Topic:Drug
The topic of drugs and horses encompasses the study of various pharmacological agents used in equine medicine for therapeutic purposes. This includes the administration of medications for pain management, disease treatment, and performance enhancement. The pharmacokinetics and pharmacodynamics of drugs in horses are key areas of research, as they determine the absorption, distribution, metabolism, and excretion of these substances. Additionally, the topic covers the detection and regulation of substances in competitive equestrian sports to ensure fair play and animal welfare. This page compiles peer-reviewed research studies and scholarly articles that explore the effects, safety, and regulatory aspects of drug use in equine health and performance.
Comparison of Recovery Quality Following Medetomidine versus Xylazine Balanced Isoflurane Anaesthesia in Horses: A Retrospective Analysis. Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was used: sedation with 7 µg·kg medetomidine or 1.1 mg·kg xylazine, anaesthesia induction with ketamine/diazepam, maintenance with isoflurane and 3.5 µg·kg·h medetomidine or 0.7 mg·kg·h xylazine, and sedation after anaesthesia with 2 µg·kg medetomidine or 0.3 mg·kg xylazine. Recovery was timed and, using vi...
Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development. There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral adm...
Increase of Adverse Events After Intravenous Injection of Gentamicin in Horses Between 2015 and 2017-From Marketing Authorization Holder’s Point of View. Between 2015 and 2017, a marked increase of anaphylactic-like reactions after intravenous administration of gentamicin was observed first in horses and, later, also in humans. This worldwide issue led to safety measures including product recalls and safety warnings. Here, a German Marketing Authorization Holder (MAH) of an early and intensely affected veterinary product containing gentamicin describes the clinical approach of the company to analyze the root cause and identify the causative agent in the active pharmaceutical ingredient (API). The pharmacovigilance data of the MAH are presented,...
Gentamicin-induced sensorineural auditory loss in healthy adult horses. Irreversible sensorineural auditory loss has been reported in humans treated with aminoglycosides but not in horses. Objective: Investigate if auditory loss occurs in horses treated using the recommended IV daily dosage of gentamicin for 7 consecutive days. Methods: Ten healthy adult horses (7-15 years; females and males, 5 each). Methods: Prospective study. Physical and neurological examinations and renal function tests were performed. Gentamicin sulfate was administered at a dosage of 6.6 mg/kg via the jugular vein on alternating sides for 7 days. Gentamicin peak and trough concentratio...
Constitutive and differential expression of transport protein genes in Parascaris univalens larvae and adult tissues after in vitro exposure to anthelmintic drugs. The equine roundworm Parascaris univalens has developed resistance to the three anthelmintic substances most commonly used in horses. The mechanisms responsible for resistance are believed to be multi-genic, and transport proteins such as the P-glycoprotein (Pgp) family have been suggested to be involved in resistance in several parasites including P. univlaens. To facilitate further research into the mechanisms behind drug metabolism and resistance development in P. univalens we aimed to develop an in vitro model based on larvae. We developed a fast and easy protocol for hatching P. univalens...
Evaluation of corneal anaesthesia after the application of topical 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine in normal horses. To compare the corneal anaesthetic effect of 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine on normal equine eyes. Methods: Prospective, blinded crossover study. Methods: A group of 10 clinically healthy horses. Methods: Corneal sensitivity was determined in each eye by measuring corneal touch threshold (CTT). The study had three phases. Each subject was randomly given one of the three treatments followed by a 72 hour washout period. Every horse received all treatments. Baseline CTT was recorded prior to anaesthetic instillation (T0) then CTT was measured 5 and 10 minutes after (T1 and ...
Pharmacokinetic properties of metamizole active metabolites in Northeastern Brazilian donkeys (Equus asinus). Metamizole (MT), also known as dipyrone, is an analgesic and antipyretic drug labeled for use in humans and domestic animals in some countries. As with other drugs, the administration of MT in donkeys is based on studies carried out with horses. In the present report, we aimed to determine the pharmacokinetics of the two main metamizole active metabolites (N-methyl-4-aminoantipyrine [MAA] and 4-aminoantipyrine [AA]) following 10 (M ) and 25 mg/kg (M ) IV metamizole doses in Northeast Brazilian donkeys (n = 10). Blood was collected at predetermined times within over 48 h; MAA and AA plasma ...
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses. The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten ( = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9...
Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both. Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or ...
Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation. Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administratio...
The Rho kinase (ROCK) inhibitor Y-27632 reduces the β2-adrenoceptor density but enhance cAMP formation in primary equine bronchial epithelial cells. The present study addresses the effect of the Rho-kinase (ROCK) inhibitor Y-27632 on the β-adrenoceptor density and β-agonist-stimulated intracellular second messenger cAMP formation in primary equine bronchial epithelial cells (EBEC). Y-27632 significantly decreased the β-adrenoceptor number (B) without markedly affecting the receptor affinity (dissociation constant, K) to the radioligand [I]-iodocyanopindolol (ICYP). In contrast, Y-27632 augmented the β-agonist-stimulated intracellular cAMP production. Herein, Y-27632 markedly increased the maximal cAMP responses (E) (isoproterenol >...
