Nonsteroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are usually defined as those agents that inhibit one or more reactions involved in the production of prostaglandins and thromboxanes, important mediators of the inflammatory process in many organs and tissues. They find use in horses in the supportive treatment of a variety of systemic states and painful musculoskeletal or soft tissue conditions. The principal action of most NSAIDs is the inhibition of cyclooxygenase (COX), the first in a series of enzymes responsible for the conversion of arachidonic acid to prostaglandins (Fig. 1). Importantly, recent research has revealed that there are two forms of COX, the first which produces physiologic levels of prostaglandins in a constitutive manner (COX 1), and an inducible form of the enzyme (COX 2) which is responsible for the elevated levels of prostaglandins observed during inflammatory events in a variety of tissues. It appears that the constitutive activity of COX 1 is responsible for many of the homeostatic properties ascribed to prostaglandins and toxicity is predominately related to sustained COX 1 inhibition. Most currently available NSAIDs inhibit the activities of both COX isoforms, however the proportion of inhibition of COX 1 vs. COX 2 varies among compounds. This effect may also vary among species, and the specific anti-inflammatory profiles of most NSAIDs used in horses remain to be explored in detail. A number of selective COX 2 inhibitors are being investigated for use in treatment of a variety of diseases in humans and, in general, have shown clinical efficacy similar to that of non-specific COX inhibitors, largely unaccompanied by typical NSAID side-effects. It is likely that a similar trend will occur in equine practice, particularly when more affordable generic forms of these drugs become available. In addition to COX inhibition, NSAIDs have other anti-inflammatory effects. For example, carprofen reduces edema and joint effusion in experimental joint disease models in horses by a non-COX mediated pathway and it has been reported that ketoprofen inhibits both lipoxygenase and COX (Fig. 1). Moreover, at least some NSAIDs are capable of inhibiting elements of cellular inflammation. Thus, it is clear that a number of NSAIDs possess anti-inflammatory actions other than COX inhibition, however the biologic significance of these effects are not clearly defined and may occur only at tissue concentrations achieved by exceeding regularly used dose rates. These side actions may also prove to complicate the premise that selective COX 2 inhibitors are devoid of side effects, particularly when used