Omneity® Pellets
All-In-One Vitamin & Mineral Pellet
Topic:Beta2 Agonist
Beta2 agonists are a class of medications that interact with beta2-adrenergic receptors, leading to smooth muscle relaxation in various tissues, including the respiratory tract. In horses, these compounds are primarily used to manage respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) by facilitating bronchodilation and improving airflow. Common beta2 agonists used in equine medicine include clenbuterol and albuterol. These agents are administered in different forms, such as oral, inhaled, or injectable, depending on the specific clinical needs. The pharmacokinetics, efficacy, and safety of beta2 agonists in horses are subjects of ongoing research, with studies exploring their impact on respiratory function, potential side effects, and regulatory considerations for use in competitive sports. This page collates peer-reviewed research studies and scholarly articles that investigate the mechanisms, therapeutic applications, and regulatory aspects of beta2 agonists in equine medicine.
A randomized, masked, crossover, clinical trial of the efficacy and safety of nebulized albuterol sulfate and dexamethasone sodium phosphate in asthmatic horses. Nebulization of injectable dexamethasone sodium phosphate (DSP; 0.01 mg/kg) to horses with severe equine asthma (SEA) was previously found to be ineffective. Horses with SEA have marked bronchoconstriction that decreases peripheral lung deposition of nebulized drugs. Administration of a bronchodilator immediately before nebulizing dexamethasone may improve efficacy. Objective: Evaluate the therapeutic effects and optimal dose of nebulized DSP after nebulized albuterol in horses with SEA. Methods: Seven horses with SEA from a research herd. Methods: In this masked randomized crossover trial, h...
Field-applicable low-intensity exercise induces bronchodilation in horses with severe asthma. Airway dysfunction in severe equine asthma (SEA) often results in early retirement or euthanasia of affected horses. Exercise-induced bronchodilation occurs in horses with SEA after intense treadmill exercise, but the effects of a lighter, field-applicable, training regimen remain largely unexplored. Objective: To evaluate the impact of submaximal aerobic exercise on airway obstruction during exacerbation of SEA. Methods: The preliminary phase explored the effects of a 25-min standardised exercise on the lung function of eight SEA horses. As notable bronchodilation occurred, the results were c...
Pharmacokinetics of Salbutamol in Thoroughbred Horses After a Single Intravenous or Inhaled Administration. Salbutamol is a short-acting and selective beta-2 adrenergic agonist. Inhaled (IH) administration of salbutamol is widely used to control lower respiratory tract disease in horses. Here, we estimated the pharmacokinetic parameters of salbutamol after a single intravenous (IV) or IH administration in six horses, and we statistically analysed the detection times with various dosing regimens. Plasma and urine concentrations of salbutamol were measured by liquid chromatography-tandem mass spectrometry, and data were modelled by using a nonlinear mixed effect model followed by Monte Carlo simulatio...
Retrospective study of the changes in dynamic compliance and ventilation/perfusion mismatch following salbutamol inhalation in hypoxaemic mechanically ventilated anaesthetized horses. To study the changes in dynamic compliance (C), ventilation/perfusion (V˙/ Q˙) mismatch and haemodynamic variables in hypoxaemic anaesthetized horses whose PaO increased following salbutamol inhalation. Methods: Retrospective, clinical, cohort study. Methods: A group of 73 client-owned horses treated with salbutamol when PaO <100 mmHg (13.3 kPa) during anaesthesia. Methods: Horses were divided into two groups: responders (R), where PaO after salbutamol ≥1.2 PaO before treatment (i.e. ≥20% increase), and non-responders (NR), where PaO after salbutamol <1.2 PaO before treatment. Demographi...
