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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.
Techniques for evaluation of right ventricular relaxation rate in horses and effects of inhalant anesthetics with and without intravenous administration of calcium gluconate. To determine the most repeatable method for evaluating right ventricular relaxation rate in horses and to determine and compare effects of isoflurane or halothane with and without the added influence of intravenously administered calcium gluconate on right ventricular relaxation rates in horses. Methods: 6 Thoroughbred horses from 2 to 4 years old. Methods: 6 models (2 for monoexponential decay with zero asymptote, 3 for monoexponential decay with variable asymptote, and 1 for biexponential decay) for determining right ventricular relaxation rate were assessed in conscious and anesthetized hor...
The role of prostanoids and nitric oxide in endotoxin-induced hyporesponsiveness of equine digital blood vessels. Endotoxin has been implicated in the pathophysiology of acute laminitis. The aim of this study was to examine the direct effects of endotoxin on isolated equine digital blood vessels. Equine digital veins (EDV), incubated in Krebs-Henseleit solution containing lipopolysaccharide (LPS) (1 microg/ml) became hyporesponsive to 5-HT after 16 h. Cycloheximide and ibuprofen blocked this effect of LPS and increased the maximum response obtained to 5-HT when compared to control vessels. L-nitroarginine methyl ester (L-NAME) reversed the hyporesponsiveness caused by LPS. Vessels maintained in culture me...
A comparison of the bioequivalence of 0.5% fenbendazole top dress pellets or 10% fenbendazole oral suspension against a spectrum of equine parasites. A controlled test was conducted to assess the efficacy bioequivalence of a single dose of 0.5% fenbendazole (FBZ) top dress pellets to a 10% FBZ suspension formulation (Panacur suspension 10%, Hoechst Roussel Vet). Thirty horses with naturally-acquired parasite infections, in replicates of three, were used. Strongyle egg per gram counts were not significantly different (P>0.1) between groups pretreatment, but FBZ treated groups were significantly different from the control group post-treatment. At necropsy, which occurred seven to nine days post-treatment, two methods of nematode recovery were...
Pulmonary distribution of aerosolized technetium Tc 99m pentetate after administration of a single dose of aerosolized albuterol sulfate in horses with recurrent airway obstruction. To determine whether pulmonary distribution of aerosolized technetium Tc 99m pentetate is improved after inhalation of a single dose of albuterol sulfate in horses susceptible to recurrent airway obstruction (heaves). Methods: 6 horses with heaves and 4 horses with normal respiratory tract function. Methods: Images were obtained during ventilation of horses at baseline (maximal change in pleural pressure during tidal breathing [deltaPpImax] >15 cm H2O) and after aerosolized albuterol sulfate (360 microg) administration, with a 24-hour washout period between experiments. The deltaPpImax was ...
Anesthesia of horses with a combination of detomidine, zolazepam, tiletamine, and isoflurane immediately after strenuous treadmill exercise. To evaluate effects of strenuous exercise in adult horses immediately before anesthesia and to determine whether prior exercise affects anesthesia induction, recovery, or both. Methods: 6 healthy Thoroughbreds in good condition and trained to run on a treadmill, each horse serving as its own control. Methods: Horses ran on a treadmill until fatigued, then were sedated immediately with detomidine hydrochloride and anesthetized with a zolazepam hydrochloride-tiletamine combination. Anesthesia was maintained with isoflurane in oxygen for another 90 minutes. Blood samples were taken before, during...
Aerosolized albuterol sulfate used as a bronchodilator in horses with recurrent airway obstruction. To determine the dose of aerosolized albuterol sulfate required to cause bronchodilation in horses with recurrent airway obstruction (RAO) and duration of this effect. Methods: 19 horses with RAO (10 in experiment 1; 9 in experiment 2). Methods: Horses were moved from pasture to stables, and airway obstruction was induced. Pulmonary function was measured in 10 horses before and 5, 10, and 30 minutes after administration of vehicle or 120, 240, 360, or 720 microg of the drug. Nine horses received vehicle or 360 or 720 microg of albuterol, and pulmonary function was measured at baseline and 5 mi...
