Overview of NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) (Beyond the Basics)

(www.uptodate.com)

NONSTEROIDAL ANTI-INFLAMMATORY DRUG OVERVIEW

Non-steroidal anti-inflammatory drugs (NSAIDs) are medications used to relieve pain and to reduce inflammation. They are some of the most commonly used medications in adults.

Because of the wide availability and frequency of use of NSAIDs, it is important to be aware of their proper use, dose, and potential side effects.

CHOOSING A NONSTEROIDAL ANTI-INFLAMMATORY DRUG

It can be difficult to know which NSAID is best for a given individual. In addition, a person’s response to a particular NSAID is hard to predict. If two people take identical drugs and doses, their individual responses may be considerably different. It is sometimes necessary to try one drug for a few weeks and to then try a different one to find the optimal NSAID.

TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Several NSAIDs are available as creams and gels for topical use. These agents have been shown to have similar benefits to taking NSAIDs in pill form in osteoarthritis and low back pain. Topical use may be safer than the pill form.

HOW NONSTEROIDAL ANTI-INFLAMMATORY DRUGS WORK

NSAIDs work to reduce pain and inflammation by inhibiting enzymes, called cyclooxygenases. By inhibiting cyclooxygenases, NSAIDs help to prevent and/or reduce pain and inflammation. Cyclooxygenase enzyme inhibition is also responsible for many of the side effects of NSAIDs.

TYPES OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

There are two main types of NSAIDs, non-selective and selective. The terms non-selective and selective refer to different NSAIDs’ ability to inhibit specific types of cyclooxygenase (COX) enzymes.

●Non-selective NSAIDs – Non-selective NSAIDs inhibit both COX-1 and COX-2 enzymes to a significant degree.

●Selective NSAIDs – Selective NSAIDs inhibit COX-2, an enzyme found at sites of inflammation, more than the type that is normally found in the stomach, blood platelets, and blood vessels (COX-1).

Non-selective NSAIDs — Non-selective NSAIDs include drugs commonly available without prescription, such as aspirin, ibuprofen and naproxen

Selective NSAIDs — Selective NSAIDs (also called COX-2 inhibitors) are as effective in relieving pain and inflammation as non-selective NSAIDs and are less likely to cause gastrointestinal injury. Celecoxib is a selective NSAID. Other selective NSAIDs include etoricoxib and lumiracoxib.

Selective NSAIDs are sometimes recommended for people who have had a peptic ulcer, gastrointestinal bleeding, or gastrointestinal upset when taking non-selective NSAIDs. Selective NSAIDs have less potential to cause ulcers or gastrointestinal bleeding.

Precautions with selective NSAIDs — People with known coronary artery disease (e.g., past history of heart attack, angina [chest pain due to narrowed heart arteries], history of a stroke, or narrowed arteries to the brain) and people who are at a higher than average risk for these conditions should avoid using COX-2 inhibitors. Of the non-selective NSAIDs, naproxen may be the safest for people with coronary artery disease.

Dose of NSAIDs — Lower doses of NSAIDs, as recommended for use. If the initial dose of NSAIDs does not improve symptoms, consider increasing the dose gradually or switching to another NSAID. Patient taking one NSAID should not be prescribed a second NSAID at the same time.

NONSTEROIDAL ANTI-INFLAMMATORY DRUG SIDE EFFECTS

Most people tolerate NSAIDs without any difficulty. However, side effects can occur. The most common side effects include the following:

●Cardiovascular system – Blood pressure may rise with use of NSAIDs. Control of treated hypertension may be adversely affected by the addition of either selective or non-selective NSAIDs.

●Gastrointestinal system – Short-term use of NSAIDs can cause stomach upset (dyspepsia). Long-term use of NSAIDs, especially at high doses, can lead to peptic ulcer disease and bleeding from the stomach.

●Liver toxicity – Long-term use of NSAIDs, especially at high doses, can rarely harm the liver. Monitoring the liver function with blood tests may be recommended in some cases.

●Kidney toxicity – Use of NSAIDs, even for a short period of time, can harm the kidneys. This is especially true in people with underlying kidney disease. The blood pressure and kidney function should be monitored at least once per year but may need to be checked more often, depending on a person’s medical conditions.

●Ringing in the ears – Ringing in the ears (tinnitus) is common in people who take high doses of aspirin, although it can also occur in people who take other NSAIDs. The ringing usually resolves when the dose is decreased.

MEDICAL CONDITIONS AND NONSTEROIDAL ANTI-INFLAMMATORY DRUGS:

People with some medical problems and those taking various medications are at increased risk of complications related to NSAIDs. Potential complications of NSAIDs include the following:

Hypertension — as noted above, the addition of either a selective or a non-selective NSAID to the medications taken by someone with hypertension can result in a loss of blood pressure control. If NSAIDs are required, they should be used at the lowest effective dose and for the shortest duration necessary for the given indication. If chronic use of NSAIDs is anticipated, changes in blood pressure medications may be required.

