Uses and Effects of NSAIDs
- Differences in anti-inflammatory activity between NSAIDs are small
- Individual patient response and tolerance to NSAIDs vary
- About 60% of patients will respond to any NSAID
- Pain relief starts soon after taking the first dose
- Full analgesic effect should normally be obtained within a week
- NSAIDs may help reduce post-operative pain
- Starting NSAID painkiller medications before surgery may be beneficial
- The risk of surgical bleeding and other complications is not well studied
- Combining NSAIDs with paracetamol may improve pain relief
- High-quality randomized controlled trials are needed for more conclusive evidence
- Aspirin irreversibly inhibits COX-1
- It is indicated for antithrombosis and prevention of cardiovascular events
- Aspirin inhibits platelet aggregation by blocking thromboxane A
- Useful for managing arterial thrombosis and heart attacks
- Aspirin has unique properties compared to other NSAIDs
- NSAIDs are useful for managing post-operative dental pain
- They are favored over paracetamol alone due to their anti-inflammatory effect
- Pre-operative analgesia may reduce post-operative pain associated with orthodontic spacers
- Adverse effects of NSAIDs are becoming increasingly common
- NSAIDs may increase the risk of kidney complications and gastrointestinal problems
- COX-2 inhibitors should not be taken with traditional NSAIDs
- Rofecoxib had fewer gastrointestinal adverse drug reactions compared to naproxen
- Cardiovascular safety of COX-2 inhibitors raised concerns
- Methotrexate can be safely used with NSAIDs in rheumatoid arthritis
- Balancing the benefit-risk profile of NSAIDs is important in chronic musculoskeletal pain treatment
Adverse Effects and Risks
- Long-term use of NSAIDs (over three months) associated with erectile dysfunction
- A 2005 Finnish survey study found this association
- A 2011 publication in The Journal of Urology received widespread publicity
- Regular NSAID use significantly increases the risk of erectile dysfunction
- Link between NSAID use and erectile dysfunction still exists after controlling for several conditions
- NSAIDs directly and indirectly irritate the gastrointestinal (GI) tract
- Inhibition of COX-1 and COX-2 reduces protective prostaglandins in the GI tract
- Common gastrointestinal side effects include nausea, vomiting, indigestion, gastric ulceration or bleeding, and diarrhea
- NSAID ulcers can occur irrespective of the route of administration and even in people with achlorhydria
- Risk of ulceration increases with therapy duration and higher doses
- NSAIDs should be used with caution in individuals with inflammatory bowel disease
- They can cause gastric bleeding and ulceration in the gastric lining
- NSAIDs have a high incidence of adverse drug reactions (ADRs) on the kidney
- Changes in kidney blood flow lead to kidney ADRs
- Prostaglandins help maintain normal kidney function, but NSAIDs block their effects
- Common ADRs associated with altered kidney function include sodium and fluid retention and hypertension
- NSAIDs may cause more severe kidney conditions such as interstitial nephritis and acute kidney injury
- Photosensitivity is a commonly overlooked adverse effect of many NSAIDs
- The 2-arylpropionic acids are most likely to produce photosensitivity reactions
- Other NSAIDs like piroxicam, diclofenac, and benzydamine have also been implicated
- Benoxaprofen, now withdrawn, was the most photoactive NSAID observed
- The mechanism of photosensitivity involves the decarboxylation of the carboxylic acid moiety
- NSAIDs are not recommended in the third trimester due to the risk of premature closure of the fetal ductus arteriosus and kidney ADRs in the fetus
- NSAIDs are linked with premature birth and miscarriage
- Aspirin can be used with heparin in pregnant women with antiphospholipid syndrome
- Indomethacin can be used to treat polyhydramnios in pregnancy
- Paracetamol (acetaminophen) is generally considered safe during pregnancy, but a study indicated a potential association with male infertility
- Allergic or allergic-like NSAID hypersensitivity reactions occur after ingestion of NSAIDs
