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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.
Actions of the novel gastrointestinal prokinetic agent cisapride on equine bowel motility. The effect of cisapride was evaluated on the normal fasting bowel motility of four ponies with chronically implanted electromechanical transducers. Cisapride was infused over 60-min periods at 0.05 mg/kg (n = 4), 0.1 mg/kg (n = 5) and 0.25 mg/kg (n = 5). It produced marked and prolonged increases in electrical and mechanical activity at all sites examined. In the stomach there was increased total contraction activity with increased contraction amplitude and a slight reduction in rate. In the small intestine there was an increase in irregular (phase II) activity with an increase in number and a...
Effects of atropine in ponies with recurrent airway obstruction. The effects of atropine on lung function and airway reactivity in two groups of ponies were measured. Principal ponies had a history of recurrent airway obstruction when housed in a barn and fed hay; control ponies had no history of airway obstruction. Principal and control ponies were paired, and measurements were made when principal ponies were in clinical remission (period A) and during an acute attack of airway obstruction (period B). Atropine did not alter pulmonary resistance (RL), dynamic compliance (Cdyn), or airway responsiveness in either group of ponies at period A or in the control...
[Pathogenesis and drug therapy of acute laminitis in horses: a literature review]. Impairment of the microcirculation in the distal part of the foot is an important factor in the aetiology of equine laminitis. To prevent the development of chronic laminitis and the resulting complications, two new therapeutical principles were tested in the treatment of acute laminitis. Thrombosis which frequently occurs in the corium of the foot, could be controlled by administration of anticoagulants such as heparin. Alpha-receptor blocking agents such as phenoxybenzamine were used, to improve the peripheral blood flow. The use of these drugs and that of anti-inflammatory agents during the...
Effect of administration of an alpha 2-adrenergic agonist, xylazine, on pulsatile gonadotrophin secretion in anoestrous horse mares. Two experiments were performed to test the hypothesis that the seasonal suppression of gonadotrophin pulse frequency in anoestrous horse mares reflects inhibitory neural mechanisms. In a preliminary experiment (Exp. 1) conducted in February, 4 anoestrous mares were sedated by repeated intravenous injections of xylazine, an alpha 2-adrenergic receptor agonist. On the day of treatment, 1-2 LH pulses were observed in xylazine-treated mares. In contrast, during a 12-h period only 1/8 untreated control mares exhibited a LH pulse. In Exp. 2, the effect of xylazine-induced sedation on pulsatile gonad...
Evaluation of ivermectin for larvicidal effect in experimentally induced Parascaris equorum infections in pony foals. A controlled test was carried out on 15 pony foals inoculated with 1,500 +/- 108.8 infective Parascaris equorum eggs. The foals were assigned to 3 treatment groups. Treatments given on postinoculation day 11 included 0.2 mg of ivermectin/kg of body weight, formulated as paste (n = 5), or liquid (n = 5), or no treatment (controls; n = 5). The foals were euthanatized on postinoculation day 25, and examined for larvae in the small intestine, lungs, and liver. Larvae were not found in foals treated with ivermectin liquid or paste, whereas significantly (P less than 0.05) higher mean numbers (960.9...
A method for reproducing fatal idiopathic colitis (colitis X) in ponies and isolation of a clostridium as a possible agent. Severe colitis was induced in two ponies after oral pretreatment with clindamycin and lincomycin, followed by intestinal content from two horses which had died from naturally-occurring idiopathic colitis. Two ponies treated with antibiotic alone, and two ponies treated with intestinal content alone, were unaffected. In a further study, three ponies treated on separate occasions with lincomycin, administered orally, died or were destroyed 67 to 72 h after initial treatment. No established salmonella, yersinia or campylobacter pathogens were isolated from these ponies, but a clostridium closely ...
