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.
Physiological, biochemical and haematological effects on horses of a phenylbutazone paste. Five matched pairs of horses were used to investigate the biochemical, haematological and general clinical effects of a new dosage schedule of a phenylbutazone paste administered under controlled feeding conditions. One group of horses received a loading dose (8.8 mg/kg) on day 1, followed by doses of 3.3 mg/kg daily on days 2 to 8, 10 and 12 with no treatment on days 9 and 11. The second group received equivalent doses of a placebo paste. Bodyweight, skin temperature, respiratory rate, glutamate dehydrogenase activity, packed cell volume, mean corpuscular volume and neutrophil count were alte...
Some metabolic and hormonal changes associated with general anaesthesia and surgery in the horse. Three different anaesthetic techniques were studied in normal, healthy Thoroughbred or Thoroughbred type horses. These were (a) acepromazine, thiopentone and suxamethonium; (b) acepromazine, glyceryl guaiacolate and a 'half-dose' of thiopentone; and (c) xylazine and ketamine. Anaesthesia was maintained with halothane vaporized in oxygen and nitrous oxide. All horses underwent either laryngeal or body surface surgery. Heart rate, packed cell volume, blood glucose and lactate, plasma non-esterified fatty acids, insulin and cortisol were measured before, during and after surgery. The greatest met...
Rapid reversible immobilization of feral stallions using etorphine hydrochloride, xylazine hydrochloride and atropine sulfate. Forty-eight newly captured free-ranging feral stallions (Equus caballus) from two different locations and six captive stallions were immobilized using combinations of etorphine hydrochloride, xylazine hydrochloride and atropine sulfate with or without acepromazine. Six animals were immobilized twice, 1 mo apart. The drugs were administered either intramuscularly (n = 13) or intravenously (n = 44). Mean immobilization time (+/- SE) after intravenous (i.v.) injection of etorphine, xylazine and atropine was 55 +/- 4 sec (range 20 to 185 sec) compared to 708 +/- 131 sec (range 390 to 1,140 sec) fo...
Plasma lidocaine concentrations in conscious horses after cervicothoracic (stellate) ganglion block with 1% lidocaine HCl solution. Arterial and/or central venous plasma concentrations of lidocaine were determined in 12 nonmedicated adult horses (422 +/- 59 kg of body weight, mean +/- SD) after injecting a 1% lidocaine HCl solution into the cervicothoracic ganglion (CTG). A mean dosage of 2.9 +/- 0.5 mg of lidocaine/kg of body weight was used to induce unilateral CTG blockade in 8 horses and 4.8 +/- 0.8 mg was used to induce bilateral CTG blockade in 4 horses. Blood samples were collected before and at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after injection. The plasma lidocaine concentrations were determined by us...
Comparative analgesia of xylazine, xylazine/morphine, xylazine/butorphanol, and xylazine/nalbuphine in the horse, using dental dolorimetry. Xylazine, morphine, butorphanol, and nalbuphine were evaluated in 5 adult male horses, using dental dolorimetry. Comparisons were made at 30, 60, and 100 minutes after IV drug administration. Peak analgesia and the time to develop peak analgesia also were compared. Xylazine induced a marked increase in the tooth pulp pain threshold measurements as did the xylazine/narcotic combinations. Statistical differences were not detectable between these treatments. Xylazine and xylazine/butorphanol were better analgesics than was butorphanol alone at 30 and 60 minutes. Xylazine resulted in peak analgesi...
HPLC determination and pharmacokinetics of thiabendazole and its major metabolite 5-OH thiabendazole in equine plasma. Separate high performance liquid chromatographic methods were developed for thiabendazole (TBZ) and 5-hydroxy thiabendazole (5-OH-TBZ) determination in horse plasma using 1-methyl-2-phenyl benzimidazole (MPBZ) as an internal standard. In both methods TBZ and 5-OH-TBZ were extracted from plasma using organic solvents, injected on to a C-18 column, and eluents monitored by a fluorescence detector. However, mobile phase composition, extraction solvent as well as detector wavelength differed in the two methods. The linear range for TBZ was 0.02 to 0.77 microgram ml-1 while that for 5-OH-TBZ was 0....
