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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.
Pharmacology of the 5-lipoxygenase inhibitors BAY Y 1015 and BAY X 1005 in the horse. Calcium ionophore A23187 induced time and concentration dependent production of immunoreactive leukotriene (LT) B4 by equine heparinized whole blood in vitro. Time dependent production of immunoreactive LTB4 by equine neutrophils and immunoreactive LTC4 by equine eosinophils in vitro was also demonstrated. The 5-lipoxygenase activating protein (FLAP) inhibitors, BAY X 1005 and BAY Y 1015, produced concentration dependent inhibition of ionophore-induced LTB4 synthesis by equine whole blood (mean +/- SEM IC50s n = 5; 6.14 +/- 0.28 microM vs. 12.30 +/- 0.75 microM for BAY Y 1015 and BAY X 1005, r...
Muscarinic signaling pathway for calcium release and calcium-activated chloride current in smooth muscle. We investigated the muscarinic activation of Ca(2+)-activated Cl- currents [ICl(Ca)] in voltage-clamped equine tracheal myocytes. The threshold of cytosolic free Ca2+ concentration ([Ca2+]i) required for activation of ICl(Ca) was 202 +/- 22 nM, and full activation of the current occurred at 771 +/- 31 nM. Hexahydro-sila-difenidol (M3 antagonist) inhibited the methacholine-induced phasic [Ca2+]i increase and ICl(Ca) in a concentration-dependent manner, whereas methoctramine (M2 antagonist) only slightly attenuated the [Ca2+]i increase and ICl(Ca) (14.8 and 21.4%, respectively), consistent with ...
Magnesium toxicosis in two horses. Magnesium sulfate, a saline laxative, is often used for treatment of intestinal impactions in horses. Clinical signs of hypermagnesemia are an uncommon complication following oral administration of magnesium sulfate. Overdose of magnesium sulfate in combination with renal insufficiency, hypocalcemia, or compromise of intestinal integrity may predispose horses to magnesium toxicosis. Establishment of diuresis with fluids and IV administration of calcium may provide successful treatment of magnesium toxicosis in horses.
Pulmonary vascular pressures of strenuously exercising Thoroughbreds after administration of varying doses of frusemide. The frusemide dose-response for attenuation of exercise-induced pulmonary capillary hypertension was studied in 7 healthy, exercise-conditioned Thoroughbred horses using previously described haemodynamic procedures. Four different doses of frusemide were tested: 250 mg regardless of bodyweight (amounting to 0.56 +/- 0.03 mg/kg bwt), 1.0 mg/kg bwt, 1.5 mg/kg bwt and 2.0 mg/kg bwt. Frusemide was administered i.v., 4 h before exercise. Haemodynamic data were obtained at rest and during treadmill exercise performed at 14.2 m/s on a 3.5% uphill grade; this workload elicited maximal heart rate of ho...
Use of Doppler ultrasonography to evaluate renal arterial blood flow in horses. To obtain Doppler ultrasonographic images of renal arteries in horses and to establish reference range values for systolic and diastolic renal arterial blood flow and resistive indices. Also to determine whether Doppler ultrasonography could be used in horses to detect changes in renal blood flow after IV administration of furosemide. Methods: 11 clinically normal adult horses. Methods: Pulsed-wave Doppler examinations were performed on arcuate arteries of 5 sedated horses. Continuous-wave Doppler examinations were performed on pyelorenal arteries in 7 nonsedated horses and were repeated in 6 ...
Anesthetic potency of desflurane in the horse: determination of the minimum alveolar concentration. To determine the minimum alveolar concentration (MAC) of desflurane (DES) in the horse. Methods: Prospective study. Methods: Six healthy adult horses (three males and three females) weighing 370 +/- 16 kg and aged 9 +/- 2 years old. Methods: Anesthesia was induced with DES vaporized in oxygen via a face mask connected to a large-animal, semiclosed anesthetic circle system. The horses were endotracheally intubated and positioned in right lateral recumbency. Inspired and end-tidal DES were monitored using a calibrated Ohmeda RGM 5250 multigas analyzer (Ohmeda-BOC, Spain). The MAC of desflurane t...
Redox regulation of large conductance Ca(2+)-activated K+ channels in smooth muscle cells. The effects of sulfhydryl reduction/oxidation on the gating of large-conductance, Ca(2+)-activated K+ (maxi-K) channels were examined in excised patches from tracheal myocytes. Channel activity was modified by sulfhydryl redox agents applied to the cytosolic surface, but not the extracellular surface, of membrane patches. Sulfhydryl reducing agents dithiothreitol, beta-mercaptoethanol, and GSH augmented, whereas sulfhydryl oxidizing agents diamide, thimerosal, and 2,2'-dithiodipyridine inhibited, channel activity in a concentration-dependent manner. Channel stimulation by reduction and inhibit...