Comparison of inhaled salbutamol and salmeterol for the treatment of arterial hypoxaemia in anaesthetized horses: a randomized clinical trial. To compare the efficacy of inhaled salbutamol with salmeterol for the treatment of arterial hypoxaemia in anaesthetized horses. Methods: Prospective, randomized, clinical study. Methods: A total of 108 client-owned horses (American Society of Anesthesiologists status I-V) anaesthetized for elective and emergency procedures. Methods: Horses were premedicated with acepromazine [intramuscularly 0.1 mg kg or intravenously (IV) 0.05 mg kg] and xylazine (0.6 mg kg IV). Midazolam (0.06 mg kg IV) and ketamine (2.2 mg kg IV) were combined to induce anaesthesia, and isoflurane in oxygen/air mixture (ins...
Effect of Clenbuterol on Muscle Activity During Exercise in Standardbred Horses. Clenbuterol (β agonist) is a commonly administered bronchodilator in race and performance horses. While long-term administration can alter exercise performance and muscle properties, little is known about its effects on these parameters following short-term administration. A single dose of clenbuterol (0.80 µg/kg) was expected to alter muscle activity of the extensor carpi radialis, semitendinosus, and longissimus dorsi during submaximal exercise. Eight mature Standardbred horses exercised for 2 minutes at 5 m/s on a high-speed treadmill following clenbuterol dosing (clenbuterol) or no dosin...
Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis. Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary "identifications" of Zilpaterol. These "identifications" occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presen...
The Effect of Inhaled Albuterol on PaO2 in Anesthetized Horses Receiving a FiO2 of 0.5 or >0.95. Impairment of oxygen uptake can occur during general anesthesia in horses resulting in hypoxemia. Multiple treatments have been investigated for correction of hypoxemia with varying levels of success. In clinical trials, albuterol, a short-acting β2 adrenergic agonist, improved arterial oxygen partial pressure (PaO2) in anesthetized horses unresponsive to adjustments in mechanical ventilation and administration of positive inotropic drugs. However, controlled studies comparing the magnitude of change and duration of effect of albuterol on PaO2 in healthy, nonhypoxemic anesthetized horses are ...
Corrigendum to: “The Rho kinase (ROCK) inhibitor Y-27632 reduces the β 2-adrenoceptor density but enhance cAMP formation in primary equine bronchial epithelial cells” [Eur. J. Pharmacol. 2021 Sep 15; 907:174323]. This research paper investigates the influence of the Rho kinase (ROCK) inhibitor Y-27632 on β2-adrenoceptor density and the generation of a cellular messenger called cAMP in horse bronchial cells. The […]
Detection and confirmation of zilpaterol in equine hair using liquid chromatography-mass spectrometry. Zilpaterol is a β -adrenergic agonist and a repartitioning agent that has a high potential for abuse in equine performance athletes. Analysis of zilpaterol in hair is an alternative sampling matrix that extends detection time periods beyond those found in urine or blood samples. Our laboratory has been screening for zilpaterol in hair for many years and recently detected and confirmed its presence in official samples. Accordingly, a liquid chromatography-mass spectrometry method was developed and validated to detect and confirm zilpaterol in equine hair. Briefly, equine hair was decontaminate...
Relaxing effects of clenbuterol, ritodrine, salbutamol and fenoterol on the contractions of horse isolated bronchi induced by different stimuli. β-adrenoceptor agonists are considered the most effective drugs to counteract bronchoconstriction in horses with asthma, but only clenbuterol is commonly employed in clinical practice. We evaluated the effects of different selective β agonists: clenbuterol, ritodrine, salbutamol, and fenoterol on the contractions of isolated bronchial muscle of horses induced by electrical field stimulation (EFS), carbachol, histamine, and KCl. All β agonists reduced the amplitude of contraction induced by the different stimuli but with variable efficacy and potency. Fenoterol and salbutamol were more effec...
The effect of single pretreatment with salbutamol on recovery of bronchoalveolar lavage fluid in horses with suspected or confirmed severe equine asthma. Bronchoalveolar lavage (BAL) is a method for the recovery of respiratory secretion from the lower airways. Objective: To investigate if the administration of a single dose of a bronchodilatator in horses with a suspected or confirmed severe equine asthma could improve recovery of bronchoalveolar lavage fluid (BALF). Methods: Twenty-eight horses with severe equine asthma. Methods: Horses were divided into 2 groups: group "treated" was given salbutamol before endoscopic examination and BALF collection, whereas group "not treated" was not given. BAL was performed with BAL-catheter by instilling 3...
