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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.
Epithelium- and mucosa-dependent relaxation and contraction of normal equine trachealis muscle in vitro. Strips of trachealis muscle were dissected from the mid-cervical portion of the trachea from horses that were free of respiratory tract disease. The epithelium and mucosa were removed from one group of tissues and were left intact in a second group of tissues. Each tissue was suspended in a bath filled with Krebs-bicarbonate solution that was aerated with 5% CO2 in oxygen and maintained at 37 degrees C. Isometric tension was continuously recorded. The contractile response to square-wave electrical stimulations increased as frequency (3, 5, 10, 15, 20, 25, and 30 Hz), voltage (10, 15, 18, and 2...
Isoproterenol- and salbutamol-induced relaxation of acetylcholine- and histamine-induced contraction of equine trachealis muscle in vitro. Strips of trachealis muscle were dissected from the midcervical portion of the trachea of horses that were free of respiratory tract disease, and the overlying epithelium and mucosa were removed. Muscle strips were suspended in tissue baths that were filled with Krebs-bicarbonate solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Isometric tension was continuously recorded. The increase in active isometric tension was concentration dependent when acetylcholine (10(-9) to 10(-4) M) or histamine (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. When t...
Comparison of the use of mass spectrometry and methylene unit values in the determination of the stereochemistry of estranediol, the major urinary metabolite of 19-nortestosterone in the horse. The stereochemistry of an isomer of 5-estrane-3,17 alpha-diol, the major metabolite of 19-nortestosterone in horse urine has been established by the use of methylene unit (MU) values. The empirical MU values of the bis-trimethylsilyl (TMS) derivatives of the eight available isomers of 5-androstane-3,17-diol and four isomers of 5-estrane-3,17 beta-diol were determined by capillary gas chromatography using three different columns. From this data the theoretical MU values for the bis-TMS derivatives of the four 5-estrane-3,17 alpha-diol isomers were predicted. Comparison of the experimentally det...
The evaluation of isoxsuprine hydrochloride for the treatment of navicular disease: a double blind study. A randomised double-blind clinical trial of 28 horses was undertaken to evaluate the efficacy of isoxsuprine hydrochloride at four different doses:- 0.0 mg/kg bodyweight (bwt) (placebo), 0.6 mg/kg bwt, 1.2 mg/kg bwt and 1.8 mg/kg bwt for treatment of navicular disease. The results showed that horses treated with isoxsuprine hydrochloride (N = 22) responded significantly with respect to clinical assessment score (P less than 0.01) when compared with the control group (N = 6). Furthermore, there were no dose-related differences in the responses of the horses treated with increasing levels of iso...
The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane-anesthetized horses. To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental ...
Effect of surgical manipulation, placental fluid, and flunixin meglumine on fetal viability and prostaglandin F2 alpha release in the gravid uterus of mares. Twenty-one pregnant mares with single or twin conceptuses between 41 and 65 days of gestational age were allotted to 5 treatment groups. A ventral median celiotomy was performed in all mares. In group-1 mares (3 mares, single conceptus), the uterus and fetus were palpated for 5 minutes. In group-2 mares (3 mares, single conceptus, flunixin meglumine), 250 ml of sterile placental fluid was injected into the nongravid uterine horn. In group-3 mares (4 mares, unicornuate twin conceptuses), group-4 mares (3 mares, unicornuate twin conceptuses, flunixin meglumine), and group-5 mares (8 mares, bicor...
Response of equine airway smooth muscle to acetylcholine and electrical stimulation in vitro. Smooth muscle strips from the midcervical portion of the trachea and bronchial smooth muscle strips from third-generation airways of horses were placed in tissue baths, and isometric contractile force was measured. Active force was measured in response to electrical stimulation and exogenous acetylcholine. Square-wave electrical stimuli were applied at various voltages (10, 12, 15, 18, 20, 25 V), frequencies (3, 5, 10, 15, 20, 25, 30 Hz), and pulse durations (0.2, 0.5, 1.0, 1.5, 2.0 ms). Isometric contractile force increased as voltage, frequency, and pulse duration increased. Maximal contract...
High frequency jet ventilation in horses: an experimental study. High frequency jet ventilation (HFJV) is a recently developed mode of ventilation that delivers small tidal volumes at frequencies greater than 60 cycles per min via an injection catheter to the animal's airway. The construction of a high frequency jet ventilator suitable for use in adult horses is described. The effectiveness of this ventilator in maintaining normal arterial blood-gas tension was evaluated in five healthy adult horses. The horses were anaesthetised with intravenous acetylpromazine, guaifenesin, and thiamylal, positioned in lateral recumbency and baseline measurements were mad...
