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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.
Combination deworming for the control of double-resistant cyathostomin parasites – short and long term consequences. Equine cyathostomin are pervasive gastrointestinal parasites with wide-spread resistance to the benzimidazole and tetrahydropyrimidine drug classes worldwide. Combination deworming has been proposed as a more sustainable parasite control strategy. Simulation studies have found combination deworming to be effective in controlling drug resistant ovine trichostrongylid parasites. One equine study demonstrated an additive effect of a combination of oxibendazole and pyrantel pamoate against cyathostomins. However, this is the only equine study evaluating combination therapy, and the effects of repe...
Inhibition of 5α-reductase alters pregnane metabolism in the late pregnant mare. In the latter half of gestation in the mare, progesterone concentrations decline to near undetectable levels while other 5α-reduced pregnanes are elevated. Of these, 5α-dihydroprogesterone and allopregnanolone have been reported to have important roles in either pregnancy maintenance or fetal quiescence. During this time, the placenta is necessary for pregnane metabolism, with the enzyme 5α-reductase being required for the conversion of progesterone to 5α-dihydroprogesterone. The objectives of this study were to assess the effects of a 5α-reductase inhibitor, dutasteride on pregnane metab...
Maintenance of equine anaesthesia over the last 50 years: Controlled inhalation of volatile anaesthetics and pulmonary ventilation. In the first edition of this journal, Barbara Weaver wrote a review titled 'Equine Anaesthesia', stating that, at that time, it was quickly becoming accepted practice that many horses were being anaesthetised 'by essentially similar procedures, i.e. premedication, induction and then maintenance by controlled inhalation'. To celebrate the 50th anniversary of the first edition of this journal, this review covers the development of understanding and practice of inhalational anaesthesia and controlled ventilation in horses over the last 50 years. We review how the perceived benefits of halothane ...
Tall fescue ergot alkaloids are vasoactive in equine vasculature. Mares grazing endophyte-infected () tall fescue () typically exhibit reproductive dysfunction rather than problems associated with peripheral vasoconstriction as a primary sign of the fescue toxicosis syndrome. Research using Doppler ultrasonography demonstrated that consumption of endophyte-infected tall fescue seed causes measurable vasoconstriction in the medial palmar artery. The objective of this study was to evaluate contractile responses of medial palmar artery and vein to increasing concentrations of various tall fescue alkaloids. Medial palmar arteries and veins were collected immedia...
Tamoxifen induces apoptotic neutrophil efferocytosis in horses. Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effec...
In vitro growth inhibition of Theileria equi by bumped kinase inhibitors. Theileria equi, an etiologic agent of equine piroplasmosis, is a tick-transmitted hemoprotozoan of the phylum Apicomplexa. Recent outbreaks of piroplasmosis in the United States have renewed interest in safe and effective treatment options. Although imidocarb dipropionate (IMD) is the drug of choice for clearance of T. equi, adverse reactions and recently documented resistance support the need for alternative therapeutic strategies. The recently described bumped kinase inhibitors (BKIs) are a new class of compounds that could potentially be used as safe and effective alternatives to IMD. In an...
Cathepsin K Localizes to Equine Bone In Vivo and Inhibits Bone Marrow Stem and Progenitor Cells Differentiation In Vitro. Selective inhibition of Cathepsin K (CatK) has a promising therapeutic potential for diseases associated with bone loss and osseous inflammation, such as osteoarthritis, periodontitis, and osteoporosis. In horses, stress-related bone injuries are common and accompanied by bone pain and inflammation resulting in excessive bone resorption and periostitis. VEL-0230 is a highly selective inhibitor of CatK that significantly decreased bone resorption and increased bone formation biomarkers. The goal of this study was to demonstrate the presence of CatK in equine bone and a simultaneous influence on...
