Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications commonly used in horses to manage pain and inflammation. These drugs work by inhibiting enzymes involved in the inflammatory process, specifically cyclooxygenase (COX) enzymes, which play a role in the production of prostaglandins. NSAIDs are frequently administered for conditions such as musculoskeletal disorders, colic, and post-surgical pain. Common NSAIDs used in equine medicine include phenylbutazone, flunixin meglumine, and ketoprofen. While effective, the use of NSAIDs in horses requires careful management due to potential side effects, such as gastrointestinal ulceration and renal impairment. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, therapeutic applications, and safety considerations of NSAIDs in equine practice.
Daels PF, Stabenfeldt GH, Hughes JP, Odensvik K, Kindahl H.The role of prostaglandin F2 alpha (PGF2 alpha) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of PGF2 alpha caused by Salmonella typhimurium endotoxin given IV. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium...
Newton TA, Rose SR.Phenylbutazone is a potent nonsteroidal, anti-inflammatory drug often used by veterinarians to treat racetrack animals. Its use in human beings is limited because of significant adverse effects and the availability of newer, safer drugs. We report the case of a 24-year-old man who ingested 17 g of equine phenylbutazone over a 24-hour period to treat the pain of a toothache. He developed grand mal seizures, coma, hypotension, respiratory and renal failure, and hepatic injury. Serum phenylbutazone concentration obtained approximately eight hours after presentation was 900 micrograms/mL. The pati...
Ross MW, Orsini JA, Richardson DW, Martin BB.Infectious arthritis of the tarsocrural joint was treated in 13 horses with closed suction drainage through a flat, fenestrated, latex (Jackson-Pratt) drain, broad-spectrum antimicrobial agents, nonsteroidal anti-inflammatory drugs, and bandage immobilization. In 11 horses, arthroscopic lavage and debridement were also performed. Ingress drains were placed for lavage in six horses. Ten horses returned to their previous level of competition or were sound. One horse raced but had lameness of the affected tarsocrural joint and dropped in racing class; one horse was euthanatized because of laminit...
Karcher LF, Dill SG, Anderson WI, King JM.Moderate to severe ulcerative colitis of the right dorsal colon was diagnosed by necropsy or by exploratory celiotomy and biopsy in 13 horses with a primary clinical complaint of either colic, diarrhea, or weight loss. Clinical signs varied from acute fulminating diarrhea (possibly with fever), colic, dehydration, endotoxic shock and death, to a chronic condition manifested by mild intermittent colic up to several months in duration, and weight loss with or without mild diarrhea. In a large percentage of the horses, those affected had been hypovolemic and received nonsteroidal anti-inflammator...
Meschter CL, Gilbert M, Krook L, Maylin G, Corradino R.Phenylbutazone, a non-steroidal anti-inflammatory drug known to produce intestinal erosions, was administered intravenously (13.46 mg/kg bodyweight) to 12 horses which were killed after 24, 48, 72 and 96 h. Eight untreated horses served as controls. Annular erosions in the duodenum and mucosal necrosis in the colon were seen after 48 h which progressed in severity. The erosions were characterised by sloughing of the surface epithelium, subepithelial cleft and bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries and microthrombosis. Large numbers o...
Meschter CL, Gilbert M, Krook L, Maylin G, Corradino R.Phenylbutazone, a nonsteroidal anti-inflammatory drug known to produce gastric ulcers, was administered intravenously (13.46 mg/kg body weight) daily to 12 horses. Horses were euthanatized daily after 24, 48, 72, and 96 hours following the initial injection. Eight untreated horses served as controls. Small multifocal pyloric erosions were seen after 24 hours and then progressed in severity over time. The erosions were characterized by sloughing of the surface epithelium, subepithelial bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries, and micro...
Brooks DE, Millichamp NJ, Peterson MG, Laratta LJ, Morgan RV, Dziezyc J.Five horses with severe nonulcerative keratouveitis had corneal lesions characterized by a pink stromal infiltrate that initially appeared in the stroma near the limbus. Unremitting iridocyclitis also was evident. In 3 horses, microscopic lesions consisted of marked corneal stromal fibrosis, with mild to severe inflammatory cellular infiltration. Corticosteroids and mydriatic/cycloplegics applied topically and corticosteroids and nonsteroidal anti-inflammatory medications administered parenterally were used with varying degrees of success to control pain and retain vision.
Pemberton AD, Slater JS, Milne EM.A method for flunixin detection in equine serum extracts involving thin layer chromatography, spraying the chromatogram with alkaline sodium hypochlorite solution and heating with a detection limit of 50 ng ml-1 is described.
