Pharmacology in horses involves the study and application of drugs and medications to diagnose, treat, and prevent diseases and conditions in equine species. This field encompasses the understanding of pharmacokinetics and pharmacodynamics specific to horses, including how drugs are absorbed, distributed, metabolized, and excreted by the equine body. Commonly studied pharmacological agents in horses include non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, sedatives, and anthelmintics. Research in equine pharmacology focuses on determining appropriate dosages, understanding drug interactions, and minimizing adverse effects. This page compiles peer-reviewed research studies and scholarly articles that investigate the efficacy, safety, and regulatory aspects of pharmacological interventions in equine veterinary practice.
Endo Y, Hobo S, Korosue K, Ootsuka K, Kitauchi A, Kikkawa R, Hidaka Y, Hagio M, Tsuzuki N.The present study evaluated the effects of single-dose filgrastim on hematology in 16 healthy horses after long-distance transportation. Horses were assigned to receive filgrastim (0.23 µg/kg, SC, once; G-CSF group; n=8) or saline (0.9% NaCl) solution (0.3 ml, SC, once; control group; n=8) ≤ 1 hr before transportation. Horses were transported 2,530 km using commercial vans over the course of approximately 44 hr. Clinical examinations and hematologic analyses were performed on all horses before and after transportation. Because the post-transportation white blood cell counts and bacillary ne...
Lefebvre D, Pirie RS, Handel IG, Tremaine WH, Hudson NP.There is a need for an improved understanding of equine post operative ileus (POI), in terms of both clinical definition and optimal management. Although the pharmacological strategies that are used to treat POI continue to evolve, little is known about the supplementary strategies used to prevent and manage this condition. Objective: To report the current strategies used to diagnose, prevent and manage POI following emergency abdominal surgeries. Methods: Cross-sectional survey. Methods: An electronic survey invitation was sent by email to 306 European college diplomates (European Colleges of...
Roscher KA, Failing K, Moritz A.This study aimed to validate a loading and maintenance clopidogrel dosing scheme for the inhibition of platelet function, measured by whole blood impedance aggregometry in healthy adult horses. Ten Warmblood horses received oral clopidogrel once daily. Doses were based on 50 kg weight categories and resulted in one loading dose of 6-6.5 mg/kg bodyweight and maintenance doses of 1.2-1.4 mg/kg over the next 4 days. Platelet function was measured via whole blood multiple electrode impedance aggregometry prior to (T0) and at 6, 12, 24, 48, 72, 96, 144, 192 and 240 h following the loading d...
Zielinski J, Mevissen M.Testosterone hydroxylation was investigated in human, canine and equine liver microsomes and in human and canine single CYPs. The contribution of the CYP families 1, 2 and 3 was studied using chemical inhibitors. Testosterone metabolites were analyzed by HPLC. The metabolites androstenedione, 6β- and 11β-hydroxytestosterone were found in microsomes of all species, but the pattern of metabolites varied within species. Androstenedione was more prominent in the animal species, and an increase over time was seen in equines. Testosterone hydroxylation was predominantly catalyzed by the CYP3A subf...
Haugaard MM, Hesselkilde EZ, Pehrson S, Carstensen H, Flethøj M, Præstegaard KF, Sørensen US, Diness JG, Grunnet M, Buhl R, Jespersen T.Small-conductance calcium-activated potassium (SK) channels have been found to play an important role in atrial repolarization and atrial fibrillation (AF). Objective: The purpose of this study was to investigate the existence and functional role of SK channels in the equine heart. Methods: Cardiac biopsies were analyzed to investigate the expression level of the most prominent cardiac ion channels, with special focus on SK channels, in the equine heart. Subcellular distribution of SK isoform 2 (SK2) was assessed by immunohistochemistry and confocal microscopy. The electrophysiologic and anti-...
Munoz T, Leclere M, Jean D, Lavoie JP.The purpose of this study is to measure the effect of long-term administration of inhaled fluticasone proprionate on cortisol concentrations in heaves-affected horses. Eleven horses with heaves were treated with fluticasone at least once daily at dosages required to improve lung function or with antigen avoidance alone for 1 year. Morning serum cortisol was measured before and after 10, 30, 110, 190, 230, 280, and 320 days of treatment. Cortisol was also measured in the afternoon of day 330. Cortisol was significantly lower in the Fluticasone group on days 30, 110, and 190 when compared with t...
