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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.
Dose-related effects of fentanyl on autonomic and behavioral responses in performance horses. The dose-related effects of intravenously administered fentanyl (0.010, 0.005, 0.0025 mg/kg) and saline were studied in mature performance horses using a rigorous experimental protocol. Fentanyl produced a dose-related prolongation of the skin twitch reflex latency but did not increase the hoof withdrawal reflex latency. Dose related increases in stepping frequency, cardiac and respiratory rats were observed following fentanyl, while changes in rectal temperature and pupil area were not. These data indicate that fentanyl, a prototypic mu-agonist, produces a syndrome characterized by analgesia,...
Colonic motor responses in the pony: relevance of colonic stimulation by opiate antagonists. The electrical and mechanical activity of the digestive tract and its response to the administration of opiate agonists and antagonists was assessed from electrodes and strain gauges chronically implanted on the jejunum and the cecocolonic segments in 3 ponies given a diet of hay and concentrates. Before the drugs were given, 10 to 17 migrating myoelectric complexes/day were recorded on the small intestine, and a rhythmic motor activity (base line) was observed on the proximal portion of the colon at the rate of 3.5 to 6.6/hour. Propagated contractions from the proximal to the distal portion o...
Endotoxin-induced eicosanoid production by equine vascular endothelial cells and neutrophils. Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin...
Endotoxin-induced hematologic and blood chemical changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone. To evaluate the effect of certain drugs on hematologic changes, blood chemical values, and survival in endotoxin shock, anesthetized ponies were given (IV) endotoxin (Escherichia coli O55:B5) and then treated as follows: Group A ponies--given a saline infusion at 5 minutes and at 3 hours after they were given endotoxin; group B ponies--given flunixin meglumine at 5 minutes and at 3, 6, 9, and 24 hours after they were given endotoxin; group C ponies--treated with dexamethasone; and group D ponies--treated with prednisolone at 5 minutes and at 3, 9, and 24 hours after they were given endotoxin. ...
Qualitative detection of corticosteroids in equine biological fluids and the comparison of relative dexamethasone metabolite/dexamethasone concentration in equine urine by micro-liquid chromatography-mass spectrometry. Several important corticosteroids were qualitatively determined in the plasma and urine of horses by micro-liquid chromatography-mass spectrometry (micro-LC-MS). The sensitivity and specificity of micro-LC-MS are demonstrated as is the ability of micro-LC-MS to deal with endogenous interferences. In turn, the relative amount of dexamethasone and its major unconjugated metabolite were determined in equine urine by micro-LC-MS; the conclusions drawn are reported.
Differential effects of phenylbutazone and local anesthetics on nociception in the equine. The effects of procaine, mepivacaine and phenylbutazone on pain perception in the equine were studied using two behavioral assays of nociception; the thermal evoked hoof withdrawal reflex and skin twitch reflex. Pain perception threshold was measured as the latency from onset of thermal stimuli to reflex withdrawal of the forelimb or contraction of the cutaneous musculature. Procaine 2% and mepivacaine 2% prolonged the hoof withdrawal reflex latency when administered locally by producing a block of the palmar and metacarpal nerves. Significant analgesia lasted 90 min and 210 min for procaine a...
Substrate-dependent kinetic behavior of horse plasma cholinesterase: evidence for kinetically distinct populations of active sites. The inhibition of horse plasma cholinesterase by propranolol showed characteristics which depended upon the identity of the substrate used. With butyrylthiocholine as substrate, the inhibition showed a first-order dependence on inhibitor concentration, and was characterized by a Ki of 8 microM (pH 7.4, 20 degrees C). With p-nitrophenylbutyrate as substrate, a biphasic v-1 versus [I] relationship was obtained. The biphasic curve could be resolved into two components, with apparent Ki's of 9 microM and 1.3 mM. Use of butyrylthiocholine as alternative substrate resulted in partial inhibition of p...
Dosage requirement of pancuronium in halothane-anesthetized ponies: a comparison of cumulative and single-dose administration. Cumulative vs single-bolus administration of pancuronium was studied in halothane-anesthetized ponies. Dosage levels were determined by giving small increments (0.01 to 0.04 mg/kg of body weight) until the desired relaxation occurred (0.125 +/- 0.038 mg/kg for 90% to 99% reduction of prerelaxant twitch height), then an additional 0.037 +/- 0.024 mg/kg for obliteration of twitch response. The dosage level defined by cumulative administration was then administered as a single bolus 2 more times, once on each of 2 days. Dosage requirements for the 2 methods correlated well. The difference in dura...
Pharmacologic and pharmacokinetic properties of methocarbamol in the horse. The hemodynamic, respiratory, and behavioral effects, as well as the pharmacokinetic properties of methocarbamol, were determined in horses. Heart rate, cardiac output, arterial and venous blood pressures, respiratory rate, and arterial blood gases did not change after IV methocarbamol (4.4, 8.8, 17.6 mg/kg) administration. There were no signs of behavior modification or ataxia observed. Analysis of plasma concentration time data indicated that the disposition of methocarbamol may be dose-dependent. Clearance and steady-state volume of distribution decreased as the dose increased. Plasma conce...
