Topic:Pharmacodynamics
Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Critical tests of thiabendazole, oxibendazole, and oxfendazole for drug resistance of population-B equine small strongyles (1989 and 1990). Critical tests were conducted in horses (n = 11) with naturally acquired infections of benzimidazole (BZ)-resistant population-B small strongyles in 1989 and 1990. Anthelmintics administered were thiabendazole (44 mg/kg of body weight, n = 4), oxibendazole (10 mg/kg, n = 3), and oxfendazole (OFZ, 10 mg/kg; n = 4). All compounds were paste formulations administered orally except for 1 of the OFZ treatments, which was a suspension formulation given by stomach tube. Aggregate mean efficacy was calculated for all species of small strongyles, drug-resistant and non-resistant. The highest efficacy w...
Pharmacokinetics of single intravenous and single and multiple dose oral administration of rifampin in mares. The disposition of rifampin in six healthy mares after single intravenous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/kg administered twice a day was investigated using a high performance liquid chromatographic (HPLC) method. Pharmacokinetic variables for rifampin determined using the HPLC method were comparable to variables reported from earlier studies utilizing a microbiological assay. Desascetylrifampin, a major metabolite of the parent compound, could not be detected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin i...
In vitro effects of alpha 2-adrenergic receptor stimulation on cholinergic contractions of equine distal airways. In horses with noninduced, reversible airway obstruction (heaves), pulmonary function is improved after sedation with the alpha 2-adrenergic agonist xylazine. The mechanism of this effect is undetermined. Because the predominant excitatory innervation of equine airways is cholinergic, the influence of alpha 2-adrenergic receptor stimulation on the response of isolated distal airways to cholinergic stimulation was determined. Distal bronchial segments from 22 healthy horses were suspended in isolated organ baths where their mechanical responses to various stimuli could be studied. Each tissue w...
Pharmacokinetics and concentrations of ceftiofur sodium in body fluids and endometrium after repeated intramuscular injections in mares. Each of 5 healthy mares was given 5 consecutive IM injections of ceftiofur sodium (2 mg/kg of body weight; 50 mg/ml) at 12-hour intervals. Ceftiofur concentrations were measured serially in serum, synovial fluid, peritoneal fluid, and urine, and were measured in CSF and endometrial tissue after the fifth dose. Mean elimination rate constant was 0.354 +/- 0.101 h-1 and elimination half-life was 2.49 +/- 0.49 hour. Mean serum ceftiofur concentrations peaked approximately 1 hour after each injection. The highest mean ceftiofur concentration was 5.09 micrograms/ml at 1 hour after the fifth dose fo...
Administration of a receptor antagonist for platelet-activating factor during equine endotoxaemia. Platelet-activating factor (PAF) is an important mediator of endotoxaemia and various PAF receptor antagonists prevent many of the adverse effects of experimental endotoxaemia in laboratory animals. In this study a specific PAF receptor antagonist was used to investigate the role of PAF in equine endotoxaemia. At an interval of not greater than 10 days, 6 horses were each challenged with endotoxin and endotoxin with concurrent administration of SRI 63-441, a PAF receptor antagonist. The order of the treatments was randomised. Clinical signs, serum biochemical and coagulation profiles, and plat...
Pharmacokinetics and applications of ampicillin sodium as an intravenous infusion in the horse. A regime for administration of ampicillin sodium by continuous intravenous infusions to horses was designed. The aim was to achieve plasma ampicillin concentrations between 5 and 10 micrograms/ml over a 4-h period. A 2 mg/kg bodyweight loading dose of ampicillin sodium was administered intravenously at the beginning of the infusion in order to achieve steady-state plasma concentrations rapidly. The infusion system subsequently administered ampicillin at a rate of approximately 19.2 micrograms/min/kg bodyweight. The plasma concentrations obtained over the infusion period correlated very well wi...
Flunixin meglumine blocks frusemide-induced bronchodilation in horses with chronic obstructive pulmonary disease. Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg ...
[Comparative enantioselectivity of the disposition of two non-steroidal anti-inflammatory agents, ketoprofen and carprofen, in man and animals]. After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant ...
Cardiovascular responses to exogenous platelet-activating factor (PAF) in anesthetized ponies, and the effects of a PAF antagonist, WEB 2086. The effects of exogenous platelet-activating factor (PAF) were determined in anesthetized ponies. Administration of PAF induced a decrease in cardiac index that resulted in systemic hypotension. This was followed by tachycardia, hypertension, and a return of cardiac index to baseline. Pulmonary arterial pressure increased markedly because of pulmonary vasoconstriction. Exogenous PAF also caused leukopenia and thrombocytopenia. The specific PAF receptor antagonist (WEB 2086) blocked all PAF-induced changes. Flunixin meglumine, a cyclooxygenase inhibitor, abolished the pulmonary hypertension and...