Pakkanen SA, Raekallio MR, Mykkänen AK, Salla KM, de Vries A, Vuorilehto L, Scheinin M, Vainio OM.To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane. Methods: Experimental, crossover study with a 14 day wash-out period. Methods: Seven healthy horses. Methods: The horses received either detomidine (20 μg kg(-1) IV) and butorphanol (20 μg kg(-1) IV) alone (DET) or with MK-467 (200 μg kg(-1) IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg(-1) ) and midazolam (0.06 mg kg(-1) ) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon ...
Dias BP, Araújo MA, Deschk M, Trein TA, Pinheiro NC, Perri SH, Rodrigues CA, Santos PS.To assess the cardiorespiratory parametes, recovery, gastrointestinal motility and serum cortisol concentrations in horses anesthetized with isoflurane with or without a continuous rate infusion (CRI) of butorphanol for orchiectomy. Methods: Twelve adult, intact, male horses weighing 332 ± 55 kg were included in the study. Xilazine was administered as premedication. Anesthesia was induced with ketamine and midazolam and maintained with isoflurane. Butorphanol (0.025 mg kg-1 bolus) or an equivalent volume of saline (0.9%) was given intravenously followed by a CRI of butorphanol (BG) (13 µg kg...
Tofflemire KL, Whitley EM, Flinn AM, Dufour VL, Ben-Shlomo G, Allbaugh RA, Griggs AN, Peterson CS, Whitley DR.To compare the effect of commercially available solution and compounded ointment formulations of dorzolamide(2%)-timolol(0.5%) on intraocular pressure (IOP) of normal horses. Methods: Eighteen clinically normal horses. Methods: A randomized, masked prospective design was used with horses divided into two equal groups. One eye of each horse was selected for topical ophthalmic treatment with either 0.2 mL of dorzolamide(2%)-timolol(0.5%) solution or 0.2 g of dorzolamide(2%)-timolol(0.5%) ointment every 12 h for 5 days. The contralateral eye of horses in both groups was untreated. Rebound tonomet...
Cook VL, Blikslager AT.To review the physiology of the cyclooxygenase (COX) enzymes with reference to the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) related to their analgesic and antiendotoxic properties as well as the mechanisms responsible for adverse gastrointestinal, renal, and coagulation effects. Methods: Human and veterinary peer reviewed literature Results: NSAIDs are frequently administered to critically ill horses for their analgesic and anti-inflammatory effects. However, NSAIDs have significant side effects principally on the gastrointestinal mucosa and kidneys. These side effec...
Endo Y, Tsuchiya T, Akiyama K, Takebe N, Nakai K, Korosue K, Ishimaru M, Tsuzuki N, Hobo S.In order to reveal the preventive effect of marbofloxacin (MRFX) administration just before transportation, we compared the occurrence of transportation-associated fever before and after introduction of MRFX administration. After the introduction of prophylactic MRFX administration, the rectal temperatures of horses after transportation were significantly lower than before the introduction of MRFX administration (P<0.01) and the number of febrile horses was significantly lower than before the introduction of MRFX administration (P<0.01). In conclusion, these results show that prophylacti...
Kramer CM, Tsang AS, Koenig T, Jeffcott LB, Dart CM, Dart AJ.To survey veterinary practitioners in Australia on how they administer pentosan polysulfate (PPS) to horses and their perceptions of the efficacy of PPS for: the prevention and treatment of osteoarthritis (OA), the treatment of OA when PPS is combined with other drugs, and the efficacy of PPS compared with other disease-modifying osteoarthritic drugs. Methods: Practitioners were contacted by email, which contained a link to an online survey. Results: A total of 76 responses (34.5%) to the survey were received. Respondents most commonly used PPS as prophylactic therapy prior to competition (80....
Wong DM, Davis JL, Alcott CJ, Hepworth-Warren KL, Galow-Kersh NL, Rice S, Coetzee JF.The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of ...
