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COX is an enzyme that produces pain and inflammation signals. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX, but can cause peptic ulcers. COX-1 is present in most cells, while COX-2 generates signals that cause inflammation and pain. Prostaglandins, produced by both types of COX, are a type of fatty acid that affect nearby cells. Omega-6 and omega-3 fatty acids can produce less inflammatory prostaglandins. Selective COX-2 inhibitors like celecoxib and etoricoxib cause less stomach irritation, but maintain other side effects like increased kidney failure and possibly an increased risk of stroke and heart attack.
Cyclooxygenase, or COX, is an enzyme that produces signals that can lead to pain and inflammation. Inhibitors of this type of enzyme are known as nonsteroidal anti-inflammatory drugs (NSAIDs). These include pain relievers and fever reducers, such as aspirin, ibuprofen and naproxen. When taken consistently, over time, for conditions like arthritis, these compounds can lead to peptic ulcers. A new generation of COX inhibitors has been developed in hopes of minimizing these side effects.
There are two main types of cyclooxygenases found in the human body. The first is known as COX-1. This enzyme is present in most cells and acts as part of normal cellular maintenance, such as maintaining the stomach lining. COX-2, on the other hand, is produced in response to a specific stress and generates signals that cause inflammation and pain.
Both types of cyclooxygenases form a class of compounds that include prostaglandins. These compounds are like hormones. They differ, however, in that the hormones act at a distance. Prostaglandins produce short-lived signals and affect only nearby cells or the same cells that produce them. These compounds are a type of fatty acid, are 20 carbon atoms long, and have a five-carbon ring at the end of the chemical.
There are many types of prostaglandins, but the parent compound is produced from the polyunsaturated fatty acid arachidonic acid. Several types of prostaglandins, which cause less inflammation, can be produced from omega-6 and omega-3 fatty acids, which are obtained from fish oil in the diet. These fatty acids may be preferentially utilized by cyclooxygenase, rather than arachidonic acid, and may help reduce inflammation.
Aspirin is a traditional and very effective cyclooxygenase inhibitor. Unfortunately, it inhibits both COX-1 and COX-2. Therefore, in addition to reducing pain and fever, it can cause serious stomach problems, such as ulcers. This is a common side effect of NSAIDs. An additional side effect includes an increased tendency to kidney failure.
These side effects led to the search for a selective COX-2 inhibitor. A new class of NSAIDs targeting primarily COX-2 has been developed. These drugs were expected not to have the side effects of the original NSAIDs.
As expected, the specific COX-2 inhibitors caused much less stomach irritation and less bleeding. Unexpectedly, they also maintained the other side effects of traditional NSAIDs, such as increased kidney failure. There’s also concern about additional possible negative side effects, such as an increased risk of stroke and heart attack.
Drugs in this class that remain available for use include celecoxib and etoricoxib. Due to concern about their potential side effects, some health professionals advise against their use. Rofecoxib, better known as Vioxx®, was withdrawn from the market in 2004 due to safety concerns.
