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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.
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...
The activity of mixed function oxidases, estimated by in vivo antipyrine clearance, is similar in horses and camels. The activity of hepatic mixed function oxidases was compared in horses and camels (Camelus dromedarius) by studying the pharmacokinetics of antipyrine in seven camels and five horses following intravenous administration of a single dose of antipyrine (25 mg/kg). The data obtained (mean +/- SEM and median in brackets) in camels and horses, respectively, were as follows: the elimination half-lives were 3.25 +/- 0.23 (3.19) and 3.09 +/- 0.25 (2.90) hr; the apparent volumes of distribution (area method) were 0.691 +/- 0.045 (0.648) and 0.642 +/- 0.034 (0.676) l/kg; the volumes of distribution at s...
Epidural injection of ketamine for perineal analgesia in the horse. To determine the analgesic, sedative, and cardiopulmonary effects of epidural ketamine in the horse. Methods: Six healthy horses (three males and three females) weighing between 350 and 450 kg. Methods: Three doses of ketamine were selected (0.5, 1, 2 mg/kg). Two months before the beginning of experiments, the carotid artery was exteriorized, and 1 week before experiments began, an epidural catheter was placed percutaneously in all animals with the tip located 12 cm cranially in the midsacrum. One week later, either saline (control) or one of three doses of ketamine was injected epidurally. Ea...
Effect of a competitive inhibitor of platelet aggregation on experimentally induced laminitis in ponies. To determining whether inhibition of platelet aggregation prevents development of carbohydrate overload-induced alimentary laminitis. Methods: 22 healthy adult ponies. Methods: Acute laminitis was induced by oral administration of corn starch/wood flour to 16 ponies, 8 of which were treated with a synthetic analogue of the platelet fibrinogen receptor antagonist peptide (RPR) RGDS (arginine-glycine-aspartic acid-serine) 110885; 6 ponies served as negative controls. Blood was collected before and at 4, 8, 12, 24, 28, and 32 hours after administration of carbohydrate overload, and PCV, total pla...
Efficacy of moxidectin 2% oral gel against second- and third-instar Gasterophilus intestinalis De Geer. In a trial designed to evaluate the efficacy of the recommended dosage of moxidectin 2% oral gel against the gastric stages of Gasterophilus spp., 14 ponies were selected from a herd on the basis of the inclusion criterion of the presence of Gasterophilus spp. eggs attached to their hair coats. After random allocation, the ponies were treated with 1 of 2 treatments, moxidectin 2% equine gel in a single dose at the commercial dosage of 400 microg moxidectin/kg body weight or placebo gel. The animals were necropsied 14 days posttreatment. Efficacies against second- and third-instar Gasterophilus...
Comparison of detomidine/ketamine and guaiphenesin/thiopentone for induction of anaesthesia in horses maintained with halothane. This prospective clinical study compared the physiological effects of two commonly used anaesthetic induction techniques in horses maintained with halothane. One hundred horses admitted for elective surgery were randomly allocated to receive either guaiphenesin (to effect) and thiopentone (5 mg/kg), or detomidine (20 microg/kg) and ketamine (2 mg/kg) for the induction of anaesthesia after acepromazine premedication. Anaesthesia was maintained with halothane in oxygen. There were no significant differences in breed, age, sex, weight, type of surgery and duration of anaesthesia between the group...
Effects of two large doses of equine recombinant growth hormone on clinical, haematological and serum biochemical variables in adult horses. To evaluate the clinical, haematological, and serum biochemical effects of two large doses of recombinant equine growth hormone. Methods: Duplicated Latin square. Methods: Three Thoroughbred and three Standardbred mares aged between 12 and 17 years. Methods: Two horses were randomly assigned into one of three groups. On each of three successive days, each horse pair received one of two dosages of growth hormone or a saline placebo so that by the end of the experiment all three horse pairs had received both dosages and the saline placebo. Dose rates selected were 50 micrograms/kg, and 100 micro...
Efficacy of moxidectin and other anthelmintics against small strongyles in horses. To compare the efficacy of moxidectin to ivermectin, oxibendazole and morantel against some gastrointestinal nematodes in horses. Methods: Faecal egg count reduction after treatment. Methods: A farm was selected where the population of small strongyles in horses was known to be resistant to oxibendazole. Horses were allocated to treatment groups based on faecal egg counts. After treatment, faecal samples were taken up to 109 days after treatment and faecal egg counts estimated. Faecal cultures were used to estimate the contribution of small and large strongyles to the faecal egg counts at each...