Pharmacokinetic disposition of theophylline in horses after intravenous administration. The pharmacokinetics of theophylline were determined in 6 healthy horses after a single IV administration of 12 mg of aminophylline/kg of body weight (equivalent to 9.44 mg of theophylline/kg). Serum theophylline was measured after the IV dose at 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 15 hours. Serum concentration plotted against time on semilogarithmic coordinates, indicated that theophylline in 5 horses was best described by a 2-compartment open model and in 1 horse by a 1-compartment open model. The following mean pharmacokinetic values were determined; elimination half-life = 11.9 hours, distri...
Controlled tests of activity of ivermectin against natural infections of migratory large strongyles and other internal parasites of equids. Four controlled tests (experiments A, B, C, and D) were conducted in naturally infected yearling equids to evaluate activity of ivermectin (0.2 mg/kg IM) against migrating Strongylus vulgaris and S edentatus in mesenteric arteries and ventral abdominal wall, respectively. Data were also obtained on activity against other internal parasites of the gastrointestinal tract and eyeworms. The type and number of equids in the experiments were as follows: experiment A-3 ponies, 2 treated and 1 non-treated; experiment B-4 mixed-bred horses, 2 treated and 2 nontreated; experiment C-5 mixed-bred horses, ...
Flunixin inhibits prostaglandin E2 production in equine inflammation. A model of acute inflammation was used in a cross-over study in Welsh mountain ponies to assess the actions of flunixin meglumine on selected components of a localised inflammatory reaction induced by injecting 0.5 ml of a 2 per cent carrageenin solution into subcutaneously implanted tissue cages. Samples of exudate were harvested at predetermined times between three and 48 hours. Increases in leucocyte numbers and protein concentration were not prevented by flunixin treatment. Prostaglandin E2-like activity was present in exudates from untreated ponies with the highest mean concentration occu...
Antagonism of pancuronium neuromuscular blockade in halothane-anesthetized ponies using neostigmine and edrophonium. Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked af...
Evaluation of ivermectin against later fourth-stage Strongylus vulgaris in ponies at two and five weeks after treatment. The efficacy of ivermectin against later fourth-stage Strongylus vulgaris larvae was studied in pony foals at 14 and 35 days after treatment. These foals had been reared parasite-free, inoculated with 500 infective larvae and 56 days later given either ivermectin at 200 micrograms/kg or a placebo intramuscularly. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was found to be highly effective (98.6%) against later fourth-stage larvae in five foals which were examined at 35 days after treatment, but not in five others examined at 14 days (72.5%). I...
A survey of adverse effects associated with ivermectin use in Louisiana horses. In a survey of 13 Louisiana equine practices, it was determined that 366 of 3,316 horses developed adverse reactions following use of ivermectin, with 3 of the horses having more than 1 reaction. Almost all of the reactions were of minor to moderate concern; however, 1 death was reported. Three hundred and thirty-two (91% of all reactions) were reported as ventral midline pruritus or edema (10% of all doses). Fifteen (0.45%) were transient injection site swelling and/or stiffness. Eleven horses (0.33%) developed limb edema. Eyelid edema was reported in 4 horses (0.12%). Two horses (0.06%) had ...
[Interaction of bis-phosphorylated methanes with mammalian esterases]. The interaction of human erythrocyte acetylcholinesterase, horse serum butyrylcholinesterase and rat liver carboxylesterase with insecticides (RO)2P(O)SCH(COOEt)SP(O)(OR)2 (I) and (RO)2P(O)SCH(COOEt)OP(S)(OR)2 (II) was studied. The type I and II compounds were not hydrolyzed by carboxylesterase and inhibited the esterases irreversibly. A complex pattern of inhibition of acetylcholinesterase and butyrylcholinesterase by these compounds was caused by kinetically-manifested formation of an enzyme-inhibitor complex. The compounds I and II were more selective towards butyrylcholinesterase than towa...
Effectiveness of ivermectin paste for removal of nematodes in the horse. Thirteen Standardbred horses, two to five years of age, were treated with ivermectin paste per os at 200 mug/kg of body weight and 13 were untreated. Two weeks after treatment, previously untreated horses were given the paste. Fecal samples were collected from all horses at the time of treatment and periodically thereafter up to 14 weeks and were examined for nematode eggs using the Cornell-McMaster dilution and the Cornell-Wisconsin double centrifugation procedures.All horses consumed the paste readily and had no signs of toxicosis. Strongyle eggs were found in the feces of all horses before ...
A health index to evaluate clinically a beta-hemolytic streptococcal infectious disease model in the horse. Quantification of the clinical manifestations of a disease has been a serious problem particularly as related to clinical trials or drug efficacy studies. Historically, this quantification has been limited to categorizing each patient into one of three or four groups, e.g. worse, no improvement, improved. This problem becomes serious when an investigation utilizes an experimentally induced animal disease model. A health index, which quantifies the clinical state of horses which have an experimentally induced beta-hemolytic streptococcal infection, is described. Aspects of experimental design a...
