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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.
Cerebrospinal fluid and blood concentrations of toltrazuril 5% suspension in the horse after oral dosing. Toltrazuril 5% suspension (Baycox, Bayer Canada, Ontario, Canada) was administered to six adult horses followed by blood collection and assay to determine the concentration of toltrazuril and its principal metabolites, toltrazuril sulfone and toltrazuril sulfoxide. From this data, the maximum concentration (C(max)), elimination half-life (T 1/2), and mean residence times of the plasma were determined from standard pharmacokinetic formulas. After a single oral dose of 10 mg/kg body weight a rapid absorption was found, with a mean peak serum concentration of 11.17 mg/L at 18 hours. Elimination w...
Affinity of isoxsuprine for adrenoreceptors in equine digital artery and implications for vasodilatory action. We used isolated equine digital arteries to study the vasodilatory mechanism of isoxsuprine, and fowl caecum preparations to investigate the affinity of the drug for beta-adrenoceptors. Isoxsuprine is a potent vasodilator of arterial smooth muscle that has been precontracted by an alpha-adrenoceptor agonist such as noradrenaline (log EC50 = -6.33 [-5.98; -6.68]). The present study indicates that its effect is due to alpha-adrenoceptor blockade since: (1) after a long lasting exposure to cumulative doses of isoxsuprine the vasoconstricting action of noradrenaline cannot be restored; (2) isoxsup...
Oral nitroglycerin paste did not lower pulmonary capillary pressure during treadmill exercise. We hypothesised that 22.5 mg of oral nitroglycerin would cause pulmonary vasodilation and therefore decrease pulmonary capillary pressure in horses during strenuous exercise. Six horses were assigned to exercise twice, once with no medication (control) and once with nitroglycerin (22.5 mg orally) in random order. Horses were exercised for 3 min each at 75, 90 and 100% of maximal heart rate (HRmax) with a 2 min period of walking between each period of exertion. Pulmonary artery and oesophageal pressures were recorded continuously. Subsequent analysis was carried out on the pulmonary arterial pr...
Effects of pre-exercise frusemide administration and post exercise anaesthesia on cardiopulmonary and acid-base parameters and blood and plasma volumes in horses exercised supramaximally to fatigue. Six horses were randomly assigned to receive either frusemide (F) (0.5 mg/kg i.v.) or an equivalent volume of saline (S) i.v., 4 h prior to treadmill exercise. Horses were instrumented to enable measurement of heart rate (HR), systolic (SAP), mean (MAP), and diastolic (DAP) carotid arterial pressures, pulmonary artery pressure (PAP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), blood gases, and cardiac output (CO). Plasma (PV) and blood volumes (BV) were measured using 2 injections of Evan's Blue dye. Baseline parameters were recorded while the horse stood quietly. Hor...
Influence of frusemide on dynamic cardiac variables during exercise. Exercising horses have extremely high right and left atrial pressures. Limitation in ventricular function (i.e. relaxation) may play a role in these high pressures. We studied relaxation characteristics of the right ventricular myocardium and the impact of frusemide (2.0 mg/kg bwt i.v.) on these characteristics in horses exercising at 8, 10, 12 and 14 m/s. Exercise tests were performed 4 h after administration of frusemide. Right ventricular (RV) pressure was analysed using Fast Fourier Transform techniques to remove non cardiac components of the pressure signal. Mean right atrial (RA) pressur...
Clinical pharmacology of nervous system diseases. The well-developed defense barriers of the CNS and the expense of drug therapy limit the pharmacologic options for the treatment of neurologic diseases in horses. New approaches to controlling inflammation in the CNS are improving the outcomes of bacterial meningitis. The appropriate treatment of EPM remains controversial. More research is needed to evaluate the pharmacokinetics and pharmacodynamics of drugs in the CNS of the horse. Behavioral pharmacology has become fashionable in human and small animal medicine, but it needs to be evaluated for the potential of unethical use in performance h...
Equine cardiac disease. Clinical pharmacology and therapeutics. Cardiac disease is often life-threatening and challenging to treat. Prolonged therapy is indicated in many cases, which can lead to problems with treatment costs, owner compliance, and potential drug toxicity. Many therapies are empirical or based on data from other species because of a lack of well-designed prospective clinical trials in horses. This article reviews the clinical pharmacology and therapeutics of heart failure, cardiac arrhythmias, myocardial disease, endocarditis, and pericardial disease.