Cardiovascular effects recorded in horses during anaesthesia after treatment with trichlorfon. Five horses were anaesthetised twice with thiopentone sodium, guaifenesin and halothane. The second anaesthesia was 16 days after the first and two days following oral administration of trichlorfon. Heart rate, carotid arterial, pulmonary arterial and right atrial pressures, cardiac output and blood temperature were measured every 15 minutes for 120 minutes. Heart rate, carotid arterial pressure and cardiac output were similar on both occasions. Pulmonary arterial and right atrial pressures were highest during anaesthesia after treatment with trichlorfon when compared with values obtained befo...
Normal intestinal motility. Perhaps because of the inherent difficulty in using horses as experimental animals, only a relatively small amount of data is as yet available regarding normal equine gut motility. However, it is clear that the horse is fundamentally similar to other mammalian species studied. The neural and humoral control of gut activity requires much exploration; it is likely that, in the horse, some of this information will be derived during the investigation of the effects of various substances that might have clinical relevance. This is alluded to in the chapter that follows (The Effects of Pharmacologic...
Effects of pharmacological agents on gastrointestinal motility. The control mechanisms of gastrointestinal motility are complex. Extrinsic neurohormonal effects modulate an intrinsic system, often called the "gut brain," composed of nervous and neuropeptide components. To exert pharmacologic influence on GI motility, use is made of agents that mimic the external control system. Agents that stimulate opioid receptors, block adrenoceptors, block or facilitate acetylcholine action, or antagonize the action of prostaglandins are used to effect changes in GI motility. The major indications for pharmacologic intervention are to increase motility in constipation,...
Effects of butorphanol tartrate on arterial pressure, jejunal blood flow, vascular resistance, O2 extraction, and O2 uptake in halothane-anesthetized ponies. The effects of butorphanol tartrate on arterial pressure, jejunal blood flow, vascular resistance, oxygen extraction, and oxygen uptake were determined in 10 anesthetized ponies ventilated with a mixture of halothane and 100% oxygen, using isolated autoperfused jejunal segments. Physiologic saline solution or butorphanol tartrate (0.2 mg/kg of body weight) was administered as a single bolus into the left jugular vein. By 2 minutes, butorphanol decreased arterial blood pressure and intestinal blood flow, and increased intestinal oxygen extraction. However, intestinal vascular resistance and oxy...
Clinical use of the neuromuscular blocking agents atracurium and pancuronium for equine anesthesia. Neuromuscular blocking agents (muscle relaxants) are useful and common adjuncts to general anesthesia for human beings, but have not been used extensively during anesthesia of large animal species. Over a 3-year period, atracurium or pancuronium were used as adjuncts to general anesthesia for 89 anesthetic procedures in 88 equids (of 18 breeds and age ranging in age from 5 weeks to 25 years) at the teaching hospital. Forty-one of the anesthetic procedures were for abdominal surgery, and orthopedic (n = 19), ophthalmologic (n = 17), thoracotomy (n = 1), and soft tissue (n = 14) procedures compo...
Evaluation of the effects of intra-articular injection of dimethylsulfoxide on normal equine articular tissues. To evaluate the effects of intra-articular injection of dimethylsulfoxide (DMSO) on normal equine articular structures, 7 adult horses with clinically normal carpi were allotted to 2 treatment groups (group A, n = 4; group B, n = 3). In each horse after collection of synovial fluid samples, the right antebrachial carpal and middle carpal joints were aseptically injected with 2 ml of a 40% solution of 90% medical grade DMSO in lactated Ringer solution, and the corresponding joints of the left forelimb (controls) were injected with 2 ml of lactated Ringer solution. In group-A horses, 2 ml of syn...
Functional and ligand binding studies suggest heterogeneity of platelet prostacyclin receptors. 1. This study describes attempts to compare prostacyclin (IP-) receptors in human, pig, horse, rabbit and rat platelets and in circular muscle of human, rabbit and dog mesenteric and pig gastroepiploic arteries. Three stable prostacyclin analogues, iloprost, cicaprost and 6a-carba-prostacyclin (6a-carba-PGI2) and a prostaglandin endoperoxide analogue EP 157 (previously shown to mimic prostacyclin on human platelets) were used. 2. Our main conclusion is that prostacyclin receptors on human, pig and horse platelets are similar in nature, but distinct from those on rabbit and rat platelets. Funct...
