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.
Jacobs CC, Schnabel LV, McIlwraith CW, Blikslager AT.Orthopaedic disorders are commonly encountered in equine veterinary medicine, and non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non-selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examine...
Waller P, Lomnicka I, Lucas C, Johnson S, Dirikolu L.The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major racetracks in Louisiana between 2016 and 2020. During this 5-year period, 27,237 blood samples and 25,672 urine samples collected during the course of normal race meeting activities were analysed by initial screening procedure utilizing Liquid Chromatography Mass Spectrometry (LC-MS/MS). Following initial screening, suspect samples were subject to quantitative or semi- quantitative confirmation analysis by LC-MS/MS. The total ...
Houck EL, Papich MG, Delk KW.Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood ...
Rhodin M, Haubro Andersen P, Holm Forsström K, Ekstrand C.Intra-articular administration of sustained-release anti-inflammatory drugs is indicated in horses suffering from joint inflammation, but no such drugs are labelled for veterinary use. To obtain initial data on synovial disposition and safety of a new sustained-release formulation of diclofenac (SYN321) in the joints of horses, an experimental interventional study of elimination and side effects of intra-articular administration of SYN321 was conducted. Nine clinically sound horses were included in the study, and SYN321 was administered by the intra-articular route. Dose ranges and sampling in...
Bishop RC, Kemper AM, Wilkins PA, McCoy AM.Equine gastric ulcer syndrome (EGUS) is a common and significant cause of morbidity in horses, with a range of clinical signs, including inappetence, colic and poor performance. Hospitalised horses are exposed to factors that may induce EGUS, including fasting and nonsteroidal anti-inflammatory drug (NSAID) administration, and may be at risk for development of squamous (ESGD) and glandular gastric disease (EGGD). Prophylactic anti-ulcer medication is often prescribed for these patients, but drug selection is complicated by different aetiology and response to treatment of ESGD and EGGD. Objecti...
Hopster K, Driessen B.One of the biggest challenges in managing laminitis in horses remains the control of pain. The best analgesic approach is a multimodal approach, including nonsteroidal anti-inflammatory drugs, opioids, and/or constant rate infusions of α-2 agonists, ketamine, and lidocaine. Recent literature indicates that amitriptyline and soluble epoxide hydrolase inhibitor might be beneficial. Clinically oriented studies will be needed if they have a place in laminitis pain management. The systemic pain control can be combined with local techniques such as long-acting local anesthetics or epidural catheter...
Lanci A, Ingallinesi M, Morini M, Freccero F, Castagnetti C, Mariella J.Hydramnios is an excessive accumulation of fluid within the amniotic compartment. It is a rare condition in mares, often associated with fetal anomalies. Hydrops of fetal membranes predisposes to the rupture of the prepubic tendon, and many authors suggest the induction of parturition to preserve mare's reproductive career. This report presents the case of a 15-year-old multiparous Quarter Horse mare, referred at 268 days of gestation for suspected hydrops. Repeated ultrasonographic exams confirmed an increase in the depth of the amniotic fluid and reduced fetal viability. During the hospitali...
Hellstrom EA, Ziegler AL, Blikslager AT.Postoperative ileus (POI), a decrease in gastrointestinal motility after surgery, is an important problem facing human and veterinary patients. 37.5% of horses that develop POI following small intestinal (SI) resection will not survive to discharge. The two major components of POI pathophysiology are a neurogenic phase which is then propagated by an inflammatory phase. Perioperative care has been implicated, namely the use of opioid therapy, inappropriate fluid therapy and electrolyte imbalances. Current therapy for POI variably includes an early return to feeding to induce physiological motil...
Mendonça FS, Navarro MA, Uzal FA.To determine if there were significant differences produced by 5 of the most prevalent causes of equine enterocolitis, we studied retrospectively the gross and microscopic pathology of 90 cases of enterocolitis submitted to the San Bernardino laboratory of the California Animal Health and Food Safety Laboratory. Included were cases caused by Clostridium perfringens type C (CP; n = 20), Clostridioides difficile (CD; n = 20), Paeniclostridium sordellii (PS; n = 15), Salmonella enterica subspecies enterica serovar Typhimurium (ST; n = 20), and NSAID intoxication (NS; n = 15). ...