Development of an immunochromatographic assay for the β-adrenergic agonist feed additive zilpaterol. Zilpaterol is a β-adrenergic agonist feed additive approved in the United States to increase weight gain and improve feed efficiency of cattle. A zilpaterol immunochromatographic assay was developed as an economical and user-friendly rapid detection method for zilpaterol and validated using urine and tissue samples derived from animal studies. The assay sensitivity was 1.7-23.2 ng g or mL across a variety of feed and animal matrices and did not cross-react with clenbuterol or ractopamine. No sample pre-treatment of cattle and sheep urine was needed, but horse urine and feed required dilution;...
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. ...
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...
Bronchopulmonary pharmacokinetics of (R)-salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses. Salbutamol is usually administered as a racemic mixture but little is known about the enantioselectivity of salbutamol pharmacokinetics in the lung. This study was designed to investigate enantiomer concentrations in lung tissue after inhaled dosing. Horses (n = 12) received racemic salbutamol 1000 μg via inhalation. Enantioselective ultra performance liquid chromatography-tandem mass spectrometry was used to determine salbutamol concentrations in pulmonary epithelial lining fluid (PELF) sampled 2, 5, 10 and 15 min after administration, in central lung (endoscopic bronchial biopsy) and per...
Detection and pharmacokinetics of salmeterol in thoroughbred horses following inhaled administration. Salmeterol is a man-made beta-2-adrenergic receptor agonist used to relieve bronchospasm associated with inflammatory airway disease in horses. Whilst judicious use is appropriate in horses in training, they cannot race with clinically effective concentrations of medications under the British Horseracing Authority's Rules of Racing. Salmeterol must therefore be withdrawn prior to race day and pharmacokinetic (PK) studies used to establish formal detection time advice. Salmeterol xinafoate (Serevent Evohaler ) was administered (0.1 mg twice daily for 4.5 days) via inhalation to six horses. Ur...
Factors affecting the efficiency of aerosolized salbutamol delivery via a metered dose inhaler and equine spacer device. Despite frequent use of metered dose inhalers (MDIs) and spacers in equine practice, limited information exists on the efficiency of aerosol delivery using such devices. We determined the particle size distribution within an MDI-generated salbutamol aerosol delivered via an equine spacer using 'best practice' delivery technique and assessed the effect of variations in MDI use technique (shaking prior to each actuation, rapid repetitive actuations, and MDI angulation) on aerosol delivery efficiency. Under optimal conditions, only 53(±18) μg salbutamol per 100 μg actuation was delivered bey...
Differential expression of skeletal muscle genes following administration of clenbuterol to exercised horses. Clenbuterol, a beta2-adrenergic receptor agonist, is used therapeutically to treat respiratory conditions in the horse. However, by virtue of its mechanism of action it has been suggested that clenbuterol may also have repartitioning affects in horses and as such the potential to affect performance. Clenbuterol decreases the percent fat and increases fat-free mass following high dose administration in combination with intense exercise in horses. In the current study, microarray analysis and real-time PCR were used to study the temporal effects of low and high dose chronic clenbuterol administr...
Pharmacokinetics of procaterol in thoroughbred horses. Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, ...
Detection and pharmacokinetics of salbutamol in thoroughbred racehorses following inhaled administration. Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC-MS/MS. Most of the determined salbutamol plasma concentrations, post l...
Concomitant inhibition of primary equine bronchial fibroblast proliferation and differentiation by selective β2-adrenoceptor agonists and dexamethasone. Altered airway cell proliferation plays an important role in the pathogenesis of human bronchial asthma and chronic obstructive pulmonary disease (COPD) as well as the equine recurrent airway obstruction (RAO) with consistent changes, i.e. narrowing the airway wall, explained by proliferation and differentiation of fibroblasts. In permanent cell lines, it has been suggested that β2-adrenoceptor agonists and glucocorticoids regulate cell proliferation via the β2-adrenoceptor pathway; indeed, no study was carried out in fresh isolated primary equine bronchial fibroblasts (EBF). We characterize...
