Effect of selective versus nonselective cyclooxygenase inhibitors on gastric ulceration scores and intestinal inflammation in horses

Richardson, Lauren M.; Whitfield-Cargile, Canaan; Cohen, Noah D.; Chamoun‐Emanuelli, Ana M.; Dockery, Hannah J.

doi:10.1111/vsu.12941

Cited by 18 publications

(34 citation statements)

References 49 publications

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“…Three studies have reported safety of firocoxib in adult horses, but the data are sparse . In two studies there was a lack of transparent reporting funded by the manufacturer, and in the third firocoxib was compared to doses of phenylbutazone in excess of its marketing authorisation . Although this study design makes comparisons with phenylbutazone impossible, it demonstrates that firocoxib can be associated with intestinal pathology at normal doses.…”

Section: Topical Nsaidsmentioning

confidence: 99%

BEVA primary care clinical guidelines: Analgesia

Bowen

Redpath

Dugdale

et al. 2019

Equine Veterinary Journal

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Summary Primary care guidelines provide a reference point to guide clinicians based on a systematic review of the literature, contextualised by expert clinical opinion. These guidelines develop a modification of the GRADE framework for assessment of research evidence (vetGRADE) and applied this to a range of clinical scenarios regarding use of analgesic agents. Key guidelines produced by the panel included recommendations that horses undergoing routine castration should receive intratesticular local anaesthesia irrespective of methods adopted and that horses should receive NSAIDs prior to surgery (overall certainty levels high). Butorphanol and buprenorphine should not be considered appropriate as sole analgesic for such procedures (high certainty). The panel recommend the continuation of analgesia for 3 days following castration (moderate certainty) and conclude that phenylbutazone provided superior analgesia to meloxicam and firocoxib for hoof pain/laminitis (moderate certainty), but that enhanced efficacy has not been demonstrated for joint pain. In horses with colic, flunixin and firocoxib are considered to provide more effective analgesia than meloxicam or phenylbutazone (moderate certainty). Given the risk of adverse events of all classes of analgesic, these agents should be used only under the control of a veterinary surgeon who has fully evaluated a horse and developed a therapeutic, analgesic plan that includes ongoing monitoring for such adverse events such as the development of right dorsal colitis with all classes of NSAID and spontaneous locomotor activity and potentially ileus with opiates. Finally, the panel call for the development of a single properly validated composite pain score for horses to allow accurate comparisons between medications in a robust manner.

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Section: Topical Nsaidsmentioning

confidence: 99%

BEVA primary care clinical guidelines: Analgesia

Bowen

Redpath

Dugdale

et al. 2019

Equine Veterinary Journal

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“…Non-steroidal anti-inflammatory drugs are one of the most commonly used drugs in horses for the management of inflammation and pain of myo-arthro-skeletal or visceral origins, with flunixin meglumine traditionally being the most used NSAID for visceral pain [ 1 , 14 , 15 ]. However, this traditional, non-selective anti-inflammatory drug inhibits both COX-1 and COX-2 isoforms and has been associated with numerous side effects, including gastrointestinal ulceration and delayed mucosal healing, and renal toxicity [ 3 , 4 , 5 , 15 , 16 , 17 ]. While COX-1 is expressed constitutively and mediates the homeostasis of gut barrier function, COX-2 is induced in pro-inflammatory states, and the use of COX-2-specific NSAIDs is warranted in order to reduce the risk of complications [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Flunixin Meglumine, Meloxicam and Ketoprofen on Mild Visceral Post-Operative Pain in Horses

Lemonnier

Thorin

Meurice

et al. 2022

Animals

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The analgesic efficacy of meloxicam and ketoprofen against equine visceral pain is unclear. The aim of this study was to compare the analgesic efficacy of meloxicam (M) and ketoprofen (K) to flunixin meglumine (F) following inguinal castration. Horses undergoing inguinal castration under general anesthesia were randomly assigned F (1.1 mg/kg), M (0.6 mg/kg) or K (2.2 mg/kg) intravenously two hours pre-operatively and 24 h later. A pain score (out of 31) was recorded blindly by a senior clinician and veterinary student before NSAIDs administration (T0), and after the first (T1) and second (T2) administrations, using a modified post-abdominal surgery pain assessment scale (PASPAS). Pain was classified as mild (score ≤ 7), moderate (score = 8–14) or severe (score > 14). Thirty horses (12 F, 10 M, 8 K) aged 6.2 ± 4.9 years, mostly warmbloods, were included. Horse welfare was not compromised regardless of the drug assigned. There was no statistically significant effect of NSAIDs on pain score. Mean pain scores were significantly higher at T1 than T0 for each NSAID (F: 5.08 ± 2.50 vs. 1.58 ± 1.38 (p < 0.001); M: 4.60 ± 2.32 vs. 1.10 ± 1.20 (p < 0.001); K: 5.25 ± 1.39 vs. 1.50 ± 1.51 (p < 0.0001)) and lower at T2 than T1 for F (2.92 ± 2.423 vs. 5.08 ± 2.50 (p < 0.001)) and M (2.90 ± 1.37 vs. 4.60 ± 2.32 (p < 0.0325)). At T1, senior pain scores were significantly different than for junior (5.56 ± 0.54 vs. 3.22 ± 0.62, p = 0.005). This study indicates that meloxicam and ketoprofen provide a similar level of analgesia to flunixin meglumine for the management of mild visceral pain in horses. PASPAS is not reliable for junior evaluators.