O'Banion MP, Sundman E, Edmonds M, Davis J.Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30 mg/kg q8h, 30 mg/kg q12h, 60 mg/kg q8h, and 90 mg/kg q12h]) and treated for nine consecutive da...
Knych HK, Arthur RM, Gretler SR, McKemie DS, Goldin S, Kass PH.Flunixin meglumine is a highly efficacious nonsteroidal anti-inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500 mg and blood and urine samples collected for up to 96 h post-administration. Serum for determination of thromboxane concentrations and whole blood samp...
Siwinska N, Zak A, Slowikowska M, Paslawska U.Reliable and simple tests are constantly being sought to enable the quick detection of acute kidney injury in humans and animals. Diagnosis of subclinical AKI in horses, mainly in field practice, is difficult. An ultrasound scan is a routine test performed when kidney disease is suspected. The aim of the study was to establish the value of the renal resistive index (RRI) in intrarenal arteries in horses with clinical AKI and compare it to that of healthy horses. The second goal was to determine whether potentially nephrotoxic agents can influence RRI. The kidney ultrasonography examination was...
van Galen G, Saegerman C, Hyldahl Laursen S, Jacobsen S, Andersson Munk M, Sjöström H, Holm Lindmark S, Verwilghen D.Non-steroidal anti-inflammatory drugs (NSAIDs) can cause right dorsal colitis, but longitudinal clinical studies are lacking. This study investigates whether NSAID treated horses develop right dorsal colonic pathology in a clinical setting. Non-gastrointestinal hospitalized horses treated with NSAIDs >4 days, and untreated hospital-owned teaching horses and non-gastrointestinal client-owned hospitalized horses were included. All horses were monitored over time with clinical examinations (focusing on presence of colic, depression, reduced appetite, unstructured feces), ultrasonographic intestin...
Whitfield-Cargile CM, Coleman MC, Cohen ND, Chamoun-Emanuelli AM, DeSolis CN, Tetrault T, Sowinski R, Bradbery A, Much M.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. Method...
Macpherson ML, Giguère S, Pozor MA, Burden CA, Berghaus LJ, Berghaus RD, Varner JC, Hayna JT, Benson SM, Randell SA, Lyle SK, Kelleman AA, Hart KA....Minimal evidence exists supporting therapeutic selections for equine placentitis. The goal of this study was to characterize the anti-inflammatory effects of firocoxib when administered to mares with placentitis. Mares (gestation D270-300) were assigned to: INFECT (n = 6; placentitis, no treatment), FIRO (n = 6; placentitis, firocoxib, 0.1 mg/kg, PO, daily), and NORM (n = 6; no infection/treatment). Allantoic fluid (8 hours, 24 hours, birth) and amniotic fluid (birth) were collected from mares after infection. Concentrations of IL-1β, IL-6, TNF-α, IL-10, PGF , and PGE in fluids were...
van Loon J, Verhaar N, van den Berg E, Ross S, de Grauw J.Pain assessment is very important for monitoring welfare and quality of life in horses. To date, no studies have described pain scales for objective assessment of pain in foals. Studies in other species have shown that facial expression can be used in neonatal animals for objective assessment of acute pain. The aim of the current study was to adapt a facial expression-based pain scale for assessment of acute pain in mature horses for valid pain assessment in foals. The scale was applied to fifty-nine foals (20 patients and 39 healthy controls); animals were assessed from video recordings (30-6...
van Loon J, Verhaar N, van den Berg E, Ross S, de Grauw J.Pain assessment is very important for monitoring welfare and quality of life in horses. To date, no studies have described pain scales for objective assessment of pain in foals. Studies in other species have shown that facial expression can be used in neonatal animals for objective assessment of acute pain. The aim of the current study was to adapt a facial expression-based pain scale for assessment of acute pain in mature horses for valid pain assessment in foals. The scale was applied to fifty-nine foals (20 patients and 39 healthy controls); animals were assessed from video recordings (30-6...