[Equine Cushing syndrome (ECS). Case report, review of its diagnosis and therapy and substantial differences from Cushing syndrome in dogs]. Equine and canine Cushing's syndrome, both of which are the result of elevated cortisol levels, show some different pathogenetical and clinical features and require different therapeutical approaches. In older horses the equine Cushing's syndrome (ECS) is not uncommon. Nearly all cases result from excessive hormone production in cells of the pars intermedia of the pituitary. Besides elevated levels of adrenocorticotrope hormone (ACTH), high peripheral levels of pro-opiomelanocortin, beta-endorphines and alpha-melanocyte-stimulating hormone can be measured. In middle-aged and geriatric dogs, Cu...
Effect of tumor necrosis factor antibody given to horses during early experimentally induced endotoxemia. To test efficacy of murine monoclonal, rabbit polyclonal recombinant equine or human tumor necrosis factor-alpha (rETNF or rHTNF, respectively) antibodies to inhibit native equine tumor necrosis factor (TNF) activity. Methods: 8 and 18 healthy adult horses for parts 1 and 2 of the study, respectively. Methods: In part 1, supernates from endotoxin-activated peritoneal macrophages were incubated with various dilutions of each rETNF antibody and subsequently tested for TNF activity. Serum was also obtained from a horse 1 hour after infusion with 20 ng of endotoxin/kg of body weight and was incuba...
L-NAME does not affect exercise-induced pulmonary hypertension in thoroughbred horses. The present study was carried out to examine the effects of nitric oxide synthase inhibition with Nomega-nitro-L-arginine methyl ester (L-NAME) on the right atrial as well as on the pulmonary arterial, capillary, and venous blood pressures of horses during rest and exercise performed at maximal heart rate (HRmax). Experiments were carried out on seven healthy, sound, exercise-trained Thoroughbred horses. Using catheter-tip manometers, with signals referenced at the point of the shoulder, we determined phasic and mean right atrial and pulmonary vascular pressures in two sets of experiments [con...
Fluid administration attenuates the haemodynamic effect of frusemide in running horses. The effect of blood volume repletion after frusemide administration on the right atrial and pulmonary artery pressure responses of horses to exercise has not been reported. We examined right atrial and pulmonary artery pressure and plasma atrial natriuretic peptide concentration (ANP) responses to an incremental exercise test in 6 Standardbred mares. Horses were treated, in a 3 way cross over design, with isotonic saline, frusemide (1 mg/kg bwt, i.v.), and frusemide followed 3 h later by lactated Ringer's solution (12 ml/kg bwt, i.v.). Three and a half hours after saline or frusemide administr...
Inhibition by CaNa2EDTA of local tissue damage induced by Bothrops asper (terciopelo) venom: application in horse immunization for antivenom production. The ability of the chelating agent CaNa2EDTA to inhibit local tissue damage induced by Bothrops asper venom was studied in mice and in horses used for polyvalent (Crotalinae) antivenom production. CaNa2EDTA was devoid of toxicity when injected i.m. or s.c. inducing only a mild edema. Preincubation of B. asper venom with CaNa2EDTA inhibited hemorrhagic and dermonecrotic activities, but did not reduce edema-forming and myotoxic effects. A group of horses initially immunized with native venoms developed less severe local tissue reactions when injected with booster doses of venom and CaNa2EDTA tha...
Role of cAMP and neuronal K+ channels on alpha 2-AR-induced inhibition of ACh release in equine trachea. To investigate the effects of changes in intracellular cAMP on alpha 2-adrenoceptor (AR)-induced inhibition of airway acetylcholine (ACh) release, we examined the effects of the alpha 2-AR agonist clonidine on electrical field stimulation-evoked ACh release from equine tracheal parasympathetic nerves before and after treatment with 8-bromo-cAMP or forskolin. We also tested whether charybdotoxin (ChTX)- or iberiotoxin (IBTX)-sensitive Ca(2+)-activated K+ channels mediate alpha 2-AR-induced inhibition by examining the effect of clonidine in the absence and presence of ChTX or IBTX on ACh release...
Contribution of K+ channels and ouabain-sensitive mechanisms to the endothelium-dependent relaxations of horse penile small arteries. 1. Penile small arteries (effective internal lumen diameter of 300 600 microm) were isolated from the horse corpus cavernosum and mounted in microvascular myographs in order to investigate the mechanisms underlying the endothelium-dependent relaxations to acetylcholine (ACh) and bradykinin (BK). 2. In arteries preconstricted with the thromboxane analogue U46619 (3-30 nM), ACh and BK elicited concentration-dependent relaxations, pD2 and maximal responses being 7.71+/-0.09 and 91+/-1 % (n=23), and 8.80+/-0.07 and 89+/-2% (n=24) for ACh and BK, respectively. These relaxations were abolished by me...