Equine endotoxemia: cardiovascular, eicosanoid, hematologic, blood chemical, and plasma enzyme alterations. Ponies with electromagnetic blood flow transducers implanted around the main pulmonary and left main coronary arteries, were used to evaluate effects of chronic sublethal endotoxin on cardiac output (CO), stroke volume, and left coronary blood flow (LCBF). Plasma thromboxane (TX), as indicated by TXB2, prostacyclin as indicated by 6-keto-prostaglandin (PG) F1 alpha, and hematologic and blood chemical values also were evaluated. Over 24 hours, 2 groups of ponies were given progressively increasing IV and intraperitoneal doses of Escherichia coli lipopolysaccharide (LPS) at 0, 6, 12, and 18 hour...
Calmodulin-mediated adenylate cyclase from mammalian sperm. Calmodulin (CaM), the calcium binding protein that modulates the activity of a number of key regulatory enzymes, is present at high levels in sperm. To determine whether CaM regulates adenylate cyclase in mammalian sperm, the actions of EGTA and selected CaM antagonists on a solubilized adenylate cyclase from mature equine sperm were examined. The activity of equine sperm adenylate cyclase was inhibited by EGTA in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of 2 mM. Equine sperm adenylate cyclase was also inhibited in a concentration-dependent manner by...
Evaluation of fenbendazole for larvacidal effect in experimentally induced Parascaris equorum infections in pony foals. Fifteen pony foals were inoculated with 1,500 +/- 298.7 infective Parascaris equorum eggs. The foals were assigned to 3 treatment groups. Treatments included 10 mg of fenbendazole/kg given once on postinoculation day (PID) 11, 10 mg of fenbendazole/kg given daily on PID 11 to 15, and no treatment (controls). The foals were euthanatized on PID 25 and examined for P equorum larvae in the small intestine, lungs, and liver. Significantly (P less than 0.05) lower mean numbers of P equorum larvae were found in the small intestine of foals treated on PID 11 to 15 (1.4 [range, 0 to 6]) than in the sma...
Atrial fibrillation in a pregnant mare: treatment with quinidine sulfate. Atrial fibrillation in a pregnant, lactating, 15-year-old mare nursing a 70-day-old foal was converted to normal sinus rhythm, using quinidine sulfate. The maximum concentration of quinidine was 4.3 mg/L in the mare's milk and was 2.6 mg/L in the mare's serum. Treatment with quinidine did not interrupt the pregnancy. Six months after treatment, the mare developed acute volvulus of the large colon and died. At necropsy, the mare did not have macroscopic or microscopic cardiac lesions. The fetus was macroscopically and histologically normal.
Actions of non-steroidal anti-inflammatory drugs on equine leucocyte movement in vitro. The direct effects of four non-steroidal anti-inflammatory drugs (NSAIDs) on equine polymorphonuclear (PMN) and mononuclear (MN) leucocyte movement were investigated using two in vitro assay systems. The Boyden chamber microfilter technique measures both chemokinetic and chemotactic locomotion, and the agarose microdroplet assay measures solely chemokinesis. Zymosan-activated plasma (ZAP) and the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as standard chemoattractants for PMN and MN leucocytes, respectively. The actions of six concentrations of each NSAID, indome...
Mixed venous oxygen tension as an estimate of cardiac output in anesthetized horses. The relationship between mixed venous O2 tension and cardiac output was studied in six anesthetized horses breathing 100% O2. Cardiac output, O2 consumption, mean arterial pressure, heart rate, and arterial and venous blood gases were measured after administration of xylazine or dobutamine to horses in lateral, sternal, and dorsal recumbencies. After approximately 3 hours, Escherichia coli endotoxin was administered while horses were in dorsal recumbency, and all measurements were repeated. Relationships between cardiac index (CI) and PVO2, heart rate, mean arterial pressure, jugular PVO2, and...
Transmural coronary vasodilator reserve and flow distribution during maximal exercise in normal and splenectomized ponies. 1. Transmural distribution of myocardial blood flow was studied using 15 micron diameter radionuclide-labelled microspheres in six normal ponies and nine splenectomized ponies at rest, and during maximal exercise performed without as well as with adenosine infusion (3 microM kg-1 min-1). The splenectomized ponies were also studied during submaximal exercise performed at 75% of the workload. 2. Maximal exertion in normal ponies increased heart rate (348%), mean arterial blood pressure (40.9%), rate-pressure product (563%), arterial O2 content (43.2%), and mean pulmonary artery pressure (247%). ...