Effects of cimetidine and ranitidine on basal gastric pH, free and total acid contents in horses. The basal gastric pH, free and total acid contents from five adult horses were determined at two-hour intervals for six- to eight-hour periods. The basal gastric pH, free and total acid contents varied from 2.14 +/- 0.08 to 2.41 +/- 0.14, 28.63 +/- 8.27 to 17.89 +/- 2.86 mmol litre-1 and 41.38 +/- 9.72 to 37.38 +/- 3.70 mmol litre-1, respectively. Cimetidine (8.8 mg kg-1 orally) and ranitidine (2.2 mg kg-1 orally) increased the basal gastric pH to above 3.6 (P less than 0.05) with a concomitant reduction of 75 per cent and 75 to 100 per cent in the basal gastric free acid content, respectively...
Oxfendazole: activity of a two-dose treatment regimen on natural infections of internal parasites of equids, with emphasis on migrating large strongyles in controlled tests in 1986 and 1987. Oxfendazole paste formulation was administered intraorally at a dosage of 10 mg/kg of body weight, twice (48 hours between treatments) in 5 controlled tests (experiments A, B, C, D, and E) to 18 equids (14 horses and 4 ponies) that were 5 to 24 months old in 1986 and 1987. Activity was evaluated against naturally acquired infections of various internal parasites, with emphasis on migratory stages of Strongylus vulgaris and S edentatus. The number of treated and nontreated equids in each experiment (horses in experiments A to D and ponies in experiment E) was: A, 1 and 1; B, 3 and 3; C, 3 and 1...
Prednisolone binding to plasma proteins in domestic species. The binding of prednisolone to total plasma proteins of dogs, horses, cows, and sheep was characterized using equilibrium dialysis. Prednisolone was bound to a first protein with high affinity but low capacity (transcortin) and to a second protein according to a nonsaturable mechanism (albumin). Interspecies differences were observed, with cows and dogs exhibiting the lowest, and sheep and horses the highest specific binding capacities. The results are in good agreement with known pharmacokinetic properties of prednisolone in domestic species.
Purification of specific heterologous F(ab)2 fragments with DEAE-Zeta-Prep cartridges for ion-exchange chromatography. A simple two-step procedure for purifying F(ab)2 fragments of horse immunoglobulins is described. In the first step, the horse plasma is diluted, made up to 12% (w/v) with ammonium sulphate and digested with pepsin. In the second step, the previously dialyzed solution is chromatographed. Instead of a normal ion-exchange resin, a DEAE-cellulose, covalently linked to a synthetic vinyl polymer, was used (DEAE-Zeta-Prep). With this assembly it is possible to perform chromatography at a high flow-rate without the problems related to the use of large columns. The yield and purity of the final produc...
Detomidine-butorphanol sedation in equine clinical practice. Combinations of detomidine (mean dose rate 13 micrograms/kg) and butorphanol (mean dose rate 26 micrograms/kg) were used to sedate 61 horses for a variety of surgical or diagnostic procedures in general equine practice. Three horses were sedated on more than one occasion. The degree of sedation was graded from 3 to 0 (deep sedation to no effect) and any side effects were recorded. Forty-three per cent of the horses were graded 3, 46 per cent were graded 2, 8 per cent were graded 1 and 3 per cent were graded 0. Bradycardia and ataxia were the major side effects. The combination was judged to be...
Histopathologic effects of dimethyl sulfoxide on equine endometrium. Endometrial fibrosis is a major cause of infertility in broodmares. Because of the proven anti-inflammatory effects of dimethyl sulfoxide (DMSO) and its influence on collagen, the effect of DMSO on the endometrium was investigated in mares. Solutions of DMSO (25%, 50%, or 75%) were infused into the uterus of clinically normal mares. Examination of serially obtained biopsy specimens revealed epithelial ulceration and stromal inflammation that were proportional to the DMSO concentration infused, but vasodilatation was not observed. In all mares, the endometrium had returned to normal by day 21 a...
