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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.
Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis. This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 μg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independe...
The effect of sodium bicarbonate and validation of beckman coulter AU680 analyzers for measuring total carbon dioxide (TCO2) concentrations in horse serum. This study evaluated the usage of Beckman Coulter AU680 analyzers for measurement of TCO in horse serum, and the effect of sodium bicarbonate administrations on serum TCO levels in resting horses. Treatment of horses with sodium bicarbonate did not result in any adverse events. Mean TCO concentration was significantly higher from 1 to 8 h in the sodium bicarbonate-treated horses compared to the untreated controls. Within an hour, administration of sodium bicarbonate increased the TCO level from 31.5 ± -2.5 (SD) to 34.0 ± 2.65 (SD) mmol/L and at 2-8 h post-administration, the TCO l...
P-glycoproteins play a role in ivermectin resistance in cyathostomins. Anthelmintic resistance is a global problem that threatens sustainable control of the equine gastrointestinal cyathostomins (Phylum Nematoda; Superfamily Strongyloidea). Of the three novel anthelmintic classes that have reached the veterinary market in the last decade, none are currently licenced in horses, hence current control regimens focus on prolonging the useful lifespan of licenced anthelmintics. This approach would be facilitated by knowledge of the resistance mechanisms to the most widely used anthelmintics, the macrocyclic lactones (ML). There are no data regarding resistance mechani...
Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome. NSAIDs are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti-inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 2...
Anthelmintic therapy of equine cyathostomin nematodes – larvicidal efficacy, egg reappearance period, and drug resistance. Cyathostomins are ubiquitous in grazing horses across the world, and anthelmintic resistance has been reported with increasing levels over past decades. The aims of the present study were (i) to investigate the efficacy against encysted larval stages of moxidectin (0.4 mg/kg) and fenbendazole (10 mg/kg daily for five consecutive days) and compare these regimens at 2 and 5 weeks post-treatment, (ii) to investigate individual cyathostomin species associated with shortened egg reappearance periods, and (iii) to document species exhibiting decreased susceptibility to the evaluated compounds....
Inhibition of microsomal prostaglandin E-synthase-1 (mPGES-1) selectively suppresses PGE2 in an in vitro equine inflammation model. 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...
In vitro susceptibility of Borrelia burgdorferi isolates to three antibiotics commonly used for treating equine Lyme disease. Lyme disease in humans is predominantly treated with tetracycline, macrolides or beta lactam antibiotics that have low minimum inhibitory concentrations (MIC) against Borrelia burgdorferi. Horses with Lyme disease may require long-term treatment making frequent intravenous or intramuscular treatment difficult and when administered orally those drugs may have either a high incidence of side effects or have poor bioavailability. The aim of the present study was to determine the in vitro susceptibility of three B. burgdorferi isolates to three antibiotics of different classes that are commonly us...
Evaluation of the use of midazolam as a co-induction agent with ketamine for anaesthesia in sedated ponies undergoing field castration. There are limited investigations comparing ketamine to a ketamine-midazolam co-induction. Objective: To compare quality and safety of general anaesthesia induced using ketamine alone with anaesthesia co-induced using ketamine and midazolam. Methods: Randomised, double blinded, placebo controlled trial. Methods: After i.v. detomidine (20 μg/kg) thirty-eight ponies undergoing field castration received either 0.06 mg/kg (0.6 mL/50 kg) midazolam (group M) or 0.6 mL/50 kg placebo (group P) with 2.2 mg/kg ketamine i.v. for anaesthetic induction. Quality of anaesthetic induction, endotracheal intuba...
Influence of sulpiride treatment on the level of prolactin and immunoglobulins in the peripheral blood of mares during the postpartum period. The aim of this study was to determine the effect of increased levels of prolactin (PRL) on the concentration of immunoglobulins in the blood, colostrum and milk of mares. The study was conducted on 12 mares of the Polish Pony breed (6 in the control and 6 in the experimental group). To induce hyperprolactinaemia in mares of the experimental group, 750 mg sulpiride was administered orally once a day. The initial PRL concentration was 52.22 ± 11.21 ng/ml in the control group and 49.39 ± 10.12 ng/ml in the experimental group. In the subsequent days, the concentration of PRL dynamically changed...
Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation. In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS) production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed. One potential neutrophil-targeting therapeutic is the PGE1 analog, m...
Antifungal Therapy in Equine Ocular Mycotic Infections. Fungi are clinically important causes of ocular infections in the horse. Keratomycosis is the most common; however, a diverse range of mycotic infections, affecting numerous ocular tissues, may be encountered. Many equine mycoses are diagnostic and therapeutic challenges. Prompt and appropriate treatment is essential to minimize morbidity and reduce the likelihood of vision loss. Knowledge of the characteristics and properties of equine ophthalmology antifungal medications is essential to selecting an optimal treatment strategy, including selection of appropriate medication and effective admin...
