Different types of COX-2 inhibitors

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

COX-2 drugs are anti-inflammatory drugs that selectively block the cyclooxygenease-2 pathway.

To better understand, let’s discuss the mechanism of action...

The membranes of cells contain a molecule called “arachadonic acid.” As cell turnover takes place, arachadonic acid is released into body tissues and blood. An enzyme called cyclooxygenase (“COX”) acts on arachadonic acid to form substances called “prostaglandins.”

There are many different types of prostaglandins. Some prostaglandins help protect the body. For example, they help the stomach resist ulcer formation. Other prostaglandins cause pain and inflammation.

In the early 1990’s it was found that there are actually two forms of COX: COX-1 and COX-2.

COX-1 is promotes the synthesis of prostaglandins that protect normal metabolic functions. COX-2 is responsible for producing prostaglandins that contribute to inflammation. Traditional non-steroidal anti-inflammatory drugs (such as ibuprofen, aspirin etc.) interfere with both COX-1 and COX-2.

So… traditional non-steroidal anti-inflammatory drugs block inflammation, but they also induce side-effects such as stomach ulcers. The aim of COX-2 drugs has been to block COX-2 but leave COX-1 untouched. Drugs that do this are referred to as selective “COX-2 inhibitors.” Selective Cox-2 inhibitors appear to have less gastrointestinal toxicity.

However there have been problems. The first is that COX-2 drugs, when combined with aspirin, do not protect the stomach any more than a non-selective NSAID does. The second is that COX-2 drugs still have the same adverse effects on kidney function as do the traditional NSAIDS.

Finally, more recently, concerns regarding cardiovascular toxicity (heart attacks and strokes) have led to the removal of rofecoxib (Vioxx) and valdecoxib (Bextra) as well as increased scrutiny of celecoxib (Celebrex).

Recent evidence though, suggests that all anti-inflammatory drugs, regardless of whether they are COX-1 or COX-2, have an increased risk of cardiovascular events associated with them. In fact, some non-selective NSAIDS probably carry a greater risk of cardiovascular events than Celebrex.

Of note, is the potential for Cox-2 drugs to prevent the development of colon cancer seen in some clinical trials.

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