What's an NSAID?
NSAIDs are a class of medications used to treat pain, fever, and other inflammatory processes in the body. NSAIDs are approved and in use for a number of species including humans, dogs, cats, and horses. These medications are further grouped 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.
But that's a lot of chemical names! How does their grouping affect how they work?
To understand how NSAIDs work, we need to look at an important enzyme cascade in the body: The Arachidonic (Cox) Pathway.
Non specific or traditional NSAIDs work at the first step of the production pathway and inhibit formation of COX-1 and COX-2 (Think aspirin, and to varying levels: meloxicam, piroxicam, ibuprofen, ketoprofen, flunixin, phenylbutazone and others. Carprofen is said to be Cox 1 sparing which is why it is better tolerated in dogs than other more non-specific NSAIDS.
Cox-2 NSAIDs work after the COX-2 step and are supposed to have minimal impact on the production of "good" prostaglandins like PGI2 and TXA2. Typical drugs in this class are firocoxib, robenacoxib, deracoxib, and others. Some COX-2 inhibitors on the human marked were associated with a greater risk of stroke and heart attack in humans (Vioxx and Bextra) and were removed from the market but to date, no recalls have been issued on the veterinary side.
Another new category under the NSAID umbrella is a drug that blocks the EP4 receptor, thereby blocking arthritis pain instead of inhibiting prostaglandin formation. Grapiprant (GalliprantP) is a new NSAID, available in tablet form, with a novel mode of action. It is a PGE2 antagonist, acting at the EP4 receptor subtype. It is not a COX-1 or COX-2 inhibitor. At higher than label dosages, gastrointestinal adverse effects may occur.
Why do we use NSAIDs?
NSAIDs are useful for treating muscle pain, dysmenorrhea, arthritic conditions, pyrexia, gout, migraines, and used as opioid-sparing agents in certain acute trauma cases in both humans and animals. They are not scheduled drugs meaning that they are not considered to have abuse or habit forming potential. In conjunction with other pain management modalities, they can be very effective at treating both acute pain and swelling and chronic pain conditions.
Why would we NOT want to use NSAIDs?
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. 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. 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 urticaria and aspirin-exacerbated respiratory disease.
How do you know if NSAIDs are appropriate for use in your pet? Ask your veterinarian or a veterinary rehabilitation professional before you give any medications- rx or over the counter!
Source credits: image - https://www.researchgate.net/figure/COX-1-and-COX-2-pathways_fig2_6690503