Spier SJ, Meagher DM.Rational perioperative management improves the success rate of abdominal surgery. Important aspects of management are discussed, including principles of fluid therapy, nutrition, intravenous catheterization, antimicrobial prophylaxis, and the use of nonsteroidal anti-inflammatory medication. Current advances in the area of immunotherapy are mentioned.
King JN, Gerring EL.Post operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre-treatment with intravenous (i.v.) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 microgram/kg bwt i.v. endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P < 0.01) for the stomach and left dorsal col...
Turner TA.Navicular syndrome can be treated in a variety of ways. This is related to the fact that it has a variety of causes. Prognostically, most horses will improve with treatment. One can expect about 50 per cent of the horses to become useably sound for 1 year, no matter what treatment is used. The disease is progressive, and affected horses eventually will need to be retired because of lameness. The author's therapeutic approach is to utilize shoeing as the primary therapy. Shoeing is performed to correct structural problems and to ensure that shoeing is physiologically sound. Nonsteroidal anti-in...
Carrick JB, Papich MG, Middleton DM, Naylor JM, Townsend HG.The effects of daily intravenous administration of flunixin meglumine at dosages of 0.55, 1.1, 2.2 and 6.6 mg/kg for five days were examined in neonatal foals. Six two day old foals were used to evaluate the effect of each dosage. Foals were examined every day and blood samples collected on days 1, 3 and 6. All foals were euthanized after six days, necropsied and examined for lesions. The major clinical abnormality was diarrhea, but the incidence was not related to the dosage of flunixin meglumine administered. The foals receiving 6.6 mg/kg of flunixin meglumine had significantly more gastroin...
de Jong EG, Kiffers J, Maes RA.Results are given for a more sensitive screening procedure for non-steroidal anti-inflammatory drugs using GC-MS-MS. By monitoring a selected characteristic reaction for each drug very low detection limits are reached even in a difficult biological matrix such as equine urine. Detection down to 5 ng ml-1 for ibuprofen, ibufenac, alclofenac, fenoprofen, ketoprofen, naproxen and diclofenac is possible in contrast to the 0.5 microgram ml-1 limit for normal GC-MS detection. Examples are given of real positive cases for diclofenac and ibuprofen.
Spurlock GH.Seemingly, propagation of a dorsal cortical fracture in the third metacarpal bone developed after continued race performance in 2 horses. Historically, both horses had intermittent lameness that had responded to nonsteroidal anti-inflammatory drugs and brief rest periods. However, lameness in both horses had increased in severity. Radiography revealed a dorsal cortical fracture of the third metacarpal bone, with propagation of the fracture plane proximally. Fractures were incomplete and healed with stall rest in both horses.
Johansson M, Anlér EL.A quantitative method for the analysis of flunixin, 2-(2-methyl-3-trifluoromethylanilino) nicotinic acid, in equine urine by gas chromatography with nitrogen-phosphorus detection has been developed. Flunixin and the internal standard, mefenamic acid, N-(2,3-xylyl) anthranilic acid, were analysed after extractive methylation of the carboxylic acid group using methyl iodide. The extraction and alkylation conditions of flunixin and mefenamic acid have been studied. The detection limit of the method was 0.25 mumol/l flunixin in urine (74 ng/ml). Flunixin was found to be conjugated to 96.5% in equi...
Markel MD.Peritonitis and adhesions in the horse are best managed through prevention. Perioperative antimicrobial therapy, nonsteroidal anti-inflammatory therapy, experienced personnel, and good surgical techniques should minimize complications after surgery. Despite preventative measures, some horses still develop peritonitis after surgery. Immediate, intensive treatment is necessary to enhance their chances for survival.
Cohen ML, Ming RH, Gogel HK, Davis M, Pitcher JL.Phenylbutazone (PBZ) is a nonsteroidal antiinflammatory drug (NSAID) that is not commonly prescribed due to the high incidence of serious adverse reactions. However, it is still used extensively in equine medicine, and is readily available to those employed in the care and management of horses. Such persons may take the drug indiscriminately, without medical supervision. We present a 33-year-old male race horse track worker who took phenylbutazone horse pills for a chronic toothache and subsequently suffered a major hemorrhage from a gastric ulcer. Human use of phenylbutazone horse pills shoul...
