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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 non-steroidal anti-inflammatory drugs (NSAIDs). These include painkillers 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 cyclooxygenase that are 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 housekeeping, such as maintaining the stomach’s lining. COX-2, in contrast, is produced in response to specific prompting and generates signals that result in inflammation and pain.
Both types of cyclooxygenase make a class of compounds including prostaglandins. These compounds are like hormones. They differ, however, in that hormones act over a distance. Prostaglandins produce signals that are short-lived and only affect nearby cells, or the same cells that produce them. These compounds are a type of fatty acid, are 20 carbons 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. Different types of prostaglandins, that 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 can be used by cyclooxygenase preferentially, instead of arachidonic acid, and can help reduce inflammation.
Aspirin is a traditional and very effective inhibitor of cyclooxygenase. Unfortunately, it inhibits both COX-1 and COX-2. Thus, in addition to reducing pain and fever, it can cause severe stomach problems, like ulcers. This is a common side effect of the NSAIDs. An additional side effect includes an increased tendency towards kidney failure.
These side effects led to the search for a COX-2 selective inhibitor. A new class of NSAID was developed that primarily targeted COX-2. It was expected that these drugs would lack 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 retained the other side effects of the traditional NSAIDs, such as increased kidney failure. There is also concern about additional possible negative side effects, such as an increased risk for 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 removed from the market in 2004 due to safety concerns.
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