Decloedt A, de Clercq D, van der Vekens N, Verheyen T, Ven S, van Loon G.Shortening of atrial fibrillation cycle length (AFCL) is a marker of atrial electrical remodelling due to atrial fibrillation (AF). Objective: To investigate the effect of administration of detomidine on AFCL measured invasively from an intra-atrial electrogram (AFCLEGM) and noninvasively by tissue Doppler imaging (AFCLTDI). We hypothesised that detomidine would have no effect on AFCL but would improve the ease of TDI measurements and facilitate noninvasive AFCL determination. Methods: Prospective clinical study. Methods: Measurements were performed before and after i.v. administration of 7.5â...
Umar MA, Fukui S, Kawase K, Itami T, Yamashita K.Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol drug combination (KMP-TIVA) were determined in 5 Thoroughbred horses undergoing surgery. The horses were anesthetized with intravenous administration (IV) of ketamine (2.5 mg/kg) and midazolam (0.04 mg/kg) following premedication with medetomidne (5 µg/kg, IV) and artificially ventilated. Surgical anesthesia was maintained by controlling propofol infusion rate (initially 0.20 mg/kg/min following an IV loading dose of 0.5 mg/kg) and constant rate infusions of ketamine (1 mg/kg/hr) and medetomidine (1.25...
Urra JA, Villaroel-EspÃndola F, Covarrubias AA, RodrÃguez-Gil JE, RamÃrez-Reveco A, Concha II.Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility...
Santos VG, Castro T, Bettencourt EM, Ginther OJ.A procedure for oxytocin (OT) administration on Day 13 postovulation was developed in mares for stimulation of a pulse of PGFM (a PGF2α metabolite) that mimics a natural PGFM pulse during luteolysis. Bolus treatment with each of five OT doses (1-10 IU/mare, n = 3) stimulated a burst of PGFM that was maximum in 4 minutes and was unlike a natural pulse. A 2-hour OT infusion of 1.25, 2.5, or 5 IU/100 kg (n = 4) induced a PGFM pulse similar to reported pulses; lower doses did not. The peak of an induced pulse (approximately 260-380 pg/mL) seemed similar to reported natural peaks (approxima...
Dembek KA, Hurcombe SD, Schober KE, Toribio RE.To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate. Methods: An 8-year-old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death. Conclusions: Atrial fibrillation is the most commonly diagnosed dysrhythmia ...
Donnell JR, Frisbie DD.This review presents the pathogenesis and medical treatment of equine osteoarthritis (OA), focusing on firocoxib. Inhibition of prostaglandin E remains a fundamental treatment for decreasing clinical symptoms (ie, pain and lameness) associated with OA in horses. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the production of prostaglandin E from the arachidonic acid pathway, continue to be a mainstay for the clinical treatment of OA. Firocoxib is a cyclooxygenase (COX)-2-preferential NSAID that has been shown to be safe and to have a 70% oral bioavailability in the horse. Three ...
McNaughten J, Pozor M, Macpherson M, Kelleman A, Woodward E, Troedsson M.Mares who have not delivered a foal early in life may experience limitations in cervical relaxation, primarily during oestrus. A closed cervix prevents intrauterine deposition of semen during natural breeding, may delay uterine clearance after insemination leading to intrauterine fluid accumulation in, and subsequent infertility. Therefore, a reliable pharmacological method of dilating the equine cervix would have practical application in veterinary medicine. The goal of this study was to investigate the effectiveness of topically applied, synthetic prostaglandin E1 analogue (PGE1 ) for stimul...
Claunch KM, Eggleston RB, Baxter GM.To compare the effects of 2 approaches and 2 injection volumes on diffusion of mepivacaine hydrochloride for local analgesia of the deep branch of the lateral plantar nerve (DBLPN) in horses. Methods: Experimental study. Methods: 16 adult horses. Methods: Either 2 mL (low volume) or 8 mL (high volume) of mepivacaine hydrochloride-iohexol (50:50 mixture) was injected by means of 1 of 2 techniques to produce analgesia of the DBLPN. For technique 1, the needle was inserted 15 mm distal to the head of the fourth metatarsal bone and directed perpendicular to the limb. For technique 2, the needle wa...
