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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.
Use of a multiple choice questionnaire to assess UK prescribing channels’ knowledge of helminthology and best practice surrounding anthelmintic use in livestock and horses. Grazing livestock and equines are at risk of infection from a variety of helminths, for which the primary method of control has long been the use of anthelmintics. Anthelmintic resistance is now widespread in a number of helminth species across the globe so it is imperative that best practice control principles be adopted to delay the further spread of resistance. It is the responsibility of all who prescribe anthelmintics (in the UK, this being veterinarians, suitably qualified persons (SQPs) and pharmacists) to provide adequate information on best practice approaches to parasite control at t...
Evaluation of 10-minute versus 30-minute tourniquet time for intravenous regional limb perfusion with amikacin sulfate in standing sedated horses. The objective of the article is to determine the synovial fluid concentrations of amikacin sulfate (AS) after performing an intravenous regional limb perfusion (IVRLP) with the tourniquet in place for 10 minutes and compare this with 30 minutes. This is a randomised crossover experimental design. Animals were seven healthy adult horses. Horses underwent two IVRLP procedures in a randomised, crossover design. The horses received IVRLP with 2 g AS diluted to 60 ml using 0.9% saline in the cephalic vein of alternate limbs with the tourniquet in place for either 10 or 30 minutes, with a ...
Cardiorespiratory and anesthetic effects of combined alfaxalone, butorphanol, and medetomidine in Thoroughbred horses. This study evaluated induction of anesthesia and cardiorespiratory and anesthetic effects during maintained anesthesia with the combination of alfaxalone, medetomidine, and butorphanol. Alfaxalone (1.0 mg/kg) was administered to induce anesthesia after premedication with medetomidine (7.0 µg/kg), butorphanol (25 µg/kg), and midazolam (50 µg/kg) in six Thoroughbred horses. Intravenous general anesthesia was maintained with alfaxalone (2.0 mg/(kg∙hr)), medetomidine (5.0 µg/(kg∙hr)), and butorphanol (30 µg/(kg∙hr)) for 60 min. Electrical stimulation of the upper oral mucosa was used to...
Accuracy and Precision of Noninvasive Blood Pressure in Normo-, Hyper-, and Hypotensive Standing and Anesthetized Adult Horses. Blood pressure is relevant to the diagnosis and management of many medical, cardiovascular and critical diseases. The accuracy of many commonly used noninvasive blood pressure (NIBP) monitors and the accuracy of NIBP measurements in hypo- and hypertensive standing horses has not been determined. Objective: The objective of this study was to investigate the accuracy of an oscillometric BP monitor in standing horses before and during pharmacologically induced hyper- and hypotension and to compare results in standing and anesthetized horses. Methods: Eight standing mares from a research herd (SG)...
Topical distribution of acyclovir in normal equine skin and equine sarcoids: An in vitro study. Topical acyclovir application is an owner-friendly treatment for occult equine sarcoids, without the caustic side-effects other topical treatments have. Variable clinical success rates have been described, but it is not known to what rate and extent acyclovir penetrates in and through equine skin from a topical formulation. In the current study, an in vitro Franz diffusion model was used to determine the permeation parameters for a generic 5% acyclovir cetomacrogol cream for both healthy and sarcoid equine skin. The distribution of acyclovir between different layers of both skin types was also...
Quantitative assessment of two methods of tiludronate administration for the treatment of lameness caused by navicular syndrome in horses. To determine effects of 2 tiludronate administration protocols on measures of lameness in horses with navicular syndrome (NS). Methods: 12 horses with bilateral forelimb NS. Methods: Horses were randomly assigned to receive tiludronate (1 mg/kg), diluted in 5 L of isotonic electrolyte solution and delivered through a jugular vein catheter (systemic treatment group; n = 6), or tiludronate (0.1 mg/kg), diluted with saline (0.9% NaCl) solution to a total volume of 35 mL and delivered into the lateral digital vein of each forelimb with an IV regional limb perfusion (IVRLP) technique (IVRLP group; ...