Zambruno T, Georgopoulos SP, Boden LA, Parkin TDH.To examine the association between prerace administration of phenylbutazone and the risk of musculoskeletal injury (MSI) and fatal injury in Thoroughbred racehorses that raced between 2006 and 2015 at 2 of the 4 official racetracks in Argentina. Methods: Data from racetrack databases and veterinary reports on 283,193 race starts. Methods: Data were collected relating to race performance and injury outcomes for starts at these tracks. The incidence of MSI and fatal injury was calculated for each year, stratified by the declared prerace administration of phenylbutazone. Univariable logistic regr...
Gobbi FP, Di Filippo PA, Mello LM, Lemos GB, Martins CB, Albernaz AP, Quirino CR.This study is "aimed" to evaluate and compare the efficacy of flunixin meglumine (FM), firocoxib (FX), and meloxicam (MX) after castration of horses. Thirty horses were submitted to open castration and divided into three groups (n = 10) depending on the anti-inflammatory drug administered: group I (GI) (FM, 1.1 mg kg1, IV, once a day [SID], 5 days); group II (GII) (FX, 0.1 mg kg1, IV, SID, 5 days), and group III (GIII) (MX, 0.6 mg kg1, IV, SID, 5 days). Clinical, behavioral, and hematological parameters and the peritoneal fluid (PF) were evaluated before (day [D] 0) and 1, 2, 3, 5, a...
Ricord M, Andrews FM, Yñiguez FJM, Keowen M, Garza F, Paul L, Chapman A, Banse HE.Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown. Objective: To evaluate the effect of omeprazole on phenylbutazone-induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD). Methods: Randomised block experimental design. Methods: Twent...
Grady SE, Lescun TB, Moore GE, Cooper BR, Davern AJ, Brunner TJ, Taylor SD.The objective was to compare the analgesic efficacy of ketorolac tromethamine (KT) and two other nonsteroidal anti-inflammatory drugs (NSAIDs), including flunixin meglumine (FM) and phenylbutazone (PB), using a heart bar shoe (HBS) model of reversible foot lameness in horses. Nine adult horses were used in a blinded, randomized, placebo-controlled crossover study. After induction of left front limb lameness using a modified HBS model, one of three NSAIDs (KT, 2.0 mg/kg IV; FM, 1.1 mg/kg IV; PB, 4.4 mg/kg IV) or saline (placebo) was administered IV as a single dose. Lameness was assessed eve...
Knych HK, Finno CJ, Baden R, Arthur RM, McKemie DS.The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of r...
Göktaş EF, Kabil E, Arıöz F.Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in therapeutic doses in human and veterinary medicine for the treatment of inflammation, pain, and fever. A method for the simultaneous determination of nine NSAIDs, known as therapeutic prohibited substances, in equine urine was developed and fully validated according to the European Commission Decision 2002/657/EC and Association of Official Racing Chemists criteria. The validation was performed for naproxen, flunixin, ketoprofen, diclofenac, eltenac, meclofenamic acid, phenylbutazone, vedaprofen, and carprofen in equine urine i...
Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A.Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would provide valuable clinical and therapeutic information. The effects of meloxicam on endotoxemia have not been studied in this species. Objective: To study the pathophysiology and gene expression associated with experimentally induced endotoxemia, and evaluate the effects of meloxicam on experimentally induced endotoxemia in donkeys and in equine monocyte cultures. Methods: Six healthy adult female donkeys. Methods: Endotoxemia was in...
Cox S, Sommardahl C, Fortner C, Davis R, Bergman J, Doherty T.Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma. M...
Knych HK, Arthur RM, McKemie DS, Baden RW, Seminoff K, Kass PH.Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects. Objective: Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators. M...
Brunner TJ, Lescun TB, Moore GE, Grady SE, Davern AJ, Taylor SD.The mechanism by which nonsteroidal anti-inflammatory drugs mitigate pain caused by a heart bar shoe (HBS) model of lameness is unknown. The purpose of this study was to determine if this HBS model of lameness induces inflammation in horses. Five healthy adult horses from a university teaching herd were enrolled. A custom HBS was applied to the left front foot of each horse, followed by induction of the American Association of Equine Practitioners Lameness Score of 4. Inflammatory markers including serum amyloid A (SAA) concentration, local venous tumor necrosis factor alpha and prostaglandin ...