Clinical usefulness of intravenous constant rate infusion of fentanyl and medetomidine under sevoflurane anesthesia in Thoroughbred racehorses undergoing internal fixation surgery. A total of 20 racehorses with longitudinal fractures underwent internal fixation surgery under sevoflurane anesthesia combined with infusion of medetomidine (3 µg/kg/hr) alone (10 horses, group M) or medetomidine and fentanyl (7 µg/kg/hr) (10 horses, group FM). In group FM, the end-tidal sevoflurane concentration during surgery was maintained significantly lower than in group M (2.8-2.9% for group M vs. 2.2-2.6% for group FM, P<0.01). The mean arterial blood pressure was maintained over 70 mmHg using dobutamine infusion (group M, 0.36-0.54 µg/kg/min; group FM, 0.27-0.65 µg/kg/min), and ...
The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses. To compare the efficacy and duration of effect of three local anesthetics on corneal sensitivity when administered subconjunctivally in horses. Methods: Eight healthy adult horses. Methods: A randomized, masked, crossover study design was used, with a two-week washout period between trials. The subconjunctival space of the randomly selected eye was injected with 0.2 mLs of bupivacaine (0.5%), lidocaine (2%), mepivacaine (2%), or saline. All horses received each medication once. The contralateral eye served as a control. The corneal touch threshold (CTT) was measured in both eyes with a Cochet-...
The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV’s). This study investigated in vitro effects of freshwater alga water extract enriched during a biosorption process in Cr(III) trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs) and extracellular microvesicles (MVs) in equine metabolic syndrome-affected horses. Chemical characterisation of natural was performed with special emphasis on: vitamin C, vitamin E, total phenols, fatty acids, free and protein-bound amino acids as well as measured Cr in algal biomass. To examine the influence of water extracts, in vitro viability, oxidative stress factor...
Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation. Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported. Objective: The aim was to study characteristics of induced AF and its modification by fl...
Pharmacokinetics of intravenous lithium chloride and assessment of agreement between two methods of lithium concentration measurement in the horse. Pharmacokinetics of lithium chloride (LiCl) administered as a bolus, once i.v. have not been determined in horses. There is no point-of-care test to measure lithium (Li ) concentrations in horses in order to monitor therapeutic levels and avoid toxicity. Objective: To determine the pharmacokinetics of LiCl in healthy adult horses and to compare agreement between two methods of plasma Li concentration measurement: spectrophotometric enzymatic assay (SEA) and inductively coupled plasma mass spectrometry (ICP-MS). Methods: Nonrandomised, single exposure with repeated measures over time. Methods: ...
Effects of transdermal lidocaine or lidocaine with prilocaine or tetracaine on mechanical superficial sensation and nociceptive thermal thresholds in horses. To evaluate the transdermal local anaesthetic effect of lidocaine or lidocaine combined with prilocaine or tetracaine in horses. Methods: Experimental, randomized study. Methods: A total of five healthy adult warmblood horses. Methods: Horses were clipped bilaterally at the withers, cranial saddle area and caudal saddle area. Baseline measurements for mechanical superficial sensation via von Frey filaments and nociceptive thermal thresholds were performed. A 5% lidocaine patch (12 hour exposure, treatment L), a lidocaine/prilocaine cream (each 2.5%, treatment LP) and a lidocaine/tetracaine cre...
[Antimicrobial susceptibility in isolates of Streptococcus equi subsp. equi from Buenos Aires province, Argentina]. Streptococcus equi subsp. equi is the etiologic agent of strangles, an infectious disease affecting the upper respiratory tract and head and neck lymph nodes of equines. Routine antimicrobial therapy includes penicillin (PEN) as antibiotic of first choice. Streptococci are usually susceptible to PEN and only a few antimicrobial studies had been performed. The aim of this work was to study the antimicrobial susceptibility profile of S. equi from Buenos Aires, Argentina. Ninety-two isolates were studied by the single disk method to PEN, cefotaxime, erythromycin (ERY), tetracycline, enrofloxacin ...
