Journal of Pain & Relief
Open Access

No steroidal anti-inflammatory drugs (NSAIDs) are a drug class FDA-approved for use as antipyretic, anti-inflammatory, and analgesic agents[1]. These effects make NSAIDs useful for treating muscle pain, dysmenorrhea, arthritic conditions, pyrexia, gout, migraines, and used as opioid-sparing agents in certain acute trauma cases.

NSAIDs are typically divided into groups based on their chemical structure and selectivity: acetylated salicylates (aspirin), non-acetylated salicylates (diflunisal, salsalate), propionic acids (naproxen, ibuprofen, acetic acids (diclofenac, indomethacin), enolic acids (meloxicam, piroxicam) anthranilic acids (meclofenamate, mefenamic acid), naphthylalanine (nabumetone), and selective COX-2 inhibitors (celecoxib, etoricoxib).

Topical NSAIDs (diclofenac gel) are also available for use in acute tenosynovitis, ankle sprains, and soft tissue injuries. Listed below are the FDA-approved NSAIDs (organized alphabetically) [2].

Non-selective NSAIDs

• Diclofenac

• Diflunisal

• Etodolac

• Fenoprofen

• Flurbiprofen

• Ibuprofen

• Indomethacin

• Ketoprofen

• Ketorolac

• Mefenamic acid

• Meloxicam

• Nabumetone

• Naproxen

• Oxaprozin

• Piroxicam

• Sulindac

• Tolmetin

COX-2 Selective NSAIDs

• Rofecoxib

• Valdecoxib

(However, rofecoxib and valdecoxib were withdrawn from the market in 2004 and 2005, respectively)

Mechanism of Action

The main mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. The therapeutic effects of NSAIDs are attributed to the lack of these eicosanoids. Specifically, thromboxanes play a role in platelet adhesion, prostaglandins cause vasodilation, increase the temperature set-point in the hypothalamus, and play a role in anti-nociception [3].

There are two cyclooxygenase isoenzymes, COX-1 and COX-2. COX-1 gets constitutively expressed in the body, and it plays a role in maintaining gastrointestinal mucosa lining, kidney function, and platelet aggregation. COX-2 is not constitutively expressed in the body; and instead, it inducibly expresses during an inflammatory response. Most of the NSAIDs are nonselective and inhibit both COX-1 and COX-2. However, COX-2 selective NSAIDs (ex. celecoxib) only target COX-2 and therefore have a different side effect profile. Importantly, because COX-1 is the prime mediator for ensuring gastric mucosal integrity and COX-2 is mainly involved in inflammation, COX-2 selective NSAIDs should provide anti-inflammatory relief without compromising the gastric mucosa.

Adverse Effect

NSAIDs have well-known adverse effects affecting the gastric mucosa, renal system, cardiovascular system, hepatic system, and hematologic system.

Gastric adverse effects are likely due to the inhibition of COX- 1, preventing the creation of prostaglandins that protect the gastric mucosa [4]. The damage is more likely in a patient that has a prior history of peptic ulcers. Since it is COX-1 specific, the use of COX-2 selective NSAIDs is a lower-risk alternative.

Renal adverse effects are because COX-1 and COX-2 facilitate the production of prostaglandins that play a role in renal hemodynamics. In a patient with normal renal function, inhibition of prostaglandin synthesis does not pose a large problem; however, in a patient with renal dysfunction, these prostaglandins play a greater role and can be the source of problems when reduced via NSAIDs [5]. Complications that can occur include acute renal dysfunction, fluid and electrolyte disorders, renal papillary necrosis, and nephrotic syndrome/ interstitial nephritis.

Cardiovascular adverse effects can also be increased with NSAID use; these include MI, thromboembolic events, and atrial fibrillation. Diclofenac seems to be the NSAID with the highest reported increase in adverse cardiovascular events.

Hepatic adverse effects are less common; NSAID-associated risk of hepatotoxicity (raised aminotransferase levels) is not very common, and liver-related hospitalization is very rare. Among the various NSAIDs, Diclofenac has a higher rate of hepatotoxic effects.'

Hematologic adverse effects are possible, particularly with nonselective NSAIDs due to their antiplatelet activity. This antiplatelet effect typically only poses a problem if the patient has a history of GI ulcers, diseases that impair platelet activity (hemophilia, thrombocytopenia, von Willebrand, etc.), and in some perioperative cases.

Other minor adverse effects include anaphylactoid reactions that involve the skin and pulmonary systems, like urticarial and aspirinexacerbated respiratory disease.

Acknowledgement:

None

Conflict of Interest:

None

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