Pharmacokinetics of dipyrone in horses: A multi-dose, dose escalation study. Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30 mg/kg q8h, 30 mg/kg q12h, 60 mg/kg q8h, and 90 mg/kg q12h]) and treated for nine consecutive da...
Ivermectin treatment in lactating mares results in suboptimal ivermectin exposure in their suckling foals. The management of equine strongyles has become problematic over the last decade because of an increased prevalence of drug-resistant isolates worldwide. Therapeutic options are therefore limited, leaving macrocyclic lactones as the most often effective drug class. However, their lipophilic properties result in a long-lasting elimination that could favour drug resistance selection. As a result, ivermectin treatment in lactating mares could promote suboptimal exposure of their foal parasites to ivermectin, thereby selecting for more resistant worms. To test for this putative transfer, we selecte...
Accelerometric Evaluation of the Locomotor Pattern After Administration of Morphine in Conscious Healthy Horses. The objective of the present study was to compare, using accelerometry, the gait changes produced after administration of a dose of 0.2 mg/kg of morphine at the walk in healthy horses. Six mature horses were used, and all animals received two different treatments with, at least, two weeks interval in between. Treatments administered consisted of a single dose of 10 ml of saline solution or a total of 0.2 mg/kg of morphine diluted in 10 ml of saline solution. A three-dimensional accelerometric device was used to collect data continuously while horses were walking. The walking test was performed...
Evaluation of intramuscular anesthetic protocols in healthy domestic horses. To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. Methods: Randomized, blinded, three-way crossover prospective design. Methods: A total of eight healthy adult horses weighing 470-575 kg. Methods: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg), ketamine (1 mg kg) and detomidine (0.04 mg kg) (treatment TKD); ketamine (3 mg kg) and detomidine (0.04 mg kg) (treatment KD); and tiletamine-zolazepam (2.4 mg ...
Antimicrobial prescribing patterns in equine ambulatory practice. Antimicrobial resistance is one of the most important public health risks facing our world today. Antimicrobials are commonly prescribed in equine veterinary medicine, but limited information exists documenting their use in practice. The goal of this study was to investigate antimicrobial prescription patterns in regards to prescription frequency, duration, drug class, clinician and affected body system in an equine ambulatory setting via retrospective analysis of billing and electronic medical records. Risk factors associated with antimicrobial prescription including the nature of the visit, ...
Kinetic disposition of diazepam and its metabolites after intravenous administration of diazepam in the horse: Relevance for doping control. In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti-doping rule violation. Therefore, a pharmacokinetic study on 6 horses was conducted using a single intravenous (...
Glucocorticoid treatment in horses with asthma: A narrative review. Despite substantial research efforts to improve the treatment and outcome of horses with asthma, glucocorticoids (GC) remain the cornerstone of drug treatment of this prevalent disease. The high efficacy of GC to relieve airway obstruction explains their extensive use despite potential deleterious effects. However, much is yet to be uncovered concerning GC use in horses with asthma, including the comparative efficacy of the different drugs, the determination of minimal effective doses and the mechanisms underlying their variable modulation of airway inflammation. The objectives of this structu...
Evaluation of Intra-Articular Amikacin Administration in an Equine Non-inflammatory Joint Model to Identify Effective Bactericidal Concentrations While Minimizing Cytotoxicity. Septic arthritis causes significant morbidity and mortality in veterinary and human clinical practice and is increasingly complicated by multidrug-resistant infections. Intra-articular (IA) antibiotic administration achieves high local drug concentrations but is considered off-label usage, and appropriate doses have not been defined. Using an equine joint model, we investigated the effects of amikacin injected at three different doses (500, 125, and 31.25 mg) on the immune and cartilage responses in tibiotarsal joints. Synovial fluid (SF) was sampled at multiple time points over 24 h, the cell...
Amiridine-piperazine hybrids as cholinesterase inhibitors and potential multitarget agents for Alzheimer’s disease treatment. We synthesized eleven new amiridine-piperazine hybrids 5a-j and 7 as potential multifunctional agents for Alzheimer's disease (AD) treatment by reacting N-chloroacetylamiridine with piperazines. The compounds displayed mixed-type reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Conjugates were moderate inhibitors of equine and human BChE with negligible fluctuation in anti-BChE activity, whereas anti-AChE activity was substantially dependent on N4-substitution of the piperazine ring. Compounds with para-substituted aromatic moieties (5g, 5h, and bis-amirid...
Novel Algorithms for Comprehensive Untargeted Detection of Doping Agents in Biological Samples. To address the limitations of current targeted analytical methods that can only detect known doping agents, a novel methodology that permits untargeted drug detection (UDD) has been developed to help in the fight against doping in sports. Fifty-seven drugs were spiked into blank equine plasma and were treated as unknowns since their exact masses and chromatographic retention times were not utilized for detection. The spiked drugs were extracted from the plasma samples and were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). The acquired LC-HRMS raw ...