Storgaard IH, Kristensen J, Larsen C, Mertz N, Østergaard J, Larsen SW.Intra-articular depot injectables based on in situ suspension formation of ester prodrugs of nonsteroidal anti-inflammatory drugs are promising for management of joint pain. As candidates for this delivery approach, 5 diclofenac ester prodrugs comprising different imidazole-containing promoieties were synthesized and their physicochemical properties characterized. In vitro hydrolysis rates were investigated in buffer solutions, in 40% (v/v) human, equine, canine, and rat plasma, and in 80% (v/v) human and equine synovial fluid. Bioconversion of the prodrugs to diclofenac was found to be enzym...
Zielinski K, Sekula B, Bujacz A, Szymczak I.Serum albumin, the most abundant transport protein of mammalian blood, interacts with various nonsteroidal anti-inflammatory drugs (NSAIDs) affecting their disposition, metabolism, and excretion. A big group of chiral NSAIDs transported by albumin, profens, is created by derivatives of 2-arylpropionic acid. The chiral center in the structures of profens is adjacent to the carboxylate moiety and often determines different pharmacological properties of profen enantiomers. This study describes crystal structures of two albumins, isolated from equine and leporine serum, in complexes with three pro...
Bowen IM, Redpath A, Dugdale A, Burford JH, Lloyd D, Watson T, Hallowell GD.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 (ove...
Furr M, Cohen ND, Axon JE, Sanchez LC, Pantaleon L, Haggett E, Campbell R, Tennent-Brown B.The use of anti-ulcer medication in the neonatal intensive care unit (ICU) is common due to the concern for development of catastrophic gastric ulcerdisease. In man, however, the use of acid-suppressive medication has been shown in some studies to be a substantial riskfactorfor the development of Clostridium difficile-associated diarrhoea (CDAD), bacteraemia and neonatal sepsis. Objective: The purpose of the study reported herein is to evaluate the influence of anti-ulcer medications on the development of diarrhoea in the neonatalfoal. Objective: The use of anti-ulcer medication does not alter...
Regan FH, Hockenhull J, Pritchard JC, Waterman-Pearson AE, Whay HR.To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. Objective: To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). Methods: Observer-blinded, placebo-controlled trial. Methods: Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20...
Wilmink JM, van Herten J, van Weeren PR, Barneveld A.In accidental wounds, trauma and infection can result in dehiscence of primarily closed wounds and in sequestrum formation when cortical bone is exposed. In experimental studies, it has been shown that second intention healing is faster and occurs with less complications in ponies than in horses. Also, a greater initial inflammatory response was seen in ponies. Based on these experimental data, it was hypothesised that accidental wounds in ponies would heal with a lower incidence of wound dehiscence and/or sequestrum formation compared to horses. A retrospective study of 89 ponies and 422 hors...
Bowen IM, Redpath A, Dugdale A, Burford JH, Lloyd D, Watson T, Hallowell GD.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 (ove...
Jacobs CC, Schnabel LV, McIlwraith CW, Blikslager AT.Orthopaedic disorders are commonly encountered in equine veterinary medicine, and non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non-selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examine...
Tomlinson JE, Wilder BO, Young KM, Blikslager AT.To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemic-injured equine jejunal mucosa after 18 hours of reperfusion. Methods: 24 horses. Methods: Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, i.v., q 12 h), flunixin meglumine (1.1 mg/kg, i.v., q 12 h), or etodolac (23 mg/kg, i.v., q 12 h). Tissue specimens were obtained from ischemic-injured and nonischemic jejunum immediately after ischemia and 18 hours after recovery from ischemia. Transepithelial electric resistance (TER) and transepithel...
Scarth JP, Teale P, Kuuranne T.A detailed understanding of equine drug metabolism is important for detection of drug abuse in horseracing and also in veterinary drug development and practice. To date, however, no comprehensive review of equine drug metabolism has been published. The majority of literature regarding equine drug metabolite profiles is derived from sports drug detection research and is generally targeted at detecting marker metabolites of drug abuse. However, the bulk of the literature on equine drug metabolism enzymology is derived from veterinary studies aimed at determining the molecular basis of metabolism...
