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NSAIDs (Nonsteroidal Antiinflammatory Drugs)

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What are NSAIDs and how do they work?

As the class name suggests, nonsteroidal antiinflammatory drugs (NSAIDs) reduce inflammation but are not related to steroids which also reduce inflammation. NSAIDs work by reducing the production of prostaglandins. Prostaglandins are chemicals that promote inflammation, pain, and fever. They also protect the lining of the stomach and intestines from the damaging effects of acid, promote blood clotting by activating blood platelets, and promote normal function of the kidneys.

The enzymes that produce prostaglandins are called cyclooxygenases (COX). There are two types of COX enzymes, COX-1 and COX-2. Both enzymes produce prostaglandins that promote inflammation, pain, and fever; however, only COX-1 produces prostaglandins that activate platelets and protect the stomach and intestinal lining.

NSAIDs block COX enzymes and reduce production of prostaglandins. Therefore, inflammation, pain, and fever are reduced. Since the prostaglandins that protect the stomach and promote blood clotting also are reduced, NSAIDs that block both COX-1 and COX-2 can cause ulcers in the stomach and intestines, and increase the risk of bleeding.

For what conditions are NSAIDs used?

NSAIDs are used for treating conditions that cause inflammation, mild to moderate pain, and fever. Examples include:

Ketorolac (Toradol) is only used for short-term treatment of severe pain that usually requires opioid treatment.

Aspirin is the only NSAID that is used for preventing strokes and heart attacks in individuals at high risk for such events.

Are there any differences between NSAIDs?

NSAIDs differ in potency and duration of action. They also differ in their tendency to cause ulcers and bleeding because they differ in their relative inhibition of COX-1 and COX-2.

  • Aspirin is the only NSAID that inhibits the clotting of blood for a prolonged period of time, four to seven days, and is therefore effective for preventing blood clots that cause heart attacks and strokes.

  • Ketorolac (Toradol) is a very potent NSAID and is used for treating severe pain that normally would be managed with narcotics. Ketorolac causes ulcers more frequently than other NSAIDs and should not be used for more than five days.

  • Celecoxib (Celebrex), blocks COX-2 but has little effect on COX-1. Therefore, celecoxib (Celebrex) is sub-classified as a selective COX-2 inhibitor, and it causes fewer ulcers and less bleeding than other "non-selective" NSAIDs.

Although NSAIDs have a similar mechanism of action, individuals who do not respond to one NSAID may respond to another. The reason for this is unclear.

What are the side effects of NSAIDs?

The most common side effects are:

NSAIDs also may cause swelling of the arms and legs due to the retention of fluid from their renal effects.

The most serious side effects are ulcers, bleeding, kidney failure, and, rarely, liver failure.

Individuals allergic to NSAIDs may experience shortness of breath after taking an NSAID and may experience a similar reaction when other NSAIDs are taken.

People with asthma are at higher risk for experiencing serious allergic reactions to NSAIDs.

Administering aspirin to children or teenagers with chickenpox or influenza has been associated with Reye's syndrome, a serious and potentially fatal disease of the liver. Therefore, aspirin and salicylates for example, salsalate (Disalcid), should not be used in children and teenagers with suspected or confirmed chickenpox or influenza.

NSAIDs (except aspirin) may increase the risk of heart attacks, stroke, and related conditions, which can be fatal. This risk may increase with duration of use and in patients who have underlying risk factors for disease of the heart and blood vessels. NSAIDs should not be used for the treatment of pain resulting from coronary artery bypass graft (CABG) surgery.

NSAIDs, particularly non-selective NSAIDs, cause an increased risk of serious, even fatal, stomach and intestinal adverse reactions such as 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 types of reaction.

Low doses of aspirin, less than 325 mg/day, taken for preventing heart attacks and strokes, also are associated with stomach and intestinal adverse reactions; however, the heart attack and stroke preventing actions of the low doses may compensate for the increased risk of these adverse reactions.

With which drugs do NSAIDs interact?

NSAIDs may reduce the benefit of drugs used for treating hypertension because NSAIDs may increase blood pressure. NSAIDs decrease the elimination of lithium (Eskalith) and methotrexate (Rheumatrex) potentially leading to their toxicity, and reduce the action of diuretics ("water pills") by reducing blood flow to the kidneys. NSAIDs increase bleeding by decreasing the activity of blood platelets and therefore formation of blood clots. When used with other drugs that also increase bleeding, for example, warfarin (Coumadin), the likelihood of bleeding complications is increased. Prolonged use of NSAIDs with drugs that increase bleeding should be avoided.

What are some examples of approved NSAIDS in the United States?

The following list contains only NSAIDs that are commonly used:

Reviewed by:
Tova Alladice, M.D.
American Board of Physical Medicine & Rehabilitation

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