In vitro contractile responses and contracture testing of skeletal muscle from Quarter Horses with exertional rhabdomyolysis. To determine whether increased sensitivity to pharmacologic agents was a general property of equine exertional myopathies, including polysaccharide storage myopathy (PSSM) in Quarter Horses. Methods: 5 adult Quarter Horses with exertional rhabdomyolysis and abnormal polysaccharide accumulation in skeletal muscle and 4 clinically normal adult Quarter or Quarter-type horses. Methods: Twitch time course measurements and contracture responses to various concentrations of caffeine and halothane for small bundles of intact external intercostal muscle fibers were measured in all horses. Results: Caff...
Cardiorespiratory effects of a tiletamine/zolazepam-ketamine-detomidine combination in horses. To determine cardiorespiratory effects of a tiletamine/zolazepam-ketamine-detomidine (TZKD) combination in horses. Methods: 8 healthy adult horses. Methods: Horses were instrumented for measurement of cardiorespiratory, acid-base, and electrolyte values. Each horse was given xylazine (0.44 mg/kg of body weight, IV) 10 to 15 minutes prior to induction of recumbency by administration of the TZKD combination. Cardiorespiratory, acid-base, and electrolyte values were measured at 5-minute intervals for > or =30 minutes. Results: All horses became recumbent within 1 minute after IV administration of...
Cimetidine inhibits nitric oxide associated nitrate production in a soft-tissue inflammation model in the horse. Cimetidine (CIM) is an H2-receptor antagonist that has been used in racehorses in an attempt to reduce the occurrence of stress-related gastric ulceration. It has also been shown to produce several useful effects other than its gastric acid suppression properties. Further, it is a well documented antagonist of cytochrome P-450 (CYP) mediated oxygenation reactions. Nitric oxide (NO), a recently discovered mediator or modifier of numerous physiological functions, is generated by several forms of nitric oxide synthase (NOS), one of which is inducible (iNOS). Inducible NOS, expressed in neutrophil...
Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses. We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the l...
Etodolac in equine urine and serum: determination by high-performance liquid chromatography with ultraviolet detection, confirmation, and metabolite identification by atmospheric pressure ionization mass spectrometry. A high-performance liquid chromatographic method was used for the detection of etodolac in equine serum and urine. The method consisted of a one-step liquid-liquid extraction, separation on a reversed-phase (RP-18) column and detection using an ultraviolet detector. Additional confirmation methods included a HPLC coupled with an atmospheric pressure chemical ionization mass spectrometer (APCI-MS). Free (unbound) etodolac and its conjugates were present in the samples. Concentrations of the drug in the serum and urine samples collected from four standardbred mares after a single oral administra...
Determination of the activity of pyrimethamine, trimethoprim, sulfonamides, and combinations of pyrimethamine and sulfonamides against Sarcocystis neurona in cell cultures. Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. The activities of pyrimethamine, trimethoprim, sulfachloropyridazine, sulfadiazine, sulfadimethoxine, sulfamethoxazole, sulfamethazine, and sulfathiazole were examined against developing S. neurona merozoites in bovine turbinate cell cultures. A microtiter plate host cell lesion based assay was used to determine the effects of agents on developing merozoites. A cell culture flask assay was used to determine if sele...
The effect of oral isoxsuprine and pentoxifylline on digital and laminar blood flow in healthy horses. To quantitate blood flow in the palmar digital artery and dorsal laminae of the hoof in standing, unmedicated, nonsedated horses, and in horses treated with oral isoxsuprine, oral pentoxifylline, and intravenous acetylpromazine as a positive control. Methods: Experimental study; treatments administered in a random cross-over design. Methods: A total of 6 healthy horses selected with at least one nonpigmented forelimb hoof wall and determined to be free of laminitis. Methods: All horses were instrumented with a flow probe placed around one palmar digital artery under general anesthesia and a la...
Alpha 2 agonists and antagonists. The alpha 2 agonists can produce reliable dose-dependent sedation and analgesia in most species. Nevertheless, they can also produce significant physiological adverse side effects depending on dose, rate, route of administration, and the concurrent use of other CNS depressants. For this reason, it may be best to use a low dose of an alpha 2 agonist as a preanesthetic agent. The alpha 2 agonists are best suited for young, healthy, exercise-tolerant patients. The combining of low doses of alpha 2, opioid, and benzodiazepine agonists results in a synergistic CNS depressant response while minimizi...