Investigation of the potential immunomodulatory effects of resveratrol on equine whole blood: An in vitro investigation. Horses affected with gastrointestinal conditions such as colic or colitis are at substantial risk for translocation of bacterial components such as lipopolysaccharide (LPS, endotoxin) from the gastrointestinal tract into circulation resulting in systemic inflammation and subsequent morbidity and mortality. Therefore, there is a need for effective preventive and treatment strategies aimed at minimizing the host's inflammatory reaction to these pathogen-associated molecular patterns (PAMPs) from gastrointestinal disease. Resveratrol (RES, trans-3,5,4'-trihydroxystilbene) is a phytoalexin commonl...
Topical delivery of diclofenac into and across equine skin from a novel liquid diclofenac epolamine formulation. The aim was to investigate diclofenac delivery into and across equine skin in vitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP; 1.3%) formulation and to compare the results to those of Surpass (1% diclofenac sodium liposomal cream) and a 1% aqueous solution of diclofenac sodium. Skin was harvested from the lower legs of Freiberger geldings immediately after slaughter and sliced to a thickness of ~2 mm. Skin samples were divided into two groups [Group 1: 1 year old (n = 2) and Group 2: 6-8 years old (n = 3)]. Cumulative permeation of diclofenac in Groups 1 and...
Pain: Its Diagnosis and Management in the Rehabilitation of Horses. This article provides a brief overview of pain physiology and its relevance to equine patients. Objective and subjective techniques for assessing pain in the horse are described in depth. Pharmacologic and interventional pain modulation treatments are discussed with a focus on the rehabilitating horse.
Chloroquine inhibits Rhodococcus equi replication in murine and foal alveolar macrophages by iron-starvation. Rhodococcus equi preferentially infects macrophages causing pyogranulomatous pneumonia in young foals. Both the vapA and rhbC genes are up-regulated in an iron (Fe)-deprived environment, such as that found within macrophages. Chloroquine (CQ) is a drug widely used against malaria that suppresses the intracellular availability of Fe in eukaryotic cells. The main objective of this study was to evaluate the ability of CQ to inhibit replication of virulent R. equi within murine (J774A.1) and foal alveolar macrophages (AMs) and to verify whether the mechanism of inhibition could be Fe-deprivation-d...
The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes. To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles whe...
Field use of N-butylscopolammonium bromide to facilitate thorough ophthalmic examination in horses. N-butylscopolammonium bromide (NBB), an anticholinergic muscarinic antagonist, was assessed as a mydriatic agent for field examination of equine eyes. Six adult horses were randomly assigned to four treatments with 2 weeks washout between treatments: (1) topical saline/IV saline (negative control); (2) topical tropicamide/IV saline (positive control); (3) topical NBB/IV saline; or (4) topical saline/IV NBB. Horizontal and vertical pupil diameters, temperature, pulse, respiration, pupillary light reflexes (PLRs) and mydriasis sufficient to perform complete fundic examination were recorded. Trop...
Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam. Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzy...
Episcleral cyclosporine A implants for the management of unilateral keratoconjunctivitis sicca in an 8-year-old mare. An 8-year-old mare was presented for investigation of a 1-month history of blepharospasm, eyelid swelling, corneal edema, and ocular discharge of the right eye (OD). Ophthalmic examination confirmed mucopurulent ocular discharge, conjunctival hyperemia, and a dry, dull appearance to the cornea OD. Schirmer tear test results confirmed an absence of tear production OD (0 mm/min) consistent with keratoconjunctivitis sicca. Treatment with topical 0.2% cyclosporine A resulted in an improvement in clinical signs. An episcleral cyclosporine A implant was placed under standing sedation 5 days after in...
The PGF2α agonists luprostiol and d-cloprostenol reliably induce luteolysis in luteal phase mares without evoking clinical side effects or a stress response. In the present study we have evaluated a possible stress reaction in response to two different PGF2α analogs-luprostiol and D-cloprostenol--and their effects on estrous cycle characteristics. In a cross-over-design eight mares received in alternating order either luprostiol (Treatment LUP; 3.75 mg im), D-cloprostenol (Treatment CLO; 22.5μg im) or saline (Treatment CON; NaCl 0.9% 0.5ml im) on day 8 after ovulation. Injection of either LUP or CLO, but not of CON resulted in a significant decline of progesterone concentration in plasma to baseline concentrations within two days (time: p<0.00...
Cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane and low-dose S-ketamine or medetomidine infusions. To evaluate cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane receiving medetomidine or S-ketamine infusions. Methods: Randomized, blinded, prospective clinical trial. Methods: Fifty horses undergoing elective surgery. Methods: After acepromazine and flunixin meglumine premedication, horses received medetomidine (7 μg kg-1 ) intravenously (IV). Anaesthesia was induced with midazolam and racemic ketamine (Med treatment group; 2.2 mg kg-1 ; n = 25) or S-ketamine (S-ket treatment group; 1.1 mg kg-1 ; n = 25) IV and maintained with isoflura...
Continuous positive airway pressure (CPAP) decreases pulmonary shunt in anaesthetized horses. To evaluate the effects of continuous positive airway pressure (CPAP) on intrapulmonary shunt, cardiac output and oxygen delivery in horses subjected to a 6 hour period of general anaesthesia. Methods: Randomized, experimental, crossover study. Methods: Ten healthy adult horses. Methods: Following medetomidine, diazepam and ketamine administration, orotracheal intubation was performed and horses positioned in dorsal recumbency. Anaesthesia was maintained with isoflurane carried in an oxygen and air mix (FiO 0.5) combined with a medetomidine infusion. Horses were anaesthetized twice and either...
Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site. Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in h...
Effects of maternal dexamethasone treatment on pancreatic β cell function in the pregnant mare and post natal foal. Synthetic glucocorticoids are used to treat inflammatory conditions in horses. In other pregnant animals, glucocorticoids are given to stimulate fetal maturation with long-term metabolic consequences for the offspring if given preterm. However, their metabolic effects during equine pregnancy remain unknown. Objective: Thus, this study investigated the metabolic effects of dexamethasone administration on pregnant pony mares and their foals after birth. Methods: Experimental study. Methods: A total of 3 doses of dexamethasone (200 μg/kg bwt i.m.) were given to 6 pony mares at 48 h intervals beg...
Differential expression of β-tubulin isotypes in different life stages of Parascaris spp after exposure to thiabendazole. Anthelmintic resistance (AR) to macrocyclic lactones (ML) has been described in Parascaris of horses world-wide. In contrast, benzimidazoles (BZ) are still effective, although reduced efficacy to this drug class was recently reported. The mode of action of BZ is binding to β-tubulin, which prevents polymerisation of microtubules. In this study, β-tubulin gene expression of isotypes 1 and 2 was investigated at seven time points (0, 6, 24, 72, 96 and 120 h) during embryogenesis and in adult worms. In addition, an in ovo larval developmental test was developed to study β-tubulin gene expressio...
Comparison of alfaxalone, ketamine and thiopental for anaesthetic induction and recovery in Thoroughbred horses premedicated with medetomidine and midazolam. There is limited information on clinical use of the new injectable anaesthetic agent alfaxalone in Thoroughbred horses. Objective: To compare anaesthetic induction and recovery characteristics and cardiopulmonary responses between alfaxalone, ketamine and thiopental in Thoroughbred horses premedicated with medetomidine and midazolam. Methods: Randomised blinded experimental cross-over study. Methods: Six Thoroughbred horses were anaesthetised 3 times with alfaxalone 1 mg/kg bwt, ketamine 2.5 mg/kg bwt or thiopental 4 mg/kg bwt after premedication with medetomidine 6 μg/kg bwt and midazola...
Cardiovascular, respiratory and metabolic responses to apnea induced by atlanto-occipital intrathecal lidocaine injection in anesthetized horses. To determine physiologic responses to apnea-induced severe hypoxemia in anesthetized horses. Methods: Prospective experimental study. Methods: Six university-owned horses with a median (range) body weight of 500 (220-510) kg and aged 13.5 (0.8-24.0) years scheduled for euthanasia. Methods: Xylazine-midazolam-ketamine-anesthetized horses breathing room air spontaneously were instrumented with a facial artery catheter for pressure measurement and blood sampling, and were made apneic with atlanto-occipital intrathecal lidocaine (4 mg kg ). Cardiopulmonary, biochemical and hematologic variable...