Tangyuenyong S, Viriyakhasem N, Peansukmanee S, Kongtawelert P, Ongchai S.Cartilage erosion in degenerative joint diseases leads to lameness in affected horses. It has been reported that andrographolide from Andrographis paniculata inhibited cartilage matrix-degrading enzymes. This study aimed to explore whether this compound protects equine cartilage degradation in the explant culture model and to determine its effect on matrix metalloproteinase-2 (MMP-2) expression, a matrix-degrading enzyme, in equine chondrocyte culture. Equine articular cartilage explant culture was induced by 25 ng/mL interleukin-1β, a key inducer of cartilage degeneration, in cultures with...
Haugaard MM, Pehrson S, Carstensen H, Flethøj M, Hesselkilde EZ, Praestegaard KF, Diness JG, Grunnet M, Jespersen T, Buhl R.Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. Objective: To study the potential of flecainide to terminate acutely induced AF of short duration (≥ 15 minutes), to examine flecainide-induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length...
Luna SP, Lopes C, Rosa AC, Oliveira FA, Crosignani N, Taylor PM, Pantoja JC.To validate a model for investigating the effects of analgesic drugs on mechanical, thermal and electrical stimulation testing. Objective: To investigate repeatability, sensitivity and specificity of nociceptive tests. Methods: Randomised experiment with 2 observers in 2 phases. Methods: Mechanical (M), thermal (TL) and electrical (E) stimuli were applied to the dorsal metacarpus (M-left and TL-right) and coronary band of the left thoracic limb (E) and a thoracic thermal stimulus (TT) was applied caudal to the withers in 8 horses (405 ± 43 kg). Stimuli intensities were increased until a clear...
Pereira GR, Lorenzo PL, Carneiro GF, Bilodeau-Goeseels S, Kastelic J, Liu IK.The objectives of this study were firstly to determine whether the stimulatory function of equine growth hormone (eGH) on equine oocyte maturation in vitro is mediated via cyclic adenosine monophosphate (cAMP); and secondly if the addition of eGH in vitro influences oocyte nuclear maturation and if this effect is removed when GH inhibitors are added to the culture. Cumulus-oocyte complexes (COCs) were recovered from follicles <25 mm in diameter and randomly allocated as follows: (i) control (no additives); and (ii) 400 ng/ml of eGH. A specific inhibitor against cyclic AMP-dependent protein ...
Rigotti C, De Vries A, Taylor PM.A prospective, randomised, blinded, clinical trial in 47 ponies compared butorphanol and buprenorphine administered intravenously with detomidine prior to castration under anaesthesia. Detomidine 12 μg/kg intravenously was followed by butorphanol 25 μg/kg (BUT) or buprenorphine 5 μg/kg (BUP) before induction of anaesthesia with intravenous ketamine and diazepam. Quality of sedation, induction and recovery from anaesthesia, response to tactile stimulation, and surgical conditions were scored. If anaesthesia was inadequate 'rescue' was given with intravenous ketamine (maximum three dose...
Sarrafian TL, Garcia TC, Dienes EE, Murphy B, Stover SM, Galuppo LD.To develop a nonterminal large animal bone defect model for assessing the efficacy of regenerative and pharmacologic treatments designed to enhance bone healing. Methods: In vivo experimental. Methods: Adult gelding horses (n = 6). Methods: Under general anesthesia, using radiographic guidance, 13.5 mm diameter bilateral, full thickness mandibular defects were created in 6 horses using a custom surgical jig and coring bit. After 16 weeks, under general anesthesia, 23 mm diameter cores that encompassed the original healing defects and surrounding parent bone material were removed for evaluation...
Pyörälä S, Taponen J, Katila T.Use of antimicrobials for veterinary indications related to reproduction in cattle and horses is reviewed. Antimicrobial compounds are widely used to treat and prevent infections of reproductive organs. Total amounts of antimicrobials for such purposes, estimated by weight, are low compared with major uses in food animals. The most common reproduction-related indication in cattle is mastitis. The number of intramammary products available for treatment of mastitis in the European Union is high. Metritis and endometritis also require antimicrobial treatment of cattle and specific products for in...