Microbial Prevalence and Antimicrobial Sensitivity in Equine Endometritis in Field Conditions. Endometritis is one of the main causes of infertility in mares. In the present study, 363 mares with a history of repetitive infertility, and positive endometrial cytology and/or vaginal discharge were included. An endometrial swab for microbiological purposes plus sensitivity test was obtained from each mare. A positive culture was obtained in 89% of mares. The main isolated genera were (25.1%), (18.2%), (17.3%) and (12.1%). With regard to species, the most isolated microorganism was (17.3%), spp. (15.6%) and spp. (13.5%). Sensitivity tests showed that the most efficient antimicrobial ...
Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium. Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain () mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-lu...
Can bronchoconstriction and bronchodilatation in horses be detected using electrical impedance tomography? Electrical impedance tomography (EIT) generates images of the lungs based on impedance change and was able to detect changes in airflow after histamine challenge in horses. Objective: To confirm that EIT can detect histamine-provoked changes in airflow and subsequent drug-induced bronchodilatation. Novel EIT flow variables were developed and examined for changes in airflow. Methods: Bronchoconstriction was induced using stepwise histamine bronchoprovocation in 17 healthy sedated horses. The EIT variables were recorded at baseline, after saline nebulization (control), at the histamine concentra...
[New drugs for horses and production animals in 2020]. In 2020, one novel pharmaceutical agent for horses or food-producing animals was released on the German market, rendering the inhaled glucocorticoid ciclesonide (Aservo EquiHaler) available for horses for the first time. The authorization of one established veterinary active ingredient was extended to an additional species: The anthelmintic fenbendazole (Gallifen) from the benzimidazole group is now also authorized for pheasants. Additionally, 3 veterinary drugs with a new combination of active ingredients (ketoprofen + tilmicosin, ketoprofen + tulathromycin, prednisolone + lidoc...
Clinical Randomized Comparison of Medetomidine and Xylazine for Isoflurane Balanced Anesthesia in Horses. To assess drug plasma levels, preanesthetic sedation, cardiopulmonary effects during anesthesia and recovery in horses anesthetized with isoflurane combined with medetomidine or xylazine. Prospective blinded randomized clinical study. Sixty horses undergoing elective surgery. Thirty minutes after administration of antibiotics, flunixine meglumine or phenylbutazone and acepromazine horses received medetomidine 7 μg kg (group MED) or xylazine 1.1 mg kg (group XYL) slowly intravenously (IV) and sedation was assessed 3 min later. Anesthesia was induced with ketamine/diazepam and maintained wi...
The Effect of the Clenbuterol-β2-Adrenergic Receptor Agonist on the Peripheral Blood Mononuclear Cells Proliferation, Phenotype, Functions, and Reactive Oxygen Species Production in Race Horses In Vitro. Clenbuterol, the β2-adrenoceptor agonist, is gaining growing popularity because of its effects on weight loss (i.e., chemical liposuction). It is also popular in bodybuilding and professional sports, due to its effects that are similar to anabolic steroids. However, it is prohibited by anti-doping control. On the other hand, it is suggested that clenbuterol can inhibit the inflammatory process. The cells from 14 untrained and 14 well-trained race horses were collected after acute exercise and cultured with clenbuterol. The expressions of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reac...
Frequency, Local Dynamics, and Genomic Characteristics of ESBL-Producing Escherichia coli Isolated From Specimens of Hospitalized Horses. Previous research identified veterinary clinics as hotspots with respect to accumulation and spread of multidrug resistant extended-spectrum β-lactamase (ESBL)-producing (EC). Therefore, promoting the prudent use of antibiotics to decrease selective pressure in that particular clinical environment is preferable to enhance biosecurity for animal patients and hospital staff. Accordingly, this study comparatively investigated the impact of two distinct perioperative antibiotic prophylaxis (PAP) regimens (short-term versus prolonged) on ESBL-EC carriage of horses subjected to colic surgery. Whil...
Causes of equine perinatal mortality. The peripartum period is critical in equine medicine for maintaining healthy mares, and ensuring the delivery of healthy neonatal foals. The field of perinatal mortality in horses is continuously evolving, with several advances being recently made in causes of perinatal fetal and foal loss. This review details the main causes of perinatal loss in horses, through late pregnancy, parturition and the neonatal period. Recent advances in identification of infectious organisms and indicators of survival in neonatal foals will be discussed. Continued advances in reproductive and neonatal medicine wil...
Antimicrobial Resistance and Extended-Spectrum Beta-Lactamase (ESBL) Genes in E. coli Isolated from Equine Fecal Samples in Turkey. The extensive use of antibacterial agents used for treatment in human and veterinary clinics to increase yield in livestock and aquaculture in developing countries causes the detection and spread of multidrug-resistant (MDR) strains in different sources. The presence of Escherichia coli strains is very common in racehorses and it's a serious problem on horse farms. Extended-spectrum beta-lactamase (ESBL) production is an important source of MDR development in Gram-negative strains such as E.coli. This study aimed to detect the presence of ESBL genes in E. coli strains isolated from horse farms...