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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.
Electroretinographic changes after intravenous lipid emulsion therapy in a dog and a foal with ivermectin toxicosis. This case report describes ivermectin-induced blindness in a dog and a foal with normal ophthalmic fundic examinations and attenuated electroretinography (ERG). Subsequent recovery in ERG was noted following intravenous lipid emulsion (ILE) therapy. A dog and a foal were evaluated for ivermectin-induced blindness. Clinical signs included dull mentation, absent pupillary light reflexes (PLRs), and absent menace on presentation. The animals had normal fundoscopic examinations; however, in both cases ERG was consistent with neurosensory retinal dysfunction. Following ILE therapy for ivermectin to...
The Effects of Mepivacaine Hydrochloride on Antimicrobial Activity and Mechanical Nociceptive Threshold During Amikacin Sulfate Regional Limb Perfusion in the Horse. To determine the effect of intravenous regional limb perfusion (IVRLP) with a combination of mepivacaine hydrochloride and amikacin sulfate on synovial fluid amikacin sulfate concentration, antimicrobial activity, and mechanical nociceptive threshold (MNT). Methods: Experimental study. Methods: Healthy adult horses (n=9). Methods: One IVRLP treatment was randomly administered by cephalic vein of each limb: amikacin alone (1 g amikacin in 60 mL saline) or amikacin with mepivacaine (1 g amikacin and 500 mg mepivacaine in 60 mL saline). Opposite treatments were repeated after a 24 hour wash-out p...
Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses. Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown. Objective: To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration. Methods: Prospective experimental study. Methods: A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior ...
The influence of environmental variables on platelet concentration in horse platelet-rich plasma. Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of envi...
Destabilase-lysozyme-2 – original recombinant thrombolytic preparation of medicinal leech inhibits horse platelets aggregation. The purpose. Identifying the capacity of the medicinal leech novel original recombinant thrombolytic preparation Destabilase-Lysozyme-2 to inhibit the blood platelet aggregation. Gene of destabilase-lysozyme. ds2 (mlDL-Ds2 ), was cloned in E.coli cells. Recombinant protein was isolated in denaturing conditions using metal-chelate chromatography followed by denaturation of the polypeptide by rapid dilution in exact accordance with the procedure described by Kurdyumov A.S. et al. ( 2016, Russian Journal of Bioorganic Chemistry, v.42, s. 42-52). Blood was collected from the jugular vein of 18 hor...
Efficacy of combination therapy with anti-thymocyte globulin and cyclosporine A as a first-line treatment in adult patients with aplastic anemia: a comparison of rabbit and horse formulations. Anti-thymocyte globulin (ATG) is a key drug in immunosuppressive therapy for patients with aplastic anemia. The mainstay of ATG therapy had been a horse ATG (hATG) formulation, Lymphoglobulin or ATGAM, but Lymphoglobulin was recently discontinued, and Thymoglobulin, a rabbit ATG (rATG) formulation, is currently used as the first-line drug in many countries, including Japan. However, a recent randomized clinical trial reported significantly unfavorable outcomes associated with the use of rATG regimens. We retrospectively analyzed clinical outcomes of adult patients with moderate to severe aplas...
In vitro analysis of the effect of supplementation with activated charcoal on the equine hindgut. The present study uses in vitro analytical techniques to investigate the effect of activated charcoal on the microbial community of the equine hindgut and the metabolites they produce. Incubations were performed in Wheaton bottles using a 50 ml incubation of a high-energy feed or a low-energy feed, plus bottles with no added food source, together with five levels of activated charcoal (0, 10, 25, 50 or 100 mg per bottle) and fecal samples as a bacterial inoculum. Using this method the rate of gas production, volatile fatty acid and ammonia concentrations, and pH values were analyzed and found ...
Efficacy of Inhaled Levalbuterol Compared to Albuterol in Horses with Recurrent Airway Obstruction. The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. Objective: To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. Methods: Nine horses w...
