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Nonsteroidal Antiinflammatory Drugs (NSAIDs)

What are NSAIDs and how do they work?

nsaidsProstaglandins are a 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 blood clotting function of platelets; 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 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 antiinflammatory 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 platelets and blood clotting also are reduced, NSAIDs can cause ulcers in the stomach 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. Ketorolac (Toradol) is only used for short-term treatment of moderately severe acute pain that otherwise would be treated with opioids. 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?

NSAIDs vary in their potency, duration of action, how they are eliminated from the body, how strongly they inhibit COX-1 and their tendency to cause ulcers and promote bleeding. The more an NSAID blocks COX-1, the greater is its tendency to cause ulcers and promote bleeding. One NSAID, celecoxib (Celebrex), blocks COX-2 but has little effect on COX-1, and is therefore further classified as a selective COX-2 inhibitor. Selective COX-2 inhibitors 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 inhibits the clotting of blood for a prolonged period (4 to 7 days). This prolonged effect of aspirin makes it an ideal drug for preventing blood clots that cause heart attacks and strokes.

Most NSAIDs inhibit the clotting of blood for only a few hours. Ketorolac (Toradol) is a very potent NSAID and is used for moderately severe acute pain that usually requires narcotics. Ketorolac causes ulcers more frequently than other NSAID. Therefore, it is 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 several side effects. The frequency of side effects varies among NSAIDs. 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 taken. 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 chickenpox or influenza has been associated with the development of Reye’s syndrome. Therefore, aspirin and non-aspirin salicylates [for example, salsalate (Amigesic)] should not be used in children and teenagers with suspected or confirmed chickenpox or influenza.

NSAIDs may increase the risk of potentially fatal, stomach and intestinal adverse reactions (for example, bleeding, ulcers, and perforation of the stomach or intestines). These events can occur at any time during treatment and without warning symptoms. Elderly patients are at greater risk for these adverse events. NSAIDs (except low dose aspirin) may increase the risk of potentially fatal heart attacks, stroke, and related conditions. This risk may increase with duration of use and in patients who have underlying risk factors for heart and blood vessel disease. NSAIDs should not be used for the treatment of pain resulting from coronary artery bypass graft (CABG) surgery.

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. When used with other drugs that also increase bleeding [for example, warfarin (Coumadin)], there is an increased likelihood of serious bleeding or complications of bleeding. Therefore, individuals who are taking drugs that reduce the ability of blood to clot should avoid prolonged use of NSAIDs.

Nonsteroidal antiinflammatory drugs also may increase blood pressure in patients with hypertension (high blood pressure) and therefore antagonize the action of drugs that are used to treat hypertension.

What NSAIDS are approved in the United States?

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

  • aspirin
  • celecoxib (Celebrex)
  • diclofenac (Voltaren)
  • diflunisal (Dolobid)
  • etodolac (Lodine)
  • ibuprofen (Motrin)
  • indomethacin (Indocin)
  • ketoprofen (Orudis)
  • ketorolac (Toradol)
  • nabumetone (Relafen)
  • naproxen (Aleve, Naprosyn)
  • oxaprozin (Daypro)
  • piroxicam (Feldene)
  • salsalate (Amigesic)
  • sulindac (Clinoril)
  • tolmetin (Tolectin)

Reference: FDA Prescribing Information

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