Cardiovascular disease — anyone who is at risk for or who has cardiovascular disease (coronary artery disease) may have a further increase in risk of heart attacks when taking an NSAID. This includes people who have experienced a heart attack, angina (chest pain due to narrowed arteries in the heart), a stroke, or narrowed arteries to the brain. As a result, people who have or who are at risk for coronary artery disease are generally advised to avoid NSAIDs or, if that is not possible, to take the lowest possible dose of NSAID for the shortest possible time.

Although aspirin is an NSAID, the recommendation to avoid or limit the use of NSAIDs does NOT apply to people who have been advised to take low-dose aspirin to treat or prevent heart attacks or strokes. However, the use of any dose of aspirin plus an NSAID is associated with an increased risk of bleeding. There is also some concern that non-selective NSAIDs may reduce the cardiovascular benefits of low dose aspirin.

Ulcer disease — Those who have had a stomach or intestinal ulcer are at an increased risk of another ulcer while taking an NSAID. People over 65 years of age have an increased risk of developing ulcers.

Reducing ulcer risk — The risk of developing ulcers can be reduced by taking an anti-ulcer medication in addition to an NSAID. Anti-ulcer agents that reduce gastrointestinal damage from NSAIDs include:

●Inhibitor of stomach acid production – High doses of antacid histamine blockers, such as famotidine, and ordinary doses of the acid production inhibitors, such as omeprazole or lansoprazole, can reduce the risk of developing an ulcer (related to use of an NSAID).

Bleeding — People who have had bleeding from the stomach, upper intestine, or esophagus have an increased risk of recurrent bleeding when taking NSAIDs.

People with platelet disorders such as von Willebrand disease, abnormal platelet function from uremia, and a low platelet count (thrombocytopenia) are advised to avoid NSAIDs.

Before surgery — Most clinicians recommend stopping all NSAIDs approximately one week before elective surgery to decrease the risk of excessive bleeding. This usually includes aspirin, ibuprofen, naproxen, and most prescription NSAIDs. Specific instructions regarding NSAIDs and surgery should be discussed with the surgeon and with the clinician who prescribed the NSAID.

Interaction with other medications

●Warfarin and heparin – People using anticoagulant medications such as warfarin (Coumadin) or heparin should generally not take NSAIDs or aspirin because of an increased risk of bleeding when both classes of drugs are used.
Celecoxib may be safe in such instances but should be used with caution and under the guidance of a clinician.

●Aspirin – As noted above, the combination of low-dose aspirin and an NSAID may increase the risk of bleeding. To preserve the benefit of low-dose aspirin for the heart, aspirin should be taken at least two hours before the NSAID.

●Phenytoin – Taking an NSAID and phenytoin can increase the phenytoin level. As a result, people who take phenytoin should have a blood test to monitor the phenytoin level when starting or increasing the dose of an NSAID.

●Cyclosporine – People who take cyclosporine (e.g., to prevent rejection after an organ transplant or for a rheumatic disease, such as rheumatoid arthritis) should take particular care when taking an NSAID. There is a theoretical risk of kidney damage when cyclosporine and NSAIDs are taken together. To monitor for this complication, blood testing may be recommended.

●People taking one NSAID should not take a second NSAID at the same time because of the increased risk of side effects.

Fluid retention — People with medical conditions that require diuretics, including heart failure, liver disease, and kidney damage, are at increased risk of developing kidney damage while taking non-selective NSAIDs (e.g., ibuprofen) as well as selective NSAIDs (e.g., Celecoxib).

Kidney disease — NSAIDs can worsen kidney function in people whose kidneys are not functioning normally. Most people with chronic kidney disease are advised to avoid NSAID. Similarly, NSAIDs should be used with extreme caution in elderly patients because of their declining kidney function.

Aspirin allergy — People who have had hives (urticaria) or other symptoms of an allergy to aspirin should generally avoid NSAIDs. People with certain types of reactions to one NSAID may be able to take another type safely. It may be necessary to consult with an allergy specialist who has experience with allergic reaction to NSAID.

Asthma: Aspirin and other NSAIDs may also cause worsening of asthma and related symptoms in some people with these conditions. This is not a true allergy but can be a significant problem for some people, who may need to avoid these medications if this occurs.

Celecoxib may be a safe alternative to aspirin in such people, but should be used with caution under the supervision of a clinician.

Pregnancy and breastfeeding — NSAIDs are not generally recommended for pregnant women during the third trimester due to an increased risk of complications in the newborn. NSAIDs are safe for use during breast feeding.