Zielinski K, Sekula B, Bujacz A, Szymczak I.Serum albumin, the most abundant transport protein of mammalian blood, interacts with various nonsteroidal anti-inflammatory drugs (NSAIDs) affecting their disposition, metabolism, and excretion. A big group of chiral NSAIDs transported by albumin, profens, is created by derivatives of 2-arylpropionic acid. The chiral center in the structures of profens is adjacent to the carboxylate moiety and often determines different pharmacological properties of profen enantiomers. This study describes crystal structures of two albumins, isolated from equine and leporine serum, in complexes with three pro...
D'Arcy-Moskwa E, Noble GK, Weston LA, Boston R, Raidal SL.Newer NSAIDs that more selectively target the induced isoform of the cyclooxygenase enzyme (COX2) activity might reduce adverse effects while preserving therapeutic benefits of these drugs. Objective: To compare the effect of oral administration of multiple dose rates of meloxicam and phenylbutazone (PBZ) on gastric mucosal integrity in horses. Methods: Twenty-five light breed horses. Methods: In vivo toxicity study. Horses were randomly assigned to 5 treatment groups, receiving placebo, PBZ (4.4 mg/kg PO q12h day 1, 2.2 mg/kg PO q12h for 4 days, 2.2 mg/kg PO q24h for 9 days), or 3 dose rates ...
Persson-Sjodin E, Hernlund E, Pfau T, Haubro Andersen P, Holm Forsström K, Rhodin M.Quantitative gait analysis has revealed that a large proportion of horses in training, perceived as free from lameness by their owners, show movement asymmetries of equal magnitude to horses with mild clinical lameness. Whether these movement asymmetries are related to orthopaedic pain and/or pathology has yet to be further investigated. Therefore, the objective of this study was to determine whether movement asymmetries in riding horses in training are affected by anti-inflammatory treatment with meloxicam. In a crossover design, horses were treated with meloxicam or placebo for four days res...
Martin EM, Till RL, Sheats MK, Jones SL.In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS) production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed. One potential neutrophil-targeting therapeutic is the PGE1 analog, m...
MacKay RJ, French TW, Nguyen HT, Mayhew IG.The effects of large doses of phenylbutazone were evaluated in clinically normal horses. The drug was given to 4 groups of 2 horses each at the rate of 30 mg/kg of body weight, orally, or 30, 15, or 8 mg/kg IV daily for up to 2 weeks. All horses became anorectic and depressed after 2 to 4 phenylbutazone treatments, and the horses given 15 or 30 mg/kg died on or between days 4 and 7 of treatment. A decrease in total blood neutrophil count occurred in all horses, and was associated with toxic left shift in horses given the 2 larger dosage schedules. The horses also had progressive increases in s...
Richardson LM, Whitfield-Cargile CM, Cohen ND, Chamoun-Emanuelli AM, Dockery HJ.To determine whether a cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug (NSAID) would reduce gastric ulceration and gastrointestinal (GI) inflammation compared with a non-COX selective NSAID. Methods: Randomized block design. Methods: Twenty-five healthy adult horses. Methods: Horses were randomly assigned to receive placebo (n = 5), phenylbutazone (n = 10), or firocoxib (n = 10) administered daily for 10 days. Gastroscopy was performed on days 0 and 10, and both squamous and glandular ulcers were scored according to established scoring criteria. Fecal samples w...
Read WK.Thirty-five cases of renal medullary crest necrosis morphologically similar to the renal papillary necrosis of analgesic nephropathy as described in man and rats are reported in horses receiving maintenance dosages of phenylbutazone. The primary lesion is a well-demarcated focal medullary necrosis resulting in sequestration of fragments of the renal crest. Renal cortical lesions are considered secondary to the medullary necrosis and consist of segmental pallor as a result of tubular dilatation, filtrate retention, and interstitial edema. Ischemia in concert with phenylbutazone is suggested as ...
Meyers KM, Lindner C, Katz J, Grant B.Nonsteroidal anti-inflammatory drugs impair platelet aggregation and secretion in man, pigs, and rabbits and inhibit platelet thromboxane/prostaglandin synthesis. The present investigation studied the effects of phenylbutazone on platelet aggregation and bleeding times in the horse. Aggregation responses to adenosine diphosphate and collagen were markedly impaired 15 minutes and 2 hours after treatment, but 4 hours after treatment, platelet responses approximated those prior to treatment. The in vivo effect of phenylbutazone correlated with its plasma concentrations. Phenylbutazone, like aspir...