- These reactions differ from toxicity reactions, which are dose-related and can occur in any treated individual
- Allergic reactions include IgE-mediated urticarial skin eruptions, angioedema, and anaphylaxis
- T cell-mediated delayed onset skin reactions can also occur, such as maculopapular rash and contact dermatitis
- Severe and potentially life-threatening t-cell-mediated delayed systemic reactions can occur, such as DRESS syndrome and Stevens-Johnson syndrome
- NSAIDs may delay healing from bone and soft tissue injuries by inhibiting inflammation
- However, they might also speed recovery from soft tissue injuries by preventing inflammatory processes from damaging adjacent muscles
- Moderate evidence suggests that NSAIDs delay bone healing
- The overall effect on soft-tissue healing is unclear
- Long-term use of NSAID analgesics and paracetamol is associated with an increased risk of hearing loss
- The use of NSAIDs for analgesia following gastrointestinal surgery is controversial due to mixed evidence of increased risk of bowel anastomosis leakage
- Common adverse drug reactions include raised liver enzymes, headache, and dizziness
- Uncommon adverse drug reactions include high level of potassium in the blood, confusion, airway spasm, and rash
- Ibuprofen may rarely cause irritable bowel syndrome symptoms
- NSAIDs are implicated in some cases of Stevens-Johnson syndrome
- NSAIDs reduce kidney blood flow and decrease the efficacy of diuretics
- They inhibit the elimination of lithium and methotrexate
- NSAIDs decrease the ability to form blood clots, increasing the risk of bleeding when combined with other drugs that also decrease blood clotting
- NSAIDs may aggrav
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.
| Non-steroidal anti-inflammatory drug | |
|---|---|
| Drug class | |
 | |
| Class identifiers | |
| Pronunciation | /ˈɛnsɛd/ EN-sed |
| Synonyms |
|
| Use | Pain, fever, inflammation, antithrombosis[citation needed] |
| ATC code | M01A |
| Mechanism of action | Enzyme inhibitor |
| Biological target | COX-1 and COX-2 |
| Legal status | |
| In Wikidata | |
The term non-steroidal, common from around 1960, distinguishes these drugs from corticosteroids, which during the 1950s had acquired a bad reputation due to overuse and side-effect problems after their initial introduction in 1948.
NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (the COX-1 and COX-2 isoenzymes). In cells, these enzymes are involved in the synthesis of key biological mediators, namely prostaglandins, which are involved in inflammation, and thromboxanes, which are involved in blood clotting.
There are two general types of NSAIDs available: non-selective, and COX-2 selective. Most NSAIDs are non-selective, and inhibit the activity of both COX-1 and COX-2. These NSAIDs, while reducing inflammation, also inhibit platelet aggregation and increase the risk of gastrointestinal ulcers and bleeds. COX-2 selective inhibitors have fewer gastrointestinal side effects, but promote thrombosis, and some of these agents substantially increase the risk of heart attack. As a result, certain COX-2 selective inhibitors—such as rofecoxib—are no longer used due to the high risk of undiagnosed vascular disease. These differential effects are due to the different roles and tissue localisations of each COX isoenzyme. By inhibiting physiological COX activity, NSAIDs may cause deleterious effects on kidney function, and, perhaps as a result of water and sodium retention and decreases in renal blood flow, may lead to heart problems. In addition, NSAIDs can blunt the production of erythropoietin, resulting in anaemia, since haemoglobin needs this hormone to be produced.
The most prominent NSAIDs are aspirin, ibuprofen, and naproxen; all available over the counter (OTC) in most countries. Paracetamol (acetaminophen) is generally not considered an NSAID because it has only minor anti-inflammatory activity. Paracetamol treats pain mainly by blocking COX-2 and inhibiting endocannabinoid reuptake almost exclusively within the brain, and only minimally in the rest of the body.
nonsteroidal anti-inflammatory drug (plural nonsteroidal anti-inflammatory drugs)