Hondalus MK, Lofstedt J.A 16-year-old pony with signs of intermittent abdominal pain was treated with phenylbutazone in excess of the recommended dosage. Endoscopy revealed ulceration of the esophagus, stomach, and proximal portion of small intestine. The pony developed diarrhea. Salmonella typhimurium was isolated from the blood and feces. Treatment included fluids, trimethoprim-sulfadiazine, sucralfate, and ranitidine hydrochloride. The diarrhea resolved, as did the gastrointestinal ulceration. This case was unusual because septicemia with salmonellosis is an uncommon finding in adult equids. Also, complications co...
Lees P, Taylor JB, Higgins AJ, Sedgwick AD.In vitro and in vivo studies of phenylbutazone binding to equine ingesta and digesta were undertaken. In vitro binding to chopped hay and powdered pony nuts in buffer solutions at 37 degrees C was found to be time-, concentration- and pH-dependent. Percentage binding generally increased with time, decreased with concentration and varied with buffer pH in an unpredictable manner. Other non-steroidal anti-inflammatory drugs (NSAIDs) also bound to hay, the degree of binding being less for meclofenamate and least for flunixin in comparison with phenylbutazone. Phenylbutazone became bound to digest...
Lees P, Higgins AJ.Five matched pairs of horses were used to investigate the biochemical, haematological and general clinical effects of a new dosage schedule of a phenylbutazone paste administered under controlled feeding conditions. One group of horses received a loading dose (8.8 mg/kg) on day 1, followed by doses of 3.3 mg/kg daily on days 2 to 8, 10 and 12 with no treatment on days 9 and 11. The second group received equivalent doses of a placebo paste. Bodyweight, skin temperature, respiratory rate, glutamate dehydrogenase activity, packed cell volume, mean corpuscular volume and neutrophil count were alte...
Yovich JV, Turner AS, Stashak TS, McIlwraith CW.Lateral or medial luxation of the metacarpophalangeal or metatarsophalangeal (fetlock) joint in 10 horses is presented. Closed and open fetlock luxation each occurred in five horses. Horses were treated by cast immobilisation after debridement of soft tissue and joint lavage in cases of open luxations. Suture apposition of a ruptured collateral ligament was attempted in three cases. Antibiotic therapy was used in all cases of open fetlock luxation but non-steroidal anti-inflammatory medication was used inconsistently. Whether closed or open, fetlock luxations had a good prognosis for return to...
Higgins AJ, Lees P, Sharma SC, Taylor JB.An accurate and reliable method for the separation of flunixin from, and measurement in, equine inflammatory exudate and plasma by high performance liquid chromatography has been developed. Flunixin can be detected in concentrations as low as 0.05 micrograms/ml using an ultraviolet spectrophotometric detector at 285 nm. Samples were acidified with 2M hydrochloric acid and extracted with dichloromethane. The extract was evaporated and reconstituted in acetonitrile. Iminodibenzyl was used as internal standard. The mean recovery of flunixin from plasma was 97.6 +/- 3.9 per cent. Particular advant...
Dawson J, Lees P, Sedgwick AD.The direct effects of four non-steroidal anti-inflammatory drugs (NSAIDs) on equine polymorphonuclear (PMN) and mononuclear (MN) leucocyte movement were investigated using two in vitro assay systems. The Boyden chamber microfilter technique measures both chemokinetic and chemotactic locomotion, and the agarose microdroplet assay measures solely chemokinesis. Zymosan-activated plasma (ZAP) and the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as standard chemoattractants for PMN and MN leucocytes, respectively. The actions of six concentrations of each NSAID, indome...
Lees P, Higgins AJ, Sedgwick AD, May SA.The development of reproducible models of acute inflammation in which inflammatory heat is easily quantified and from which inflammatory exudate is readily harvested has facilitated studies in the horse of the actions of steroids and non-steroidal anti-inflammatory drugs (NSAIDS). Blockade of the synthesis of eicosanoids and suppression of inflammatory heat by clinical dose rates of NSAIDS suggests a causal link between the two events and provides further evidence for a role of these compounds in acute equine inflammation. The tendency for enolic and carboxylic acids NSAIDS to accumulate in in...
Sedgwick AD, Lees P, Dawson J, May SA.The migration of leucocytes to sites of acute and chronic inflammation is an event of central importance to the maintenance of inflammatory processes; extravascular leucocytes are responsible for generating chemical mediators of inflammation and the phagocytosis of particulate matter. They may also be involved in the conversion of acute to chronic inflammatory lesions. Leucocytes are attracted to sites of tissue injury by a range of chemoattractants. This paper describes the development of a method for separating on Percoll gradients purified populations of equine polymorphonuclear and mononuc...
