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COX-2 inhibitors
COX-2 inhibitors are a class of drugs which selectively inhibit COX-2, an enzyme involved in the inflammation pathway, while sparing COX-1, thereby reducing gastrointestinal toxicity. COX-2 selective inhibitors are the newest of the NSAIDs (nonsteroidal anti-inflammatory drugs).
n April 2005, The U.S. Food and Drug Administration announced actions which will be taken regarding the marketing of NSAIDs (non-steroidal anti-inflammatory drugs). The actions include changes for COX-2 inhibitors, as well as prescription and non-prescription (over-the-counter) NSAIDs.
These actions by the FDA follow scrutiny of NSAIDs and COX-2 inhibitors provoked by the voluntary withdrawal of Vioxx by Merck in September 2004.
COX-2 inhibitors are newly developed drugs for inflammation that selectively block the COX-2 enzyme. Blocking this enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation. Cox-2 inhibitors are a new class of nonsteroidal anti-inflammatory drugs (NSAIDs). Because they selectively block the COX-2 enzyme and not the COX-1 enzyme, these drugs are uniquely different from traditional NSAIDs.
NSAIDs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications for the inflammation of arthritis and other body tissues, such as in tendinitis and bursitis. Examples of NSAIDs include Aspirin, indomethacin (Indocin), ibuprofen (Motrin), naproxen (Naprosyn), piroxicam (Feldene), and nabumetone (Relafen).
Common Side Effects of NSAIDs
The major common side effects of NSAIDs are related to the gastrointestinal system. Some 10%-50% of patients are unable to tolerate NSAID treatment because of side effects, including abdominal pain, diarrhea, bloating, heartburn, and upset stomach (dyspepsia). Approximately 15% of patients on long- term NSAID treatment develop ulceration of the stomach and duodenum. Even though many of these patients with ulcers do not have symptoms and are unaware of their ulcers, they are at risk of developing serious ulcer complications such as bleeding or perforation of the stomach.
Risk of NSAIDs
NSAIDs are taken regularly by approximately 33 million Americans! The annual risk of serious complications is 1%-4% with chronic NSAID treatment. The risk of complications is higher in elderly patients, rheumatoid arthritis sufferers, patients taking blood thinning medications (anticoagulants such as Coumadin and heparin) or prednisone (cortisone medication), and patients with heart disease or a prior history of bleeding ulcers.
NSAIDs cause stomach ulcers and bleeding
Prostaglandins are natural chemicals which are involved in body inflammation. By inhibiting the body's production of certain chemical messengers (prostaglandins), NSAIDs decrease inflammation. However, certain prostaglandins are also important in protecting the stomach lining from the corrosive effects of stomach acid as well as maintaining the natural, healthy condition of the stomach lining. By disrupting the production of prostaglandins in the stomach, NSAIDs can cause ulcers and bleeding.
Traditional NSAIDs and newly designed COX-2 inhibitors
Cyclooxygenase-1 (COX-1) is an enzyme which is normally present in a variety of areas of the body, including sites of inflammation and the stomach. The COX-1 enzyme of the stomach produces certain chemical messengers (called prostaglandins) that ensure the natural mucus lining which protects the inner stomach. Common anti-inflammatory drugs like aspirin block the function of the COX-1 enzyme along with another enzyme, COX-2 (see below). When the COX-1 enzyme is blocked, inflammation is reduced, but the protective mucus lining of the stomach is also reduced, which can cause stomach upset, ulceration, and bleeding from the stomach and intestines.
Another enzyme, cyclooxygenase-2 (COX-2), also produces these chemical messenger molecules, but the COX-2 enzyme is located specifically in areas of the body that are responsible for inflammation and not in the stomach. When the COX-2 enzyme is blocked, inflammation is reduced. Since the COX-2 enzyme does not play a role in the normal function of the stomach or intestinal tract, medications which selectively block COX-2 do not present the same risk of injuring the stomach or intestines.
Newly developed drugs that selectively block the COX-2 enzyme are called COX-2 inhibitors. Blocking this enzyme impedes the production of the prostaglandins that cause the pain and swelling of arthritis inflammation. The common anti-inflammatory drugs (like aspirin, ibuprofen, and naproxen) all act by blocking the action of both the COX-1 and COX-2 enzymes.
The COX-2 inhibitors represent a new class of drugs that do not affect COX-1, but selectively block only COX-2. This selective action provides the benefits of reducing inflammation without irritating the stomach. These drugs pose a advantage in comparison to previous anti- inflammatory drugs because their mechanism of action carries nowhere near the risk of stomach ulceration and bleeding. The COX-2 inhibitor is now on the market in the form of celecoxib (Celebrex). It is widely expected that COX-2 inhibitors will be of great value to people with arthritis and variety of pain conditions.
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