COX-2 Inhibitors - Targeting an Enzyme Associated With Inflammation

COX-2 Are Gastroprotective NSAIDs

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Cyclooxygenase (COX) is an enzyme that is involved with formation of prostanoids. There are three main groups of prostanoids (prostaglandins, prostacyclins, and thromboxanes), each playing a role in the inflammatory response. Researchers identified two different COX enzymes in the 1990s, called COX-1 and COX-2.

COX-1 and COX-2

Cyclooxygenase-1 (COX-1) is present in most tissues. COX-1 maintains the normal lining of the stomach and it is also involved in kidney and platelet function.

Cyclooxygenase-2 (COX-2) is mostly present at sites of inflammation. While both COX-1 and COX-2 convert arachidonic acid to prostaglandin, causing pain and inflammation, their other functions in the body make COX-1 inhibition undesirable, while COX-2 inhibition was thought to be more desirable.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for arthritis and have been for years. The drugs work by inhibiting prostaglandins. It is known that traditional NSAIDs (such as ibuprofen, naproxen) can cause gastrointestinal problems, including bleeding ulcers. Traditional NSAIDs inhibit both COX-1 and COX-2. The inhibition of COX-2 by traditional NSAIDs produces the anti-inflammatory effect, but inhibition of COX-1 can lead to the undesirable side effects.

On the other hand, COX-2 inhibitors inhibit COX-2 while sparing COX-1, reducing the risk of side effects, especially gastrointestinal toxicity.

The first COX-2 selective NSAID developed was Celebrex (celecoxib). Then, Vioxx (rofecoxib), and Bextra (valdecoxib) followed.

FDA Adds Warnings

In April 2005, the U.S. Food and Drug Administration (FDA) announced actions that would affect the marketing of prescription and non-prescription NSAIDs, as well as the newer COX-2 inhibitors.

The actions followed scrutiny of NSAIDs and COX-2 inhibitors after the withdrawal of Vioxx by Merck in September 2004.

Based on scientific data, including post-marketing data, and a joint meeting of the FDA's Arthritis and Drug Safety and Risk Management Advisory Committees held in February 2005, the FDA decided to remove Bextra from the market (removed in April 2005) and add warnings to the label of all NSAIDs.

Two other COX-2 inhibitors which were being developed, Arcoxia and Prexige, were rejected by the FDA. Prexige was also removed from the market in Australia and Canada due to the risk of liver complications.

It is believed that COX-2 may play a role in certain normal body functions, besides its role in inflammation. As with any treatment, each individual patient must weigh benefits and risks before using NSAIDs or Celebrex, the one remaining COX-2 inhibitor. Discuss the drugs with your doctor.


Prostanoid Biology and Its Therapeutic Targeting. Leslie J. Crofford. Part 8 Chapter 59. Kelley's Textbook of Rheumatology. Elsevier. Ninth edition.

COX-1 and COX-2 Inhibitors. PubMed. Hawkey CJ. 2001 Oct.

COX-2 Inhibitors and Cardiovascular Risk. Mike Schachter. Br J Cardiol 10(4):288-292, 2003. Accessed via Medscape.

Questions and Answers: FDA Regulatory Actions for the COX-2 Selective and Non-Selective Non-Steroidal Anti-inflammatory drugs (NSAIDs). FDA/Center for Drug Evaluation and Research. April 7, 2005.

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