Dart AJ, Cries L, Jeffcott LB, Hodgson DR, Rose RJ.To evaluate the effect of intramuscular administration of recombinant equine growth hormone on healing of full thickness skin wounds on equine limbs. Methods: Experimental. Methods: Nine Standardbred horses. Methods: In study 1, standardized full thickness skin wounds (2.5 x 2.5 cm) were made over the dorsomedial aspect of the mid-cannon bone of 1 forelimb and 1 hindlimb in 9 horses. Wounds were bandaged without treatment (control subjects) and videorecorded twice weekly until healed. Then, in study 2, similar wounds were created on the opposite limbs; 6 horses were administered intramuscular ...
Lyons ET, Tolliver SC, Collins SS.Population B, drug-resistant small strongyles have been studied in naturally infected horses in Kentucky for more than 40 years. These parasites first were found to be resistant to phenothiazine (PTZ) and thiabendazole (TBZ), later to other parasiticides. Studies have been on evaluation of antiparasitic efficacy of several compounds, especially the benzimidazoles, against Population B small strongyles in clinical (field) tests (1959-1983) on the commercial farm of origin and in clinical and critical tests (1966-2001) at the University of Kentucky (UK) research farm. Research on these nematodes...
Eyre P, Elmes PJ, Strickland S.Spirally cut digital arteries and veins were mounted isotonically in organ baths containing oxygenated Krebs' Q-Henseleit solution. Twelve arterial and 12 venous preparations all contracted dose dependently when epinephrine, norepinephrine, serotonin, or histamine were added to the bathing fluid. Addition of hydrocortisone or betamethasone alone did not cause contractions in any of the tissues tested. However, when hydrocortisone or betamethasone was added to vessel strips that were partially contracted (40% to 60% maximal) by epinephrine, norepinephrine, or serotonin, each vessel strip invari...
Stahl J, Kietzmann M.The effect of physical and chemical permeation enhancers on in vitro transdermal permeation of lidocaine was investigated in the horse.Therefore, the effect of six vehicles (phosphate-buffered saline (PBS), 50% ethanol, 50% propylene glycol, 50% isopropylalcohol, 50% isopropylalcohol/isopropylmyristate and 50% dimethylsulfoxide) was examined as well as the effect of microneedle pretreatment with different needle lengths on transdermal drug delivery of lidocaine.The skin was obtained from the thorax of six Warmblood horses and was stored up to two weeks at - 20°C. Franz-type diffusion cells we...
Underwood C, van Eps AW, Ross MW, Laverman P, van Bloois L, Storm G, Schaer TP.Liposomes are phospholipid nanoparticles that extravasate at sites of increased vascular permeability. They have potential in equine medicine for targeted drug delivery and diagnostic imaging of infectious, inflammatory and neoplastic lesions. Objective: This study evaluates the safety and biodistribution of i.v. polyethyleneglycol(PEG) liposomes in normal horses. Methods: PEG-liposomes were prepared by the film hydration method and labelled using (99m) Tc-hexamethyl-propylene-amine-oxime. A single dose of 0.24 µmol/kg bwt (99m) Tc-PEG-liposomes and 2.4 µmol/kg bwt unlabelled PEG-liposomes...
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...
Welsh JC, Lees P, Stodulski G, Cambridge H, Foster AP.The effects of access to hay and of restricted feeding on the pharmacokinetics of flunixin administered orally to six healthy ponies were compared in a cross-over study. No access to feed for a few hours before and after flunixin administration resulted in rapid absorption with a mean peak plasma concentration of 2.84 +/- 0.28 micrograms/ml attained in an average time of 0.76 +/- 0.18 h, followed by an exponential decline in plasma concentration. A lower peak plasma concentration was obtained when ponies had free access to hay before and after drug dosing. The mean maximum concentration (Cmax)...
Duz M, Parkin TD, Cullander RM, Marshall JF.To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. Methods: 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. Methods: 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and p...
Guschlbauer M, Hoppe S, Geburek F, Feige K, Huber K.Post operative ileus (POI) in horses is a severe complication after colic surgery. A commonly used prokinetic drug is lidocaine, which has been shown to have stimulatory effects on intestinal motility. The cellular mechanisms through which lidocaine affects smooth muscle activity are not yet known. Objective: To examine the effects of lidocaine on smooth muscle in vitro and identify mechanisms by which it may affect the contractility of intestinal smooth muscle. Objective: Ischaemia and reperfusion associated with intestinal strangulation can cause smooth muscle injury. Consequently, muscle ce...
