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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 estradiol and progesterone on antistaphylococcal activity of neutrophils from ovariectomized mares. Neutrophils isolated from jugular blood of ovariectomized mares were studied for the effect of estradiol and progesterone on bactericidal activity against Staphylococcus aureus. In experiment 1, neutrophils obtained from 4 mares were tested for bactericidal activity by adding estradiol (43 pg/ml) or progesterone (6.4 ng/ml) to the bactericidal assay. In experiment 2, 3 of the 4 ovariectomized mares were given 2 mg of estradiol, IM, daily for 3 days. Eighteen days after the initial estradiol injection, mares were given 300 mg of progesterone, IM, for 6 days. Neutrophils from these mares were te...
Management of twin conceptuses by manual embryonic reduction: comparison of two techniques and three hormone treatments. One hundred mares carrying twin conceptuses between gestation days (GD) 12 and 30 were assigned to 4 groups. Group-1 mares (n = 20) were given a placebo (sterile saline solution, IV, and sesame oil, IM). Group-2 mares (n = 32) were given a single dose of progesterone (625 mg, IM) in sesame oil. Group-3 mares (n = 28) were given multiple progesterone treatments (625 mg, IM) at 6-day intervals until GD 42. Group-4 mares (n = 20) were given a single treatment of flunixin meglumine (500 mg, IV) and progesterone (625 mg, IM). Each group was further assigned to equal subgroups A and B according to t...
Imidocarb and parvaquone in the treatment of piroplasmosis (Babesia equi) in equids. The therapeutic efficacies of imidocarb and parvaquone were tested against Babesia equi of European origin in carrier horses and for induced acute infections in splenectomized ponies. Imidocarb, at a dosage of 4 mg/kg of body weight, given IM at 72-hour intervals 4 times, was ineffective in eliminating B equi-carrier infection in 9 mature geldings. A single IM administration of 4 mg/kg was not therapeutic in acutely infected splenectomized ponies. When given at 3 different dosages and treatment schedules, parvaquone was ineffective in clearing carrier infection. Parvaquone given IM once at a d...
Effects of physiologic and pharmacologic agents on serum prolactin concentrations in the nonpregnant mare. Four studies were conducted to evaluate the effects of several physiologic and pharmacologic agents on serum prolactin concentrations in the nonpregnant mare. An increase in prolactin measured in response to administration of thyrotropin-releasing hormone (TRH; 50 micrograms, iv) was found not to vary (P = .20) in mares in estrus compared with mares in diestrus (5 to 10 d post-ovulation). Administration in the dopamine receptor blocker, metoclopramide (25 or 100 mg, im), rapidly increased serum prolactin, and the response was dependent on dose administered (total prolactin measured for 420 min...
[Circulatory and respiratory effects of ketamine in horses anesthetized with halothane]. Ketamine (0.3 mg/kg) administered intravenously to 12 halothane anesthetized horses caused a significant respiratory depression during ten minutes when respiration was spontaneous. Significant hemodynamic effects were not observed except for cardiac index. Clinical application was also discussed. Ketamine (0.3 mg/kg) administered intravenously to 12 halothane anesthetized horses caused a significant respiratory depression during ten minutes when respiration was spontaneous. Significant hemodynamic effects were not observed except for cardiac index. Clinical application was also discussed.
Effect of ranitidine on gastric acid secretion in young male horses. Gastric cannulas were placed surgically in 5 young male horses. After a 2-week recovery period, horses were studied once a week. Horses were fasted for 24 hours, and gastric fluid output was collected for 5 continuous hours. Volumes were recorded every 15 minutes, and pH and hydrogen ion concentration were determined in an aliquot from each period. In 10 basal experiments, using 5 horses, volume, pH, and hydrogen ion concentration were continuously variable. Mean acid output was 45.1 +/- 2.02 microEq/15 min/kg (mean +/- SEM). In 6 experiments, using 3 horses, 0.5 mg of ranitidine/kg of body we...
In vitro febantel transformation by sheep and cattle ruminal fluids and metabolism by hepatic subcellular fractions from different animal species. Febantel and one of its main metabolites, febantel sulphoxide, are chemically modified to only a slight extent when incubated in vitro with sheep and cattle ruminal fluids; other major metabolites, fenbendazole and oxfendazole, are respectively, oxidized to oxfendazole and reduced to fenbendazole. Febantel is negligibly metabolized by hepatic cytosol fractions but microsome preparations effect more extensive metabolic transformations. Important differences in this respect were found between microsome preparations from rat, horse, pig, cattle, sheep, chicken and trout livers.
Systemic distribution of blood flow in ponies during 1.45%, 1.96%, and 2.39% end-tidal isoflurane-O2 anesthesia. Effects of 1.1, 1.5, and 1.8 minimal alveolar concentration (MAC) isoflurane-O2 (1.45%, 1.96%, and 2.39% end-tidal isoflurane, respectively) anesthesia on cardiac output, blood pressure, and blood flow to the brain, thyroid glands, adrenal glands, kidneys, and splanchnic organs were examined in 9 healthy isocapnic adult ponies. Tissue blood flows were studied using 15-micron diameter radionuclide-labeled microspheres that were injected into the left ventricle, and comparisons were made with data obtained from ponies in the conscious state. Isoflurane anesthesia caused dose-related reduction in...