Owens JG, Kamerling SG, Stanton SR, Keowen ML.The analgesic effects of the nonsteroidal anti-inflammatory drugs, ketoprofen (2.2 and 3.63 mg/kg bwt) and phenylbutazone (4.4 mg/kg bwt) were compared in 7 horses with chronic laminitis. Hoof pain was quantified objectively by means of an electronic hoof tester and lameness was subjectively graded on a modified Obel scale. Ketoprofen at a dose of 3.63 mg/kg bwt (phenylbutazone equimolar dose) reduced hoof pain and lameness to a greater extent than the 2.2 mg/kg dose and phenylbutazone. These effects were still present at 24 h in 3 of the 4 pain tests, including lameness grade. These data sugg...
Pusterla N, Watson JL, Affolter VK, Magdesian KG, Wilson WD, Carlson GP.The medical records of 53 horses with purpura haemorrhagica were reviewed. Seventeen of them had been exposed to or infected with Streptococcus equi, nine had been infected with Corynebacterium pseudotuberculosis, five had been vaccinated with S. equi M protein, five had had a respiratory infection of unknown aetiology, and two had open wounds; the other 15 cases had no history of recent viral or bacterial infection. The horses were between six months and 19 years of age (mean 8.4 years). The predominant clinical signs were well demarcated subcutaneous oedema of all four limbs and haemorrhages...
Johnson CB, Taylor PM, Young SS, Brearley JC.Horses undergoing surgery were randomly assigned to one of three groups to receive phenylbutazone at 4 mg/kg (n = 72), flunixin at 1 mg/kg (n = 68) or carprofen at 0.7 mg/kg (n = 63) by slow intravenous injection at the end of surgery, just before they were disconnected from halothane. Pain was assessed by either of two resident surgical clinicians (who did not know which non-steroidal anti-inflammatory drug had been given) when the horses first stood up, two and four hours later and the next morning. If repeated doses of analgesic drugs were given the time was recorded and taken as an end poi...
Silver K, Desormaux A, Freeman LC, Lillich JD.Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the suppression of inflammation and pain. However, the analgesic properties of NSAIDs are also associated with significant negative side effects, most notably in the gastrointestinal (GI) tract. Increasingly, evidence indicates that the ulcerogenic properties of some NSAIDs are not exclusively the result of inhibition of cyclooxygenase isoforms in the GI tract, and other mechanisms, including inhibition of cell migration and epithelial restitution, are being explored. Recently, microarray analysis was used ...
Hellstrom EA, Ziegler AL, Blikslager AT.Postoperative ileus (POI), a decrease in gastrointestinal motility after surgery, is an important problem facing human and veterinary patients. 37.5% of horses that develop POI following small intestinal (SI) resection will not survive to discharge. The two major components of POI pathophysiology are a neurogenic phase which is then propagated by an inflammatory phase. Perioperative care has been implicated, namely the use of opioid therapy, inappropriate fluid therapy and electrolyte imbalances. Current therapy for POI variably includes an early return to feeding to induce physiological motil...
Banse H, Cribb AE.The efficacy of oral phenylbutazone [PBZ; 4.4 mg/kg body weight (BW), q12h], a non-selective non-steroidal anti-inflammatory drug (NSAID), and oral meloxicam (MXM; 0.6 mg/kg BW, q24h), a COX-2 selective NSAID, were evaluated in 2 experimental pain models in horses: the adjustable heart bar shoe (HBS) model, primarily representative of mechanical pain, and the lipopolysaccharide-induced synovitis (SYN) model, primarily representative of inflammatory pain. In the HBS model, PBZ reduced multiple indicators of pain compared with the placebo and MXM. Meloxicam did not reduce indicators of pain rela...
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...