In vivo evaluation of effects of sedation on results of acoustoelastography of the superficial digital flexor tendons in clinically normal horses. OBJECTIVE To assess the effects of sedation on results of acoustoelastography of the superficial digital flexor tendons (SDFTs) in clinically normal horses. ANIMALS 27 clinically normal horses. PROCEDURES For each horse, the pathology index (PI) for the SDFT of each thoracic limb was determined by use of acoustoelastography at 4 locations (5, 10, 15, and 20 cm distal to the accessory carpal bone). Horses were evaluated before and after they were sedated with a combination of detomidine hydrochloride (0.01 mg/kg, IV) and butorphanol tartrate (0.01 mg/kg, IV). A repeated-measures ANOVA was used ...
Preliminary investigation of orally administered benazepril in horses with left-sided valvular regurgitation. Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation. Objective: Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation. Methods: Prospective, randomised double-blind, placebo-controlled trial. Methods: Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug...
Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses. OBJECTIVE To determine the safety of topical administration of 1% atropine ophthalmic solution in healthy horses by objectively measuring gastrointestinal transit time. DESIGN Randomized, masked, controlled crossover study. ANIMALS 6 adult geldings. PROCEDURES Horses were randomly assigned (3/group) to first receive topical treatment of the left eye with 1% atropine or artificial tears solution; the right eye was left untreated. After 24 hours of treatment every 6 hours, 200 nontoxic beads were administered to each horse via nasogastric intubation and treatment frequency was decreased to every...
Effects of selective α2 -adrenergic receptor agonists on electrical field-stimulated contractions of isolated bronchi in horses. We investigated the effects of different selective α -adrenergic receptor (AR) agonists (detomidine, medetomidine, xylazine, and brimonidine) on the contractions of horse-isolated bronchi induced by electrical field stimulation (EFS) and by carbachol. No effects were observed on the contraction induced by carbachol, while α -AR agonists reduced EFS-evoked contractions in a concentration-related fashion. The rank order of potency (pD ) was brimonidine (7.40 ± 0.20) >medetomidine (7.09 ± 0.24) >detomidine (6.13 ± 0.55) >xylazine (4.59 ± 0.16). The maximal effects (E ) were -56.3% ...
Expression of inflammatory and structural matrix genes in synovial fluid following intra-articular administration of isoflupredone acetate to exercised horses. Intra-articular use of corticosteroids is commonplace in performance horses. Isoflupredone acetate (IPA) is one of four Food and Drug Administration approved corticosteroids for intra-articular use in horses. The lack of published reports describing the efficacy and duration of effects of this drug warrant further study. Objective: To assess the effects of intra-articular administration of IPA on the expression of selected anti- and pro-inflammatory and structural matrix genes following intra-articular administration to exercised Thoroughbred horses and to correlate these effects with drug con...
Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin E2 concentrations. In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups....
Equine Intestinal Mucosal Pathobiology. The equine intestinal mucosa is intimately involved in maintaining homeostasis both on a systemic level by controlling extracellular fluid movement and at the local level to maintain barrier function. Horses are particularly susceptible to the clinical syndrome of colic, with the most severe cases involving strangulating obstruction that induces ischemia. Because of the mucosal vascular architecture, the mucosal epithelium is particularly susceptible to ischemic injury. The potential for reperfusion injury has been investigated and found to play a minimal role. However, inflammation does affec...
Neosaxitoxin, a Paralytic Shellfish Poison toxin, effectively manages bucked shins pain, as a local long-acting pain blocker in an equine model. Local anesthesia is an effective method to control pain. Neosaxitoxin is a phycotoxin whose molecular mechanism includes a reversible inhibition of voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. The present study was designed to evaluate the clinical efficacy of Neosaxitoxin as a local long-acting pain blocker in horse bucked shins, and it was found to effectively control pain. While Neosaxitoxin and Gonyautoxin, another Paralytic Shellfish Poison (PSP) toxin, have been successfully used in humans as long-lasting pain blockers, this finding marks the fir...
In vitro evaluation of ivermectin, moxidectin, albendazole and pyrantel against cyathostomins of horses. Cyathostomins are the most prevalent nematodes of horses, and multidrug resistance has been reported worldwide. There is a need to implement alternative drug monitoring analytical tests. The objective of this study was to determine the consistency (5 repetitions) of the larval migration on agar test (LMAT) using ivermectin, moxidectin, pyrantel or albendazole against cyathostomin infective-stage larvae in eight different concentrations. LMAT showed a strong coefficient of determination (R2 > 0.91), between the test repetitions (n=5). The average 50% effective concentration (EC50) for iverme...