Pharmacokinetics of xylazine in ponies: influence of yohimbine. Twenty healthy ponies were given i.v. 1.1 mg/kg of xylazine from 2 manufacturers and the pharmacokinetic parameters calculated from the disposition curves. The disposition curves for the 2 commercial preparations were not different. Yohimbine, an antagonist of the pharmacologic effects produced by xylazine, did not alter the disposition of xylazine in the plasma. A single i.v. bolus of xylazine was completely described in 17 of 20 animals by the biexponential equation: Cp = 1.30e(-0.3955t) + 0.58e(-0.033t) where Cp represents the concentration of xylazine in the plasma at time t (min). The t1/...
Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses. The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two-compartment open model. Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg). Total clearance was also rapid (approximately equal to 13 ml/min.kg). Concentrations of t...
Ethoxyformylation of histidine residues in equine growth hormone. Reactivity of histidine residues in equine growth hormone to ethoxyformic anhydride was studied. The existence of two kinetically different sets was demonstrated: one of them including only the slow reacting histidine 169 (k = 0.164 min-1) and the other containing fast reacting histidines 19 and 21 (k = 0.892 min-1). A correlation between the decrease in the capacity to compete with 125I-labeled hormone for rat liver binding sites and the degree of ethoxyformylation of the fast group was found. Circular dichroism studies indicated no significant conformational changes in the protein with all t...
Effects of polysulfated glycosaminoglycan on chemical and physical defects in equine articular cartilage. The effect of intra-articular polysulfated glycosaminoglycan (PSG) on repair of chemical and physical articular cartilage injuries was evaluated in 8 horses. In each horse, a partial- and a full-thickness articular cartilage defect was made on the distal articular surface of the radial carpal bone. In the contralateral middle carpal joint, a chemical articular cartilage injury was induced by injecting 50 mg of Na monoiodoacetate (MIA). Four of the 8 horses were not treated (controls), and 4 horses were treated by intra-articular injection of 250 mg of PSG into both middle carpal joints once a ...
Immunoassay detection of drugs in horses. I. Particle concentration fluoroimmunoassay detection of fentanyl and its congeners. We investigated the use of particle concentration fluorescence immunoassay (PCFIA) as a technique for drug detection in racing horses. The test was constructed from an antiserum to a carboxyfentanyl-BSA conjugate and carboxyfentanyl linked to b-Phycoerythrin. Using these reagents and a PCFIA apparatus levels of fentanyl as low as 0.1 ng/ml could be detected by the assay. In addition, cross-reactivity studies on this assay showed that the anti-serum cross-reacted well with carfentanil, sufentanil and the methylated analogs of fentanyl. We therefore evaluated the ability of these agents to produ...
Effects of a specific thromboxane synthetase inhibitor in equine endotoxaemia. Thromboxane A2 may play a major role in circulatory shock. In some species, thromboxane synthetase inhibitors have a beneficial effect on shock induced by endotoxin, trauma, sepsis and administration of arachidonate. In some shock models, however, results with thromboxane synthetase inhibitors have been conflicting. The effect of UK-38,485, a selective thromboxane inhibitor, was evaluated in ponies injected with endotoxin intraperitoneally. Four groups of ponies were used to compare the effects of endotoxin alone, UK-38,485 alone, treatment with UK-38,485 before endotoxin challenge and treatme...
Analysis of detomidine in horse blood, plasma and urine samples utilizing a sensitive gas chromatography-mass spectrometry method. Chemical ionization- and electron impact ionization-selective ion monitoring provided a simple and sensitive method for measuring detomidine (Domosedan), a potent sedative-analgesic drug for horses and cattle. Chemical ionization was at least 10 times more sensitive than electron impact ionization. By using propranolol as an internal standard, we found that the recovery of detomidine from the extraction procedure used in this study was greater than 75% for plasma, whole blood, or urine samples. Approximately 68% of detomidine was bound to plasma protein and 53% was bound to red blood cells.
A review of the pharmacology and clinical uses of ivermectin. The avermectins were introduced in 1981 and constitute a potent new class of anthelmintic agents. They are naturally-derived products of microbial action displaying an exceptionally wide range of antiparasitic efficacy against internal and external parasites of domestic animals. This paper reviews their isolation and chemistry, mechanism of action, chemical efficacy and safety in cattle, sheep, swine, horses and dogs.
Effect of halothane, enflurane and isoflurane on bronchomotor tone in anaesthetized ponies. The effects of halothane, enflurane and isoflurane on bronchial calibre were investigated in five anaesthetized ponies using a computer-aided forced airflow oscillation technique to derive specific lower airways conductance (s.Glaw) and expiratory reserve volume (ERV). All the agents tended to increase s.Glaw (indicating bronchodilatation), but ERV was reduced by halothane and enflurane, and increased by isoflurane. It was concluded that the effects of these agents on bronchomotor tone were similar to those which occur in man. However, the reasons for the differences in their effects on ERV co...
Pharmacokinetics of phenolsulfonphthalein in horse and pony mares. Pharmacokinetics of phenolsulfonphthalein (PSP) in horse and pony mares was determined after injection of 1 mg/kg of body weight, IV. A plasma PSP concentration vs time curve was described adequately in horses and ponies by an open, 2-compartment model. There were significant differences in the elimination phase parameters, apparent volume of distribution at steady state, and apparent volume of distribution of horses and ponies. The harmonic mean elimination half-life of PSP in horses was significantly longer (P less than 0.001) than that in the ponies (16.4 and 10.0 minutes, respectively). Th...
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...
