The Nsaid Debate

NSAIDs of all types are commonly used for pain that is mild to moderate in intensity. They can be used for pain that is inflammatory and as an analgesic for low-level pain or as a coanalgesic. They are available in different combinations in both prescription strength and over-the-counter preparations. They do have a maximum dose that limits dose escalation beyond the maximum dose ceiling (Exhibit 3.2).

NSAIDs have two different types of actions: selective and non-selective.

■ Selective NSAIDs protect the prostaglandins that coat the stomach lining but do affect the other type of prostaglandins found elsewhere in the body.

■ Nonselective NSAIDs affect all types of prostaglandins found in the stomach, kidneys, heart, and other organs of the body.

The most common use of NSAIDs is to treat pain that is caused by inflammation, such as arthritis or common musculoskeletal injuries (APS, 2008; D'Arcy, 2007).

NSAIDs have long been a standard for pain relief in older patients. Relatively cheap, they are easily accessible at most supermarkets or drug stores. They are available as over-the-counter formulations and in prescription strength as well. The most common uses are for arthritis pain, headaches, and minor sprains and strains.

Exhibit 3.2

Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs.)

(See the end of this Medication Guide for a list of prescription NSAID medicines.)

What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:

• with longer use of NSAID medicines

• in people who have heart disease

NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft (CABG)."

NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:

• can happen without warning symptoms

The chance of a person getting an ulcer or bleeding increases with:

• taking medicines called "corticosteroids" and "anticoagulants"

• drinking alcohol

• having poor health

NSAID medicines should only be used:

• exactly as prescribed

• at the lowest dose possible for your treatment

• for the shortest time needed

What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:

• different types of arthritis

• menstrual cramps and other types of short-term pain

Who should not take a Non-Steroidal

Anti-Inflammatory Drug (NSAID)?

Do not take an NSAID medicine:

• if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine

• for pain right before or after heart bypass surgery

Tell your healthcare provider:

• about all of your medical conditions.

• about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist.

• if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.

• if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Serious side effects include:

• high blood pressure

• heart failure from body swelling (fluid retention)

• kidney problems including kidney failure

• bleeding and ulcers in the stomach and intestine

• life-threatening skin reactions

• life-threatening allergic reactions

• liver problems including liver failure

• asthma attacks in people who have asthma

Other side effects include:

• constipation



Get emergency help right away if you have any of the following symptoms:

• shortness of breath or trouble breathing

• weakness in one part or side of your body

• slurred speech

• swelling of the face or throat

Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:

• more tired or weaker than usual

• your skin or eyes look yellow

• flu-like symptoms

• there is blood in your bowel movement or it is black and sticky like tar

• skin rash or blisters with fever

• unusual weight gain

• swelling of the arms and legs, hands and feet

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.

Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines. Some of these NSAID medicines are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

NSAID medicines

that need a


Generic Name





Cataflam, Voltaren, Arthrotec (combined with misoprostol)




Lodine, Lodine XL


Nalfon, Nalfon 200




Motrin, tab-profen, Vicoprofen* (combined with hydrocodone), Combunox (combined with oxycodone)







mefenamic acid







Naprosyn, Anaprox, Anaprox DS, EC-Naprosyn, Naprelan, PREVACID NapraPAC (copackaged with lansoprazole)








Tolectin, Tolectin DS, Tolectin 600

*Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC) NSAIDs, and is usually used for less than 10 days to treat pain. The OTC NSAID label warns that long term continuoususe may increase the risk of heart attack or stroke.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

There are two basic classes of NSAIDs: nonselective and selective NSAIDS and COX-2 selective medications. The nonselective NSAIDs, such as ibuprofen (Motrin, Advil), naproxen (Naprosyn), and ketoprofen (Orudis), affect production of the prostaglandins that coat and protect the lining of the stomach and those that are found in other organs of the body, such as the kidneys and heart. The only COX-2 medication available at this time is Celebrex, which spares the stomach prostaglandins and does not affect platelet aggregation, so blood clotting is not affected.