Doherty TJ.Surgical manipulation of the intestines activates intestinal macrophages that release cytokines and nitric oxide, which results in inhibition of intestinal motility. Subsequent infiltration of circulating leukocytes into the intestinal wall contributes to cytokine and nitric oxide release and exacerbates ileus. Other factors contributing to ileus are endotoxemia; edema of the intestine wall subsequent to excessive fluid therapy; hypocalcemia; and long abdominal incisions. Because treatment of ileus with prokinetic drugs has not proven to be very effective, efforts should be directed at reducin...
Blikslager A, Gonzalez L.The equine intestinal mucosa is intimately involved in maintaining homeostasis both on a systemic level by controlling extracellular fluid movement and at the local level to maintain barrier function. Horses are particularly susceptible to the clinical syndrome of colic, with the most severe cases involving strangulating obstruction that induces ischemia. Because of the mucosal vascular architecture, the mucosal epithelium is particularly susceptible to ischemic injury. The potential for reperfusion injury has been investigated and found to play a minimal role. However, inflammation does affec...
Thomasy SM, Slovis N, Maxwell LK, Kollias-Baker C.This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum f...
McKellar QA, Bogan JA, von Fellenberg RL, Ludwig B, Cawley GD.Carprofen, a non-steroidal anti-inflammatory drug (NSAID) was administered to three Thoroughbred geldings and three Shetland ponies to determine its plasma disposition and tolerance. The main pharmacokinetic characteristics of carprofen in horses and ponies were a volume of distribution of 0.08 to 0.32 litres/kg (mean +/- se = 0.23 +/- 0.04) a systemic clearance of 26.4 to 78.5 ml/min (mean +/- se = 44.9 +/- 8.0) and a plasma elimination half-life of 14.5 to 31.4 h (mean +/- se = 21.9 +/- 2.3). There was no evidence of any accumulation of carprofen in plasma when the drug was given orally at a...
Martínez Aranzales JR, Cândido de Andrade BS, Silveira Alves GE.Phenylbutazone (PBZ) is widely used in equine medicine, and its side effects on the gastrointestinal tract are well known. The inhibition of prostaglandins and the oxidative stress induced by nonsteroidal anti-inflammatory drugs (NSAIDs) are described as mechanisms of gastric mucosal injury in humans. In horses, only the secondary effect of changes in cyclooxygenases is related to gastric mucosal injury. The objective of this study was to evaluate the effect of PBZ on certain antioxidative/oxidative parameters of the gastric mucosa. The concentrations of antioxidants and oxidants (superoxide d...
Lees P, McKellar Q, May SA, Ludwig B.The pharmacokinetics and pharmacodynamics of the nonsteroidal anti-inflammatory drug (NSAID) carprofen have been evaluated in 6 horses using a model of acute non-immune inflammation. Following intravenous administration of 0.7 mg racemic carprofen/kg bwt, mean values for pharmacokinetic parameters were 18.1 h (elimination half-life); 0.25 l/kg (volume of distribution, Vd[area]); 58.9 ml/min (clearance); and 57.9 micrograms/ml.h (area under plasma concentration time curve). Mean exudate:plasma concentration ratios exceeded 1.0 at all sampling times between 2 and 48 h. Swelling at the site of ac...
Koblischke P, Kindahl H, Budik S, Aurich J, Palm F, Walter I, Kolodziejek J, Nowotny N, Hoppen HO, Aurich C.We tested the hypothesis that subclinical endometritis occurs after embryo transfer (ET) in the horse. Recipient mares were treated with meclofenamic acid (M) or flunixin meglumin (F) after ET or were left untreated (n=9 per group). Embryos were re-collected 4 days after transfer. Endometrial biopsies were taken for histology and analysis of cyclooxygenase-2 (COX-2) by immunohistochemistry and for PCR. Bacteriological swabs were collected from the uterus and lavage fluid of donor and recipient mares. Progesterone and prostaglandin F(2alpha) release was analysed in recipient mares after ET. Fou...
Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A.Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would provide valuable clinical and therapeutic information. The effects of meloxicam on endotoxemia have not been studied in this species. Objective: To study the pathophysiology and gene expression associated with experimentally induced endotoxemia, and evaluate the effects of meloxicam on experimentally induced endotoxemia in donkeys and in equine monocyte cultures. Methods: Six healthy adult female donkeys. Methods: Endotoxemia was in...
