Selective COX-2 inhibitors

background

Selective COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that are used to reduce inflammation (swelling) and pain (analgesic). The term "nonsteroidal" is used to distinguish the drugs from steroids, which have similar eicosanoid-depressing and anti-inflammatory properties. NSAIDs are non-narcotic and are therefore non-addictive.
There are two types of NSAIDS: traditional (non-selective) NSAIDs and selective COX-2 inhibitors. Traditional NSAIDs, such as ibuprofen (Motrin® or Advil®), block the actions of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, the key enzymes that stimulate inflammation. COX-1 protects the stomach lining from harsh acids and digestive chemicals and helps maintain kidney function. The body produces COX-2 when the joints are injured or inflamed.
Selective COX-2 inhibitors are prescription drugs that only target the COX-2 enzyme. They are commonly used to treat pain and inflammation associated with arthritis.
Celecoxib (Celebrex®) is currently the only U.S. Food and Drug Administration (FDA) approved COX-2 inhibitor. Two other selective COX-2 inhibitors, rofecoxib (Vioxx®) and valdecoxib (Bextra®), were removed from the market after reports of serious side effects such as heart attack and stroke.
Celebrex® has also been linked to an increased risk of serious heart-related problems, including heart attack and stroke. It is also well documented that COX-2 inhibitors increase the risk of stomach bleeding, which can be life threatening. It appears that these risks also apply to traditional NSAIDs as well. Therefore, the FDA requires that all NSAIDs, including COX-2 inhibitors, print serious warning labels that highlight the risk of potential heart-related side effects and stomach bleeding. The labels must also state that patients who have recently had heart surgery should not take NSAIDs.

Related Terms

Analgesic, anti-inflammatory, arthritis, biological mediators, cardiovascular events, Celebrex®, COX, COX 1, COX 2, COX enzymes, cyclooxygenase, edema, eicosanoid-depressing inflammation, fluid retention, heart attack, inflammation, liver damage, nonsteroidal anti-inflammatory drugs, NSAIDS, osteoarthritis, pain relief, pain relievers, prostaglandins, rheumatoid arthritis, stomach ulcers, stroke, swelling, ulcers.

function

The cyclooxygenase (COX) enzymes are responsible for producing prostaglandins, which are biological mediators that cause inflammation. COX-1 enzymes protect the stomach lining from harsh acids and digestive chemicals and helps maintain kidney function. The body produces COX-2 enzymes when the joints are injured or inflamed.
COX-2 inhibitors, such as celecoxib (Celebrex®), only target the COX-2 enzyme that stimulates inflammation. Since these medications do not block the actions of the COX-1 enzyme, these medications generally do not cause the kind of stomach upset that is often associated with traditional nonsteroidal anti-inflammatory drugs (NSAIDs).
However, some studies have not shown any difference between the incidence of gastrointestinal side effects from traditional NSAIDs and COX-2 inhibitors. Also, COX-2 inhibitors do not offer the same kind of protection against heart disease as traditional NSAIDs. COX-2 inhibitors are often prescribed for long-term conditions, such as arthritis, because they may be safer for the stomach than traditional NSAIDs.

preparations

Celecoxib (Celebrex®): Celecoxib (Celebrex®) is currently the only U.S. Food and Drug Administration (FDA) approved COX-2 inhibitor. However, the FDA is currently evaluating several studies, including long-term studies conducted by the National Institutes of Health (NIH), which suggest that the risk of cardiovascular events (such as heart attack and stroke) may be increased in patients taking Celebrex®.
Rofecoxib (Vioxx®): On September 27, 2004 rofecoxib (Vioxx®) was voluntarily withdrawn from the market due to an increased risk of heart attack and stroke. Currently, it is unclear whether this side effect occurs with other COX-2 inhibitors as well, or if it is specific to Vioxx®. When the medication was withdrawn, Vioxx® was one of the most widely used medications in the world.
Valdecoxib (Bextra®): On April 7, 2005, Pfizer agreed to suspend sales and marketing of Bextra® in the United States, pending further discussions with the FDA.

uses

Selective COX-2 inhibitors are used to relieve pain and reduce inflammation. They are commonly used to relieve symptoms of osteoarthritis (type of arthritis that causes the cartilage to deteriorate), rheumatoid arthritis (autoimmune disorder that causes pain and inflammation of the joints), as well as to manage sudden pain in adults (such as short-term pain after a dental or surgical operation) and to treat painful menstruation cycles. They have also been used to reduce the number of colorectal polyps (abnormal growths in the colon and rectum) in patients who have familial adenomatous polyposis (FAP). Celebrex® is typically used along with the usual treatment for FAP patients.

side effects

General: Celebrex® has recently been linked to an increased risk of serious heart-related side effects, including heart attack and stroke. Selective COX-2 inhibitors have also shown to increase the risk of stomach bleeding, which can be life threatening. It appears that these risks also apply to traditional NSAIDs as well. Therefore, the U. S. Food and Drug Administration (FDA) requires that all NSAIDs, including COX-2 inhibitors, print serious warning labels that highlights the risk of potential heart problems and stomach bleeding. The labels must also state that patients who have recently had heart surgery should not take NSAIDs.
Fluid retention: COX-2 inhibitors may cause fluid retention (retaining water in the body) and swelling. Fluid retention can be a serious problem in patients who have high blood pressure or heart failure.
Stomach ulcers that bleed: The risk of developing stomach ulcers that bleed increases the longer the drug is taken. However, stomach ulcers can also develop suddenly. Patients are advised to stop taking medication and consult their healthcare providers if they experience a burning stomach pain, black bowel movements that look like tar, or vomit that contains blood or looks like coffee grounds.
Kidney problems: COX-2 inhibitors can cause kidney problems, including sudden kidney failure. Patients who have existing kidney problems may experience a worsening of symptoms.
Liver damage: COX-2 inhibitors may cause liver damage. Symptoms of liver damage include nausea, vomiting, tiredness, loss of appetite, itching, jaundice (yellow skin or eyes), flu-like symptoms and dark urine. Patients who experience such symptoms should consult their qualified healthcare providers.
Other: Other common but less severe symptoms include headache, indigestion, upper respiratory tract infection, diarrhea, sinus inflammation, stomach pain, and nausea.

precautions

Avoid in patients who have had an allergic-type reaction to sulfa medicines because these patients are likely to experience an allergic reaction to selective COX-2 inhibitors as well.
Avoid in patients who have experienced asthma, hives, or allergic-type reactions after taking aspirin or other NSAIDs.
Avoid in patients who have heart problems (such as high blood pressure) and in those who recently had heart surgery because they have an even higher risk of experiencing heart problems, such as heart attack or stroke.
Avoid in patients with kidney or liver disease because selective COX-2 inhibitors may worsen their symptoms.
Avoid if pregnant or breastfeeding because the drug can crossover to the placenta or enter breast milk and potentially cause side effects in the fetus or infant.
Patients should tell their healthcare providers if they are taking any drugs (prescription or over-the-counter), herbs, or supplements because they can potentially interact with COX-2 inhibitors. COX-2 inhibitors are known to interact with ACE inhibitors (blood pressure medications) such as enalapril (Vasotec® or Renitec®), ramipril (Altace®, Tritace®, Ramace®, or Ramiwin®), furosemide (Lasix®, fluconazole (Diflucan®), ketoconazole (Nizoral®), phenytoin (Dilantin®), warfarin (Coumadin®), and aspirin (Bayer® or Excedrin®).