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.
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...
Severe hypoglycemia attributable to surreptitious injection of insulin in a mare. A mare with signs of hypoglycemia had high serum insulin concentrations before it was euthanatized. High pressure liquid chromatography revealed that the insulin in the mare's blood was of commercial origin. Surreptitious insulin injection has been suspected as the cause of several suspicious deaths of insured horses. The use of high-pressure liquid chromatography should help put an end to this practice.
Neuromuscular and cardiovascular effects of atracurium administered to healthy horses anesthetized with halothane. Neuromuscular and cardiovascular effects of atracurium, a nondepolarizing neuromuscular blocking agent, were evaluated in 10 halothane-anesthetized adult horses. Hind limb digital extensor tension (hoof twitch) was measured with a strain gauge to quantitate the muscle relaxant effects of atracurium. Response of facial muscles was compared with hoof twitch. Five injections of atracurium were given. Initial mean (+/- SEM) dosage of 0.07 +/- 0.01 mg of atracurium/kg of body weight caused 98.6 +/- 0.8% reduction of the preinjection hoof twitch. Subsequent dosages of 0.04 +/- 0.003 mg/kg induced a ...
Effects of flunixin meglumine on jejunal blood flow, motility, and oxygen consumption in ponies. Using isolated autoperfused intestinal segments, the effects of flunixin meglumine administration on systemic arterial blood pressure, jejunal blood flow, vascular resistance, motility, arteriovenous oxygen difference, and oxygen consumption were determined in 10 anesthetized ponies ventilated with a mixture of halothane and oxygen. Saline solution or flunixin meglumine (1.1 mg/kg of body weight) was infused as a single bolus into the left jugular vein. By 10 minutes, flunixin meglumine increased systemic arterial blood pressure and increased intestinal vascular resistance. The jejunal blood f...
Verification of ineffectual activity of ivermectin against adult Onchocerca spp in the ligamentum nuchae of horses. Ivermectin paste formulation (200 micrograms/kg) was administered orally to 27 horses (13 Thoroughbreds and 14 of mixed breeding) to evaluate activity against adult Onchocerca spp in the ligamentum nuchae. Ages, known or estimated, of the horses ranged from 1 to 22 years. Single or multiple doses (1 to 5) of the drug were given to each horse. When multiple doses were administered, the intervals between treatments ranged from 7 to 92 days. At 27 to 171 days after initial treatment (single dose or first of multiple doses), the horses were killed. Some of the horses treated more than once were ki...
Immunoassay detection of drugs in racing horses. VI. Detection of furosemide (Lasix) in equine blood by a one step ELISA and PCFIA. A one step enzyme-linked immunosorbent assay (ELISA) and a particle concentration fluorescent immunoassay (PCFIA) test for furosemide were evaluated as part of a panel of pre- and post-race tests for illegal medication of racing horses. These tests are very sensitive to furosemide with an I-50 for furosemide of about 20 ng/ml. The test is also rapid; an average pre-race complement of 10 samples can be analyzed in 90 minutes or less. The ELISA test results can be read with an inexpensive spectrophotometer, or even by eye. Both the PCFIA test and the ELISA test readily detect the presence of fur...
Possible resistance of small strongyles from female ponies in The Netherlands against albendazole. To determine resistance of small strongyles to albendazole, 3 female ponies (group 1) were grazed on a pasture from May to November 1985 and were treated with 7.5 mg of albendazole/kg of body weight, PO, 2 days before turnout in May and again in June and in July. Three other female ponies (group 2) grazed on a similar pasture from May to July, were treated with 7.5 mg of albendazole/kg, and were removed to another pasture until November. In December, ponies from both groups were treated with 7.5 mg of albendazole/kg, and 8 days later, they were euthanatized and necropsied for a critical test. ...
The effects of corticosteroid administration on the migration, phagocytosis and bactericidal capacity of equine neutrophils. Neutrophil function was evaluated in six clinically normal adult horses, immediately before and 3-6 hours after they were given one dose of hydrocortisone sodium succinate (1 mg/kg body weight). Random migration, stimulated migration to zymosan-activated serum, bacterial phagocytosis and bactericidal capacity of neutrophils were determined in vitro. The mean indices of stimulated migration (net migration and migration ratio) were significantly greater after CS administration (net migration = 62 +/- 23 micron; migration ratio = 11.5 +/- 6.7) than before CS administration (net migration = 44 +/-...
Species-dependent binding of disopyramide enantiomers. Serum protein binding of the basic enantiomers of disopyramide were studied in several animal species. (S)-(+)-Disopyramide was more highly bound than the (R)-(-)-enantiomer to serum protein in the man, gorilla, and pig. The reverse was true in cow serum, and in serum and albumin from sheep. Enantioselective differences in binding were due to differences in association constants. No enantioselective differences in binding were observed in serum protein from horse and goat, or in albumin from cow and pig. Disopyramide was highly bound to two sites on horse albumin. The association constant char...
