Non-steroidal anti-inflammatory agent

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Non-steroidal anti-inflammatory agents, also called non-steroidal anti-inflammatory drugs (NSAIDs) are defined as "anti-inflammatory agents that are not steroids. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenases, which convert arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Certain NSAIDs also may inhibit lipoxygenase enzymes or phospholipase C or may modulate T-cell function."[1]

The clinical characteristics of NSAISs have been reviewed.[2]

In general, they have been too toxic for veterinary medicine, although there is now limited use in dogs and extremely limited use in cats. Meloxicam, for example, is approved only for a single post-surgical dose in cats, but is used off-label in cancer treatment. One of the attractions of NSAIDs here is that they appear to inhibit some cancers, such as squamous cell carcinoma that expresses cyclooxygenase 1. Nevertheless, they can cause sudden and life-threatening reactions, such as gastric bleeding.


Non-selective inhibitors of cyclooxygenase

These drugs inhibit both cyclooxygenase isozymes. An example is aspirin.

Selective inhibitors of cyclooxygenase 2

For more information, see: Cyclooxygenase 2 inhibitors.

More selective inhibitors, which do not suppress COX-1 and thus are less likely to result in gastric irritation, seemed extremely promising until postmarketing surveillance indicate that they increase the risk of serious cardiac events. Only one remains on the market in the United States. There are reports, however, that COX-2 inhibitors can relieve pain that other NSAIDs do not.

COX-inhibiting nitric oxide donator (CINOD)

COX-inhibiting nitric oxide donators (CINODs or NO-NSAIDs), an example is nitronaproxen, may have less drug toxicity.[3]

Adverse reactions


Non-steroidal anti-inflammatory agents should be avoided in geriatrics according to clinical practice guidelines.[4]


Risk factors for developing dyspepsia with NSAIDs are:[5]

  • prior history of dyspepsia
  • prior UGI complication
  • age 65

Peptic ulcer disease

Clinical practice guidelines address the prevention of peptic ulcer disease among patients on NSAIDs.[6]

NSAIDs may contribute to gastrointestinal ulceration including peptic ulcer disease.[7][8] A meta-analysis concluded "ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those withnaproxen and indomethacin."[9]

The risk of peptic ulcer disease is higher if NSAIDs are combined with corticosteroids.[5][10][8]

Eradication of Helicobacter pylori may help prevent complications. Clinical practice guidelines state:[6]

"All patients regardless of risk status who are about to start long-term traditional NSAID therapy should be considered for testing for H. pylori and treated, if positive."


NSAIDs may cause acute kidney injury due to acute tubular necrosis. Although this is usually interstitial nephritis, NSAIDS can also cause minimal-change disease in the glomerulus.[11]

Damage from NSAIDS may rarely occur after just a few doses.[11]


Hypersensitivity may cause rhinitis, asthma, and urticaria or angioedema.[12][13]

Vascular disease

NSAIDs, especially diclofenac, may cause recurrence of vascular disease among patients with prior myocardial infarctions.[14]


Some NSAIDs - diclofenac, ibuprofen, ketoprofen, and piroxicam but not indomethacin and benzydamine - can be effective with topical administration.[15]

Combined with acetaminophen

According to a systematic review sponsored by industry, combining acetaminophen with non-steroidal anti-inflammatory agents may help treatment of posteroperative pain.[16]

For lumbalgia, acetaminophen one gram orally four times a day combined with diclofenac, a non-steroidal anti-inflammatory agent, was not better than acetaminophen alone in a randomized controlled trial.[17]

For reducing fever, acetaminophen combined with ibuprofen may be better than either drug alone according to a randomized controlled trial.[18]

Aspirin resistance

Aspirin resistance may reduce the abilitiy of aspirin to protect against coronary heart disease.[19][20]


  1. National Library of Medicine. Non-steroidal anti-inflammatory agents. Retrieved on 2007-11-19.
  2. Chou R, Helfand M, Peterson K, Dana T. (2004). Class Review of Cyclo-oxygenase (COX)-2 Inhibitors and Non-steroidal Anti-inflammatory Drugs (NSAIDS). Center for Evidence-based Policy: Effectiveness Review Project (DERP)
  3. (2007) "Naproxcinod: AZD 3582, HCT 3012, naproxen nitroxybutylester, nitronaproxen, NO-naproxen.". Drugs R D 8 (4): 255-8. PMID 17596112.
  4. The American Geriatrics Society - Education - AGS Clinical Practice Guideline: Pharmacological Management of Persistent Pain in Older Persons.
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  9. Henry D, Lim LL, Garcia Rodriguez LA, et al (June 1996). "Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis". BMJ 312 (7046): 1563–6. PMID 8664664. PMC 2351326[e]
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  15. Massey T, Derry S, Moore RA, McQuay HJ (2010). "Topical NSAIDs for acute pain in adults.". Cochrane Database Syst Rev 6: CD007402. DOI:10.1002/14651858.CD007402.pub2. PMID 20556778. Research Blogging.
  16. Ong CK, Seymour RA, Lirk P, Merry AF (2010). "Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.". Anesth Analg 110 (4): 1170-9. DOI:10.1213/ANE.0b013e3181cf9281. PMID 20142348. Research Blogging.
  17. Hancock MJ, Maher CG, Latimer J, et al (2007). "Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial". Lancet 370 (9599): 1638–43. DOI:10.1016/S0140-6736(07)61686-9. PMID 17993364. Research Blogging.
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