Antagonism of a specific dopaminergic receptor agonist with metoclopramide in horses. Changes in lateral cecal arterial blood flow, mean internal carotid arterial pressure, and heart rate caused by nasogastric administration of fenoldopam (3, 6, and 9 mg/kg of body weight), a selective agonist of dopaminergic receptors, were recorded in 7 healthy horses. Cecal arterial blood flow was significantly increased within 30 minutes after administration of fenoldopam at all 3 dosages, with the peak increases from baseline (67.8 +/- 17.5 ml/min) being 125 +/- 28, 120 +/- 22, and 153 +/- 32 ml/min for 3, 6, and 9 mg/kg, respectively. Although carotid arterial pressure did not change sign...
Vancomycin kinetics in plasma and synovial fluid following intravenous administration in horses. Vancomycin hydrochloride was infused intravenously (i.v.) over a 30-min period in five horses at doses of 6.6, 11.0 and 15.4 mg/kg. Vancomycin concentration in plasma and synovial fluid samples was measured using a polarization immunoassay. A pharmacokinetic model was developed to accommodate the special features of the present study. The data were described by a two compartment open model with synovial fluid as an additional compartment in exchange with plasma. Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were measured for Staphylococcus aureus and Enteroco...
Pharmacokinetics of intravenously and orally administered pyrimethamine in horses. Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the...
Effect of xylazine on the arrhythmogenic dose of epinephrine in thiamylal/halothane-anesthetized horses. The effect of xylazine on the arrhythmogenic dose of epinephrine (ADE) was studied in 9 horses. Anesthesia was induced by administration of guaifenesin (50 mg/kg of body weight, IV) followed by thiamylal (4 to 6 mg/kg, IV) and was maintained at 1 minimal alveolar concentration (MAC) of halothane (0.89%). Base apex ECG and facial artery pressure were recorded. Epinephrine was infused in a sequence of arithmetically spaced increasing rates (initial rate 0.25 micrograms/kg/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate to the nearest 0.25 micrograms/...
Pharmacokinetics, penetration into cerebrospinal fluid, and hematologic effects after multiple oral administrations of pyrimethamine to horses. Pharmacokinetics, CSF penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The CSF samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and CSF was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a ...
Temporal effects of inhaled histamine and methacholine aerosols on the pulmonary mechanics of thoroughbred horses. This paper presents a method for on-line determination of pulmonary mechanics in standing, non-sedated horses during and following inhalation of aerosolized drug solutions. This method was used to evaluate the temporal effects of inhaled histamine and methacholine aerosols on pulmonary mechanics in 18 Thoroughbred horses. The following were concluded from this study. The extremely large between-breath variation, for all variables used to evaluate pulmonary mechanics in the horse, limits the usefulness of these variables for modeling the non-specific pulmonary responses to inhaled stimulants on...
Effects of furosemide and pentoxifylline on blood flow properties in horses. The effects of furosemide and pentoxifylline on blood flow properties in horses were investigated. Hematologic and rheologic changes were examined in 4 horses before and 3 minutes after administration of epinephrine (1 mg, IV). The next day, hemorheologic changes were determined before and 3 hours after administration of furosemide (1 mg/kg of body weight, IM), and after administration of epinephrine at the sampling at 3 hours. Hematologic and rheologic changes were evaluated weekly in 3 horses given pentoxifylline (8.5 mg/kg, q 12 h, PO) for 28 days. In addition, hemorheologic responses to ep...
Additive and synergistic pharmacologic inhibition of equine fibrinoligase (factor XIIIa*-like) biochemical activity. A selected group of pharmaceutical compounds were evaluated for the ability to inhibit the biochemical activity of fibrinoligase (coagulation factor XIIIa*) in pooled equine plasma. Criteria for the pharmaceuticals selected were based on the mechanism of the transglutamination biochemical reaction mediated by coagulation factor XIIa*. These criteria were complemented by recognition of the molecular configuration and chemical composition of amino acid residue side chains involved in the process of covalent fibrin monomer polymerization (cross-linking, transglutamination) mediated by this enzyme...