Pharmacologic considerations in the treatment of neonatal septicemia and its complications. This article focuses on the pharmacologic properties of drugs commonly used in the treatment of neonatal septicemia and its complications. Rational therapy demands an awareness of not only the pharmacology of individual drugs but also the interactions and anticipated fate of such drugs in the rapidly changing physiologic environment of the neonate. Further research in the area of equine neonatal pharmacology should greatly assist our understanding of the impact of the disease state on the unique physiology of the newborn and should allow us to better predict the ultimate fate of drugs commonly...
Analgesia. Critical to reducing patient morbidity as well as heightened ethical awareness, alleviation of pain in animals has become integral to medical case management and surgical procedures. Pharmacotherapy is directed at peripheral nociceptors, primary and secondary spinal neurons, and pain-processing areas in the CNS. Accordingly, three primary pharmacologic strategies have evolved: drugs that bind to and activate opioid receptors, drugs that bind to and activate alpha 2 receptors, and drugs that reduce de novo prostaglandin synthesis. In horses, the two predominant types of pain encountered are mus...
Monthly, daily, and circadian variations of measurements of pulmonary mechanics in horses with chronic obstructive pulmonary disease. To determine temporal variations of pulmonary function in horses without respiratory tract disease (controls) and horses with chronic obstructive pulmonary disease (COPD) and determine whether reversibility of airway obstruction after environmental control can be predicted by response to atropine administration. Methods: 7 COPD-affected and 5 control horses. Methods: Pulmonary function testing was performed monthly during 3 consecutive months, daily for 5 consecutive days, and at 6-hour intervals for 24 hours before and after administration of atropine (0.02 mg/kg of body weight, i.v.) and aft...
Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses. To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. Methods: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. Methods: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumi...
Pharmacokinetic interactions between flunixin and sulphadimidine in horses. The pharmacokinetic aspects of sulphadimidine were studied in clinically healthy (control) and Flunixin-medicated horses after a single intravenous and oral administration of 100 mg/kg body weight. Plasma sulphadimidine concentration were determined by high-performance liquid chromatography (HPLC). Following the intravenous injection, all plasma sulphadimidine data were best approximated by a two-compartment open model using sequential, weight non-linear regression. Flunixin induced a 67% increase in the rate of sulphadimidine return to the central compartment from peripheral tissues (K21) and...
Disposition and tolerance of suxibuzone in horses. Suxibuzone (SBZ), a nonsteroidal anti-inflammatory drug, was administered to 6 horses at a dose rate of 7.5 mg/kg bwt by intravenous (i.v.) route. Plasma and synovial fluid concentrations of suxibuzone and its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ), were measured simultaneously by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Plasma SBZ concentrations rapidly decreased and were not detectable beyond 20 min after treatment. The parent drug was not detected in...
Effects of ketamine on the equine electroencephalogram during anesthesia with halothane in oxygen. To investigate the effects of ketamine on the electroencephalogram (EEG) of the horse. Methods: Prospective experimental study. Methods: Eight Welsh mountain pony geldings weighing between 280 and 330 kg, 5 to 9 years old. Methods: During halothane anesthesia at an end-tidal halothane concentration between 0.75 and 0.85%, the EEG frequency power spectrum and the auditory evoked potential were recorded while an infusion of ketamine was given. Ketamine 200 mg was infused over 5 minutes in 8 ponies. The effects of ketamine on the EEG were recorded continuously during the infusion and for a furthe...
Detection and identification of flunixin after multiple intravenous and intramuscular doses to horses. The objectives of the study were to compare various methods to determine flunixin in test samples collected periodically from horses after intramuscular (IM) and intravenous (IV) dosing at the maximum recommended dosage and to document detection times for this drug in test samples. Flunixin, a nonsteroidal anti-inflammatory drug approved for use in horses, was administered to eight mares in five consecutive daily doses of 1.1 mg per kilogram of body weight by the IM or IV route. Flunixin was detected in urine samples collected at various times after drug administration by flunixin enzyme-linke...
Pharmacology of anthelmintic resistance in cyathostomes: will it occur with the avermectin/milbemycins? Anthelmintic-resistance has emerged as a problem in several animal industries. In the horse, cyathostome resistance to all available treatments except for the avermectin/milbemycins means that these drugs provide the cornerstone of control. Ivermectin has been available for several years; the related compound moxidectin is more recent. Although we do not know for sure, aspects of moxidectin such as its persistent action and its efficacy against mucosal stages of cyathostomes, may enhance the rate of development of resistance. On the other hand, selection pressure would be reduced if the persis...
