The Pros and Cons of Cyclooxygenase

Medications to curb COX might not be a good thing

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Pain and inflammation, a primary complaint of most people at some point in their lives and a common daily occurrence for many people with arthritis, is chiefly caused by cyclooxygenase, or COX, for short. 

COX is an enzyme that forms prostanoids—prostaglandins, prostacyclins, and thromboxanes—which are all responsible for the inflammatory response.

It turns out that COX is not all bad, it is even necessary for normal cellular processes.

Drugs aimed at inhibiting COX for relieving inflammation, seem like a good idea, but by inhibiting COX, there is a downside.

COX-1 Versus COX-2

In the 1990s, it was discovered there were two forms of the enzyme COX-1 and COX-2. The latter is the less desirable of the two. COX-1 is known to be present in most tissues. In the gastrointestinal tract, COX-1 maintains the normal lining of the stomach and protects the stomach from the digestive juices. The enzyme is also involved in kidney and platelet function. COX-2 is primarily found at sites of inflammation.

Both COX-1 and COX-2 can cause pain and inflammation, but since COX-1 is such a beneficial enzyme, using drugs to inhibit might not be such a good idea. 

NSAIDs Inhibit COX

Nonsteroidal anti-inflammatory drugs (NSAIDs), commonly prescribed to treat arthritis, work by inhibiting prostaglandins. Traditional NSAIDs, like ibuprofen and naproxen, can cause gastrointestinal problems including ulcers.

These NSAIDs are nonselective, meaning they inhibit both COX-1 and COX-2. The inhibition of COX-2 by traditional NSAIDs is helpful for its anti-inflammatory effects, but the downside is the inhibition of COX-1 can lead to side effects such as ulcers, prolonged bleeding time and kidney problems.

COX-2 Selective NSAIDs

In the late 1990s, drug companies developed several medications that targeted COX-2 only, these NSAIDs were Celebrex, Vioxx, and Bextra.

Of these, Celebrex is the only drug that remains on the market in the United States and has a black box warning that its carries a risk of heart attack and stroke.

Since the withdrawal of Vioxx in 2004, the U.S. Food and Drug Administration scrutinized the entire class of drugs, including all NSAIDs and COX-2 inhibitors that were sold over-the-counter or by prescription, and added black box warnings to the prescribing instructions.

Two other COX-2 inhibitors, Arcoxia and Prexige, which are in use in other countries, have been rejected by the FDA. Prexige was removed from the market in Australia and Canada due to related liver complications.

Some researchers believe, after finding low levels of COX-2 in some non-inflamed tissue, that COX-2 may also play a role in certain normal functions of the body other than inflammation. Researchers in the U.K. have found that COX-2 may protect against atherosclerosis, the medical term for artery hardening, narrowing and clogging.

While NSAIDs and COX-2 inhibitors are considered significant treatment options for arthritis patients, the benefit and risks must be considered for each individual patient. Cardiac risk and the best type of NSAID to use should be evaluated.


Arthritis Foundation. NSAIDs.

Bathon, Joan M. Discussion of Specific COX-2 Inhibitors. Johns Hopkins Arthritis Center. 

Kirkby N, Lundberg M, Wright W, Warner T, Paul-Clark M, Mitchell, J. COX-2 Protects against Atherosclerosis Independently of Local Vascular Prostacyclin: Identification of COX-2 Associated Pathways Implicate Rgl1 and Lymphocyte Networks. PLOS One. June 2, 2014.