Semrad SD, Hardee GE, Hardee MM, Moore JN.The efficacy of low doses of flunixin meglumine in reducing eicosanoid generation and clinical signs in response to experimentally induced endotoxaemia was investigated. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in serum and plasma by radioimmunoassay. Plasma flunixin concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters derived non-compartmentally. In horses administered flunixin meglumine before endotoxin challenge, a significant suppression in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha generation was observe...
Barclay WP, McCracken RJ, Phillips TN, Foerner JJ.Chronic nongranulomatous intestinal inflammation was found during laparotomy in 7 horses. The clinical signs consisted of recurrent abdominal pain in all horses. Anti-inflammatory agents (corticosteroidal and nonsteroidal agents) appeared to be effective for controlling the signs. Surgical removal of the involved intestine also was effective. Nonocclusive or temporary mesenteric ischemia was proposed as a cause of the intestinal lesions.
Climent F, Carmona JU, Cuenca R, Prades M.Eosinophilic synovitis (ES) is a rare disease described in human and veterinary medicine. Only three cases have been reported in the horse. A case of tarsocrural synovitis in an Hispano-Arabian gelding is presented in this report. The patient presented with severe joint effusion and lameness of the right tarsocrural joint on admission. Synovial fluid analysis revealed an increased WBC of 12800 leukocytes/microliter with 76% of eosinophils. Lavage of the diseased joint and medical treatment with antibiotics and non-steroidal anti-inflammatory drugs produced remission of the clinical problem.
Markel MD.Peritonitis and adhesions in the horse are best managed through prevention. Perioperative antimicrobial therapy, nonsteroidal anti-inflammatory therapy, experienced personnel, and good surgical techniques should minimize complications after surgery. Despite preventative measures, some horses still develop peritonitis after surgery. Immediate, intensive treatment is necessary to enhance their chances for survival.
Brooks DE, Millichamp NJ, Peterson MG, Laratta LJ, Morgan RV, Dziezyc J.Five horses with severe nonulcerative keratouveitis had corneal lesions characterized by a pink stromal infiltrate that initially appeared in the stroma near the limbus. Unremitting iridocyclitis also was evident. In 3 horses, microscopic lesions consisted of marked corneal stromal fibrosis, with mild to severe inflammatory cellular infiltration. Corticosteroids and mydriatic/cycloplegics applied topically and corticosteroids and nonsteroidal anti-inflammatory medications administered parenterally were used with varying degrees of success to control pain and retain vision.
Xue C, Segabinazzi L, Hall A, Dzikiti TB, French H, Gilbert R.Clinically, flunixin meglumine (FM) and phenylbutazone (PBZ) are preferentially selected for the treatment of visceral and musculoskeletal pain, respectively, in horses. In donkeys, there is no information to support or refute this conventional conjecture. Objective: To compare postoperative outcomes in a group of jennies treated with intravenous FM or oral PBZ. Methods: Fourteen jennies unilaterally ovariectomised by standing left flank laparotomy. Methods: Retrospective cohort study. Methods: Data from medical records of ovariectomised jennies (case details, weight, non-steroidal anti-inflam...
Spurlock GH.Seemingly, propagation of a dorsal cortical fracture in the third metacarpal bone developed after continued race performance in 2 horses. Historically, both horses had intermittent lameness that had responded to nonsteroidal anti-inflammatory drugs and brief rest periods. However, lameness in both horses had increased in severity. Radiography revealed a dorsal cortical fracture of the third metacarpal bone, with propagation of the fracture plane proximally. Fractures were incomplete and healed with stall rest in both horses.
Prügner W, Huber R, Lühmann R.Two controlled studies to determine efficacy in the horse were performed with eltenac, a new injectable, non-steroidal anti-inflammatory drug (NSAID). Clinical trials were carried out with a dose rate of 1 mg/kg body weight in a randomized, placebo-controlled, double-blind design to assess therapeutic efficacy in acute inflammatory disorders and in animals with orthopaedic conditions. In a preliminary pharmacokinetic investigation in six horses mean elimination half-life was 1.7 h after i.v. administration. In the first clinical study, analgesic activity on pain-related lameness was determined...
Cohen ML, Ming RH, Gogel HK, Davis M, Pitcher JL.Phenylbutazone (PBZ) is a nonsteroidal antiinflammatory drug (NSAID) that is not commonly prescribed due to the high incidence of serious adverse reactions. However, it is still used extensively in equine medicine, and is readily available to those employed in the care and management of horses. Such persons may take the drug indiscriminately, without medical supervision. We present a 33-year-old male race horse track worker who took phenylbutazone horse pills for a chronic toothache and subsequently suffered a major hemorrhage from a gastric ulcer. Human use of phenylbutazone horse pills shoul...