Structure of glycan moieties responsible for the extended circulatory life time of fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase. Cholinesterases are serine hydrolases that can potentially be used as pretreatment drugs for organophosphate toxicity, as drugs to alleviate succinylcholine-induced apnea, and as detoxification agents for environmental toxins such as heroin and cocaine. The successful application of serum-derived cholinesterases as bioscavengers stems from their relatively long residence time in the circulation. To better understand the relationship between carbohydrate structure and the stability of cholinesterases in circulation, we determined the monosaccharide composition, the distribution of various oligo...
Use of yohimbine to reverse prolonged effects of xylazine hydrochloride in a horse being treated with chloramphenicol. A 1-year-old Standardbred gelding had received xylazine hydrochloride (0.75 to 1.00 mg/kg [0.34 to 0.45 mg/lb] of body weight, IV) during 2 surgeries for debridement of a wound. The horse was given chloramphenicol (55 mg/kg [25 mg/lb], PO, q 6 h) for 5 days, and was anesthetized a third time with xylazine (0.75 mg/kg, IM). Five hours after administration of xylazine, the horse remained markedly sedated and had clinical signs of gaseous distention of the large bowel (bloat) requiring trocharization. Administration of yohimbine (0.03 mg/kg [0.01 mg/lb], i.v.) eliminated signs of sedation within ...
Relaxation of equine tracheal muscle in vitro by different adrenoceptor drugs. Strips of tracheal smooth muscle from 12 horses were contracted by carbachol in tissue baths under isometric conditions. This contraction (approximately 50% of maximum: EC50) was relaxed completely with adrenoceptor drugs. The only exception was clenbuterol, where the degree of relaxation was approximately 90%. In all horses the EC50-value for isoprenaline (mean 1.6 x 10(-8) M) was less than that for adrenaline (mean 9.6 x 10(-8) M) and noradrenaline (mean 1.8 x 10(-6) M). The potency ratio was 1 < 6 < 110 which indicates that the beta 2-subtype dominates among the beta-adrenoceptors of ...
Prejunctional alpha 2-adrenoceptors inhibit nitrergic neurotransmission in horse penile resistance arteries. To study the influence of alpha-adrenergic stimuli on non-adrenergic non-cholinergic (NANC) neurogenic relaxation in isolated horse penile resistance arteries. Methods: Deep intracavernous penile arteries with an internal lumen diameter of 200-500 microns., isolated from the corpus cavernosum of young horses, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation (EFS) of autonomic nerve terminals. Results: In the presence of guanethidine (10(-5) M) and atropine (10(-7) M) tone of the arteries was raised by the thromboxane analogue, U46619. EFS...
Lack of local anaesthetic efficacy of Sarapin in the abaxial sesamoid block model. Sarapin is a distillate of the pitcher plant that has long been used in human and veterinary medicine for 'regional analgesia'. The mechanism of the reported analgesic response is unknown; however, the agent is purported to provide more effective analgesia for slow, chronic pain than for sharp, acute pain. Reportedly, Sarapin is also widely used as an analgesic agent in the horse, generally in combination with corticosteroids and other agents. To determine its local anaesthetic efficacy in the horse, we tested Sarapin in a unilateral abaxial sesamoid block model at two dose levels, 2 mL and 10...
Controlled dose confirmation study of a 2% moxidectin equine gel against equine internal parasites in The Netherlands. The efficacy of a 2% moxidectin equine gel at a dosage rate of 0.4 mg kg-1 was evaluated in a controlled trial at Utrecht University. Twelve yearling castrated male Shetland ponies grazed a pasture of 2 ha from May 1994 until housing in November. Six ponies were treated with moxidectin, whereas the others served as non-treated controls. Necropsy was carried out 35 days after treatment. Greater than 99% efficacy of moxidectin was observed on faecal egg output. No effect of moxidectin was observed on mucosal inhibited early cyathostome L3 (EL3) or on the total numbers of mucosal developing stage...