Treatment of Fasciola hepatica infection in horses with triclabendazole. Thirteen thoroughbred foals with an adult infection and a presumed immature infection with Fasciola hepatica were treated with 12 mg triclabendazole/kg bodyweight. The absence of eggs from samples of faeces examined at intervals up to 110 days after treatment showed that all the animals were cured. In a second trial the same dose of triclabendazole cured 11 of 12 foals whereas nitroxynil at 7 mg/kg cured only six of 12 foals. No side effects were observed after treatment.
Combined use of detomidine with opiates in the horse. The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Sid...
Cardiorespiratory and sedative effects of a combination of acepromazine, xylazine and methadone in the horse. Cardiorespiratory and sedative effects of a combination of acepromazine, xylazine and methadone were studied in the horse. Acepromazine and xylazine produced cardiovascular effects whereas methadone mainly affected respiratory rate. Decreases in heart rate, arterial blood pressure and respiratory rate were seen. Sedation was superior to that of acepromazine, xylazine or a combination of these. No serious side effects were seen.
Detomidine (Domosedan) in foals: sedative and analgesic effects. Detomidine was administered twice to six foals (14 to 94 days old) using three different doses (10, 20 and 40 micrograms/kg bodyweight intravenously) in a double blind trial. Sedation, analgesia, heart rate and clinically observed side-effects were recorded. Detomidine showed strong sedative effects at all doses tested. Sedation deepened very little by increasing the dose from 10 to 40 micrograms/kg bodyweight, but the duration of the effect was longer. Analgesia was considered good with the largest dose (40 micrograms/kg), and moderate or non-existent with the lower doses. Detomidine caused a...
Hypovolemia, hyperosmolality, and acidosis associated with intraperitoneal infusion of nitrofurazone solution in healthy horses. Nitrofurazone solution containing 0.2% nitrofurazone and 99.8% polyethylene glycol was given to 4 healthy horses (2 L in 2 L of lactated Ringer solution, intraperitoneally). Horses developed hypovolemia, hyperosmolality, and mixed respiratory and metabolic acidosis. These changes were largely attributable to polyethylene glycol, but a contribution of nitrofurazone cannot be excluded. Intraperitoneal infusion of nitrofurazone solution in horses is contraindicated.
Dose-related effects of detomidine on autonomic responses in the horse. 1. Detomidine is a novel veterinary sedative analgesic which is thought to act by stimulation of alpha 2 adrenoreceptors. The present study was undertaken to determine the direction, time course, and dose-response relationship of detomidine on specific autonomic responses in the unanaesthetized horse. 2. Detomidine was administered intravenously to eight adult thoroughbred racehorses at doses of 0.010-0.040 mg kg-1, according to a double-blind Latin square crossover design. Cardiac and respiratory rates, pupil diameter and rectal temperature were monitored for 180 min postinjection. 3. Detomid...
Detomidine: a preliminary analysis of its duration of action in the horse by variable interval responding. Variable interval (VI) reinforcement scheduling is a specific type of operant conditioning that is sensitive to drug effects even when overt clinical signs of the drug have diminished. Six horses were conditioned to break a light beam with a head-bobbing movement and this behaviour was reinforced with a reward of clean oats (approximately 30 mg/reinforcement). Initial training procedures included familiarisation with the behavioural equipment and fixed-ratio reinforced scheduling. To establish baseline rates of behaviour, the horses were converted to a variable interval (60 secs) reinforcement...
The effect of drugs used in the treatment of osteoarthrosis on stromelysin (proteoglycanase) of equine synovial cell origin. There is increasing evidence that the proteoglycan-degrading neutral metalloproteinase, stromelysin, is a key enzyme in the pathogenesis of osteoarthrosis. Equine synovial lining cells were stimulated in vitro to produce stromelysin, and phenylbutazone, flunixin, betamethasone, sodium hyaluronate and polysulphated glycosaminoglycan (PSGAG) were tested for their ability to inhibit the action of this enzyme on 14C-labelled casein substrate. Only PSGAG possessed inhibitory activity at concentrations likely to be achieved therapeutically in the equine fetlock joint.
