Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse.

Weak organic acids possessing anti-inflammatory, analgesic and antipyretic properties--commonly known as aspirin-like drugs--have been used in equine medicine for almost 100 years. These non-steroidal anti-inflammatory drugs (NSAIDs) may be classified chemically into two groups; the enolic acids such as phenylbutazone and carboxylic acids like flunixin, meclofenamate and naproxen. All NSAIDs have similar and possibly identical modes of action accounting for both their therapeutic and their toxic effects. They block some part of the cyclo-oxygenase enzyme pathway and thereby suppress the synthesis of several chemical mediators of inflammation, collectively known as eicosanoids. The available evidence indicates that some of the newer NSAIDs have a reasonable safety margin but further studies are required. The toxicity of phenylbutazone in the horse has been investigated very thoroughly in recent years and it has been shown to cause renotoxicity and, most significantly, ulceration of the gastrointestinal tract when relatively high doses are administered. Several factors may predispose towards phenylbutazone toxicity in the horse, including breed and age, but high dosage is considered to be particularly important. The absorption into, and fate within, the body of NSAIDs are considered and particular attention is drawn to the ways in which these pharmacokinetic properties relate to the drugs' toxicity and clinical efficacy. In reviewing current knowledge of the clinical pharmacology of this important group of drugs, it is hoped to provide the clinician with a rational, scientific basis for their safe and effective use in equine practice.