H2S Activated Drug Release from Protein Cages. We took advantage of gasotransmitter HS as a chemical reaction-based trigger for controlled release of doxorubicin which is precoordinated by copper ions and enclosed in horse spleen apoferritin. The nanocomposite is stable at physiological pH and temperature before HS activation. The drug release process avoids disassembly of protein shells and is controllable by the strong affinity of sulfide with copper ions. The in vitro cytotoxicity assay indicates the antitumor effect of doxorubicin toward tumor cells could be achievable by HS activation.
Effect of topical application of 2% lidocaine gel on corneal sensitivity of clinically normal equine eyes. To assess the degree and duration of corneal anaesthesia provided by topical application of a non-ophthalmic 2% lidocaine gel in horses. Methods: Experimental, 'blinded', randomized prospective study. Methods: Twelve adult horses without relevant ocular abnormalities. Methods: Baseline corneal touch threshold (CTT) measurements were obtained bilaterally by use of a Cochet-Bonnet aesthesiometer just prior to topical treatment. A volume of 0.2mL of 2% lidocaine gel was administered in one randomly selected eye and the same volume of a viscous lubricant in the other eye to serve as control. The C...
Identification of hypoglycin A binding adsorbents as potential preventive measures in co-grazers of atypical myopathy affected horses. Intestinal absorption of hypoglycin A (HGA) and its metabolism are considered major prerequisites for atypical myopathy (AM). The increasing incidence and the high mortality rate of AM urgently necessitate new therapeutic and/or preventative approaches. Objective: To identify a substance for oral administration capable of binding HGA in the intestinal lumen and effectively reducing the intestinal absorption of the toxin. Methods: Experimental in vitro study. Methods: Substances commonly used in equine practice (activated charcoal composition, di-tri-octahedral smectite, mineral oil and activat...
The effects of multiple anaesthetic episodes on equine recovery quality. Although rare, 70% of equine fatalities during recovery from general anaesthesia (GA) are due to catastrophic fractures from poor recovery quality. Objective: To determine the effect of repeated GA recovery on GA recovery quality. Methods: Experimental blinded trial. Methods: Eight adult horses underwent six GA events on sevoflurane for distal limb MRI examination over a 14-week period. Prior to GA recovery, xylazine was administered. Randomly ordered video-recorded GA recoveries were scored by three blinded board certified veterinary anaesthesiologists, unaware of patient identity or GA event...
Effects of dobutamine, dopamine, phenylephrine and noradrenaline on systemic haemodynamics and intestinal perfusion in isoflurane anaesthetised horses. In the horse, effects of cardiovascular-active drugs on local perfusion of the gastrointestinal tract are poorly understood. Objective: To determine the effect of drugs commonly used to support blood pressure, on local intestinal blood flow and tissue oxygenation under isoflurane anaesthesia. Methods: In vivo randomised crossover experiment. Methods: Ten horses were anaesthetised with isoflurane. After 90 min of equilibration three doses (μg/kg bwt/min) of dobutamine (DOB 0.5/1/3), dopamine (DA 1/2/5), noradrenaline (NA 0.1/0.2/0.5) and phenylephrine (PHE 0.5/1/3) were infused for 15 min, in ...
Sedative and cardiopulmonary effects of dexmedetomidine infusions randomly receiving, or not, butorphanol in standing horses. Dexmedetomidine (DEX) alone, or combined with butorphanol (BUT), may be administered by constant rate infusions (CRIs) in standing horses. This blinded, randomised, crossover study in six healthy adult horses aimed to determine the sedative and cardiopulmonary effects of DEX (dexmedetomidine (3.5 µg/kg+5 µg/kg/hour CRI) and DEX/BUT (dexmedetomidine (3.5 µg/kg+3.5 µg/kg/hour CRI) and butorphanol (20 µg/kg+24 µg/kg/hour CRI)). Head height above ground (HHAG), ataxia, responses to tactile/auditory stimuli and cardiopulmonary variables were recorded before, at 5/15/30/60/90 min...
Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma. Asthmatic airways are inflamed and undergo remodelling. Inhaled corticosteroids and long-acting β2-agonist combinations are more effective than inhaled corticosteroid monotherapy in controlling disease exacerbations, but their effect on airway remodelling and inflammation remains ill-defined. This study evaluates the contribution of inhaled fluticasone and salmeterol, alone or combined, to the reversal of bronchial remodelling and inflammation. Severely asthmatic horses (6 horses/group) were treated with fluticasone, salmeterol, fluticasone/salmeterol, or with antigen avoidance for 12 weeks. ...
Adaptation of a 96-well plate larval migration inhibition test for measuring the sensitivity of cyathostomins to macrocyclic lactone anthelmintics. The use of macrocyclic lactone drugs for control of equine cyathostomins is threatened by increasing levels of resistance. Detection of changes in drug sensitivity is important for effective and sustainable management of cyathostomins, however, at present such detection relies on the use of the faecal egg count reduction test, which is known to be an insensitive method. The present study therefore aimed to examine the use of a 96-well plate larval migration inhibition test for detection of resistance to macrocyclic lactone drugs in cyathostomins. We optimised conditions for migration of larvae...
Review of triazine antiprotozoal drugs used in veterinary medicine. Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.
