Are COX-2 Selective NSAIDs Associated with Less GI, Renal, and Cardiovascular Side Effects: Evidence from Animals Treated with NSAIDs

Abstract

Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat both acute and chronic pain in animals, especially when the pain is resulted from inflammatory conditions. NSAIDs work by inhibition of cyclooxygenases (COX) enzymes and reduce the production of key inflammatory mediators prostaglandins and associated chemicals. Prostaglandins have important roles in pain signalling and haemostasis, including platelet aggregation and gastric mucosal protection. There are two known isoforms of cyclooxygenases enzymes, namely COX-1 and COX-2. Notable adverse effects commonly resulted from NSAIDs uses include gastrointestinal ulceration, compromised haemostasis and renal toxicity, which are due to inhibition of COX-1 isoform. Despite the development of COX-2 selective medicines and continuing effort to improve the safety of NSAIDs in routine veterinary practice, adverse effects of NSAIDs still exist and require closed monitoring. This study aims to summarise and evaluate the current literature on reported adverse effects of NSAIDs used in animals and to compare COX-2 selective versus non-selective agents. Methodology: Literature on reported adverse effects of NSAIDs used in animals over the last decade has been systematically reviewed. Some older sources from the primary literature search have also been included to determine the background information leading to current rationale behind NSAIDs’ therapeutic uses, dosage and route of administration, observed adverse effects and COX-2 selective versus non-selective agents. The primary focus of this study is NSAIDs administered to animals in prospective randomised placebo-controlled blinded trials. Results: A total of 12 studies that met the inclusion criteria were included in the review, with total 13 NSAIDs being discussed, including meloxicam, phenylbutazone, deracoxib, carprofen, aspirin, firocoxib, vedaprofen, etorolac, ketoprofen, tepoxalin, rofecoxib, licofelone and flunixin. It was found that there were variable findings in comparing the adverse effects associated with COX-2 selective NSAIDs and non-selective NSAIDs. COX-2 selective NSAIDs have been found associated with no adverse effects in some studies and minimal adverse effects in other studies. Severe adverse effects were reported for COX-2 selective NSAID administered at higher than recommended doses or for a long duration and some studies reported reduced adverse effects in COX-2 selective NSAIDs when compared to non-selective NSAIDs. Overall, gastrointestinal adverse effects were predominantly reported, followed by adverse findings relating to haemostasis and renal function.  Conclusion: Collectively, the findings suggest COX-2 selective NSAIDs provide a clinically useful improvement over non-selective NSAIDs as well as reduce adverse effects when given at recommended dose.