Effects of dopamine administration on cecal mechanical activity and cecal blood flow in conscious healthy horses. Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity of the circular and longitudinal muscle layers of the cecal body were measured in 7 conscious healthy horses during IV infusion of physiologic saline solution for 60 minutes (control), during a 60-minute IV infusion of dopamine (at dosages of 1, 2.5, and 5 micrograms/kg/min), and for 60 minutes after IV infusion of dopamine. The mean values for lateral cecal arterial blood flow during IV infusion of dopamine at a dosage of either 1 or 2.5 micrograms/kg/min were not significantly different from the...
GC/MS confirmatory method for etorphine in horse urine. A highly sensitive procedure for GC/MS determination of etorphine in horse urine is described. This assay provides both specificity and reliability and is particularly well suited for the confirmation of radioimmunoassay screening procedures usually used for etorphine. After solvent extraction and purifications, the etorphine is characterized as a pentafluoroacetic derivative (PFAA) by using mass fragmentography. The detection limit is 0.1 ng/mL in urine; the coefficient of variation of the estimations is 10.9%. The procedure has been validated after on-field administration of 5 to 90 microgra...
Effects of xylazine and/or butorphanol or neostigmine on myoelectric activity of the cecum and right ventral colon in female ponies. Effects of xylazine HCl (0.5 mg/kg of body weight, IV) and/or butorphanol tartrate (0.04 mg/kg, IV) or neostigmine methylsulfate (0.022 mg/kg, IV) on myoelectric activity of the cecum and right ventral colon were studied in 4 conscious female ponies. Eight bipolar Ag/AgCl electrodes were sequentially placed on the seromuscular layer of the cecum (6 electrodes) and right ventral colon (2 electrodes). Recordings began 30 minutes before and continued for 90 minutes after drug administration. Each drug or drug combination was studied on 2 occasions in each pony. Two major patterns of coordinated s...
The role of cyclooxygenase products in the acute airway obstruction and airway hyperreactivity of ponies with heaves. Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. To document the role of cyclooxygenase products of arachidonic acid metabolism in the pathogenesis of heaves, we measured plasma and bronchoalveolar lavage (BAL) fluid concentrations of metabolites of thromboxane (TX)A2 and prostaglandins (PG) I2 and D2 in five affected ponies and their age- and gender-matched controls prior to and during acute airway obstruction precipitated by housing the ponies in a barn and exposing them to hay dust. P...
Efficacy of ivermectin in oral drench and paste formulation against migrating larvae of experimentally inoculated Parascaris equorum. Twenty-one mixed-breed pony foals, reared and maintained under parasite-free conditions, were used to test the efficacy of ivermectin in oral drench and paste formulations (200 micrograms/kg) against 11-day-old migrating larvae of Parascaris equorum. Three replicates of 4 foals and 3 replicates of 3 foals were formed on the basis of age. Foals in replicates of 4 were randomly allocated to be indicators, or to receive vehicle (control) or ivermectin paste or ivermectin liquid. Foals in replicates of 3 were randomly allocated to receive vehicle or ivermectin paste or ivermectin liquid. The recov...
The lipoxygenase pathway and chemiluminescence in horse eosinophilic leukocytes. It was shown in several cell types that the dual lipoxygenase and cyclooxygenase inhibitor eicosatetraynoic acid but not the cyclooxygenase inhibitor acetylsalicylic acid suppressed luminol-dependent chemiluminescence. Since lipoxygenase is known to generate chemiluminescence in vitro, these observations were interpreted as evidence for a direct contribution of the lipoxygenase pathway to light emission in intact cells. We have investigated a possible contribution of the lipoxygenase to the chemiluminescence of horse eosinophils by directly comparing the formation of the byproduct chemilumines...
Equine peritoneal macrophage production of thromboxane and prostacyclin in response to platelet activating factor and its receptor antagonist SRI 63-441. The formation of eicosanoids may be a primary route through which platelet activating factor (PAF) exerts its effects during endotoxemia. Since endotoxemia is a common cause of death in horses, a study was conducted to determine whether PAF could stimulate equine macrophage release of thromboxane A2 (TxA2) and prostacyclin (PGI2) and whether a PAF-receptor antagonist would alter macrophage eicosanoid synthesis. Equine peritoneal macrophages were cultured from clinically normal horses and exposed to various concentrations of PAF, the PAF-receptor antagonist SRI 63-441, endotoxin, or a combinati...