Extracellular calcium regulates protein tyrosine phosphorylation through calcium-sensing receptor (CaSR) in stallion sperm. Protein tyrosine phosphorylation (PY), a hallmark of sperm capacitation, is inhibited by extracellular calcium in stallion sperm. The objective of this study was to determine the presence and influence of the calcium-sensing receptor (CaSR) in this phenomenon. First, the presence of the CaSR was demonstrated in stallion sperm. We then tested its function in these gametes using its inhibitor NPS2143 or its agonist AC34356. Sperm were capacitated for 4 hr in modified Whitten's medium with 25 mM bicarbonate plus NPS2143 and 2.4 mM calcium or AC34356 alone, followed by analysis of PY. Inhibi...
Quantification of horse plasma proteins altered by xylazine using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry. In the doping tests currently used in horse racing, prohibited substances or their metabolites are usually directly detected in urine or blood samples. However, despite their lasting pharmaceutical effects, some prohibited substances are rapidly eliminated from horse urine and blood, making them difficult to detect. Therefore, new indirect biomarkers for doping, such as plasma proteins that are increased by the prohibited substances, have recently attracted much attention. Here, a fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) method was adopted for hor...
The effect of isosorbide dinitrate on uterine and ovarian blood flow in cycling and early pregnant mares: A pilot study. Poor uterine perfusion has been proposed as a cause of infertility in mares. The objective of this study was to investigate the effect of isosorbide dinitrate (ISDN), a nitric oxide donor, on uterine and ovarian blood flow resistance during diestrus and early pregnancy in mares. Six Trotter mares, aged 7 to 14 years, were examined daily during the first 11 days of three diestrous periods, and five of those mares were also examined during the first 11 days of two pregnancies. Six mares randomly received a placebo, a low dose (30 mg, ISDN30), or a high dose of ISDN (60 mg, ISDN60) through t...
Regional heterogeneity in the reactivity of equine small pulmonary blood vessels. Regional differences in large equine pulmonary artery reactivity exist. It is not known if this heterogeneity extends into small vessels. The hypothesis that there is regional heterogeneity in small pulmonary artery and vein reactivity to sympathomimetics (phenylephrine and isoproterenol) and a parasympathomimetic (methacholine) was tested using wire myography on small vessels from caudodorsal (CD) and cranioventral (CV) lung of 12 horses [9 mares, 3 geldings, 8.67 ± 0.81 (age ± SE) yr, of various breeds that had never raced]. To study relaxation, vessels were precontracted with U46619 (10(-...
P2Y(1) receptors mediate purinergic relaxation in the equine pelvic flexure. In the equine large intestine, the knowledge of the basic mechanisms underlying motility function is crucial to properly treat motility disorders. P2Y1 receptors are responsible for mediating purinergic colonic relaxation in several species. In vitro experimental studies of the circular muscle from the equine pelvic flexure (n = 6) were performed to characterize inhibitory and excitatory neuromuscular transmission. Electrophysiological studies showed that electrical field stimulation (EFS) evoked biphasic inhibitory junction potentials (IJPs) in smooth muscle cells: a fast IJP (IJPf) follo...
The use of dexmedetomidine continuous rate infusion for horses undergoing transvenous electrical cardioversion–A case series. Five horses were presented for treatment of atrial fibrillation by transvenous electrical cardioversion (TVEC). A dexmedetomidine infusion was administered for sedation during positioning of the cardioversion catheters, and continued during general anesthesia. Shocks were applied until return to sinus rhythm. Dexmedetomidine infusion provided excellent conditions for TVEC catheter placement and procedure. Utilisation d’une perfusion continue de dexmedetomidine lors de cardioversion électrique transveineuse chez le cheval: une série de cas. Cinq chevaux présentant une fibrillation atriale ...
Aptamer based peptide enrichment for quantitative analysis of gonadotropin-releasing hormone by LC-MS/MS. Over recent years threats to racing have expanded to include naturally occurring biological molecules, such as peptides and proteins, and their synthetic analogues. Traditionally, antibodies have been used to enable detection of these compounds as they allow purification and concentration of the analyte of interest. The rapid expansion of peptide-based therapeutics necessitates a similarly rapid development of suitable antibodies or other means of enrichment. Potential alternative enrichment strategies include the use of aptamers, which offer the significant advantage of chemical synthesis onc...