Systemic dexamethasone concentration in horses after continued topical treatment with an ophthalmic preparation of dexamethasone. To determine concentrations of dexamethasone in serum and urine of horses treated repeatedly with a topically administered ophthalmic dexamethasone preparation. Methods: 4 clinically normal horses (2 mares, 2 geldings). Methods: 0.1% dexamethasone ophthalmic ointment was administered to the left eye of each horse every 5 to 9 hours for 8 consecutive days, yielding an estimated cumulative dexamethasone dose of 6.4 microg/kg of body weight. Serum and urine samples were obtained before the first dexamethasone treatment, on days 4 and 8 of treatment, and 24, 48, and 96 hours after cessation of tre...
In vitro dose-dependent effects of enrofloxacin on equine articular cartilage. To determine whether enrofloxacin has detrimental, dose-dependent effects on equine articular cartilage in vitro. Methods: Cartilage explants were developed from 6 healthy horses between 0 and 96 months old. Methods: Patellar cartilage explants were incubated in 5 concentrations of enrofloxacin (2 microg/ml, 10 microg/ml, 1,000 microg/ml, 10,000 microg/ml, and 50,000 microg/ml) for 72 hours. Proteoglycan synthesis (Na35SO4 incorporation for 24 hours), proteoglycan degradation (Na35SO4 release for 72 hours), endogenous proteoglycan content (dimethylmethlene blue assay), and total protein conten...
Modulation of ACh release from airway cholinergic nerves in horses with recurrent airway obstruction. To evaluate the functional status of neuronal alpha2-adrenoceptors (ARs) and beta2-ARs on ACh release in horses with recurrent airway obstruction (RAO), we examined the effects of the physiological agonists epinephrine (Epi) and norepinephrine (NE) and the beta2-agonists RR- and RR/SS-formoterol on ACh release from airway cholinergic nerves of horses with RAO. Because SS-formoterol, a distomer of the beta2-agonist, increases ACh release from airways of control horses only after the autoinhibitory muscarinic receptors are blocked by atropine, we also tested the hypothesis that if there is an M2...
[O,O-dialkyl-S-bromomethylthiophosphates–inhibitors of mammalian choline- and carboxyl esterases: structure-activity relationship]. The interaction kinetics of potential pesticides, O,O-dialkyl S-bromomethylthiophosphates (RO)2P(O) SCH2Br (R = Et, i-Pr, n-Pr, n-Bu, or n-Am) with acetylcholinesterase, butyryl cholinesterase, and carboxyl esterase from warm-blooded animals was studied. All the compounds irreversibly inhibit these esterases, with k1 (M-1 min-1) being 1.8 x 10(4) - 1.9 x 10(6) for acetylcholinesterase, 2.0 x 10(6) - 4.1 x 10(7) for the more sensitive butyryl cholinesterase, and 2.3 x 10(7) - 2.3 x 10(8) and higher for the most sensitive carboxyl esterase. By using the Hansch and Kubinyi technique of multiple r...
Aryl acylamidase activity exhibited by butyrylcholinesterase is higher in chick than in horse, but much lower than in fetal calf serum. Several side activities have been attributed to butyrylcholinesterase (BChE), including aryl acylamidase (AAA) activity, which is an amidase-like activity with unknown physiological function splitting the artificial substrate o-nitroacetanilide. For avians, extensive developmental data have pointed to neurogenetic functions of BChE, however, a possible AAA activity of BChE has not been studied. In this study, we first compare the relative levels of AAA exhibited by BChE in whole sera from chick, fetal calves (FCS) and horse. Remarkably, FCS exhibits a 400-fold higher ratio of AAA/BChE than hor...
Effects of extrathoracic airway obstruction on intrathoracic pressure and pulmonary artery pressure in exercising horses. To determine whether dorsal displacement of the soft palate (DDSP) results in pulmonary artery hypertension and leads to increases in transmural pulmonary artery pressure (TPAP); to determine whether pulmonary hypertension can be prevented by prior administration of furosemide; and to determine whether tracheostomy reduces pulmonary hypertension. Methods: 7 healthy horses. Methods: Horses were subjected to 3 conditions (control conditions, conditions after induction of DDSP, and conditions after tracheostomy). Horses were evaluated during exercise after being given saline (0.9% NaCl) solution ...