Rusiecki KE, Nieto JE, Puchalski SM, Snyder JR.To determine the effect of continuous infusion of lidocaine on fecal transit time in normal horses. Methods: Experimental randomized cross-over study. Methods: Healthy horses (n=6). Methods: Barium-filled microspheres were administered to horses by nasogastric intubation and feces were collected every 2 hours for 4 days. A bolus of 2% lidocaine (1.3 mg/kg) was administered randomly, followed by a continuous infusion of lidocaine (0.05 mg/kg/min) for 3 days or an equivalent volume of saline. The washout period was 10 days. Variables assessed included defecation frequency, weight of feces produc...
Kvaternick V, Malinski T, Wortmann J, Fischer J.A sensitive reversed-phase HPLC-UV method was developed for the determination of firocoxib, a novel and highly selective COX-2 inhibitor, in plasma. A 1.0 mL dog or horse plasma sample is mixed with water and passed through a hydrophobic-lipophilic copolymer solid-phase extraction column to isolate firocoxib. Quantitation is based on an external standard curve. The method has a validated limit of quantitation of 25 ng/mL and a limit of detection of 10 ng/mL. The validated upper limit of quantitation was 2500 ng/mL for horses and 10,000 ng/mL for dogs. The average recoveries ranged from 88-93% ...
Kamerling SG, DeQuick DJ, Weckman TJ, Tobin T.The dose-related effects of intravenously administered fentanyl (0.010, 0.005, 0.0025 mg/kg) and saline were studied in mature performance horses using a rigorous experimental protocol. Fentanyl produced a dose-related prolongation of the skin twitch reflex latency but did not increase the hoof withdrawal reflex latency. Dose related increases in stepping frequency, cardiac and respiratory rats were observed following fentanyl, while changes in rectal temperature and pupil area were not. These data indicate that fentanyl, a prototypic mu-agonist, produces a syndrome characterized by analgesia,...
Dacquet C, Loirand G, Rakotoarisoa L, Mironneau C, Mironneau J.1. Specific binding of the calcium-antagonist dihydropyridine derivative, (+)-[3H]-PN 200-110 (isradipine), to cell membranes of equine portal vein smooth muscle was compared with binding to intact strips isolated from rat portal veins. 2. Specific binding to vascular smooth muscle membranes was of high affinity, saturable and reversible. The dissociation constant obtained from association and dissociation kinetics of (+)-[3H]-PN 200-110 was similar to that obtained from equilibrium binding and competition experiments. 3. Specific binding of (+)-[3H]-PN 200-110 was completely displaced by unla...
Maes A, Weiland L, Sandersen C, Gasthuys F, De Backer P, Croubels S.A sensitive method for the quantification of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in animal plasma using high-performance liquid chromatography combined with electrospray ionization mass spectrometry is described. The sample preparation includes a liquid-liquid extraction with methyl tert-butylmethyl ether after addition of 2M sodium hydroxide. Ethylmethylglycinexylidide (EMGX) is used as an internal standard. For chromatographic separation, an ODS Hypersil column was used. Isocratic elution was achieved with 0.01 M ammonium acetate and aceto...
Schmitz A, Demmel S, Peters LM, Leeb T, Mevissen M, Haase B.Cytochrome P450 enzymes (CYP450s) represent a superfamily of haem-thiolate proteins. CYP450s are most abundant in the liver, a major site of drug metabolism, and play key roles in the metabolism of a variety of substrates, including drugs and environmental contaminants. Interaction of two or more different drugs with the same enzyme can account for adverse effects and failure of therapy. Human CYP3A4 metabolizes about 50% of all known drugs, but little is known about the orthologous CYP450s in horses. We report here the genomic organization of the equine CYP3A gene cluster as well as a compara...
King SS, Young DA, Nequin LG, Carnevale EM.To determine whether specific sugars inhibit adhesion of Streptococcus zooepidemicus, Pseudomonas aeruginosa, and Escherichia coli to equine endometrial epithelial cells in vitro. Methods: Endometrial biopsy specimens collected during estrus from 7 healthy mares. Methods: Endometrial specimens on glass slides were incubated for 30 minutes at 4 C with suspensions of S. zooepidemicus, P. aeruginosa, or E. coli in phosphate-buffered saline solution (PBSS) alone or with various concentrations of D-(+)-mannose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-(+)-glucose, galactose, or N-acetyl-...