Newer research from the FDA indicates that all NSAIDs, not just the COX-2 selective medications such as Celebrex, have the potential for increased cardiovascular risk, renovascular risk, stroke, and myocardial infarction (D'Arcy, 2007). GI bleeding with NSAIDs continues to be a risk; for those patients who are taking aspirin as a cardiac prophylaxis, the risk increases several fold with concomitant NSAID and aspirin use (D'Arcy, 2007).

GI Risks With NSAIDs

One of the major risks with nonselective NSAIDs is gastric ulceration. Gastric ulcers develop in about 30% of patients started on nonselective NSAIDs within a week. Most patients with these ulcers are asymptomatic and only seek medical care when the bleeding becomes obvious with tarry stools or hematemesis.

In an effort to lessen the risk of GI bleeding, some practitioners commonly use a proton pump inhibitor (PPI), such as omeprazole (Prilosec), which only provides protection for the upper GI system. Adherence of patients taking a PPI for protection is also suspect. A recent study found that by the time the patients received three prescriptions for a PPI as NSAID prophylaxis, the nonadherence rate for patients taking PPIs was 60.8%.

Because many older patients are also using an aspirin a day for cardioprotective effect, adding the incidence of ulcer formation with aspirin to the NSAID risk only increases the potential for GI bleeding.

Higher doses and older age are associated with a higher incidence of GI side effects. Additionally, chronic alcohol use with these medications increases the risk of GI bleeding and ulceration. Whether GI issues are a consideration depends largely on the individual patient's history and medical situation.

Cardiovascular Risks With NSAIDs

Thiere are certain patient groups who are at higher risk for cardiovascular events and for whom NSAIDs are not recommended, including those patients who have had recent heart bypass surgery, patients with heart disease, and patients who have had transient ischemic attacks, or strokes. For these patients, an alternate form of analgesic is recommended.

When trying to determine which NSAID to offer a patient, consider that there are indications that naproxen interferes with the inhibitory effect of aspirin, and the same effect may be seen with concomitant use of ibuprofen, acetaminophen, and diclofenac. Overall, for patients taking aspirin as a prophylaxis, there is an increased risk of GI events, and using NSAIDs may decrease the effectiveness of the aspirin.

In general, the recommendations for using NSAIDs for pain relief indicate that the medication should be used at the lowest dose for the shortest period of time. That being the case, older patients should be aware that continuing to take NSAIDs long term for arthritis or other chronic conditions could cause serious, life-threatening effects.

New Options with NSAIDs

In an effort to minimize the adverse effects of NSAIDS newer formulations of NSAIDs have been developed to help circumvent the need for the medications to be taken orally. Some of the medications are in patch form while others are in liquid or cream form to be applied directly to the joints. These medications include

■ Diclofenac sodium (Voltaren) 1% gel. Used for localized relief of pain in joints, elbows or knees. The gel is applied four times per day and it is readily absorbed into the skin.

■ Diclofenac epolamine topical patch 1.3% (Flector). Applied directly to the site of injury this patch is used for the pain of minor strains and sprains with repeated application showing diclofenac sodium levels well below the plasma level of a single oral dose (Rusca, Mautone, Sun, Magelli, Johnson, 2008)

■ Diclofenac topical solution 1.5% (Pennsaid). A new liquid NSAID analgesic used for osteoarthritis of the knee. Uses dimethyl sulfoxide (DMSO) as a vehicle to penetrate the skin. To use the solution the patient applies 10 drops to each side of the knee with a total dose of 40 drops four times per day (See Chapter 5).

Although these medications are topical they still have the potential risks of all NSAIDs. As with all NSAIDs these topical preparations should still be used for limited time and cardiac, skin and renovascular complications are still a possibility. Patients should be educated about the potential adverse effects of these drugs and instructed to call their care provider if any unexpected effects occur.

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