Nonsteroidal anti-inflammatory drug

Nonsteroidal anti-inflammatory drugs, or NSAIDs, are a class of medications used to treat pain, inflammation, and fever, and they also have blood-thinning effects. Their mechanism involves blocking the activity of two cyclooxygenase enzymes, COX-1 and COX-2, which the body uses to produce prostaglandins (involved in inflammation) and thromboxanes (involved in clotting). The term "nonsteroidal" came into common use around 1960 to set these drugs apart from corticosteroids, another class of anti-inflammatories that had developed a poor reputation in the 1950s due to overuse and side effects after their introduction in 1948.

Most NSAIDs are non-selective, meaning they inhibit both COX-1 and COX-2. This reduces inflammation but also interferes with platelet aggregation and raises the risk of gastrointestinal ulcers and bleeding. COX-2 selective inhibitors cause fewer stomach problems but can promote thrombosis, and some, like rofecoxib, have been taken off the market because they significantly increase the risk of heart attack. These differences stem from the distinct roles and locations of each COX enzyme in the body. By interfering with normal COX activity, NSAIDs can also harm kidney function, and the resulting water and sodium retention, along with reduced renal blood flow, may contribute to heart problems. Well-known examples include aspirin, ibuprofen, diclofenac, and naproxen, all available over the counter. Paracetamol (acetaminophen) is generally not considered an NSAID because it has only minor anti-inflammatory effects.

Side effects depend on the specific drug, dose, and how long it is used, but they largely include a higher risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease. An estimated 10–20% of people taking NSAIDs experience indigestion. In the 1990s, high doses of prescription NSAIDs were linked to serious upper gastrointestinal issues.

**Medical uses** NSAIDs are often recommended for acute or chronic conditions involving pain and inflammation. They are used for symptomatic relief in a variety of situations. For chronic pain and cancer-related pain in children and adolescents, the evidence is not clear due to a lack of high-quality randomized controlled trials.

Differences in anti-inflammatory activity among individual NSAIDs are small, but patients vary widely in their response and tolerance. About 60% of patients will respond to any given NSAID; those who do not respond to one may respond to another. Pain relief begins soon after the first dose, with full analgesic effect usually within a week, while an anti-inflammatory effect may take up to three weeks. If no appropriate response occurs within these timeframes, a different NSAID should be tried.

For surgical pain, there is low-certainty evidence that starting NSAIDs in adults before surgery may reduce post-operative pain and the amount of opioids needed afterward. The risks of increased surgical bleeding, gastrointestinal bleeding, heart attacks, or kidney injury have not been well studied. Combining NSAIDs with paracetamol may improve pain relief after surgery.

Aspirin is unique among NSAIDs because it irreversibly inhibits COX-1, making it useful for preventing blood clots and managing arterial thrombosis, such as heart attacks. It works by blocking thromboxane A2, which stops platelets from clumping together.

In dentistry, NSAIDs are useful for managing pain after invasive procedures like tooth extraction. When not contraindicated, they are preferred over paracetamol alone because of their anti-inflammatory effect. Weak evidence suggests that taking painkillers before orthodontic spacer placement under local anaesthetic may reduce the length of post-operative pain.

For Alzheimer’s disease, observational studies and randomized controlled trials show that NSAID use is not effective for treatment or prevention.

**Contraindications** NSAIDs should be used with caution in people over age 50 who have a family history of gastrointestinal problems, and in those who have had previous gastrointestinal issues from NSAID use.

**Adverse effects** The widespread use of NSAIDs has made their adverse effects increasingly common. These include gastrointestinal problems, kidney disease, and cardiovascular events. When used for post-operative pain, there is evidence of increased kidney complications. Their use after gastrointestinal surgery remains controversial because mixed evidence suggests a possible increased risk of leakage from bowel anastomosis.