The induction of equine laminitis with an aqueous extract of the heartwood of black walnut (Juglans nigra). An aqueous extract of the heartwood of black walnut (Juglans nigra) was given via stomach tube to 10 horses. Eight developed Obel grade 3 or 4 laminitis within 12 hr. Limb edema and mild sedation were the only other clinical signs observed. One horse was euthanized due to severe signs. The other 7 recovered within 6 days. Gas chromatography/mass spectrometry of aqueous extracts of heartwood, bark and nuts of black walnut identified juglone in the bark and nuts, but not in the heartwood. It was concluded that the aqueous extract of heartwood is laminogenic to horses, but the active ingredient i...
Skeletal muscle perfusion during prolonged 2.03% end-tidal isoflurane-O2 anesthesia in isocapnic ponies. Effects of 1.55 minimum alveolar concentration isoflurane O2 anesthesia (2.03% end-tidal isoflurane) on blood flow in the up-(nondependent) and down-(dependent) positioned skeletal muscles were studied at 60, 120, and 180 minutes in 6 healthy isocapnic ponies in right lateral recumbency on a nonpadded hardwood floor. Measurements were made, using 15-micron diameter radionuclide-labeled microspheres injected into the left ventricle, and comparisons were made with data obtained from ponies in the conscious state. Isoflurane administration caused a sharp reduction in cardiac output and systemic p...
Inflammation: a clinical perspective. The Ciba-Geigy Prize for Research in Animal Health. The cardinal signs of acute inflammation have been recognised for almost 2000 years, but it is only in the last hundred years that significant progress has been made in understanding the underlying cellular response. Our knowledge of the chemical messengers which regulate and in some cases lead to persistence of the inflammatory process is, as yet, incomplete, but it is hoped that further research at this level will lead to the development of more effective therapeutic agents.
Applications of equine models of acute inflammation. The Ciba-Geigy Prize for Research in Animal Health. The development of reproducible models of acute inflammation in which inflammatory heat is easily quantified and from which inflammatory exudate is readily harvested has facilitated studies in the horse of the actions of steroids and non-steroidal anti-inflammatory drugs (NSAIDS). Blockade of the synthesis of eicosanoids and suppression of inflammatory heat by clinical dose rates of NSAIDS suggests a causal link between the two events and provides further evidence for a role of these compounds in acute equine inflammation. The tendency for enolic and carboxylic acids NSAIDS to accumulate in in...
Cellular aspects of inflammation. The Ciba-Geigy Prize for Research in Animal Health. The migration of leucocytes to sites of acute and chronic inflammation is an event of central importance to the maintenance of inflammatory processes; extravascular leucocytes are responsible for generating chemical mediators of inflammation and the phagocytosis of particulate matter. They may also be involved in the conversion of acute to chronic inflammatory lesions. Leucocytes are attracted to sites of tissue injury by a range of chemoattractants. This paper describes the development of a method for separating on Percoll gradients purified populations of equine polymorphonuclear and mononuc...
Metabolic and hormonal responses to neuroleptanalgesia (etorphine and acepromazine) in the horse. Administration of etorphine and acepromazine to horses was associated with an increase in haematocrit, blood glucose, blood lactate and plasma non-esterified fatty acids (NEFA). The rise in plasma NEFA was most striking following injection of the antagonist diprenorphine and could contribute to the production of cardiac arrhythmias. Plasma insulin was depressed at the end of surgery. These changes, plus profuse sweating, are indirect evidence of strong sympathetic stimulation. Plasma cortisol did not alter significantly due to wide individual variation. Venous blood pH fell, reflecting the ris...
Effect of povidone-iodine on in vitro locomotion of equine neutrophils. Incubation of equine neutrophils with povidone-iodine solutions of greater than or equal to 0.2 per cent resulted in total inhibition of migration under agarose. This was caused by the cytotoxic effects of the solutions as shown by pyknosis and cell lysis. Lower concentrations of povidone-iodine, however, did not adversely affect neutrophil viability or locomotion.
Evaluation of ivermectin paste in the treatment of ponies for Parascaris equorum infections. Twenty ponies less than 18 months of age and infected with Parascaris equorum were treated with either 0.2 mg of ivermectin/kg of body weight (n = 10) or a placebo (n = 10; controls). Five control and 5 ivermectin-treated ponies were euthanatized 14 and 35 days after treatment, respectively. At necropsy, the small intestinal contents, lungs, and liver were examined for larvae and/or adult P equorum. Significantly (P less than 0.02) higher mean total numbers of P equorum were found in the small intestinal contents of the controls on day 14 (51) and on day 35 (21) than in the ivermectin-treated ...