Endotoxin induction of nitric oxide synthase and cyclooxygenase-2 in equine alveolar macrophages. To determine the amount of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes induced in vitro in equine alveolar macrophages in response to lipopolysaccharide (LPS). Sample Population-Alveolar macrophages obtained from 12 horses. Methods: Alveolar macrophages were collected by bronchoalveolar lavage from 12 horses and incubated for 6 hours with LPS (0.001 to 10 microg/ml) or vehicle. Total RNA was extracted and purified. After first-strand cDNA synthesis, mRNA induction was measured, using a polymerase chain reaction (PCR) technique for COX-2, iNOS, and glyceraldehyde...
Lack of local anaesthetic efficacy of fentanyl in the abaxial sesamoid block model. Fentanyl and other opioid drugs have their effect in the central nervous system; however, activity at peripheral sites has also been demonstrated. Pain-suppression activity at peripheral sites raises the possibility of skilled individuals producing local anaesthetic effects with small doses of opioid drugs that would be difficult to detect forensically and could be used to affect the outcome of a race. Therefore, the local pain-suppression effect (peripheral nerve inhibition) of fentanyl was tested using an abaxial sesamoid block/hoof withdrawal model. With this model, fentanyl did not produce...
Use of phenytoin to treat digitalis-induced cardiac arrhythmias in a miniature Shetland pony. Two miniature Shetland ponies showing clinical signs of Digitalis purpurea (foxglove) poisoning were examined. One animal died shortly afterwards, but the second was treated successfully with the anti-arrhythmic agent, phenytoin, and was discharged after 16 days.
Determinants of the maximal change in pleural pressure during tidal breathing in COPD-affected horses. In six COPD-affected horses, we analysed the factors responsible for the changes in pleural pressure (delta Pplmax) that occur during tidal breathing. Four-hundred-and-sixty-eight measurements of each parameter: pulmonary resistance (RL), dynamic elastance (Edyn), air flow rates, and the timing of breathing, were gathered during a trial of the bronchodilator pirbuterol. Data were placed into seven ranks, based on the magnitude of delta Pplmax; rank 1: 5-15; rank 2: 15-25; rank 3: 25-35; rank 4: 35-45; rank 5: 45-55; rank 6: 55-65; and rank 7 > 65 cm H2O. Up to rank 4 (45 cm H2O), the increa...
Comparison of the effects of halothane, isoflurane and methoxyflurane on the electroencephalogram of the horse. We have investigated in eight ponies the effects of three different end-tidal concentrations of halothane, isoflurane and methoxyflurane on median (F50) and 95% spectral edge (F95) frequencies of the EEG and the second differential (DD) of the middle latency auditory evoked potential (MLAEP). The three concentrations of each agent were chosen to represent approximately the minimum alveolar concentration (MAC), 1.25 MAC and 1.5 MAC for each agent. During halothane anaesthesia, F95 decreased progressively as halothane concentration increased, from mean 13.9 (SD 2.6) at 0.8% to 11.9 (1.1) at 1.2%...
Presence and comparison of angiotensin converting enzyme in commercial cell culture sera. This study was conducted to determine the presence of the angiotensin converting enzyme in commercial sera used in cell culture medium. The aim of the research was to bring the presence of proteinases (angiotensin converting enzyme) to cell culture users' knowledge and to give some data for solving problems about the development of peptides as useful drugs. The enzymes, purified from foetal bovine, adult bovine, foetal equine, adult equine, and human sera, showed molecular weights of about 170 kDa. Captopril and lisinopril inhibited enzyme activities at nanomolar concentrations. The enzymes we...
Presumed moxidectin toxicosis in three foals. Outcome and complications associated with administration of moxidectin gel to 3 foals < 4 months old are described. Two foals became comatose but survived following supportive treatment. One foal died following loss of consciousness associated with moxidectin administration. Risk of moxidectin overdose exists, because horse owners often fail to read or comprehend the package insert instructions pertaining to use of the syringe-locking mechanism. In addition, moxidectin should not be administered to foals < 4 months old, because it is likely that treated foals will become comatose.
The effect of motilin on the regulation mechanism of intestinal motility in conscious horses. Laparotomy was performed on seven thoroughbreds to attach a force transducer to the proximal jejunum, distal jejunum, and ileum, as well as to the serous membrane of the cecum. Following observation of intestinal motility in conscious horses, they were intravenously injected with motilin (0.6 microgram/kg) to examine its effect on intestinal motility. Strong contractions peculiar to horses were observed in small intestine. Further, motilin caused strong contractions in the proximal jejunum. The results suggested the involvement of motilin in the regulation mechanism of intestinal motility.
