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

Abstract

Summary 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.

Comparison of a new metamizole formulation and carprofen for extended post-operative analgesia in dogs undergoing ovariohysterectomy

“…Individual plasma levels varied too greatly with both drugs to allow correlation of plasma levels with analgesic effect; the same has been shown before for carprofen at similar plasma concentrations (Lascelles et al, 1998). Studies in horses and calves concluded that plasma drug concentrations of NSAID are not a useful guide to therapeutic activity at any given time (Higgins and Lees, 1984;Lees and Higgins, 1985).…”

Beyond muscles: The untapped potential of creatine

“…As a follow-up to this initial study, they tested the efficacy of oral creatine as a mediator of acute and chronic inflammation in rats, as well as the ability of creatine to function as an analgesic [19]. In a model of carrageenan-induced acute inflammation of the foot paw, creatine suppressed inflammation as effectively as the control drug phenylbutazone [19], a nonsteroidal anti-inflammatory drug (NSAID) used in animals [196,197]. Because serotonin (also referred to as 5-HT) plays a significant role in the early stages of inflammation in the carrageenan model [189,192], the authors utilized the serotonin-induced model of paw edema to verify the utility of oral creatine as an anti-inflammatory agent [198] and found that creatine-fed animals had reduced inflammation compared to control-treated animals [198].…”

Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish

“…The precise site and mode of action are still unknown but it may act peripherally in inflamed tissue, probably by inhibiting the enzyme COX to decrease the formation of precursors of prostaglandins and possibly by inhibiting other local mediators of the inflammatory response (Lees and Higgins, 1985). In our study, flunixin meglumine was not an effective drug for the provision of analgesia in 5 dpf zebrafish, as fish spent significantly less time swimming compared with control larvae.…”