Characterization of muscarinic receptors in equine tracheal smooth muscle in vitro. This study was undertaken to assess the importance of muscarinic receptor subtypes in equine airway disease. Smooth muscle strips from the mid-cervical portion of the trachea of horses were placed in tissue baths and isometric contractile force was measured. Active force was measured in response to metacholine and the selective muscarinic receptor agonists McN-A-343 (M1-selective) and pilocarpine (M2-selective) in cumulative concentrations (10(-9)M through 10(-3)M), with and without preincubation with three or four concentrations of the selective muscarinic receptor antagonists pirenzepine (M1...
Pharmacological characterization of adrenoceptors in horse corpus cavernosum penis. 1. The presence and types of alpha and beta-adrenoceptors in the corpus cavernosum of the horse were studied in vitro by using selected ligands of adrenoceptors and isometric tension recording. 2. Noradrenaline and phenylephrine induced concentration-dependent contractions in corpus cavernosum preparations. B-HT 920 had no effect. 3. Phentolamine and prazosin produced a shift to the right of the dose-response curve of noradrenaline, while the alpha(2)-antagonist, rauwolscine had no effect on the response to noradrenaline. Phenylephrine-evoked contractions of corporal strips were significantly ...
The effect of neomycin on the kidney function of the horse. The toxic effect of neomycin on the horse kidney was studied. Twelve horses were used, and were divided at random into three groups of four. The first group was treated twice a day with 10 mg/kg I.M. for 15 days and then euthanised; kidney and liver samples were studied and no histopathological changes were observed. Group 2 was treated with neomycin sulphate as in group 1, and group 3 was used as control. Blood samples were taken at 8.00 h and 20.00 h daily from both neomycin treated and control horses. Serum creatinine, potassium, sodium and urinary creatinine remained without change. On day...
Effect of sodium bicarbonate administration on blood constituents of horses. To describe changes in blood constituents of horses after oral and i.v. administration of sodium bicarbonate (NaHCO3), and to determine whether the changes are dose dependent. Methods: 6 adult Standardbred mares. Methods: 3 oral doses (1,500, 1,000, and 250 mg/kg of body weight) or 1 intravenous dose (250 mg/kg, 5% solution) of NaHCO3 in 3 L of water, or water (3 L orally), were given to the mares; then changes in blood constituents were measured. Access to food and water was denied during the experiment. Blood samples were collected immediately before treatment and at hourly intervals for 12 ...
Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet function. To determine whether synthetic peptides containing the arginine-glycine-aspartate (RGD) sequence inhibit equine platelet function. Methods: For in vitro studies of blood, 3 healthy Thoroughbreds; for in vivo and ex vivo studies of administration of RGD-containing peptides, 4 young adult pony mares. Methods: Blood was incubated with and without addition of aspirin or RGD-containing peptides (RGDS, RPR 110885) and platelet aggregation responses and platelet adhesion to subendothelial collagen were determined. RPR 110885 was administered IV, and platelet function was evaluated. Platelet aggregati...
Temporal effects of an infusion of dopexamine hydrochloride in horses anesthetized with halothane. To evaluate the hemodynamic effects of a 60-minute infusion of dopexamine in horses anesthetized with halothane. Methods: 7 adult Thoroughbreds. Methods: Measurements of left ventricular function obtained by transesophageal Doppler echocardiography and cardiac catheterization. Results: Infusion of dopexamine (4 micrograms/kg of body weight/min) significantly increased heart rate, cardiac output, maximal rates of increase and decrease of left ventricular pressure, and maximal acceleration and maximal velocity of aortic blood flow. Left ventricular ejection time significantly increased, and pre-...
Role of endothelium and nitric oxide in the response of equine colonic arterial rings to vasoconstrictor agents. To determine the in vitro contractile responses of equine colonic arteries to angiotensin II, histamine, serotonin, norepinephrine, prostaglandin F2 alpha, vasopressin, and a thromboxane-B2-analogue. Methods: The tension generated in colonic arterial rings placed in organ baths with oxygenated Tyrode's solution at 37 degrees C after exposure to the previously mentioned chemical agents was measured using force-transducers interfaced with a polygraph. Methods: Large colon arterial rings collected from eight horses. Methods: The rings were allowed to equilibrate for 45 minutes after applying 2 g ...
Distribution and functional effects of neuropeptide Y on equine ureteral smooth muscle and resistance arteries. The distribution of neuropeptide Y (NPY)-immunoreactive (IR) nerves, as well as the functional effects of NPY and the Y1- and Y2-receptor agonists, [Leu31,Pro34]NPY and NPY(13-36), respectively, have been investigated in vitro in both visceral and arterial smooth muscle of the horse intravesical ureter. NPY-IR nerve fibres were widely distributed along the entire length of the ureter, although the intravesical part was the most richly innervated region, and the only one where NPY-IR ganglion cells were found. NPY (10(-7) M) did not affect either basal tone or spontaneous rhythmic contractions ...
