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Topic:Pharmacology
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.
Dextran-70 inhibits equine platelet aggregation induced by PAF but not by other agonists. Dextrans of mean molecular weight 70 kDa (dextran-70) have had clinical use as anti-thrombotics in man. A major part of the anti-thrombotic action is mediated via inhibition of platelet function. Greatorex (1975, 1977) treated thromboembolic colic in horses with infusions of dextran-70 and reported a 90% recovery rate, but this treatment is nonetheless rarely used. We have used an in vitro method to examine the effect of dextran-70 on equine platelet suspensions, in the hope that understanding the mechanism of action of dextran-70 might lead to the development of alternative therapeutic agents...
Recovery from sevoflurane anesthesia in horses: comparison to isoflurane and effect of postmedication with xylazine. To compare recovery from sevoflurane or isoflurane anesthesia in horses. Methods: Prospective, randomized cross-over design. Methods: Nine Arabian horses (3 mares, 3 geldings, and 3 stallions) weighing 318 to 409 kg, 4 to 20 years old. Methods: Horses were anesthetized on three occasions with xylazine (1.1 mg/kg), Diazepam (0.03 mg/kg intravenously [i.v.]), and ketamine (2.2 mg/kg i.v.). After intubation, they were maintained with isoflurane or sevoflurane for 90 minutes. On a third occasion, horses were maintained with sevoflurane and given xylazine (0.1 mg/kg i.v.) when the vaporizer was tur...
Controlled-release products for the control of the estrus cycle in cattle, sheep, goats, deer, pigs, and horses. This paper describes the estrus cycles of a number of livestock breeds and reviews the controlled-release drug delivery systems that are currently available for the purpose of controlled breeding. The bovine estrus cycle is reviewed in detail, and the estrus cycles of other species are described in a manner that highlights similarities and differences between species. Pertinent formulation and pharmacokinetic information about current drug delivery systems is presented and discussed, and recent advances in this area are also described.
Anti-inflammatory effects of topically applied dimethyl sulfoxide gel on endotoxin-induced synovitis in horses. To evaluate the effect of topically applied dimethylsulfoxide (DMSO) on lipopolysaccharide (LPS)-induced synovitis in the mid-carpal joint. Methods: 6 sound, healthy, adult horses (12 carpi). Methods: In a double-blinded, crossover, paired study with a 1-week washout period, mid-carpal joints were allocated to group 1 (DMSO, n = 6) or group 2 (control, n = 6). Each joint was injected with 1.3 ml (0.0125 ng/dl) of LPS to induce synovitis. For group-1 joints, DMSO gel (15 g; 90%) was applied after injection of LPS and at 12-hour intervals for 60 hours. Joints of group 2 received LPS, but not DMS...
Development of an ELISA to assess the potency of horse therapeutic polyvalent antibothropic antivenom. The objective of this study was the search for a suitable venom antigen to be used in an in vitro alternative immunoassay, to the standard antivenom neutralization assay using mice. Bothrops jararaca venom was fractionated in DEAE-Sephacel columns and the fractions were tested for a correlation between antibody capture enzyme linked immunosorbent assay (ELISA) absorbance values and the 'in vivo' antivenom potency. Individual antivenoms from 14 horses and 15 separate FUNED polyspecific Bothrops ampouled antivenoms (final product) were used. Fractions showing the higher correlations were further...
Neutralizing potency of horse antibothropic antivenom. Correlation between in vivo and in vitro methods. The correlation coefficients between in vivo neutralization of lethal toxicity (ED50), neutralization of the hemolytic activity (PLA2) and levels of antibodies measured by ELISA, was investigated to test the potency of horse anti-bothropic antivenom. Twenty six horses were hyperimmunized with Bothrops venoms (B. alternatus, B. jararaca, B. jararacussu, B. neuwiedii and B. moojeni). To set up an indirect ELISA, for neutralization of PLA2 activity and for determination of ED50 in Swiss mice, the whole Bothrops jararaca venom (reference venom for assessing the bothropic antivenom potency in Brazi...
Complications associated with administration of detomidine into the caudal epidural space in a horse. A 364-kg (800-lb) 15-month-old sexually intact cryptorchid male Quarter Horse was admitted to the veterinary teaching hospital for castration. The horse was placed in standing stocks, and a caudal epidural injection of 18 mg of detomidine hydrochloride (50 micrograms/kg [23 micrograms/lb] of body weight) was administered. Fifteen minutes after injection, the horse unexpectedly collapsed to the floor, first into sternal, and then into lateral, recumbency. Because the horse would not get up, the decision was made to perform the surgery with the horse under general anesthesia. The horse required ...