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“…Equine gastric ulcer syndrome (EGUS) is a frequently encountered disease in horses that results in high morbidity, loss of use, and high cost of diagnosis and treatment to the owner 20 . Although the causes of EGUS are unknown, NSAIDs have long been associated with inducing gastric ulcers in people and other animal species, specifically equine glandular gastric disease (EGGD) in horses 4,33 . The best approach to prevent NSAID‐induced ulcers in both people and animals is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13] Furthermore, we have determined that both phenylbutazone and firocoxib induce GI inflammation, gastric ulceration, and dysbiosis in horses. 4,6 In addition, specific bacteria and their metabolites have been shown to enhance intestinal barrier function in both homeostasis and disease, and conversely, loss of such bacteria can result in increased intestinal permeability. Specific to NSAID administration, evidence indicates that both probiotics and microbiota-derived metabolites can prevent NSAID-induced intestinal inflammation in people and animal models.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the source of 16S rDNA is unknown and it could be solely related to upper GI injury, because EGGD was prevented in horses receiving the nutritional therapeutic and that group also had decreased 16S rDNA as compared with phenylbutazone-treated horses. Also, we scored EGGD using the same scoring system used for EGUS because the relationship between any of the reported EGGD scoring systems to histopathologic diagnosis of EGGD remains unknown, and our previous studies have had similar findings, regardless of the scoring system used 4,52. Additionally, we used fecal samples to examine the microbiota.…”

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confidence: 99%

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Effects of phenylbutazone alone or in combination with a nutritional therapeutic on gastric ulcers, intestinal permeability, and fecal microbiota in horses

Whitfield-Cargile

Coleman

Cohen

et al. 2021

Veterinary Internal Medicne

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Background: Gastrointestinal (GI) injury and dysbiosis are adverse events associated with nonsteroidal anti-inflammatory drug (NSAID) use in horses. Phenylbutazone has been shown to alter GI barrier function both in vitro and ex vivo, but its effects on barrier function have not been assessed in vivo. In addition, the ability of nutritional therapeutics to prevent these changes is not known. Objective: Our objectives were to determine whether (a) phenylbutazone affected barrier function in vivo and (b) if phenylbutazone-induced GI injury could be ameliorated by the use of a nutritional therapeutic. Animals: Thirty healthy horses were randomly assigned to 3 groups (n = 10 per group): control, phenylbutazone, or phenylbutazone plus nutritional therapeutic. Methods: This study was conducted as a blinded, randomized block design. All horses were managed identically throughout the study period. Samples were collected throughout the study period to monitor fecal microbiota changes and gastric ulcers before and after treatment. Quantification of the bacterial 16S rRNA gene in blood was used as a marker of intestinal permeability. Results: Phenylbutazone increased amounts of bacterial 16S rDNA in circulation 3.02-fold (95% confidence interval [CI], 0.1.89-4.17), increased gastric ulceration score by a mean of 1.1 grade (P = .02), and induced specific changes in the microbiota, including loss of Pseudobutyrivibrio of family Lachnospiraceae. These changes were attenuated by nutritional treatment.

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Effect of selective versus nonselective cyclooxygenase inhibitors on gastric ulceration scores and intestinal inflammation in horses

Abstract: These findings suggest that both classes of NSAID induce GI injury in horses; however, at the dosages used in this study, the COX-2 selective NSAID firocoxib resulted in less severe injury.

Cited by 18 publications

References 49 publications

BEVA primary care clinical guidelines: Analgesia

BEVA primary care clinical guidelines: Analgesia

Comparison of Flunixin Meglumine, Meloxicam and Ketoprofen on Mild Visceral Post-Operative Pain in Horses

Effects of phenylbutazone alone or in combination with a nutritional therapeutic on gastric ulcers, intestinal permeability, and fecal microbiota in horses

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