What are NSAIDs and how do they work?

Prostaglandins are a related family of chemicals that are produced by the cells of the body and have several important functions. They promote inflammation, pain, and fever , support the function of platelets that are necessary for the clotting of blood, and protect the lining of the stomach from the damaging effects of acid. Prostaglandins are produced within the body's cells by the enzyme cyclooxygenase (Cox). There actually are two Cox enzymes, Cox-1 and Cox-2 . Both enzymes produce prostaglandins that promote inflammation, pain, and fever. However, only Cox-1 produces prostaglandins that support platelets and protect the stomach. Nonsteroidal anti-inflammatory drugs (NSAIDs) block the Cox enzymes and reduce prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced. Since the prostaglandins that protect the stomach and support the platelets and blood clotting also are reduced, NSAIDs can cause ulcers in the stomach and promote bleeding. (NSAIDs do not cause bleeding, but they make bleeding worse, for example, when there is a cut.) NSAIDs differ in how strongly they inhibit Cox-1 and, therefore, in their tendency to cause ulcers and promote bleeding.

For what conditions are NSAIDs used?

NSAIDs are used primarily to treat inflammation, mild to moderate pain, and fever. Specific uses include the treatment of headaches, arthritis , sports injuries, and menstrual cramps . Aspirin (also an NSAID) is used to inhibit the clotting of blood and prevent strokes and heart attacks in individuals at high risk. NSAIDs also are included in many cold and allergy preparations.

Are there any differences between NSAIDs?

Yes. NSAIDs vary in their potency, duration of action, and the way in which they are eliminated from the body. Another important difference is their ability to cause ulcers and promote bleeding. The more an NSAID blocks Cox-1, the greater is its tendency to cause ulcers and promote bleeding Two NSAIDs, celecoxib (Celebrex) and rofecoxib (Vioxx), block Cox-2 but have little effect on Cox-1. These drugs are referred to as selective Cox-2 inhibitors and cause less bleeding and fewer ulcers than other NSAIDs. Aspirin is a unique NSAID, not only because of its many uses, but because it is the only NSAID that is able to inhibit the clotting of blood for a prolonged period (4 to 7 days). This prolonged effect of aspirin makes it an ideal drug for preventing the blood clots that cause heart attacks and strokes. (Most other NSAIDs inhibit the clotting of blood for only a few hours.) Ketorolac (Toradol) is a very potent NSAID and is used for moderately severe pain that usually requires narcotics. Ketorolac causes ulcers more frequently than any other NSAID and is, therefore, not used for more than five days. Although NSAIDs have a similar mechanism of action, individuals who do not respond to one NSAID may respond to another.

What are the side effects of NSAIDs?

NSAIDs are associated with a number of side effects. The frequency of side effects varies between the drugs. The most common side effects are nausea, vomiting, diarrhea , constipation , decreased appetite, rash, dizziness, headache, and drowsiness. NSAIDs may also cause fluid retention, leading to edema. The most serious side effects are kidney failure, liver failure, ulcers and prolonged bleeding after an injury or surgery. Some individuals are allergic to NSAIDs and may develop shortness of breath when an NSAID is administered. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID. Use of aspirin in children and teenagers with chicken pox or influenza has been associated with the development of Reye's syndrome. Therefore, aspirin and nonaspirin salicylates (e.g. salsalate ) should not be used in children and teenagers with suspected or confirmed chicken pox or influenza.

With which drugs do NSAIDs interact?

NSAIDs reduce blood flow to the kidneys and therefore reduce the action of diuretics and decrease the elimination of lithium (Eskalith) and methotrexate (Rheumatrex). NSAIDs also decrease the ability of the blood to clot and therefore increase bleeding time. When used with other drugs that also increase bleeding time, there is an increased likelihood of bleeding complications. Therefore, individuals who are taking drugs that reduce the ability of blood to clot should avoid prolonged use of NSAIDs. Nonsteroidal anti-inflammatory drugs may also increase blood pressure in patients with hypertension and therefore antagonize the action of drugs that are used to treat hypertension.

What are approved NSAIDS in the United States?

The complete list of approved NSAIDs is very long. The following list contains only NSAIDs that are commonly used:

• Aspirin
• Salsalate (Amigesic)
• Diflunisal (Dolobid)
• Ibuprofen (Motrin)
• Ketoprofen (Orudis)
• Nabumetone (Relafen)
• Piroxicam (Feldene)
• Naproxen (Aleve, Naprosyn)
• Diclofenac (Voltaren)
• Indomethacin (Indocin)
• Sulindac (Clinoril)
• Tolmetin (Tolectin)
• Etodolac (Lodine)
• Ketorolac (Toradol)
• Oxaprozin (Daypro)
• Rofecoxib (Vioxx)
• Celecoxib (Celebrex)

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