Imipramine-induced erection, masturbation, and ejaculation in male horses. Imipramine hydrochloride was administered to five male horses (400-500 kg b.wt.): one experienced young stallion, two mature normal breeding stallions, one 5-year-old stallion with erection and ejaculatory dysfunction, and one long-term castrated male horse. Oral imipramine treatment (100 to 600 mg, twice daily) led to frequent erection and masturbation while at rest in the stall in a nonsexual context. Intravenous imipramine treatment over a range of doses (50 to 1000 mg) similarly induced erection and masturbation in all animals. Erection typically occurred within 10 minutes after injection,...
Absorption of neomycin from the equine uterus: effect of stage of oestrous cycle and volume of vehicle. Plasma concentrations of neomycin were measured following intrauterine infusion of 3.3 mg/kg bodyweight neomycin sulphate. Mares in oestrus absorbed approximately 6 per cent of neomycin infused whereas mares in a luteal phase absorbed 56 per cent. The volume of infusate also affected absorption as increased volume resulted in decreased absorption. The decreased absorption both during oestrus and when large volumes were used was probably due to reflux of antibiotic through the cervix.
Responses of horses to acepromazine maleate administered orally in a paste. The effects of acepromazine maleate (ACP), given orally in a paste form, were examined in six standard-bred geldings over a 12 hour period. Three dose rates, zero (placebo paste), 0.13 mg kg-1 and 0.26 mg kg-1, given before or after feeding, were investigated. The data were divided into two sampling periods for analysis, one from zero to 120 minutes and the other from four to 12 hours. Sedation was assessed by a score (TS score) based on general appearance, anal sphincter relaxation and penile protrusion. This TS score was significantly elevated 40 minutes after dosing with ACP, irrespective o...
Cardiovascular effects of intravenous sodium penicillin, sodium cefazolin, and sodium citrate in awake and anesthetized horses. Sodium penicillin, sodium cefazolin, and sodium citrate were administered to six adult horses on separate occasions, when awake and during anesthesia. The order of administration was randomized and studies were separated by a minimum of 7 days. Arterial blood pressure decreased significantly (less than 0.05) from control 5 minutes after intravenous (IV) sodium penicillin in awake and anesthetized horses. Systolic arterial blood pressure remained significantly (less than 0.05) decreased 10 minutes after IV sodium penicillin in anesthetized horses. Sodium cefazolin and sodium citrate did not sig...
Effects of multiple low doses of flunixin meglumine on repeated endotoxin challenge in the horse. Previous work has shown repeated low doses of flunixin meglumine (FM) inhibit thromboxane production in normal horses. Enhanced concentrations of thromboxane in serum occurred after the drug therapy was discontinued. Our study was performed to evaluate the effects of low doses of FM in horses repeatedly challenged with endotoxin. Group I horses received E. coli endotoxin (0.1 microgram/kg IV) at 0 and 90 h. Group II horses received endotoxin and were also treated with FM (0.25 mg/kg IV) at 2, 10, 18, 26, 34, and 42 h after the initial administration of endotoxin. Clinical signs of endotoxemia ...
Development of an enzyme-linked immunosorbent assay for the detection of phenothiazine tranquillisers in horses. An acepromazine (ACP) hapten was synthesised, coupled to bovine serum albumin and injected into a horse to produce antibodies to the drug. A competitive ELISA was developed whereby ACP attached to the solid phase via lysozyme competed with free ACP present in phosphate buffered saline, horse serum or horse urine for limiting amounts of antibody. The assay could detect the presence of ACP and, or, some of its metabolites in horse urine for at least 25 hours after intravenous injection of 0.1 mg kg-1 ACP maleate, but because of non-specific interference, horse serum could not be used. As little ...
2-Hydroxypyridine-N-oxides: effective new chelators in iron mobilisation. The 2-hydroxypyridine-N-oxide derivatives, 2-hydroxypyridine-N-oxide, 2,4-dihydroxypyridine-N-oxide, 2-hydroxy-4-methoxypyridine-N-oxide and 2-hydroxy-4-(2'-methoxyethoxy)pyridine-N-oxide have been shown to remove iron from human transferrin and horse spleen ferritin at pH 7.4 at levels higher than those caused by desferrioxamine. Their reactions with transferrin were mainly biphasic and took 2-5 h to reach completion but iron mobilisation from ferritin was slower and their reactions continued after 40 h of incubation. The intraperitoneal and intragastric administration of 2,4-dihydroxypyridin...