Cytologic evaluation of bronchoalveolar lavage fluid from horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. To determine cytologic changes in horses with recurrent airway obstruction (heaves) after administration of aerosolized beclomethasone dipropionate and dexamethasone parenterally. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone, parenterally administered dexamethasone, aerosolized propellant), and pulmonary inflammation was evaluated by serial cytologic examination of bronchoalveolar lavage (BAL) fluid samples obtained on days 0, 7...
Pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. To determine changes in clinical signs of disease and response to pulmonary function testing in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure (challenge) to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone dipropionate, parenterally administered dexamethasone, aerosolized propellant [control]), and respiratory frequency and s...
Alteration in adrenocortical function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. To determine alteration in adrenocortical function in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days (natural challenge). Horses then underwent treatment (aerosolized beclomethasone, parenterally administered dexamethasone, and aerosolized propellant) for 7 days. Horses remained in the mold-contaminated environment for 7 days after discontinuat...
Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies. This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively)....
Haemodynamic effects of a sixty minute infusion of dopamine hydrochloride in horses anaesthetised with halothane. To describe the haemodynamic effects of a 60 min infusion of dopamine 4 microg/kg bwt/min during halothane anaesthesia, 7 mature Thoroughbred horses were studied. The infusion began 1 h after induction of anaesthesia by romifidine (100 microg/kg) and ketamine (2.2 mg/kg bwt). Throughout the period of dopamine infusion and for 30 min after its discontinuation, the horses were ventilated by intermittent positive pressure to maintain PaCO2 between 4.6-5.4 KPa. Inspired halothane concentration was adjusted to maintain an end tidal halothane concentration of 0.9%. Haemodynamic variables were measur...
Absence of detectable pharmacological effects after oral administration of isoxsuprine. Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To define the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCl (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activ...
Effect of cisapride on gastric emptying in horses following endotoxin treatment. The effect of cisapride pretreatment on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen, a drug known to be readily absorbed in the small intestine but not in the stomach. The time to reach maximum serum acetaminophen concentrations (Tmax), the maximum serum concentrations (Cmax) and the area under the serum acetaminophen concentration vs. time curves (AUC) were compared among treatment groups. In the first part of the study, the effect of orally administered cisapride (0.1, 0.2 and 0.4 mg/kg bwt) on gastric emptying was examined in 6 normal fasted ...
Acetaminophen as a marker of gastric emptying in ponies. Gastric emptying was evaluated in ponies using the acetaminophen (AP) method. Fifteen minutes after i.v. administration of metoclopramide, erythromycin, yohimbine, atropine or saline, the ponies were given AP by stomach tube. Blood samples for AP analysis were collected at baseline and 15, 30, 45, 60, 75, 90, 105 and 120 min after AP administration. Time to reach peak serum concentration (Tmax), maximum serum concentration (Cmax) and area under the AP serum concentration vs. time curve (AUC) were determined for each treatment group. In the control group, Tmax was 31 min and this decreased sign...
Increase in blood viscosity in the sprinting horse: can it account for the high pulmonary arterial pressure? Blood was taken from 49 Thoroughbred horses before and after racing at the track to determine if frusemide modified the apparent viscosity of the blood and to determine the effects of changes in shear rate and packed cell volume (PCV), associated with strenuous exercise, on apparent and relative viscosities. Small increases in apparent viscosity of the blood (at a specified PCV and shear rate) occurred in horses given frusemide compared to those receiving no frusemide; however, no differences were seen in relative viscosity. Although 2 groups of horses, those receiving frusemide before racing ...
The potential of collagenase as a new therapy for separation of human retained placenta: hydrolytic potency on human, equine and bovine placentae. The purpose of this study was to determine to what degree bacterial collagenase may digest human placentae compared to equine and bovine placentae. Placenta samples from human, equine and bovine were incubated with bacterial collagenase solution at various concentrations. The degree of hydrolysis and collagen breakdown was measured by the release of total proteins and hydroxyproline into the incubation media. Also, whole placentae were injected via umbilical cord arteries with collagenase solution (200 U/ml, 200 ml total volume in human and 1000 ml in equine) and hydrolysis determined chemical...
Screening of chlorpropamide in horse plasma by high-performance liquid chromatography with ultraviolet absorbance detection, and confirmation by gas chromatography-mass spectrometry. A chromatographic method was developed to detect and confirm the presence of chlorpropamide (I) in horse plasma samples, for antidoping control. The plasma sample (1 ml) was extracted with dichloromethane and screened by high-performance liquid chromatography, and confirmation of the drug's presence was accomplished by using gas chromatography-mass spectrometry (GC-MS). The limit of detection was found to be 3.5 ng/ml at a signal-to-noise ratio of three. Derivatization of I with N,O-bis-(trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane allowed for highly stable, accurate and sen...
Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP. 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...