Effects of deoxynivalenol (DON), zearalenone (ZEN), and related metabolites on equine peripheral blood mononuclear cells (PBMC) in vitro and background occurrence of these toxins in horses. Both deoxynivalenol (DON), zearalenone (ZEN), and their metabolites are known to modulate immune cells in various species whereby viability and proliferation are influenced. Such effects were rarely examined in horses. Therefore, one aim of the present study was to titrate the inhibitory concentrations of DON, 3-acetyl-DON (3AcDON), de-epoxy-DON (DOM-1), ZEN, and α- and β-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC50) and 10 % (IC10) in vitro. For evaluation of practical relevance of the in vitro findings, a further aim was to screen horses...
Evaluation of activity of fenbendazole, oxibendazole, piperazine , and pyrantel pamoate alone and combinations against ascarids, strongyles, and strongyloides in horse foals in field tests on two farms in Central Kentucky in 2014 and 2015. Activity of fenbendazole (FBZ), oxibendazole (OBZ), piperazine (PIP) and pyrantel pamoate (PRT) alone and combinations of OBZ and PIP and of OBZ and PRT was evaluated against parascarids, strongyles and strongyloides in horse foals (n=281).This was on two farms - Farm A - mixed light-horses (n=26) and Farm B-Thoroughbreds (n=255) - in Central Kentucky in field tests in 2014 and 2015. Foals on both farms were treated one to three times each; an exception was that seven foals on Farm A were nontreated controls. Before treatment, the foals on Farm A were all weighed on scales but weights for Farm...
Polyphenols from Silybum marianum inhibit in vitro the oxidant response of equine neutrophils and myeloperoxidase activity. A recent study showed that silymarin, a standardized extract of S. marianum might be used in the prevention of equine laminitis. We investigated the effects of quercetin and some compounds found in silymarin (silybin, taxifolin and dehydrosilybin) on reactive oxygen species (ROS) production and myeloperoxidase (MPO) release by stimulated equine neutrophils (PMNs) and on MPO activity. All compounds (tested between 100 nm and 100 μm) inhibited superoxide anion production by stimulated PMNs in a dose-dependent manner. Dehydrosilybin and quercetin inhibited superoxide production and MPO release...
Pharmacokinetics of ketoprofen enantiomers following intravenous and oral administration to exercised Thoroughbred horses. Ketoprofen (KTP) is currently only available as an injectable formulation for intravenous administration to horses. The primary goal of the study reported here was to characterize the pharmacokinetics of KTP, including determination of bioavailability following oral administration of the currently available injectable formulation as well as a paste formulation. KTP was administered intravenously and orally, and blood and urine samples were collected at various time points up to 96 h. KTP enantiomer concentrations were determined using LC–MS/MS, and pharmacokinetic analyses were performed. Me...
Randomised clinical trial on the effect of a single oral administration of l-tryptophan, at three dose rates, on reaction speed, plasma concentration and haemolysis in horses. Tryptophan (TRP) is marketed as a calmative for horses despite reservations about its efficacy. The aim of this study was to measure the effect of oral TRP administration on the reaction speed of horses. Sixty mature horses were used in a two stage randomised, blind, cross-over study, receiving a placebo and an oral dose of TRP (30, 60 or 120 mg/kg body weight), before undergoing a reaction speed test. Blood samples were taken up to 96 h after TRP administration, to identify signs of acute haemolytic anaemia. Plasma TRP concentrations were increased (P <0.001) by the administration of...
The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids. Glucocorticoids (GCs) are the most effective drugs for the treatment of human asthma. However, a subgroup of asthmatic patients with neutrophilic airway inflammation is insensitive to GCs. Interleukin-17 (IL-17), a cytokine upregulated in the airways of a subset of human asthmatic patients, contributes to the recruitment of neutrophils and induces a glucocorticoid resistance in human airway epithelial cells. We hypothesized that IL-17 similarly activates neutrophils and contributes to their persistence in the asthmatic airways in spite of glucocorticoid therapy. To determine whether IL-17 dire...
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...
