitors.  Several scientists thought that their use was associated with a increased risk of cardiovascular events such as heart attack. 

Beginning in 1999, researchers reported that this class of drugs also appears to suppress prostacyclin (PGI2), a hormone-like substance that enlarges blood vessels and decreases blood clotting.

Prostacyclin is largely produced   by vascular endothelium and smooth muscle. Inhibiting the COX-2 enzyme may also inhibit endothelial cell function.  Endothelial cell are the cells that make up the inside of the wall of the blood vessels. 

The endothelial cells produce PGI2 (vasodilators) as well as other anti-coagulants such as T-PA, thrombomodulin, nitrate oxide (NO) and heparin sulfates.  These complex chemicals keep the blood vessels wide open and free of tiny blood clots.

The scientists supposed that when a COX 2 inhibitor blocks pain and swelling caused by cyclooxygenase, the COX-2 inhibitor also restrains the backing protective mechanisms that the human body has developed to insure that blood clots remain under control.

The other group of scientists said that this outcome had not been verified conclusively and that COX-2's are less harmless than an aspirin and other NSAIDS since they are gentler on the stomach and cause less bleeding and perforation, and that this stomach safety outweighs the unproven heart attack claims.

As an act of caution, Merck voluntarily withdrew Vioxx from the market.  This action brought about an avalanche of lawsuits by people claiming that they or their loved ones suffered heart attacks as a result of taking Vioxx.