The effects of intra-articular methylprednisolone and exercise on the mechanical properties of articular cartilage in the horse. Intra-articular corticosteroids are widely used as anti-inflammatory agents for symptomatic management of arthritis, but their administration with concurrent exercise remains controversial. Biochemical and morphologic analysis of treated cartilage has revealed conflicting results, but previous biomechanical assessment has not been undertaken. Objective: To compare the biomechanical properties of intra-articular methylprednisolone acetate (MPA) and diluent treated cartilage in treadmill exercised horses. Methods: Eight 2-year-old female horses had MPA or diluent administered into contralateral ...
Effects of local anesthetics on Na+ channels containing the equine hyperkalemic periodic paralysis mutation. We examined the ability of local anesthetics to correct altered inactivation properties of rat skeletal muscle Na+ channels containing the equine hyperkalemic periodic paralysis (eqHPP) mutation when expressed in Xenopus oocytes. Increased time constants of current decay in eqHPP channels compared with wild-type channels were restored by 1 mM benzocaine but were not altered by lidocaine or mexiletine. Inactivation curves, which were determined by measuring the dependence of the relative peak current amplitude after depolarization to -10 mV on conditioning prepulse voltages, could be shifted in...
Regional differences in endothelial function in horse lungs: possible role in blood flow distribution? We investigated regional differences of in vitro responses of pulmonary arteries (6-mm OD) from the dorsocaudal (top) and cranioventral (bottom) lung regions to endothelium-dependent vasodilators (methacholine, bradykinin, and calcium ionophore A-23187). Methacholine relaxed endothelium-intact top vessels; however, in bottom vessels, a small relaxation preceded a profound contraction. In top vessels, removal of endothelial cells converted relaxation to contraction, and in bottom vessels it abolished relaxation and enhanced contraction. Bradykinin and A-23187 were more potent and caused greater...
Fusion pore expansion in horse eosinophils is modulated by Ca2+ and protein kinase C via distinct mechanisms. Using the patch-clamp technique, we studied the role of protein phosphorylation and dephosphorylation on the exocytotic fusion of secretory granules with the plasma membrane in horse eosinophils. Phorbol 12-myristate 13-acetate (PMA) had no effect on the amplitude and dynamics of degranulation, indicating that the formation of fusion pores is insensitive to activation of protein kinase C (PKC). Fusion pore expansion, however, was accelerated approximately 2-fold by PMA, and this effect was abolished by staurosporine. Elevating intracellular Ca2+ to 1.5 microM also resulted in a 2-fold accelera...
Phenylbutazone prevents the endotoxin-induced delay in gastric emptying in horses. The effect of phenylbutazone on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal fasted horses (n = 6), horses given endotoxin intravenously (n = 6), horses given intravenous phenylbutazone (n = 6), and horses given intravenous phenylbutazone plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration versus time curve (AUC) were compared among treatment groups. Phenylbutazone...
[Historical aspects on the development of doping research on the horse in the Veterinary College in Berlin 1925-1945]. Since the early twenties several institutes of the Veterinary College in Berlin were involved in the development of microchemical analyzing methods for doping-alkaloids and clinical studies in doped race horse. This research made it possible to build national acting structures against the abuse of doping in race horses, which soon became a model for similar activities in other countries, for instance Greece, Japan and the United States. Concerning the results of their research, the scientists of the Veterinary College in Berlin have got an enormous part in fighting against doping in race horse...
Effect of the 5-lipoxygenase inhibitor, fenleuton, on antigen-induced neutrophil accumulation and lung function changes in horses with chronic obstructive pulmonary disease. The leukotrienes (LT) LTD4 and LTB4 have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5-lipoxygenase inhibitor, fenleuton, on antigen-induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre-treatment on...
Review of furosemide in horse racing: its effects and regulation. Furosemide has been used empirically and has been legally approved for many years by the US racing industry for the control of exercise-induced pulmonary haemorrhage (EIPH) or bleeding. Its use in horses for this purpose is highly controversial and has been criticized by organizations outside and inside of the racing industry. This review concentrates on its renal and extra-renal actions and the possible relationship of these actions to the modification of EIPH and changes in performance of horses. The existing literature references suggest that furosemide has the potential of increasing perfo...
Inhibition of glutathione S-transferase activity by the quinoid metabolites of equine estrogens. The risk factors for women developing breast and endometrium cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy (ERT) in particular has been correlated with a slight increased cancer risk, although the numerous benefits of ERT may negate this harmful side effect. Equilenin and equilin are equine estrogens which make up between 30% and 45% of the most widely prescribed estrogen replacement formulation, Premarin (Wyeth-Ayerst). In this study we have synthesized the catechol metabolites of equilenin [4-hydroxyequilenin (4-OHEN)] and equilin [4-hydroxyequ...