Efficacy of ivermectin in the oral paste formulation against naturally acquired adult and larval stages of Parascaris equorum in pony foals. The efficacy of ivermectin in oral paste formulation at a dosage of 200 micrograms/kg of body weight was tested against naturally acquired larval and adult stages of Parascaris equorum, in a controlled study. Twenty infected pony foals 18 to 27 weeks of age were randomly allocated to 2 groups of 10 each and were placed in dry lots. Foals in 1 group were given ivermectin on day 0. Necropsies and parasite recoveries from small intestines and lung tissues were performed on 5 foals in each group at 2 weeks after treatment (WAT) and on the remaining foals at 5 WAT. Ivermectin was 100% effective aga...
Objective assessment of detomidine-induced analgesia and sedation in the horse. The effects of detomidine, a veterinary sedative analgesic, were studied in the horse. Novel objective techniques were employed to assess the analgesic and sedative potency of this compound. Intravenous doses of 0.010, 0.020 and 0.040 mg/kg were administered to eight adult Thoroughbred racehorses according to a double-blind crossover design. Analgesia was measured by determining the latency to onset of the skin twitch and hoof withdrawal reflexes following noxious thermal stimulation of the withers and fetlock, respectively. Sedation was assessed by quantifying spontaneous locomotor activity i...
The effect of various antibacterial preparations on the in vitro morphology and chemotactic response of equine neutrophils. Two independent assay systems were used to study the effect of three antibacterial preparations on in vitro morphology and chemotaxis of equine neutrophils. Incubation of neutrophils with high (200 micrograms/ml) and medium (20 micrograms/ml) concentrations of neomycin impaired their response to standard chemoattractants. Trimethoprim/sulfadoxine (0.4/2.0 micrograms/ml-40/200 micrograms/ml) and benzylpenicillin (0.25-25 micrograms/ml) had no effect. Neutrophils collected from geldings 2 and 24 h after neomycin (5 mg/kg) administration had impaired responses to standard chemoattractants. Benzyl...
Adverse reaction to procaine penicillin G in horses. Adverse reactions to intramuscular injections of procaine penicillin G are reported in 11 horses, five of which died. The clinical findings are presented and suggest central nervous involvement in most cases. Post mortem findings in one horse were consistent with anaphylaxis whereas in other cases the clinical findings, duration of treatment, speed of onset and subsequent completion of treatment supports diagnosis of an acute procaine toxicity syndrome.
Development of a novel in vitro equine anthelmintic assay. An in vitro assay involving the use of a horse strongyle (Strongylus edentatus) and the micromotility meter has been developed to test for equine anthelmintic activity. Three commercially available equine anthelmintics (dichlorvos, ivermectin, and pyrantel pamoate) and an investigational drug (p-toluoyl chloride phenylhydrazone) were evaluated in this assay at four concentrations. After a 24-h incubation, greater than or equal to 10 micrograms/ml of all four drug treatments significantly (P less than or equal to 0.05) reduced the motility of ensheathed L-3 S. edentatus larvae, thereby indicati...
Use of a narcotic antagonist (nalmefene) to suppress self-mutilative behavior in a stallion. Nalmefene, an opioid antagonist, caused a decrease in self-mutilative behavior in a 500-kg stallion. Self-mutilative attempts were counted during a control period and on 4 subsequent occasions after the IM administration of 100 mg, 200 mg, 400 mg, or 800 mg of nalmefene. The frequency of self-mutilation decreased with increasing doses of nalmefene and was virtually abolished with the 800-mg dose.
Beta-adrenergic blockade in ponies with recurrent obstructive pulmonary disease. Ponies with recurrent airway obstruction have hyperresponsive airways during acute disease exacerbations but not during clinical remission. We examined the effect of beta-adrenergic blockade with propranolol on airway responsiveness to aerosol histamine in six ponies with recurrent airway obstruction and six age- and gender-matched controls. Measurements were made with principal ponies in clinical remission (period A) and during an acute period of airway obstruction (period B). beta-Adrenergic blockade did not change airway responsiveness, dynamic compliance (Cdyn), or pulmonary resistance (RL...
Determination of clenbuterol and mabuterol in equine plasma by ion-pair liquid chromatography with electrochemical detection. Chromatographic and electrochemical characteristics. A method for the routine determination of the beta-adrenergic drugs clenbuterol and mabuterol in equine plasma has been developed. The drugs were isolated from alkalinized plasma by liquid-liquid extraction. The organic phase was evaporated to dryness and the residue was dissolved in the mobile phase prior to injection. The recoveries were 98% and 95% for clenbuterol and mabuterol, respectively. The drugs were separated by reversed-phase high-performance liquid chromatography and quantitated by a use of a coulometric detector set at +0.75 V vs. the internal reference electrode. The influence o...
Effects of xylazine and acepromazine on bronchomotor tone of anaesthetised ponies. The effects of xylazine (an alpha 2-adrenoceptor agonist) and acepromazine (an alpha-adrenoceptor antagonist) on bronchomotor tone were investigated in seven anaesthetised, apnoeic ponies using a computer aided forced oscillation technique, which separates changes in bronchial calibre from changes in lung volume. Both agents produced bronchodilatation and a decrease in lung volume.