Slocombe JO.Aims of this study with 43 equids naturally infected with Anoplocephala perfoliata in two dose titration trials were to document (i) the usefulness of a critical test with a 48 h treatment to necropsy period, (ii) efficacy of an oral paste of 0.5-2.0 mg praziquantel/kg body weight, and (iii) when after treatment would fecal egg counts provide best estimates of the tapeworm's prevalence in a herd. All feces passed by an equid after treatment and collected in successive 12 h batches were examined for tapeworms. At necropsy, tapeworms were identified as attached to the mucosa or unattached. Tapew...
Alexander SL, Irvine CH.Alpha-2-adrenoceptor activation may lower adrenocorticotropic hormone (ACTH) by reducing secretagogue input and/or increasing the release of an inhibitory factor (CIF). To investigate this, we gave clonidine, an alpha-2-agonist, to seven horses, and collected pituitary venous blood every minute for 20 min before treatment and 40 min after treatment. Six horses were given saline vehicle. Mean secretion rates of corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and ACTH were calculated before and during four 5-min then two 10-min periods after clonidine or saline. Reduction in A...
Bettschart-Wolfensberger R, Bowen IM, Freeman SL, Weller R, Clarke KW.To search for long-term total i.v. anaesthesia techniques as a potential alternative to inhalation anaesthesia. Objective: To determine cardiopulmonary effects and anaesthesia quality of medetomidine-ketamine anaesthesia induction followed by 4 h of medetomidine-propofol anaesthesia in 6 ponies. Methods: Sedation consisted of 7 microg/kg bwt medetomidine i.v. followed after 10 min by 2 mg/kg bwt i.v. ketamine. Anaesthesia was maintained for 4 h with 3.5 microg/kg bwt/h medetomidine and propofol at minimum infusion dose rates determined by application of supramaximal electrical pain stimuli. Ve...
Martin EM, Jones SL.Inhibition of prostaglandin E2 (PGE2) production effectively limits inflammation in horses, however nonspecific prostaglandin blockade via cyclooxygenase (COX) inhibition elicits deleterious gastrointestinal side effects in equine patients. Thus, more selective PGE2 targeting therapeutics are needed to treat inflammatory disease in horses. One potential target is microsomal prostaglandin E-synthase-1 (mPGES-1), which is the terminal enzyme downstream of COX-2 in the inducible PGE2 synthesis cascade. This enzyme has yet to be studied in equine leukocytes, which play a pivotal role in equine inf...
Klei TR, Rehbein S, Visser M, Langholff WK, Chapman MR, French DD, Hanson P.Two trials were conducted to confirm the efficacy of ivermectin paste against endoparasites of horses. In these trials, 20 ponies were treated with ivermectin oral paste at 200 mcg x kg body weight once on Day 0, and 20 ponies served as unmedicated controls. The animals carried naturally acquired parasite infections as confirmed by pretrial fecal examination. The animals were necropsied for worm recovery on Days 14, 15 or 16. Parasites recovered were identified to species. Horses treated with ivermectin had significantly (P99.0% reduction) adult small strongyles (Coronocyclus spp including C. ...
Johnson CB, Bloomfield M, Taylor PM.To investigate the effects of ketamine on the electroencephalogram (EEG) of the horse. Methods: Prospective experimental study. Methods: Eight Welsh mountain pony geldings weighing between 280 and 330 kg, 5 to 9 years old. Methods: During halothane anesthesia at an end-tidal halothane concentration between 0.75 and 0.85%, the EEG frequency power spectrum and the auditory evoked potential were recorded while an infusion of ketamine was given. Ketamine 200 mg was infused over 5 minutes in 8 ponies. The effects of ketamine on the EEG were recorded continuously during the infusion and for a furthe...