Anderson D, Kollias-Baker C, Colahan P, Keene RO, Lynn RC, Hepler DI.The liposomal cream formulation of diclofenac, an NSAID, is an effective, safe, and convenient way to treat localized areas of inflammation in horses. The results of this study reveal urinary and serum concentrations of diclofenac following topical administration of 1% liposomal diclofenac cream for 10 days at the labeled dose and at 2X and 4X the labeled dose. These results demonstrate the slow absorption and elimination of 1% liposomal diclofenac cream and may be useful when estimating the withdrawal time needed before a competition in order to prevent an inadvertent positive drug test.
Baker RE, Schlipf JW, Brady JV, Gorman ME.A 6-year-old Cheval Canadien mare was presented for clinical signs related to acute kidney injury after receiving a course of nonsteroidal anti-inflammatory therapy. Cytologic examination of concentrated urine revealed small protozoal organisms that were later identified as Klossiella equi. Both sporocysts and free-floating sporozoites were identified in the urine, which has not been previously documented. The mare responded well to intravenous fluid therapy, and as she regained tubular function, the presence of the protozoa in the urine also abated. The mare was discharged from the hospital a...
Pilsworth RC, Head MJ.The differential diagnoses of tarsal joint infection, fracture and peritarsal focal infection are of particular importance in practice. The objective of the present report is to provide additional clinical data to assist in the understanding of one of these conditions. The haematological parameters, clinical signs, treatment and outcome of 10 cases of severe lameness associated with peritarsal infection are reviewed. All horses had a significant rise in rectal temperature. The majority of cases (6/10) had haematological changes consistent with acute bacterial infection on the day of first exam...
Kim JY, Kim SJ, Paeng KJ, Chung BC.A gas chromatographic-mass spectrometric (GC-MS) method for the determination of ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), in horse urine by selected ion monitoring (SIM) mode is described. Urine samples (2 mL) were extracted by liquid-liquid extraction with diethyl ether. The residues were then evaporated, derivatized and injected into the GC-MS system. Validation of the GC-MS method in the SIM mode using flurbiprofen as the internal standard (IS) included linearity studies (10-10 000 ng/mL), recovery (95%) and limit of quantitation (LOQ) (10 ng/mL). The response was linear,...
Barclay WP, McCracken RJ, Phillips TN, Foerner JJ.Chronic nongranulomatous intestinal inflammation was found during laparotomy in 7 horses. The clinical signs consisted of recurrent abdominal pain in all horses. Anti-inflammatory agents (corticosteroidal and nonsteroidal agents) appeared to be effective for controlling the signs. Surgical removal of the involved intestine also was effective. Nonocclusive or temporary mesenteric ischemia was proposed as a cause of the intestinal lesions.
Dyke TM.Tables of values of pharmacokinetic variables (volume of distribution, total body clearance, and plasma elimination half-life) of drugs frequently administered to performance horses are accompanied by explanatory notes. Drugs described include the nonsteroidal anti-inflammatory drugs, corticosteroids, anabolic steroids, central nervous system-modifying drugs, respiratory system drugs, diuretics, local anesthetics, and antibacterial drugs.
Sarkar P, McIntosh JM, Leavitt R, Gouthro H.Nimesulide is a nonsteroidal anti-inflammatory drug recently detected in equine blood and urine samples taken at the race track. The detection of the drug in a blood sample led to the identification of an unknown thin-layer chromatographic (TLC) spot in track urine samples as a metabolite of nimesulide. Characterization of the unknown TLC spot and comparison with the synthesized compound shows that the unknown TLC spot is a previously unreported equine metabolite of nimesulide. The metabolite was identified as resulting from the reduction of the nitro group on nimesulide to an amino group. Thi...
Van Hoogmoed LM, Snyder JR, Harmon FA.To evaluate the effect of 2 cyclooxygenase (COX)-2 inhibitors on contractile activity of the circular smooth muscle layer of the equine dorsal and ventral colon. Methods: Samples of the dorsal and ventral colon obtained from 10 healthy horses. Methods: Full-thickness tissue samples were collected from the dorsal colon in the area of the diaphragmatic flexure and the ventral colon in the area of the sternal flexure. Samples were cut into strips oriented along the fibers of the circular muscle layer and mounted in a tissue bath system for determination of contractile strength. Incremental amount...