Local anaesthetics or their combination with morphine and/or magnesium sulphate are toxic for equine chondrocytes and synoviocytes in vitro. Chondrotoxic effects of local anaesthetics are well reported in humans and some animal species but knowledge on their toxic effects on synoviocytes or equine chondrocytes or the effects on cellular production of inflammatory cytokines is limited. The purpose of this study was to evaluate the in vitro effects of local anaesthetics, morphine, magnesium sulphate (MgSO4) or their combinations on cell viability and pro-inflammatory cytokine gene expression of equine synoviocytes and chondrocytes. Equine synoviocytes and cartilage explants harvested from normal joints in a co-culture system were exp...
Hemodynamics of the corpus luteum in mares during experimentally impaired luteogenesis and partial luteolysis. The aim of the current project was to characterize the luteal vascularity and the plasma concentrations of progesterone (P4), prolactin (PRL) and 13,14-dihydro-15-keto-PGF (PGFM) in mares with luteal disturbances during early and mid-diestrus. In Experiment 1, twenty-one mares were treated with 2 mL of 0.9% NaCl, or 1 mg Dinoprost, or 10 mg Dinoprost on day two after ovulation (Control-D2, 1/10PGF-D2 and PGF-D2 groups, respectively; n = 7 mares/group). In Experiment 2, similar treatments were performed eight days post-ovulation using a different cohort of 21 mares (Control-D8, 1/10PGF-D8 ...
Effectiveness of furosemide in attenuating exercise-induced pulmonary haemorrhage in horses when administered at 4- and 24-h prior to high-speed training. Due to the high prevalence of EIPH in racehorses and its potential impact on the horse's health, furosemide administration is permitted up to 4-h prior to post time in most North American racing jurisdictions. Anecdotal reports suggest that administration of furosemide 24-h prior to strenuous exercise may be equally effective in decreasing the severity of EIPH. Objective: To 1) compare the efficacy of furosemide in reducing the presence and severity of EIPH when administered 4- or 24-h prior to strenuous exercise 2) characterise electrolyte and blood parameters following administration of furo...
Half a century of equine reproduction research and application: A veterinary tour de force. Over the past 50 years, per season pregnancy rate in Thoroughbred mares have risen from 70 to >90% and foaling rates from 55 to >80%. Some of the significant pharmacological treatments and diagnostic methods which have driven this marked improvement in breeding efficiency are reviewed. They include the application of artificial lighting to hasten the onset of ovulatory oestrous cyclicity in early Spring, rapid steroid hormone assays to aid in determining the stage and normality of the mare's cycle, prostaglandin analogues, synthetic progestagens and Gonadotrophin-releasing Hormone (GnRH) anal...
Xylazine infusion in isoflurane-anesthetized and ventilated healthy horses: Effects on cardiovascular parameters and intestinal perfusion. To investigate the effects of a xylazine infusion during isoflurane anesthesia on global perfusion parameters and gastrointestinal oxygenation and microperfusion, 8 adult warmblood horses were sedated with xylazine and anesthesia induced with midazolam and ketamine. Horses were mechanically ventilated during anesthesia. After 3 h of stable isoflurane anesthesia (FIso 1.3 Vol %), a xylazine infusion with 1 mg/kg body weight (BW) per hour was started for 1 h and then stopped. Before, during, and after xylazine infusion, heart rate (HR), arterial blood pressure (MAP), cardiac output (CO), central...
Pulmonary disposition and pharmacokinetics of minocycline in adult horses. OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration. ANIMALS 7 healthy adult horses. PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL ...
Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of Acutely Induced Atrial Fibrillation in Horses. Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or noncardiac toxicity. Efficacy can be improved by combining 2 compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined. Dofetilide, ranolazine, and a combination of these were administered in 4 incremental dosing regimens to horses with acutely ...
