All nonsteroidal anti-inflammatory drugs (NSAIDs) act via a similar mechanism, which is to inhibit synthesis of prostaglandins (PGs) via inhibition of the cyclo-oxygenase (COX) enzyme.

Some of the inhibited PGs promote inflammation, while some perform important body functions.

NSAIDs can either inhibit the inflammatory PGs (via COX-2) or the important constitutive PGs (via COX-1) or both (non selective). Older NSAIDs such as ibuprofen, phenylbutazone, naproxen, piroxicam, and flunixin are nonselective and inhibit both COX-1 and COX-2. Newer NSAIDs such as the COXIB (celecoxib), carprofen and meloxicam, are mildly COX-2 selective and relatively COX-1 sparing, although this is based on in vitro studies and it may vary among species. The recently introduced deracoxib and firocoxib are COX-2 selective drugs, and tepoxalin is a COX and lipo-oxygenase (LOX) inhibitor.

COX-2 selective (COXIB) Deracoxib(Deramaxx®), firocoxib (Previcox®).
Mildly COX-2 selective Carprofen (Rimadyl®), meloxicam (Metacam®).
COX and LOX inhibitors Tepoxalin (Zubrin®); this product is not selective for COX-2, but has some LOX inhibition.

No proven advantage has been established in terms of efficacy or safety, of one over another, but there are few good studies comparing the different drugs. In a comparison study of firocoxib and etodolac, no difference in efficacy or safety was found, whereas studies in the US comparing tepoxalin and carprofen, and in Europe comparing tepoxalin and meloxicam found that tepoxalin had a slight trend toward better efficacy and safety. Based on endoscopic studies, carprofen has been shown to have an advantage over aspirin in terms of GI toxicosis.

GI toxicosis
• No proven advantage of COXIBs over mildly COX-2 selective drugs from controlled studies conducted in dogs or cats.
• Need to be wary of studies looking at gastric lesions, as more severe lesions tend to be located in the proximal small intestine.
• FDA has received some reports of GI ulceration associated with deracoxib administration; mostly involving small intestinal ulcers.
• Unsure of predisposing causes of the deracoxib cases but it may be that pre-existing GI damage results in upregulation of COX-2, which plays a role in healing of the GI tract.
• Animals with low protein may be at increased risk for side effects due to the highly protein-bound nature of NSAIDs (not an absolute contraindication, but need to dose these animals carefully and monitor them closely).
  
  
Hepatic toxicosis
• Any of the NSAIDS can cause acute, idiosyncratic hepatotoxicosis. Deracoxib is also a sulfonamide, so it should be used with caution in breeds predisposed to sulfonamide hypersensitivity (Doberman pinscher, Samoyed and other white-coated breeds, miniature schnauzer).
• It is uncertain whether carprofen causes hepatic toxicosis more often than other NSAIDs, but it has been associated with liver problems more than other drugs according to the FDA's adverse event reporting data.
• There is no evidence that prior hepatic disease predisposes to NSAID-induced liver injury. Pre-existing liver enzyme elevation is not a predictor of hepatic toxicosis from NSAIDs.
• Although these drugs are all highly metabolized by the liver for most drugs, pre-existing liver disease does not seem to affect metabolism (due to liver function reserve).
  
  
Renal toxicosis
• COX-1 and COX-2 both play important roles in renal function.
• High doses of NSAIDs may cause renal damage (tubular ischemia and degeneration), although this is seen rarely at therapeutic doses.
• Animals with pre-existing renal damage and those with reduced renal blood flow may be predisposed to renal toxicosis.
  
  
Effects on platelet function (COX-1 inhibition)
• NSAIDs are capable of inhibiting platelet function and so are not recommended for patients predisposed to or with pre-exiting hemostatic disorders (e.g. von Willebrand disease, hemophilia, thrombopathia).
• Any NSAID with appreciable COX-1 inhibitory function could affect platelet function (e.g. ketoprofen), although no blinded clinical trials have confirmed this concern.