Use of a novel one-nostril mask-spacer device to evaluate airway hyperresponsiveness (AHR) in horses after chronic administration of albuterol. Inflammatory airway disease (IAD) is very common in stabled horses. Short-acting beta agonist (SABA) drugs are often used to relieve clinical signs, although long-term exposure to these drugs may result in rebound bronchoconstriction. The purpose of this study was twofold: i) to describe the deposition of radiolabeled drugs using a novel one-nostril design mask-spacer combination with a breath-activated inhaler (BAI), and ii) to determine whether treatment for 10 d with inhaled albuterol using this device would impair the ability of albuterol to prevent bronchospasm during a histamine challeng...
Parturition in horses is dominated by parasympathetic activity of the autonomous nervous system. External and internal stressors prolong parturition in different species. At parturition, sympathoadrenal activation should be avoided because an increased sympathetic tone may cause uterine atonia via β2-receptors. We hypothesized that at physiological parturition, horses are under parasympathetic dominance, and stress-response mechanisms are not activated during delivery of the foal. To evaluate stress responses, heart rate, heart rate variability, catecholamines, and cortisol were analyzed in mares (n = 17) throughout foaling. Heart rate decreased from 2 hours before (51 ± 1 beats/minute)...
Effect of clenbuterol on tracheal mucociliary transport in horses undergoing simulated long-distance transportation. Pneumonia is observed in horses after long-distance transportation in association with confinement of head position leading to reduction in tracheal mucociliary clearance rate (TMCR). Objective: Clenbuterol, a beta-2 agonist shown to increase TMCR in the horse, will ameliorate the effects of a fixed elevated head position on large airway contamination and inflammation in a model of long-distance transportation model. Methods: Six adult horses. Methods: A cross-over designed prospective study. Horses were maintained with a fixed elevated head position for 48 hours to simulate long-distance tran...
Effects of oral clenbuterol on the clinical and inflammatory response to endotoxaemia in the horse. Pro-inflammatory cytokines, such as IL-1β and TNFα, play a major role in activating leukocytes and endothelial cells during the systemic inflammatory response to endotoxin in the horse. β2 agonist drugs, such as clenbuterol, inhibit leukocyte activation. This study aimed to determine the effects of oral clenbuterol on clinical and leukocyte responses, including production of TNFα, in an in vivo endotoxin challenge model. In a randomised crossover design, horses received either clenbuterol or a placebo product prior to the administration of low dose endotoxin (30 ng/kg over 30 min). Clinica...
Clenbuterol toxicosis in three Quarter Horse racehorses after administration of a compounded product. 3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product. Results: All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry. Results: Propranolol (0.01 mg/kg [0.005 mg/lb], I...
Analysis of β-agonists by HPLC/ESI-MS(n) in horse doping control. A sensitive method using LC/ESI-MS(n) has been developed on a quadrupole linear ion trap mass analyser for the detection of nine β(2) agonists (cimaterol, clenbuterol, fenoterol, formoterol, mabuterol, terbutaline, ractopamine, salbutamol and salmeterol) in horse urine. The method consists of solid-phase extraction on CSDAU cartridges before analysis by LC/ESI-MS(n) . The efficiency of extraction combined with the sensitivity and the selectivity of MS(n) allowed the detection of these compounds at pg/mL levels. Administration studies of fenoterol and formoterol are reported and show their pos...
Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi. Equine obstructive pulmonary disease, also known as heaves or recurrent airway obstruction (RAO) is a common equine pulmonary disease with some similarities to human asthma and COPD, which represents a major cause of morbidity and loss of lung performance. Salbutamol has been widely used for the treatment of human airway diseases and has usually been prepared as the racemic form of the drug. However, recently the R-enantiomer of salbutamol has been introduced into clinical practice in the treatment of asthma in humans and this has been suggested to be an improvement on the racemic form of the ...
