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Nonsteroidal anti-inflammatory drugs

This is a group of drugs very commonly used in Pain treatment. The ones most commonly used include Paracetamol, Aspirin and Ibuprofen. This group of drugs has been used for many years: aspirin is derived from willow-bark, which was an old-fashioned folk remedy for pain.

These drugs are normally taken by mouth, though they can be given by injection, as suppositories or as creams absorbed locally through the skin.

How do they work?

NSAID’s work by preventing the formation of chemicals called prostaglandins which are involved in the production of pain, and the increased sensitisation to pain. More detail on how prostaglandins do this is given elsewhere on this site.

They work by reducing the actions of an enzyme called "cyclo-oxygenase" (COX). COX is present in many tissues throughout the body and inhibition of this enzyme reduces the amount prostaglandins present in these sites.

Prostaglandins have both beneficial and harmful roles. The harmful roles include inflammation and sensitisation of nerve endings.

More recent research has led to the discovery that there are at least two forms of COX. COX-1 is more involved in maintenance of normal function in the stomach and kidney and exists normally in these tissues. Inhibition of COX-1 can affect blood flow in these areas with potential side-effects. COX-2, however, is made more in the body as a result of inflammation and is involved in the harmful effects of prostaglandins. Most of the older-fashioned NSAIDs inhibit both COX-1 and COX-2 to varying degrees.

Recently, a few NSAIDs that selectively inhibit COX-2 have become available. These "COX-2 selective inhibitors" may reduce the risks of some of the side effects associated with NSAID therapy. This group of drugs includes Meloxicam and the “coxibs” including celecoxib, rofecoxib, etoricoxib and others.

Paracetamol has its effects at a slightly different site in the body from the other NSAID’s. It acts principally within the brain to reduce pain sensation.

What sort of pains do they work for?

NSAID’s are used for many different pains, chiefly those with an inflammatory basis. They are less effective for nerve pains.

There is a large variation between patients in how they respond to individual NSAID’s – there is therefore a potential benefit in trying a range to see if any particular one works best, taking into account the potential side-effects.

Are there any side-effects?

Side effects are relatively common with the NSAIDs. Gastrointestinal (GI) symptoms occur in about 10% of patients treated with the nonselective COX-1 and COX-2 NSAIDS, and ulcers occur in about 2%. The factors that have been associated with an increased risk of ulcers include advanced age, higher NSAID dose, administration of a corticosteroid drug along with the NSAID, a history of either ulcer disease or previous GI complications from NSAIDs, and probably heavy alcohol or cigarette use. Nausea and abdominal pain are poor predictors of serious GI toxicity and most patients who develop ulcers actually have no symptoms at all before the ulcer appears.

The risk of GI symptoms and ulcers also varies from drug to drug. In the large group of nonselective COX-1 and COX-2 NSAIDs, some are relatively less likely to cause these problems compared to the others. More importantly, the newer COX-2 selective drugs have been shown to reduce the risk of both GI symptoms and ulcer formation. The availability of these selective COX-2 selective drugs is widely considered to be an important advance for this reason. Still, there have not been enough scientific studies performed to know for sure whether the added cost of these drugs is balanced by their possible advantages. Most experts now feel that these drugs should be considered first-line at least for those patients who have a relatively increased risk of GI toxicity. The largest population for which this guideline would apply is the elderly.

The risk of ulcer also can be reduced by administering a so-called "gastroprotective" therapy along with the NSAID. The protective drugs include misoprostol; the so-called proton pump inhibitors, such as omeprazole and lansoprazole; and possibly higher doses of the H2 blockers, such as famotidine. Antacids can reduce symptoms but do not decrease ulcer risk.

All NSAIDs, including the selective COX-2 drugs, can cause kidney damage and must be used cautiously in patients who have known kidney disease or may have kidney disease because of advanced age or a disease. The kidney problems range from just swelling from fluid retention all the way to renal failure. Patients who receive these drugs should have kidney function monitored from time to time.

The nonselective NSAIDs inhibit the effects of platelets, which are cells in the blood stream that play an important role in clotting. Patients who take these drugs, therefore, have a relatively higher risk of bleeding. The selective COX-2 drugs have no effect on platelets.

Other useful pages:

The Arthrtis Research UK site has further excellent information on nonsteroidals.

 

 Links

Gloucestershire Joint Formulary website

 

 

 

 

 

 

 

 

 

 

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Pain Service Website, Gloucestershire Hospitals NHS Foundation Trust
Webmaster Dr J G de Courcy, Consultant in Pain Medicine and Anaesthesia
email: pain.webmaster[at]glos.nhs.uk

Page updated 19/02/2016