Biotransformation of chlorzoxazone by hepatic microsomes from humans and ten other mammalian species. The 6-hydroxylation of chlorzoxazone (CLZ) is currently being used in both in vivo and in vitro studies to quantify cytochrome P450 2E1 (CYP2E1) activity in humans. Comparatively little is known with regard to the biotransformation of this drug in other species. The NADPH-dependent biotransformation of CLZ was therefore studied using hepatic microsomes derived from humans and ten other mammalian species. In all species, 6-hydroxychlorzoxazone (6OH-CLZ) was the only metabolic product that could be identified by HPLC with ultraviolet detection. Enzyme kinetic analysis was used to characterize th...
Hyperkalemic periodic paralysis. Hyperkalemic periodic paralysis is an autosomal codominant genetic disease of horses who are descendants of the quarter horse sire Impressive. It produces a muscular phenotype that has been selected by show judges, which has resulted in the rapid dissemination of this disease. Clinical attacks are characterized by muscle fasciculation and spasm, and they respond to treatments for the concurrent hyperkalemia.
Plasma pharmacokinetics of ranitidine HCl in adult horses. Plasma pharmacokinetics of ranitidine HCl were investigated after intravenous (i.v.) and oral (p.o.) administration of 2.2 mg/kg drug to six healthy adult horses. Concentrations of ranitidine were determined using normal-phase, high-performance liquid chromatography. Plasma concentrations of ranitidine HCl declined from a mean of 5175 ng/mL at 5 min to 37 ng/mL at 720 min after i.v. administration. A three-exponent equation, Cp = A1 x e-k1t + A2 x e-k2t + A3 x e-k3t, best described data for all horses. Mean values for model-independent values calculated from the last quantifiable time point we...
Adverse reactions to veterinary drugs reported in Sweden during 1991-1995. The present article gives a summary of suspected adverse reactions reported by Swedish veterinarians during the period 1991-1995. The summary shows that severe adverse drug-reactions sometimes occur in Swedish veterinary practice. In horses, several cases of acute reactions in animals treated with procaine benzylpenicillin were reported and seven horses died within a few minutes after intramuscular injections of the drug. In cattle and swine most reports referred to the use of antimicrobial agents. In dogs reactions to vaccines were the most frequently reported adverse effects. The reactions w...
Modification of cardiopulmonary and intestinal motility effects of xylazine with glycopyrrolate in horses. Xylazine (XYL) administration in horses is accompanied by significant cardiovascular depression characterized by a 25-35% decrease in cardiac output (CO) which is likely to compromise tissue oxygen delivery (DO2), and usually vagally mediated bradycardia is an important cause of this reduced cardiovascular performance. To examine the possible benefit of preventing the bradycardiac response, 6 healthy horses were treated with intravenous (IV) saline (SAL) or 2.5 micrograms/kg glycopyrrolate (GLY) in a blinded, randomized, crossover trial. Fifteen minutes later, 1 mg/kg XYL was administered IV a...
Prolactin, gonadotropin, and hair shedding responses to daily sulpiride administration in geldings in winter. This experiment was designed to determine 1) the efficacy of daily s.c. injections of a dopamine antagonist, sulpiride, for increasing prolactin secretion in geldings in winter and 2) whether increasing prolactin concentrations would hasten the onset of hair shedding or enhance gonadotropin secretion. Five geldings each received vehicle (vegetable oil) or sulpiride (100 mg in vehicle) daily from February 8 through March 29. On February 8 and every 7 d thereafter through March 29, blood samples were drawn around treatment injections and hair samples were collected. On March 30, all geldings rec...
Corneal concentrations and preliminary toxicological evaluation of an itraconazole/dimethyl sulphoxide ophthalmic ointment. The objectives of this study were to determine the concentration of itraconazole achieved in corneal tissue and aqueous humour after topical application of a 1% itraconazole ointment: to determine the effect of including dimethyl sulphoxide (DMSO) in the ointment on achievable ocular tissue itraconazole concentrations; and to assess if any gross or histopathologic ocular toxicity results from the topical application of 1% itraconazole with or without the addition of DMSO. The experimental trial consisted of 6 horses considered to have normal eyes. Each horse had one eye treated with 0.3 mL of ...
