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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.
Effect of high volume epidural morphine, ketamine and butorphanol on halothane minimum alveolar concentration in ponies. This study determined the effects of epidurally administered morphine, ketamine and butorphanol on halothane minimum alveolar concentration (MAC) in ponies. Seven ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure was maintained within normal limits. Following the determination of baseline halothane MAC for the pelvic and thoracic limbs the ponies were given morphine (0.1 mg/kg bwt), ketamine (0.8 or 1.2 mg/kg bwt), butorphanol (0.05 mg/kg bwt) or saline, epidurally, to a final volum...
Effect of acepromazine and butorphanol on halothane minimum alveolar concentration in ponies. The effect of i.v. acepromazine (0.05 mg/kg bwt), butorphanol (0.05 mg/kg bwt) and a combination of acepromazine and butorphanol on halothane minimum alveolar concentration (MAC) was determined in 7 mixed-breed ponies. Ventilation was controlled, and blood pressure and temperature were maintained within normal limits. Following the determination of baseline MAC, treatments were administered to each pony in a random manner. The control treatment was normal saline. The baseline halothane dMAC for the control group was 0.91 +/- 0.04%, and no significant change occurred after saline administration...
Aerosol deposition in equine lungs following ultrasonic nebulisation versus jet aerosol delivery system. Therapeutic aerosols pay an increasing role in the treatment of equine respiratory disorders. This route of delivery permits concentration of significant amounts of drugs at the site of action without unwanted high systemic concentration and resultant side effects. The efficiency of such a topical therapy depends on the quantity of inhaled drugs deposited in the lungs and, for some drugs, on the proportion retained in specific parts of the lungs. The objective of this study was to define and to compare quantitative (dose deposited) and qualitative (regional distribution) deposition of an aeros...
Role of endothelium and nitric oxide in the in vitro response of equine colonic venous rings to vasoconstrictor agents. To determine in vitro contractile responses of equine colonic veins to various vasoconstrictor agents. Methods: Colonic veins collected from 8 adult horses. Methods: Veins were cut into 4-mm-wide rings, placed in organ baths at 37 C, and attached to a force-transducer interfaced with a polygraph; 2 g of tension was applied, and rings were allowed to equilibrate for 45 minutes. Bath solution was replaced, and tension was reapplied at 15-minute intervals. Cumulative concentration responses (10(-8) to 10(-4) M) were determined for each agent, using separate rings (n = 8). Three vein groups were e...
In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse. As domestic animals such as cat, horse, and dog increasingly become the clinical targets for drug discovery programs, the need to understand how these animals metabolize xenobiotics becomes more important. In the present study, substrates and inhibitors that were reported to be selective for particular P450 isozymes were used as probes to study in vitro metabolism in horse, dog, cat, and human liver microsomes. Seven selective catalytic activity markers for cytochrome P450-mediated reactions were measured: phenacetin O-deethylase (P4501A1/2), coumarin 7-hydroxylase (P4502A6), tolbutamide hydro...
Airway response of horses with COPD to dry powder inhalation of ipratropium bromide. To determine the effects of the dry powder inhalation (DPI) of ipratropium bromide (ipratropium) on the airways of health horses and the dose-response curve in horses suffering from chronic obstructive pulmonary disease (COPD) by means of pulmonary function tests, five healthy horses were first studied. Ipratropium (2400 micrograms ipratropium horse-1) was contained in gelatine capsules and administered using a dry powder device connected to an adapted face mask. Pulmonary function tests were recorded before inhalation and 15 and 60 min after inhalation. No modification of pulmonary function w...
Effect of alpha-phenyl-tert-butylnitrone on endotoxin toxemia in horses. Lipopolysaccharide (LPS), or endotoxin, is a component of the cell wall of gram-negative bacteria and is toxic to humans and animals. The GI tract of horses contains large numbers of endotoxins which may cause disease if gut wall integrity is compromised. The objective of this study was to develop a unique therapeutic approach to the treatment of endotoxemia with a sulfonyl analog of the alpha-phenyl-N-tert-butyl-nitrone (PBN) spin-trap molecule which may prevent the LPS-induced cytokine cascade. Following challenge with 55 mg/kg LPS, the survivability of ICR Swiss mice was significantly impro...