Pyrimidine nucleotide-evoked inhibition of cyclic AMP accumulation in equine epithelial cells. Uridine triphosphate (UTP) evoked inhibition of adrenaline-evoked cAMP accumulation in cultured equine epithelial cells (EC50, 1.8 +/- 0.2 microM) and this effect was mimicked by 5-Br-UTP (EC50, 6.6 +/- 1.8 microM) and uridine diphosphate (UDP; EC50, 96 +/- 26 microM). This inhibitory action of UTP was abolished by pre-treating cells with pertussis toxin (10 ng ml-1, 24 h). UTP (EC50, 2.3 +/- 0.3 microM) and 5-Br-UTP (EC50, 29.4 +/- 9.4 microM) also increased intracellular free calcium ([Ca2+]i) whilst UDP did not; the two effects are thus differentially sensitive to these pyrimidine nucleotid...
Drug disposition and dosage determination of once daily administration of gentamicin sulfate in horses after abdominal surgery. To evaluate pharmacokinetics of once daily i.v. administration of gentamicin sulfate to adult horses that had abdominal surgery. Methods: Prospective study. Methods: 28 adult horses that underwent abdominal surgery for colic. Methods: 14 horses were treated with each dosage of gentamicin (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemi...
Attenuation by phenylbutazone of the renal effects and excretion of frusemide in horses. The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide...
In vitro effects of nonsteroidal anti-inflammatory agents and prostaglandins I2, E2, and F2alpha on contractility of taenia of the large colon of horses. To determine the in vitro effect of various prostaglandins (PG) and nonsteroidal anti-inflammatory drugs (NSAID) on contractile activity of the large-colon taenia of horses. Methods: 14 healthy horses. Methods: The taenia was collected from the ventral colon, cut into strips (2 X 10 mm), and mounted in a tissue bath system (20-ml capacity) that contained oxygenated Krebs buffer solution warmed to 37.5+/-0.5 C. After equilibration, incremental doses of PGE2, PGF2alpha, PGl2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and contractile activity was recor...
Comparison of sedative effects of romifidine following intravenous, intramuscular, and sublingual administration to horses. To compare sedative effects of romifidine following IV, IM, or sublingual (SL) administration in horses. Methods: 30 horses that required sedation for routine tooth rasping. Methods: Horses (n = 10/group) were given romifidine (120 microg/kg) IV, IM, or SL. Heart rate, respiratory rate, head height, distance between the ear tips, thickness of the upper lip, response to auditory stimulation, response to tactile stimulation, and degree of ataxia were recorded every 15 minutes for 180 minutes. Tooth rasping was performed 60 minutes after administration of romifidine, and overall adequacy of sedat...
Investigations on the stereoselective action of isoxsuprine on alpha- and beta-adrenoceptors in equine common digital artery. The affinity and functional effects of isoxsuprine enantiomers were investigated to determine the enantiospecificity of the beta-agonistic and alpha-blocking effects. Functional assays on isolated smooth muscle preparations from equine common digital artery were performed to determine the apparent affinity (pD(2)) and intrinsic activity (alpha(E)) of (-)erythro-isoxsuprine (alphaS, betaR, gammaR) and (+)erythro-isoxsuprine (alphaR, betaS, gammaS). The affinity of two enantiomers for the different adrenoceptor types was studied by radioligand binding assays on membrane preparations from the sam...
Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation. The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedat...
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 ...
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...
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...
Mepivacaine: its pharmacological effects and their relationship to analytical findings in the horse. Mepivacaine is a local anaesthetic drug that is widely used in equine medicine and is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 foreign substance that may cause regulators to impose significant penalties if residues are identified in post-race urine samples. Therefore, an analytical/pharmacological database was developed for this agent and its metabolites. Using an abaxial sesamoid local anaesthetic model, it was determined that the highest no-effect dose (HNED) for its local anaesthetic effect was 2 mg. Using enzyme-linked immunosorbent assay (ELI...
A pharmacodynamic and pharmacokinetic study with vedaprofen in an equine model of acute nonimmune inflammation. The pharmacodynamics and enantioselective pharmacokinetics of vedaprofen were studied in six ponies in a two period cross-over study, in which a mild acute inflammatory reaction was induced by carrageenan soaked sponges implanted subcutaneously in the neck. Vedaprofen, administered intravenously at a dosage of 1 mg/kg, produced significant and prolonged inhibition of ex vivo serum thromboxane B2 (TXB2) synthesis and short-lived inhibition of exudate prostaglandin E2 (PGE2) and TXB2 synthesis. Vedaprofen also partially inhibited oedematous swelling and leucocyte infiltration into exudate. Vedap...
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...
