The effect of nonsteroidal anti‐inflammatory drugs on the equine intestine

Abstract

SummaryNonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the management of pain and endotoxaemia associated with colic in the horse. While NSAIDs effectively treat the symptoms of colic, there is evidence to suggest that their administration is associated with adverse gastrointestinal effects including right dorsal colitis and inhibition of mucosal barrier healing. Several studies have examined the pathophysiology of NSAID associated effects on the large and small intestine in an effort to avoid these complications and identify effective alternative medications. Differences in the response of the large and small intestines to injury and NSAID treatment have been identified. Flunixin meglumine has been shown in the small intestine to inhibit barrier function recovery and increase permeability to lipopolysaccharide (LPS). A range of NSAIDs has been examined in the small intestine and experimental evidence suggests that those NSAIDs with cyclooxygenase independent anti-inflammatory effects or a COX-2 selective mode of action may offer significant advantages over traditional NSAIDs. evj_398 140..144

Nitric oxide and malondialdehyde in gastric contents and blood in an equine model of gastric ulcer induced by phenylbutazone

“…This finding is characteristic in horses treated with PBZ or horses with severe endotoxemia (McConnico et al, 2008;El-Ashker et al, 2012). The role of infiltrating neutrophils in damaged intestine is well known (Gayle et al, 2000;Tomlinson and Wilder, 2004); however, there is evidence of response variability in segments of the digestive tract of horses in accordance with the nonsteroidal anti-inflammatory drug (NSAID) type (Marshall and Blikslager, 2011).…”

Ischemia in equine intestine – mechanisms of injury and methods of treatment

“…While FM can effectively treat the clinical signs of colic, there is evidence to suggest that its administration has adverse gastrointestinal effects, such as right dorsal colitis and impaired recovery of the mucosal barrier (Marshall and Blikslager 2011). In equine right dorsal colon in vitro, phenylbutazone caused apoptosis and blocked anion secretion, but did not affect mucosal permeability (Richter et al 2002).…”

“…COX-2 is expressed at low levels in normal tissue, but is upregulated in response to injury and is the enzyme responsible for many of the harmful responses associated with ischemic intestinal injury in the horse. In the equine gastrointestinal tract, both COX-1 and COX-2 are constitutively expressed in the jejunum and pelvic flexure (Tomlinson et al 2004, Marshall et al 2011. COX-2 expression may contribute to resolution of gastrointestinal tract inflammation, and it might be crucial in regulating mucosal healing , Krause and DuBois 2000, Wallace and Devchand 2005, Fukuta et al 2006.…”

“…Recent studies have examined the in vitro measurements of recovery in intestine that was subjected to ischemic injury in vivo, comparing the effects of different NSAIDs on recovery of mucosal barrier function (Marshall and Blikslager 2011). Whether the NSAIDs were given in vivo or added to the bathing solution in vitro, the histological measures of recovery were largely unaffected by these drugs.…”

“…NSAIDs with a more COX-2 selective profile (e.g. firocoxib) may support repair of mucosal barrier defects compared with the more traditional NSAIDs, such as FM (Marshall and Blikslager 2011). There is a difference in the response of the large and small intestines to ischemic injury and NSAID treatment.…”