Persistent penile prolapse associated with acute blood loss and acepromazine maleate administration in a horse. Prolonged penile prolapse in horses has been reported in association with administration of phenothiazine tranquilizers, trauma, neuropathies, severe general debilitation or exhaustion, starvation, rabies, herpes myeloencephalitis, equine infectious anemia, and purpura hemorrhagica. A 5-year-old gelding was admitted for treatment of prolonged penile prolapse of 12 days' duration that developed after acepromazine maleate was administered to allow examination of a laceration that had resulted in severe blood loss. The horse was sedated, and the penis was replaced in the preputial cavity by use o...
Diseases and surgery of the cecum. The cecum is an important site of water and electrolyte absorption, as well as microbial digestion of soluble and insoluble carbohydrates. These functions of the cecum and ascending colon require that ingesta be mixed constantly and retained long enough to complete the digestion of cellulose. Parasites, changes in regional blood flow, diet, and various pharmacologic agents are associated with alterations in normal cecal motility patterns.
In vitro responses of equine small airways and lung parenchyma. In vitro responses of equine small peripheral airways (SA) and lung parenchyma (LP) were studied. We examined their contractile and relaxant responses and investigated effects of histamine, and endogenous prostanoids as these mediators may play a role in development or recurrent airway obstruction in horses (heaves). SA and LP electrical field stimulation (EFS) induced nearly maximal and partial frequency-dependent contractions, respectively. These contractions were virtually abolished in SA but only partially inhibited in LP by atropine (ATR) and tetrodotoxin (TTX). Methacholine (MCh) contrac...
Influence of melatonin and oestradiol on the opioidergic regulation of LH and prolactin release in pony mares. The aim of this study was to investigate the influence of oestradiol, melatonin and season on the opioid regulation of LH and prolactin release. Effects of the opioid antagonist naloxone (0.5 mg/kg) on LH and prolactin secretion were determined in ovariectomized pony mares. In experiment 1, mares in January (n = 6) were pretreated with oestradiol benzoate (5 micrograms/kg) for 20 days. In experiment 2, beginning in May, mares (n = 7) received melatonin (15 mg) for 15 days and subsequently a combination of melatonin plus oestradiol for 20 days. In experiment 3, beginning in May, mares (n = 6) w...
Alpha-adrenoceptors in equine digital veins: evidence for the presence of both alpha1 and alpha2-receptors mediating vasoconstriction. Rings of equine digital vein examined under conditions of isometric tension recording constricted to alpha-adrenoceptor agonists with an order of potency of 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline bitartrate (UK 14304) = noradrenaline > 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d) azepine (BHT-920) > phenylephrine > dopamine > methoxamine. The maximum force generated was greatest for the non-selective agonist noradrenaline and lowest for the alpha2-selective agonist BHT-920 with the other agonists between these two extremes. Selective inactivation of alpha1-adreno...
Effects of airway obstruction on transmural pulmonary artery pressure in exercising horses. To determine whether laryngeal hemiplegia would increase transmural pulmonary artery pressure (TPAP). Methods: 6 horses. Methods: Horses were studied under 5 conditions: control conditions, after induction of left laryngeal hemiplegia, during obstruction of the left nostril, after placement of an instrumented tracheostomy, and after placement of an open tracheostomy. Horses were evaluated after being given saline solution and after being given furosemide. Methods: Horses were exercised on a high speed treadmill, using a maximum speed of 13 m/s. During each exercise, airway pressures, airflow, ...
Effects of flunixin meglumine on short circuit current in equine colonic mucosa in vitro. To study the effect of flunixin meglumine on short circuit current (Isc) in equine right ventral colon in vitro. Methods: Intestinal mucosa from healthy horses and ponies. Methods: Isc was measured in mucosa from the right ventral colon mounted in Ussing chambers. In experiment 1, collection and incubation solutions were: control (no additions); flunixin meglumine, 4 micrograms/ml; indomethacin, 10(-6) M; and flunixin meglumine (4 micrograms/ml) with 10(-6) M prostaglandin E2. In experiment 2, incubation conditions were: control [plain Krebs-Ringer bicarbonate [KRB] solution]; flunixin meglumi...
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 ...