Immunoassay detection of drugs in racing horses. VII. Detection of acepromazine in equine urine and blood by ELISA and PCFIA. We have developed and evaluated a one step enzyme-linked immunosorbent assay (ELISA) test and a particle concentration fluorescence immunoassay (PCFIA) test for acepromazine as part of a panel of pre- and post-race tests for illegal medications in racing horses. These tests are rapid, sensitive and economical and development of the tests occurred in less than seven months. The ELISA test detects acepromazine with an I-50 of about 150 pg/ml. In vivo, it readily detects the presence of acepromazine or its metabolites in equine blood and urine from 8 to 72 hours or longer, respectively, after adm...
In vitro evaluation of a sustained-release veterinary peroral pellet preparation. In a preceding in vivo study in horses, wide interindividual variation was found in the extent of bioavailability and time to reach peak concentration after peroral administration of one specific theophylline sustained-release dosage form. The purpose of the present study was to investigate the factors of potency, the pH of dissolution medium, the enzymes in the dissolution medium, and the crushing of the pellets on in vitro performance. The results show a wide variation in potency for the individual units, an increase in release rate with increasing pH, and an increase in release rate if the ...
The effect of detomidine (Domosedan) on the maintenance of equine pregnancy and foetal development: ten cases. Detomidine was administered throughout 10 pregnancies in eight mares. An intravenous injection of 20 micrograms/kg body weight was given weekly from Day 14 to Day 60 of gestation and thereafter every four weeks until parturition. One mare suffered torsion of the large colon and was destroyed on Day 86; the foetus was normally developed. A further mare aborted at 167 days. The remaining eight pregnancies continued to full term. One foal was delivered by caesarean section because of torticollis and, of the seven foals born spontaneously, one had bilateral upward patellar fixation at one month ol...
Experimental chemotherapy in horses infected with benzimidazole-resistant small strongyles. The presence of benzimidazole-resistant strains of equine small strongyles was confirmed in horses at two properties in north west England by a series of faecal egg counts and larval cultures after treatment with mebendazole. A trail formulation of mebendazole in combination with piperazine citrate gave greater reductions in faecal egg counts than mebendazole alone but was much less effective than pyrantel embonate or dichlorvos.
Molecular mechanics calculation of geometries of NAD+ derivatives, modified in the nicotinamide group, in a ternary complex with horse liver alcohol dehydrogenase. The geometry of seven NAD+ analogues bound to horse liver alcohol dehydrogenase (LADH) modified only in their nicotinamide group, have been studied using AMBER molecular mechanics energy-minimization procedures. Starting geometries were taken from X-ray crystallographic data for NAD+/Me2SO/LADH reported by Eklund and co-workers. In this study the NAD+ analogues were encaged by the constituent amino acids of the enzyme within a range of 0.6 nm from the initial NAD+/Me2SO/Zn2+ complex. The calculational method used is able to rationalize individual substituent effects and to evaluate the essenti...
Platelet function testing in the pony. Platelet isolation techniques and platelet function were evaluated in 35 adult ponies. Platelet recovery from whole blood was consistent and the preparation of platelet rich plasma was facilitated by an enhanced erythrocyte sedimentation rate. All platelet samples aggregated in response to 10 microM ADP. However, concentrations of ADP as high as 100 microM did not elicit significant 14C-serotonin release. Collagen induced irreversible platelet aggregation and 14C-serotonin release in all samples. The threshold dose for collagen in most ponies was 1.5 micrograms. Arachidonic acid (500 microM) f...
Alpha 1-adrenergic-induced airway obstruction in ponies with recurrent pulmonary disease. We examined the response of five ponies with recurrent airway obstruction (principals) and five age- and gender-matched controls to the aerosol alpha-adrenergic agonist phenylephrine after blockade with propranolol and atropine. Measurements were made with principal ponies in clinical remission (period A) and during acute airway obstruction (period B). The blockade had no effect on base-line pulmonary mechanics in control ponies during periods A and B or in the principal ponies during period A. However, in the principal ponies during period B, blockade increased dynamic compliance (Cdyn) and d...