Effects of xylazine on airway function in ponies with recurrent airway obstruction. The effect of IV administration of the alpha 2-adrenoceptor agonist xylazine hydrochloride (0.5 mg/kg of body weight) was examined in ponies with recurrent obstructive pulmonary disease, commonly called heaves. Six ponies with the disease (principals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding of dusty hay. Six control ponies were also studied. In principal ponies with airway obstruction, xylazine administration significantly (P < 0.05) decreased pulmonary resistance and increased dynamic compliance, but did n...
Effects of pentoxifylline on equine neutrophil function and flow properties. Pentoxifylline has been reported to improve peripheral vascular circulation by altering the flow properties of blood. To determine if the hemorrheological effects of pentoxifylline were mediated by alterations in neutrophil function and/or flow properties, we evaluated the drug's effects on equine neutrophils in vitro. Pentoxifylline, at a concentration of 1 x 10(-1) M, but not at concentrations of 1 x 10(-6) M to 1 x 10(-2) M, markedly suppressed neutrophil superoxide production, zymosan phagocytosis and adherence to nylon wool. Pentoxifylline failed to improve neutrophil filterability throug...
Effect of the somatostatin analogue octreotide on gastric fluid pH in ponies. The effect of the somatostatin analogue, octreotide, on gastric fluid pH was investigated in 4 ponies. Gastric fluid pH was determined after SC administration of octreotide or physiologic saline solution (control). A baseline sample of fluid was obtained, the agent was given, and 8 additional samples were collected hourly. Administration of octreotide at all dosages tested (0.1, 0.5, 1.0, and 5.0 micrograms/kg of body weight) increased gastric pH to > 5.0. Baseline values were consistently 4.0 for 2.4 +/- 1.2, 4.8 +/- 0.8, 5.7 +/- 1.3, and 5.4 +/- 2.6 (mean +/- SD) continuous hours, respec...
Respiratory mucociliary clearance in the horse in health and disease, and its pharmaceutical modification. The structure and possible functions of respiratory secretions are reviewed. In the equine, goblet (mucus producing) cells are the main source but little information is available on the volume or composition of equine respiratory secretions. Airway mucus has complex and incompletely understood physical characteristics which can be partially assessed by a wide range of in vitro and biological techniques. The complex relationship between mucus structure and its propulsion by the airway cilia are discussed, both in health and with pulmonary disease. Mucokinesis in the horse has been assessed visu...
Synovial and serum levels of triamcinolone following intra-articular administration of triamcinolone acetonide in the horse. Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were as...
Effect of a histamine H2 type receptor antagonist (WY 45, 727) on the healing of gastric ulcers in ponies. Using video gastroscopy, the efficacy of a Histamine-H2 type receptor antagonist (WY 45, 727) was investigated in young ponies with spontaneous and experimentally induced gastric ulcers. Oral administration of WY 45, 727 at 2 mg/kg and 10 mg/kg of body weight every 12 hours for 14 days resulted in complete healing of spontaneous gastric ulcers in the non-glandular portion of the stomach in 2/5 (40%) and 3/4 (75%) of the ponies, respectively, compared (P < 0.05) to 0/5 (0%) placebo-treated ponies. After intramuscular administration of flunixin meglumine at 1.5 mg/kg body weight every 8 hours fo...
Effect of probenecid on disposition kinetics of ampicillin in horses. The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present...
Parasympathetic influence on the arrhythmogenicity of graded dobutamine infusions in halothane-anesthetized horses. We investigated the influence of parasympathetic tone on the arrhythmogenicity of graded dobutamine infusions in horses anesthetized under clinical conditions. Six horses were used in 9 trials. Two consecutive series of graded dobutamine infusions were given IV; each continuous graded dobutamine infusion was administered for 20 minutes. The dobutamine infusion dosage (5, 10, 15, and 20 micrograms/kg of body weight/min) was increased at 5-minute intervals. Isovolumetric saline solution vehicle (v) or atropine (A; 0.04 mg/kg) was administered IV, or bilateral vagotomy (VG) was performed as a tre...
Regional perfusion of the equine carpus for antibiotic delivery. Regional perfusion of carpal tissues by forced intramedullary administration of fluids was evaluated in 10 horses. Results of subtraction radiography after perfusion with a contrast medium demonstrated that perfusate was delivered to the carpal tissues by the venous system. Perfused India ink was distributed uniformly in the antebrachiocarpal and middle carpal synovial membranes. Histologically, the ink was within the venules of the synovial villi. Immediately after perfusion with gentamicin sulfate (1 g), the gentamicin concentrations in the synovial fluid and synovial membrane of the antebra...
Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview. The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect. Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release parenteral preparations (procaine penicillin G). When absorption influences the rate of elimination ('flip-flop' phenomenon), the apparent half-life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.). Absorption genera...