Veronesi MC, Battocchio M, Faustini M, Gandini M, Cairoli F.The aim of this study was to evaluate the possible relationship of pharmacological induction of estrous and/or ovulation with the occurrence of twin pregnancies in Thoroughbred mares. Out of 680 mares, 356 received one of the following treatments during the estrous cycle in which they became pregnant: injection of 0.5mg of cloprostenol at the ultrasonographic detection of a CL (n=86); injection of 5000 IU human chorionic gonadotropin (hCG) immediately before mating (n=221); injection of 0.5mg of cloprostenol at the ultrasonographic detection of a CL plus injection of 5000 IU hCG immediately be...
Totorikaguena L, Olabarrieta E, Lolicato F, Romero-Aguirregomezcorta J, Smitz J, Agirregoitia N, Agirregoitia E.The cannabinoid (CB) system has been involved in many aspects of reproduction and it is known that the systemic chronic use of exogenous CBs are deleterious to reproductive processes. Even so, it is not known what happens in relation to the physiology of the ovary when CB receptors are absent. The present study investigated the effect of the lack of CB1 and CB2 receptors in mice ovarian morphology, folliculogenesis, oocyte retrieval, and oocyte maturation and evaluated the use of Δ9-tetrahydrocannabinol (THC) on oocyte in vitro maturation (IVM) by comparing classical IVM and two-step IVM by a...
Klei TR, Torbert BJ.The controlled test method was used to evaluate the antiparasitic efficacy of IM inoculated 22,23-dihydroavermectin B1 (ivermectin) against gastrointestinal parasites of horses (ponies). Parasite infections were naturally acquired in southern Louisiana. Dose levels of the drug tested were 0.2 mg/kg, 0.3 mg/kg, and 0.5 mg/kg. Ivermectin at all dose levels tested had an efficacy greater than 97% (P less than 0.05) against Gasterophilus intestinalis larvae, Trichostrongylus axei, Oxyuris equi larvae, Strongylus vulgaris, S edentatus, 15 species of small strongyles, and small strongyle larvae. Pon...
Hinchcliff KW, Muir WW.Furosemide, a diuretic, is frequently administered to horses for the prophylaxis of exercise-induced pulmonary hemorrhage and the treatment of a number of clinical conditions, including acute renal failure and congestive heart failure. Furosemide increases the rate of urinary sodium, chloride, and hydrogen ion excretion. Plasma potassium concentration decreases after furosemide administration but urinary potassium excretion in horses is minimally affected. Renal blood flow increases after furosemide administration. Systemically, furosemide increases venous compliance and decreases right atrial...
Padjasek M, Qasem B, Cisło-Pakuluk A, Marycz K.Cyclosporine A (CsA) is a selective and reversible immunosuppressant agent that is widely used as a medication for a wide spectrum of diseases in humans such as graft versus host disease, non-infectious uveitis, rheumatoid arthritis, psoriasis, and atopic dermatitis. Furthermore, the CsA is used to treat keratoconjunctivitis sicca, chronic superficial keratitis, immune-mediated keratitis and equine recurrent uveitis in animals. The selective activity of Cyclosporine A (CsA) was demonstrated to be an immunomodulation characteristic of T-lymphocyte proliferation and inhibits cytokine gene expres...
Recio P, López PG, Hernández M, Prieto D, Contreras J, GarcÃa-Sacristán A.The involvement of nitric oxide (NO) and the mechanisms mediating neurogenic relaxation were investigated in the horse corpus cavernosum. NADPH-diaphorase activity was expressed in nerve fibres around arteries and muscular bundles in the horse trabecular tissue. Relaxations in response to electrical field stimulation were tetrodotoxin (10(-6) M)-sensitive, indicating their neurogenic origin. The NO synthase inhibitor, L-NO-arginine (L-NO-Arg, 3 x 10(-5) M), abolished the electrically induced relaxations, which were significantly reversed by L-arginine (3 x 10(-3) M). Exogenous NO (10(-6)-10(-3...
Mercer MA, McKenzie HC, Byron CR, Pleasant RS, Bogers SH, Council-Troche RM, Werre SR, Burns T, Davis JL.Acetaminophen has been used clinically in horses alone or combined with traditional non-steroidal anti-inflammatory drugs for treatment of musculoskeletal pain in horses. Objective: To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control. Methods: In vivo experiment. Methods: Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2â...