Evaluation of an intravaginal triptorelin acetate gel for inducing ovulation in mares. The objective of these studies was to investigate the efficacy of an intravaginal triptorelin acetate (TA) gel as an ovulation-inducing agent in mares. In Exp. 1, 24 mares were blocked using a combination of parity and age and randomly assigned to 1 of 3 treatment groups: 5 mL TA gel (TA5), 10 mL TA gel (TA10), or 5 mL vehicle gel only (CON). Following the appearance of a follicle ≥ 25 mm, a blood sample was obtained for measurement of LH from each mare every 24 h until treatment administration. When a follicle ≥ 35 mm was observed, treatments were administered intravaginally. Following tr...
Effects of polymyxin-B on TNF-α production in equine whole blood stimulated with three different bacterial toxins. Polymyxin-B is used to treat equine systemic inflammation. Bacterial toxins other than lipopolysaccharide (LPS) contribute to systemic inflammation but the effects of polymyxin-B on these are poorly defined. Whole blood aliquots from six healthy horses diluted 1:1 with RPMI were incubated for 21 hr with 1 μg/ml of LPS, lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of polymyxin-B (10-3000 μg/ml). A murine L929 fibroblast bioassay was used to measure TNF-α activity. Polymyxin-B significantly inhibited the effects of all three bacterial toxins. ...
Right ventricular function during pharmacological and exercise stress testing in horses. The disproportionate rise of pulmonary artery pressure compared to systemic blood pressure during exercise can lead to detrimental right ventricular remodelling in endurance athletes. Horses may act as an extreme model of these athletic cardiovascular adaptations, as they show a three fold increase in pulmonary pressures during exercise. Right ventricular function was examined in ten healthy horses using post-exercise and pharmacological stress echocardiography in a randomised cross-over design. Exercise testing was performed on a treadmill while pharmacological testing was performed using an ...
A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses. AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments....
Pharmacological characterization of the interaction between tiotropium and olodaterol administered at 5:5 concentration-ratio in equine bronchi. Equine airways represent a suitable ex vivo model to study the functional impact of pharmacological treatments on human chronic obstructive pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD). We aimed to characterize the pharmacological interaction between the long-acting muscarinic antagonist (LAMA) tiotropium and the long-acting β-agonist (LABA) olodaterol in equine airways. The effect of tiotropium and olodaterol, administered alone and in combination at the ratio of concentrations reproducing ex vivo the concentration-ratio delivered by the currently avai...
Effect of exogenous progesterone administration on luteal sensitivity to PGF during the early development of the corpus luteum in mares and cows. The objective of this study was to determine the effect of exogenous progesterone administration at ovulation and during the early development of the CL, on its future sensitivity to a single administration of PGF2a in mares and cows. Horse Retrospective reproductive data from an equine clinic in the UK during three breeding seasons were used. Mares were divided into: control group, cycles with single ovulations; double ovulation group cycles with asynchronous double ovulations; and PRID group: cycles with single ovulations and treatment with intravaginal progesterone device (CIDR) immediately...
Successful medical treatment of an Aspergillus terreus mycetoma of the nostril/lip in a 16-year-old Fjord pony gelding with pituitary pars intermedia dysfunction. Mycetoma is a chronic, proliferative lesion of cutaneous/subcutaneous tissue characterized by draining tracts and granules in the discharge caused by actinomycetes (actinomycetoma) or filamentous fungi (eumycotic mycetoma). Objective: This case report describes the unusual finding of a cutaneous mycetoma of the lateral wing of the right nostril in a gelding. Methods: A 16-year-old Fjord gelding with suspected pituitary pars intermedia dysfunction (PPID) was presented for evaluation of a nonpainful, firm and raised mass involving the lateral wing of the right nostril and the lip. Results: Cytol...
The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation. Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whe...
Esthesiometric evaluation of corneal analgesia after topical application of 1% morphine sulfate in normal horses. To evaluate whether topical ocular application of 1% morphine sulfate would change corneal sensitivity and to identify the duration of action. Methods: Eight healthy adult horses. Methods: Corneal touch threshold (CTT) was measured in the center of one randomly selected eye of each horse by Cochet-Bonnet esthesiometer (Luneau Cochet-Bonnet Esthesiometer; Western Ophthalmics, Lynnwood, WA, USA). Immediately following baseline CTT measurement, 0.3 ml of 1.0% preservative-free morphine sulfate (Morphine Sulfate 25 mg/ml Preservative-free; Hospira, Lake Forest, IL, USA) (3 mg) was applied to th...
Determination of vitacoxib, a novel COX-2 inhibitor, in equine plasma using UPLC-MS/MS detection: Development and validation of new methodology. Vitacoxib is an imidazole derivative and the novel COX-2 selective inhibitor to be marketed for veterinary use as nonsteroidal anti-inflammatory drugs. No analytical assay to quantify vitacoxib in equine plasma samples has been published to date. In the current study, we aim to develop and validate a brief, quick and sensitive UPLC-MS/MS method for quantification of vitacoxib in equine plasma samples. Plasma samples were precipitated with methyl tert-butyl ether. The Phenomenex column (Kinetex 50×2.1mm i.d. particle size=2.6μm, C18, 100Å) at 25°C was used in chromatographic separation with...
