Cyclooxygenase: COX-1 and COX-2 Explained

What you need to know about Cyclooxygenase

Hand osteoarthritis. BSIP/UIG/Getty Images

The inflammatory response in your body involves an enzyme, cyclooxygenase (COX), that is responsible for the formation of prostanoids. The three main groups of prostanoids—prostaglandins, prostacyclins, and thromboxanes are key parts of how inflammation develops. But this is not the only action of the different forms of COX, which are involved in many normal cellular processes. COX is a target for drugs aimed at relieving inflammation, but by inhibiting COX, these drugs can have unwanted side effects.

Two Forms of Cyclooxygenase (COX)

In the 1990s, researchers discovered that two different COX enzymes existed, now known as COX-1 and COX-2. Cyclooxygenase-1 (COX-1) is known to be present in most tissues. In the gastrointestinal tract, COX-1 maintains the normal lining of the stomach. The enzyme is also involved in kidney and platelet function. Cyclooxygenase-2 (COX-2) is primarily present at sites of inflammation.

While both COX-1 and COX-2 convert arachidonic acid to prostaglandin, resulting in pain and inflammation, their other functions make inhibition of COX-1 undesirable while inhibition of COX-2 is considered desirable.

NSAIDs Inhibit COX

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

Traditional NSAIDs are considered "nonselective" because they inhibit both COX-1 and COX-2.

The inhibition of COX-2 by traditional NSAIDs accounts for the anti-inflammatory effect of the drugs while the inhibition of COX-1 can lead to NSAID toxicity and associated side effects (ulcers, prolonged bleeding time, kidney problems).

COX-2 Selective NSAIDs

In the late 1990s, the first COX-2 selective NSAID (Celebrex) was developed, and others soon followed.

Theoretically, drugs which were developed as COX-2 selective inhibitors—Celebrex, Vioxx, and Bextra—should have been preferred over traditional NSAIDs.

Vioxx and Bextra have since been removed from the market/ Celebrex remains available in the United States but has a black box warning that it carries a risk of heart attack and stroke. Since the withdrawal of Vioxx, the FDA scrutinized the entire class of drugs (all NSAIDs and COX-2 inhibitors, sold over-the-counter or by prescription only) and added black box warnings to the prescribing instructions.

Two other COX-2 inhibitors in development, Arcoxia, and Prexige have so far been rejected by the FDA. Prexige has also been 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. 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.

The research will be continuing into the use of these drugs and their side effects.


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

Hawkery, CJ. COX-1 and COX-2 Inhibitors. PubMed. 2001 Oct;15(5):801-20. 

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

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