The effects of slow infusion of a low dosage of endotoxin in healthy horses. The effects of slow intravenous (i.v.) infusion of a very low dosage of endotoxin (a cumulative dosage of 0.03 microgram/kg bodyweight [bwt] infused over 60 mins) were evaluated in six conscious healthy horses. Duodenal, right ventral colon, and caecal contractions were detected with strain gauge force transducers. Lateral caecal arterial blood flow was measured using transit time ultrasonic blood flow probes. Duodenal contractile activity was not significantly altered by infusion of endotoxin. In contrast, the contractile activity of the right ventral colon 90 and 270 mins after infusion of e...
In-vitro plasma protein binding of propafenone and protein profile in eight mammalian species. The protein binding of propafenone in vitro was assessed in plasma of mouse, rat, rabbit, dog, sheep, man, cow, and horse at two concentration levels. In all species and at both concentrations propafenone was found highly bound (86-99%) to plasma proteins. No significant relationship was found between free propafenone and the plasma protein fractions. A concentration-dependency was seen in plasma of mouse, sheep, man, and horse, in which the free fraction of propafenone became larger on raising the concentration. Qualitative and quantitative differences were observed in the protein plasma prof...
Serum angiotensin converting enzyme activity and response to angiotensin I in horses. The activity of serum angiotensin converting enzyme (ACE) for healthy horses was 64 +/- 13 mUnits/ml. In vitro, equine serum ACE was sensitive to the following inhibitors (IC50): enalapril (570 nM or 215 ng/ml), captopril (190 nM or 41.3 ng/ml), and enalaprilat (6 nM or 2.1 ng/ml). The intravenous (i.v.) administration of angiotensin I to six healthy horses produced a dose proportional pressor response. The maximal increase in mean arterial pressure over baseline values was 65.6 mmHg at angiotensin I doses of 500 ng/kg bodyweight (bwt). The attenuation of this response to angiotensin I was fur...
Critical and controlled tests of activity of a macrocyclic lactone (compound F28249-alpha) against natural infections in internal parasites of equids. Thirteen critical tests (n = 11 horses and 2 ponies) and 4 controlled tests (n = 4 donkeys and 6 horses) were performed to evaluate the activity of the experimental macrocyclic lactone compound F28249-alpha against internal parasites of equids. In the critical tests, activity was determined mainly against the large parasites, but 1 critical test also included benzimidazole-resistant small strongyles. In the controlled tests, evaluation of drug activity included large parasites and stomach worms in all 4 tests, and lungworms in 2 tests. The period between treatment and euthanasia was 6 to 9 day...
A study of the effect of isoflurane anaesthesia on equine skeletal muscle perfusion. The effects of 1.1, 1.5 and 1.8 MAC (minimum alveolar concentration) isoflurane-02 anaesthesia on skeletal muscle blood flow, 02 delivery and vascular resistance were studied in the non-dependent region of seven healthy normothermic, isocapnoeic ponies. Muscle blood flow was determined with 15 microns diameter radionuclide labelled microspheres that were injected into the left ventricle. Muscle blood flow during anaesthesia was compared to unanaesthetised (control) measurements. Isoflurane administration caused a dose dependent decrease in mean aortic pressure, and skeletal muscle (temporalis,...
Comparison of detomidine, butorphanol, flunixin meglumine and xylazine in clinical cases of equine colic. Detomidine hydrochloride, butorphanol tartrate, flunixin meglumine and xylazine hydrochloride were evaluated in a blind multi-centre clinical trial in 152 horses with abdominal pain. The drugs were administered as follows: detomidine 20 or 40 micrograms/kg bodyweight (bwt); butorphanol 0.1 mg/kg bwt; flunixin meglumine 1.0 mg/kg bwt; xylazine hydrochloride 0.5 mg/kg bwt. Each centre compared responses to the two doses of detomidine with those to one of the other analgesics. The drugs were administered intravenously (i.v.) after clinical assessment of the degree of sweating, kicking, pawing, he...
Cisapride in the prophylaxis of equine post operative ileus. Cisapride and domperidone were both effective in restoring electrical and mechanical activity, coordination between gastric and small intestinal activity cycles and the stomach to anus transit time in three ponies in which post operative ileus was induced experimentally. Cisapride (0.1 mg/kg bodyweight intramuscularly) for three to eight doses prevented idiopathic post operative ileus in 22 clinical cases requiring colic surgery. The only side effects after cisapride were increased bowel sounds and slight, transient sounds of discomfort. No adverse side effects were seen in 16 cases following ...
